Name: 2244-16-8|(S)-2-Methyl-5-(prop-1-en-2-yl)cyclohex-2-enone|98%
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1
[ 2244-16-8 ]
(-)-cis-Carveol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With lithium aluminium hydride In diethyl ether at -78℃; for 0.25h; Inert atmosphere;
99%	With potassium hydroxide; hydrogen In isopropanol at 28℃; for 3.5h;
99%	With lithium aluminium hydride In dichloromethane at 20℃; for 12h;

99%	With lithium aluminium hydride In tetrahydrofuran at -78 - 20℃; for 3h; Inert atmosphere;	1a General method lb: Forming hydroxylated derivatives General procedure: To a cold solution (-78°C) of terpene/terpenoid in solvent and a hydroalumination system was added dropwise and the mixture was stirred for 3 hours, warming to room temperature. The reaction was quenched by slow addition of a quenching system. The aqueous layer was extracted with Et20 (3x) . Combined organic layers were washed with brine, dried and solvent was evaporated to yield the product. General method lb was used. Reagents and amounts used: • carvone (13.0 mL, 83.3 mmol) • solvent and a hydroalumination system: THF (250 mL) LiAlH4 (100 mL, 100 mmol, 1M in THF) • quenching system: water (25 mL), aqueous solution of NaOH (50 mL, 1M in H20) and water (75 mL). Product obtained: 12.6 g (99% yield) of ( li?,5S)-2-methyl-5 -(prop- l -en-2-yl)cyclohex- 2-enol as a colourless oil that becomes solid after storing at low temperature. Stereochemical assignment (based on literature precedent - L. Garver, P. Eikeren J. Org. Chem. 1976, 41, 2773) [a]D22 -40 (c 2.6, CHC13). JH-NMR (400 MHz, CDC13): δ = 5.50 (ddt, J = 5.2, 2.6, 1.4 Hz, 1H), 4.73 (m, 2H), 4. 19 (bs, 1H), 2.3-2.2 (m, 1H), 2.2-2. 1 (m, 1H), 2. 1 -2.0 (m, 1H), 2.0- 1.9 (m, 1H), 1.76 (td, J = 2.5, 1.4 Hz, 3H), 1.74 (s, 3H), 1.6- 1.5 (m, 2H). "C-NMR (100 MHz, CDC13) : δ = 148.9 (s), 136.2 (s), 123.7 (d), 109.0 (t), 70.8 (d), 40.4 (d), 37.9 (t), 3 1.0 (t), 20.5 (q), 18.9 (q) . HRMS (ESI-MS): calcd. for Ci0H16NaO : 175. 1093, found: 175. 1091.
98%	With lithium aluminium hydride In diethyl ether at -50℃; for 2h;
98%	With lithium aluminium hydride In diethyl ether at -78℃; for 1h;
98%	Stage #1: (R)-Carvone With lithium aluminium hydride In dichloromethane at -78 - 20℃; for 3h; Inert atmosphere; Stage #2: With lithium hydroxide monohydrate; sodium hydroxide In dichloromethane at 20℃; for 1h; diastereoselective reaction;
97%	With sodium tetrahydridoborate; cerium(III) trichloride heptahydrate regioselective reaction;
96%	With lithium aluminium hydride In diethyl ether at -78℃;
96%	With LiPyrrBH₃ In tetrahydrofuran at 25℃; for 3h;
96%	With lithium aluminium hydride In diethyl ether at -70℃; for 2h;
95%	With lithium aluminium hydride In diethyl ether
92%	With lithium aluminium hydride In diethyl ether at -78℃;
90%	With sodium tetrahydridoborate; cerium chloride monohydrate In tetrahydrofuran at 0℃;
90%	With sodium tetrahydridoborate; cerium(III) trichloride In methanol
90%	With sodium tetrahydridoborate; cerium chloride heptahydrate In methanol at 20℃; for 0.0833333h;
89%	With lithium aluminium hydride
88%	With sodium tetrahydridoborate; glacial acetic acid; calcium(II) chloride In tetrahydrofuran at -40℃; for 19h; Inert atmosphere;
85%	With zirconocene dichloride; methyl dimethoxy silane; diethylamine In toluene at 35℃; Inert atmosphere;
80%	With sodium tetrahydridoborate; cerium(III) trichloride heptahydrate In methanol at 20℃; for 0.0833333h; stereoselective reaction;	3.2.1. Reduction of (-)-Carvone (1) and (+)-Carvone (2) General procedure: Sodium borohydride (2.5 g, 66.1 mmol) was added at 20°C to a solution of 1 or 2 (10 g,67 mmol), and CeCl3 7H2O (25 g, 148.5 mmol) in methanol (500 mL). The mixture was stirredfor 5 min. Then, diethyl ether (100 mL) and water (100 mL) were added. The organic layer wasseparated, and the aqueous layer was extracted with diethyl ether (3 100 mL). The organic layerswere combined and dried over Na2SO4, and filtered. The filtrate was concentrated under reducedpressure, and the residue was subjected to column chromatography on silica gel using a mixtureof ethyl hexane and ethyl acetate (8:2) as eleuent. (-)-cis-Carveol (3) and (+)-cis-carveol (4) wereobtained with 80% (53.46 mmol) and 78% (52.0 mmol) yields, respectively [27,28]. (3): [α]29 D = 33.7 (CHCl3, c 0.03); IR (KBr) υmax: 3461, 2945, 2900, 1650, 1500, 1050, 900 cm-1; 1H-NMR(CDCl3): δ5.44-5.39 (1H, m), 4.93 (2H, s), 4.25-4.21 (1H, dd, J = 8 Hz), 2.42-2.26 (5H, m), 2.22-2.12(3H, m), 1.65 (3H, s), 1.56 (1H, s); 13C-NMR (CDCl3) : δ146.3, 134.2, 125.3, 106.5, 68.7, 38.3, 36.7, 28.2,27.2, 26.5. CAS 7632-16-8.
80%	With [Re(NH{CH₂CH₂P(iPr₂)}₂)(CO)₃]Br; potassium-t-butoxide; hydrogen In toluene at 110℃; for 17h; Inert atmosphere; Glovebox; Autoclave;
75%	With sodium tetrahydridoborate; cerium(III) trichloride In methanol
75%	With sodium tetrahydridoborate; cerium(III) trichloride In methanol Inert atmosphere;
75%	With anhydrous silver tetrafluoroborate; diphenylsilane; C₃₃H₄₃ClN₃ORh In dichloromethane at 40℃; for 24h; Glovebox; Sealed tube; diastereoselective reaction;
70%	With lithium aluminium hydride In diethyl ether at -78℃;
	With lithium aluminium hydride; diethyl ether
	With lithium aluminium hydride
	With lithium aluminium hydride
	With lithium aluminium hydride In ethanol for 0.5h; Ambient temperature;
	With lithium aluminium hydride In tetrahydrofuran at 0℃;
	With sodium tetrahydridoborate; cerium(III) trichloride
	With lithium aluminium hydride at -70℃;
	With sodium tetrahydridoborate; cerium(III) trichloride In methanol
	With lithium aluminium hydride In diethyl ether at -90℃;
	With sodium tetrahydridoborate; cerium(III) trichloride
	With sodium tetrahydridoborate In methanol
	With methanol; sodium tetrahydridoborate; cerium(III) trichloride for 0.166667h;
> 99 %Chromat.	With sodium tetrahydridoborate; erbium trifluoromethanesulfonate In 2-methyltetrahydrofuran at 20℃; for 0.0833333h; Green chemistry; regioselective reaction;	8 4.2 General procedure for the stereoselective reduction of α,β-unsaturated carbonyl compounds General procedure: To a suspension of α,β-unsaturated carbonyl compound (2.0 mmol) and Er(OTf)3 (0.1 mmol) in 2-MeTHF (3 mL) an equimolar quantity of NaBH4 (2.0 mmol) was added. The reaction mixture was stirred at room temperature and monitored by GC/MS until consumption of starting material. The crude reaction mixture was quenched with H2O (3 mL), the organic phase was dried on dry Na2SO4 and the solvent was evaporated under reduced pressure. The desired product was obtained pure after work-up.
	With sodium tetrahydridoborate; cerium(III) trichloride heptahydrate In methanol at 0℃; for 0.25h;
	With lithium aluminium hydride In diethyl ether at -78℃;
	With diisobutylaluminium hydride In dichloromethane at -78℃;
90 % de	With glutamate dehydrogenase; D-glucose; LfSDR₁ M₅₀ varient; β-nicotinamide adenine dinucleotide phosphate, oxidized form In aq. phosphate buffer; ethanol at 30℃; for 12h; Enzymatic reaction; diastereoselective reaction;
	Multi-step reaction with 2 steps 1: Di-n-butylmagnesium / toluene; n-heptane / 2 h / 23 °C / Sealed tube; Inert atmosphere 2: methanol / 0.5 h
	With lithium aluminium hydride In diethyl ether at -78℃; for 1h; Inert atmosphere;
	With lithium aluminium hydride In diethyl ether at -78℃; Inert atmosphere;

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2
[ 2244-16-8 ]
[ 5524-05-0 ]
(+)-isodihydrocarvone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With zinc In ethanol Yields of byproduct given;
50%	With zinc In ethanol Yield given;
1: 41% 2: 11%	With Mn(CO)<SUB>3</SUB>Br(k<SUP>2</SUP>P,N-Ph<SUB>2</SUB>PN(H)Py); potassium <i>tert</i>-butylate; hydrogen In toluene at 80℃; for 18h; Glovebox; Autoclave; Inert atmosphere; regioselective reaction;

	With potassium hydroxide; zinc
	With sodium hydrogen telluride In ethanol Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
	With sodium phosphate buffer; Synechococcus sp. PCC 7942 whole cells at 25℃; for 72h; Irradiation; Title compound not separated from byproducts;
	With iodine pentoxide; Dimethylphenylsilane In dichloromethane at 20℃; for 5h; Title compound not separated from byproducts;
	With zinc
	With formic acid; C₁₅H₁₆IrN₂O₃⁽¹⁺⁾*O₄S^(2-) In water at 40℃; for 1.5h; Inert atmosphere; optical yield given as %de; chemoselective reaction;
	With methanol; potassium hydroxide; zinc optical yield given as %de; enantioselective reaction;
	With β-D-glucose 6-phosphate; pentaerythritol tetranitrate reductase His₈ H₁₈₁A; pentaerythritol tetranitrate reductase His₈ H₁₈₄R; NADPH In N,N-dimethyl-formamide at 30℃; for 48h; phosphate buffer; Inert atmosphere; anaerobic; Enzymatic reaction; optical yield given as %ee; diastereoselective reaction;
	With baker's yeast In water at 30℃; for 4h; Potassium phosphate/citric acid buffer; Microbiological reaction; Ionic liquid; Enzymatic reaction; optical yield given as %de; diastereoselective reaction;
	With β-D-glucose at 25℃; for 120h; Microbiological reaction; stereoselective reaction;
	With hydrogen In methanol at 99.84℃;	2.3. Catalytic experiments (-)-Carvone, (-)-carvone oxime and (2R,5R,E)-dihydrocarvoneoxime were used as substrates, while methanol was applied as asolvent. The reactions were carried out in a stainless steel reactorequipped with an electromagnetic stirrer (1100 rpm) and the sam-pling system. In a typical experiment, a mixture of the substrate(5 mmol), solvent (15 ml) and 1.9 wt.% Au/TiO2catalyst (140 mg)was intensively stirred at 100C under H2or N2atmosphere (9 bar).At regular time intervals, the samples were withdrawn and ana-lyzed by gas chromatography (Tsvet-500) using a Carbowax-20 Mcolumn (length 50 m, inner diameter 0.2 mm and film thickness0.5 m) at 160C and a flame ionization detector operating at250C. Additionally the structure of reaction products was con-firmed by analysis with a gas chromatography-mass spectrometer(Agilent Technologies 7000 GC/MS Triple Quad, HP-5MS column)as well as by NMR spectroscopy. The chemical shifts of the cis- and trans-dihydrocarvones were determined in accordance with [29].1H NMR spectra were recorded by Bruker AV-400 spectrometer(400.13 MHz (1H)) in the CDCl3solutions of the reaction mixture.
	Multi-step reaction with 2 steps 1: sodium acetate; hydroxylamine hydrochloride / methanol; water / 96 h / 20 °C 2: ; hydrogen / methanol / 99.84 °C / 6750.68 Torr
	With reduced flavin mononucleotide; alpha-D-glucopyranose; glucose dehydrogenase from Thermoplasma acidophilum; old yellow enzyme 1 from Saccharomyces pastorianus; old yellow enzyme, W₁₁₆A variant In aq. buffer at 20℃; for 4h; Enzymatic reaction;	4.5 Enzymatic activity assay for OYE1 variants General procedure: Ene-reductase activity assays were performed at ambient temperature under anaerobic conditions (Coy Laboratory, Grass Lake, MI). For preparing reaction stock solution, individual substrates (see below) were dissolved in 50mM Tris-HCl (pH 7.5), supplemented with 200μM NADP+, 100mM glucose, and glucose dehydrogenase (GDH) from Thermoplasma acidophilum (2 units for IVTT reactions, 5 units for purified enzyme reactions). Individual substrate concentrations were chosen to ensure vmax conditions or maximum solubility. At these substrate levels, reaction times were adjusted for 10-50% substrate conversion. To assay OYE activity in IVTT experiments, 20μL of the reaction stock solution was mixed with 2-10μL IVTT reaction mixture and the total assay volume was adjusted to 30μl with 50mM Tris-HCl (pH 7.5). To assay purified OYE1 variants, the enzyme (final concentration: 250nM) was added to 500μl reaction stock solution. Reaction progress was monitored by removing 30-μl aliquots from the assay solution and quenching them by mixing thoroughly with 30μL of ethyl acetate containing 1mM cyclohexanone as internal standard. A sample of the organic phase was collected and analyzed by GC (protocols: see below). The enantio/diasteriomeric excess were calculated by integration of product and substrate peak areas. Relative rates of conversion for individual substrates were calculated by dividing the measured rate of conversion for OYE1 variant over the corresponding rate for wild type OYE1.
69 % de	With tetrabutylphosphonium (S)-(+)-prolinate; hydrogen; palladium dichloride at 20℃; for 18h; Schlenk technique; Inert atmosphere; Green chemistry; diastereoselective reaction;
62 % de	With glucose-6-phosphate In dimethyl sulfoxide at 24℃; for 24h; Sealed tube; Darkness; Enzymatic reaction; stereoselective reaction;
89 % de	With D-glucose; mutant of saccharomyces pastorianus OYE 1 with methionine at 116 position In aq. phosphate buffer at 20℃; for 24h; Enzymatic reaction; stereoselective reaction;
56 % de	With D-glucose; mutant of saccharomyces pastorianus OYE 1 with valine at 116 position In aq. phosphate buffer at 20℃; for 24h; Enzymatic reaction; stereoselective reaction;
18 % de	With glucose-6-phosphate dehydrogenase; glucose-6-phosphate; 12-oxophytodienoate reductase from S_. lycopersicum OPR₃; NAD In aq. buffer at 28℃; for 3h; Enzymatic reaction;
70 % de	With glutamate dehydrogenase; D-glucose; PETNR; nicotinamide adenine dinucleotide phosphate In aq. phosphate buffer; ethanol at 25℃; for 12h; Enzymatic reaction; diastereoselective reaction;
70 % de	With glutamate dehydrogenase; D-glucose; OYE₁ W₁₁₆A, T₃₇A variant; nicotinamide adenine dinucleotide phosphate In aq. phosphate buffer; Petroleum ether at 25℃; for 12h; Enzymatic reaction; diastereoselective reaction;
	With Saccharomyces cerevisiae old yellow enzyme 2; Pseudomonas sp. glucose dehydrogenase; NAD In aq. phosphate buffer at 30℃; for 24h; Enzymatic reaction; Overall yield = 82 %; Optical yield = 85 %de;

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[19]Powell, Robert W.; Buteler, M. Pilar; Lenka, Sunidhi; Crotti, Michele; Santangelo, Sara; Burg, Matthew J.; Bruner, Steven; Brenna, Elisabetta; Roitberg, Adrian E.; Stewart, Jon D. [Catalysis science and technology, 2018, vol. 8, # 19, p. 5003 - 5016]
[20]Powell, Robert W.; Buteler, M. Pilar; Lenka, Sunidhi; Crotti, Michele; Santangelo, Sara; Burg, Matthew J.; Bruner, Steven; Brenna, Elisabetta; Roitberg, Adrian E.; Stewart, Jon D. [Catalysis science and technology, 2018, vol. 8, # 19, p. 5003 - 5016]
[21]Iqbal, Naseem; Stewart, Jon D.; Macheroux, Peter; Rudroff, Florian; Mihovilovic, Marko D. [Tetrahedron, 2018, vol. 74, # 52, p. 7389 - 7394]
[22]Guo, Jiyang; Zhang, Rui; Ouyang, Jingping; Zhang, Feiting; Qin, Fengyu; Liu, Guigao; Zhang, Wenhe; Li, Hengyu; Ji, Xiaohong; Jia, Xian; Qin, Bin; You, Song [ChemCatChem, 2018, vol. 10, # 23, p. 5496 - 5504]
[23]Guo, Jiyang; Zhang, Rui; Ouyang, Jingping; Zhang, Feiting; Qin, Fengyu; Liu, Guigao; Zhang, Wenhe; Li, Hengyu; Ji, Xiaohong; Jia, Xian; Qin, Bin; You, Song [ChemCatChem, 2018, vol. 10, # 23, p. 5496 - 5504]
[24]Issa, Issa S.; Toogood, Helen S.; Johannissen, Linus O.; Raftery, James; Scrutton, Nigel S.; Gardiner, John M. [Chemistry - A European Journal, 2019, vol. 25, # 12, p. 2983 - 2988]

3
[ 2244-16-8 ]
[ 33375-08-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen In benzene for 120h;
100%	With Wilkinson's catalyst; hydrogen In toluene at 20℃; for 2h; Inert atmosphere;
99%	With hydrogen at 25℃;

98%	With Wilkinson's catalyst; hydrogen In benzene at 20℃; for 48h;
98%	With hydrogen In benzene at 25℃; for 40h;
95%	With hydrogen In ethanol for 6h; Ambient temperature;
94%	With hydrogen
93%	With Wilkinson's catalyst; hydrogen In benzene at 20℃; for 16h;
85%	With RhCl(PPh₃)3; hydrogen In benzene
82%	With Wilkinson's catalyst; hydrogen In benzene at 20℃;
82%	With hydrogen
	With acetic acid; platinum Hydrogenation;
	With hydrogen In ethanol
	With hydrogen
	With hydrogen
	With hydrogen In ethanol at 20℃; Yield given;
38 % Chromat.	With hydroxylamine In various solvent(s) at 70℃;
	With platinum(IV) oxide; hydrogen In ethyl acetate at 20℃; for 5h;
	With palladium on carbon; hydrogen
	With platinum(IV) oxide; hydrogen for 14h; Inert atmosphere;	1.1 1) (1S,4R,6S)-4-isopropyl-1-methyl-7-oxabicyclo[4.1.0]Synthesis 21 R) - (-) - carboxylic (4.13 mL, 26.3 mmol) in, PtO2 (6.0 mg, 26.3μmol) was added, and the mixture was stirred under 14 hours hydrogen atmosphere vigorously. Then do the Celite filtration, and the filtrate was concentrated under reduced pressure. Aqueous dioxane solution of the compound obtained crude product of (1) (10%, 220 mL) to, NBS (23.4 g, 132 mmol) and 1N perchloric acid (78.9 mL, 78.9 mmol) and was added, 0 ° C. in and the mixture was stirred for 4 hours. Quenched with saturated aqueous sodium thiosulfate solution and saturated aqueous sodium bicarbonate sulfate, and extracted with reaction EtOAc. The combined organic layer was dried over Na2SO4, and concentrated under reduced pressure, it was dissolved crude material obtained in the CH2Cl2 (88 mL), DBU (3.90 mL, 26.3 mmol) and the mixture was stirred for 10 minutes at room temperature. The reaction was diluted with EtOAc, and the organic layer was washed three times with water. The resulting organic layer was dried with Na2SO4, and concentrated under reduced pressure. The resulting crude material by column chromatography (silica gel 200 g, hexane: EtOAc = 80: 1) By performing the purification, compound as a colorless oil (2) (2.44 g, 3 steps, 55%) was obtained.
	With platinum(IV) oxide; hydrogen In neat (no solvent) at 20℃; for 14h; Inert atmosphere; regioselective reaction;
	With platinum(IV) oxide; hydrogen In methanol at 20℃; for 5h; regioselective reaction;

Reference： [1]Srikrishna; Gharpure, Santosh J. [Journal of the Chemical Society. Perkin Transactions 1 (2001), 2000, # 19, p. 3191 - 3193]
[2]Hinchcliffe; Hughes; Pears; Pitts [Organic Process Research and Development, 2007, vol. 11, # 3, p. 477 - 481]
[3]Deslongchamps; Belanger; Berney; Borschberg; Brousseau; Doutheau; Durand; Katayama; Lapalme; Leturc; Liao; MacLachlan; Maffrand; Marazza; Martino; Moreau; Ruest; Saint-Laurent; Saintonge; et al. [Canadian Journal of Chemistry, 1990, vol. 68, # 1, p. 127 - 152]
[4]Srikrishna, Adusumilli; Dinesh, Chikkana [Tetrahedron Asymmetry, 2005, vol. 16, # 14, p. 2393 - 2395]
[5]Fuerstner, Alois; Hannen, Peter [Chemistry - A European Journal, 2006, vol. 12, # 11, p. 3006 - 3019]
[6]McChesney; Wycpalek [Journal of Pharmaceutical Sciences, 1983, vol. 72, # 10, p. 1131 - 1134]
[7]Paquette, Leo A.; Dahnke, Karl; Doyon, Julien; He, Wei; Wyant, Kenetha; Friedrich, Dirk [Journal of Organic Chemistry, 1991, vol. 56, # 21, p. 6199 - 6205]
[8]Hemmersbach, Lars; Romanski, Steffen; Botov, Svetlana; Adler, Andreas; Neudörfl, Jörg-Martin; Schmalz, Hans-Günther [Organometallics, 2021, vol. 40, # 16, p. 2909 - 2914]
[9]Hua, Duy H; Takasu, Kiyosei; Huang, Xiaodong; Millward, Gail S; Chen, Yi; Fan, Jingmei [Tetrahedron, 2000, vol. 56, # 38, p. 7389 - 7398]
[10]Ceccarelli, Simona M; Piarulli, Umberto; Gennari, Cesare [Tetrahedron, 2001, vol. 57, # 40, p. 8531 - 8542]
[11]Fang, Lijing; Bi, Fuqiang; Zhang, Chen; Zheng, Guojun; Li, Yulin [Synlett, 2006, # 16, p. 2655 - 2657]
[12]Nagasawa [1938, vol. 19, # 4, p. 1,21][Chem.Abstr., 1940, p. 219]
[13]Carman,R.M.; Venzke,B.N. [Australian Journal of Chemistry, 1973, vol. 26, p. 1977 - 2007]
[14]Schiendorfer, Michael; Mattay, Jochen [Synthesis, 2005, # 16, p. 2701 - 2712]
[15]Chen, Peiling; Chen, Yanping; Carroll, Patrick J.; Sieburth, Scott McN. [Organic Letters, 2006, vol. 8, # 15, p. 3367 - 3370]
[16]Kitahara; Kurata; Matsuoka; Mori [Tetrahedron, 1985, vol. 41, # 23, p. 5475 - 5485]
[17]Gaviglio, Carina; Doctorovich, Fabio [Journal of Organic Chemistry, 2008, vol. 73, # 14, p. 5379 - 5384]
[18]Location in patent: experimental part Padhi, Santosh Kumar; Bougioukou, Despina J.; Stewart, Jon D. [Journal of the American Chemical Society, 2009, vol. 131, p. 3271 - 3280]
[19]Location in patent: scheme or table Chen, Peiling; Carroll, Patrick J.; Sieburth, Scott McN. [Organic Letters, 2010, vol. 12, # 20, p. 4510 - 4512]
[20]Current Patent Assignee: THE KITASATO INSTITUTE - JP2016/8191, 2016, A Location in patent: Paragraph 0136-0137
[21]Ohtawa, Masaki; Arima, Shiho; Ichida, Naoki; Terayama, Tomiaki; Ohno, Hironao; Yamazaki, Takaya; Ohshiro, Taichi; Sato, Noriko; Omura, Satoshi; Tomoda, Hiroshi; Nagamitsu, Tohru [ChemMedChem, 2018, vol. 13, # 5, p. 411 - 421]
[22]Dethe, Dattatraya H.; Dherange, Balu D. [Journal of Organic Chemistry, 2018, vol. 83, # 6, p. 3392 - 3396]

4
[ 2244-16-8 ]
[ 26127-86-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	With pyridine; hydroxylamine hydrochloride In ethanol Reflux;	General procedure for ketone oximation General procedure: 50 mL of ethanol, 5 mL of pyridine, 6.50 mmol ketone and 60 mmol hydroxylamine hydrochloride were added into a 100 mL round-bottom flask. The reaction was monitored with thin layer chromatography. After the complete reaction of the substrates, 300 mL of distilled water was added to the mixture. The beaker was placed in the refrigerator to accelerate product crystallization. The crystals were filtered under reduced pressure. The crude product was sufficiently pure for use in the next stage of the reaction and microbiological assays.
	With hydroxylamine hydrochloride; potassium acetate
	With hydroxylamine hydrochloride; sodium acetate In methanol; water at 20℃; for 96h;	2.2. Synthesis of (-)-carvone oxime and (2R,5R,E)-dihydrocarvone oxime First to obtain (-)-carvone oxime a 100-ml round-bottom flaskwas charged with hydroxylamine hydrochloride (13.4 mmol,0.93 g), sodium acetate (13.4 mmol, 1.10 g), (-)-carvone(6.67 mmol, 1.00 g, []20D= -58 (c = neat)), methanol (20 ml) andwater (17 ml). The solution was stirred for 4 days at r.t. and thenwater (100 ml) was added. The reaction mixture was extractedwith ethyl acetate (EtOAc) (3 × 50 ml). The combined organicphase was washed with saturated sodium bicarbonate (2 × 25 ml),brine (2 × 25 ml) and then dried (Na2SO4). As a result, (-)-carvoneoxime (0.83 g (75%)) was obtained. The synthesized (-)-carvoneoxime was characterized by13C and1H NMR (supplementary data,Figs. S1 and S2 , respectively). The13C NMR spectral characteristicsof (-)-carvone oxime corresponded to those described in theliterature [27].

Reference： [1]Grabowiecka, Agnieszka; Grela, Ewa; Macegoniuk, Katarzyna; Kozioł, Agata; Lochyński, Stanisław [Natural Product Research, 2020, vol. 34, # 8, p. 1074 - 1079]
[2]Timmermans [Bulletin des Societes Chimiques Belges, 1930, vol. 39, p. 239,240, 246] Voigt; Rogers; Fischer [Journal of the American Pharmaceutical Association (1912), 1938, vol. 27, p. 643,651] Nagasawa [1938, vol. 19, # 4, p. 19][Chem.Abstr., 1940, p. 219]
[3]Suga, Takayuki; Hirata, Toshifumi; Futatsugi, Masayuki [Phytochemistry, 1984, vol. 23, # 6, p. 1327 - 1328]
[4]Demidova, Yu. S.; Suslov; Simakova; Volcho; Salakhutdinov; Simakova; Murzin, D. Yu. [Journal of Molecular Catalysis A: Chemical, 2016, vol. 420, p. 142 - 148]

5
[ 75-77-4 ]
[ 2244-16-8 ]
[ 116399-80-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With triethylamine; sodium iodide In acetonitrile at 20℃; for 1h;
93%	Stage #1: (R)-Carvone With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -80℃; for 0.333333h; Inert atmosphere; Stage #2: chloro-trimethyl-silane In tetrahydrofuran; hexane at -80 - 0℃; for 1.5h; Inert atmosphere;
	With lithium diisopropyl amide 1.) THF, -78 deg C, 30 min; 2.) -78 deg C, 2 h; Yield given. Multistep reaction;

	With Phenanthroline; lithium diisopropyl amide 1.) THF, -78 deg C, 20 min, 2.) from -78 deg C to room temperature, 1 h.; Multistep reaction;
	With sodium hexamethyldisilazane In tetrahydrofuran at 0℃;
	With lithium diisopropyl amide
	Stage #1: (R)-Carvone With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Stage #2: chloro-trimethyl-silane In tetrahydrofuran at -78 - 0℃;

Reference： [1]Dos Santos, Reginaldo B.; Brocksom, Timothy J.; Zanotto, Paulo R.; Brocksom, Ursula [Molecules, 2002, vol. 7, # 2, p. 129 - 134]
[2]Ardashov, Oleg V.; Pavlova, Alla V.; Il'ina, Irina V.; Morozova, Ekaterina A.; Korchagina, Dina V.; Karpova, Elena V.; Volcho, Konstantin P.; Tolstikova, Tat'yana G.; Salakhutdinov, Nariman F. [Journal of Medicinal Chemistry, 2011, vol. 54, # 11, p. 3866 - 3874]
[3]Barner, Bruce A.; Liu, Yalei; Rahman, Md. Abdur [Tetrahedron, 1989, vol. 45, # 19, p. 6101 - 6112]
[4]Baranovsky, Alexander V.; Jansen, Ben J. M.; Meulemans, Tommi M.; De Groot, Aede [Tetrahedron, 1998, vol. 54, # 21, p. 5623 - 5634]
[5]Kim, Hee Jin; Koo, Sangho [Organic and Biomolecular Chemistry, 2005, vol. 3, # 19, p. 3479 - 3481]
[6]Location in patent: scheme or table Valeev; Bikzhanov; Selezneva; Gimalova; Miftakhov [Russian Journal of Organic Chemistry, 2011, vol. 47, # 9, p. 1287 - 1292]
[7]Kim, Danhee; Lim, Hee Nam [Organic Letters, 2020, vol. 22, # 19, p. 7465 - 7469]

6
[ 4519-46-4 ]
[ 2244-16-8 ]
[ 74285-22-6 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1980,p. 963 - 977

7
[ 308363-12-4 ]
[ 2244-16-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With (η3-allyl)(N,N'-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene)chloropalladium(II); 2,4-dichlorotoluene; sodium t-butanolate In toluene at 120℃; for 0.166667h; Microwave irradiation; Inert atmosphere;
91%	With Oxone; sodium ortho-iodobenzenesulfonate; sodium sulfate In ethyl acetate at 70℃; for 8h; Inert atmosphere;
66%	With oxygen; nitric acid; 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane; water at 20℃; for 18h; Sealed tube;

61%	With potassium phosphate; copper(l) iodide; 1,10-Phenanthroline In 1,4-dioxane at 80℃; Schlenk technique;	General Procedure-2 [For the open air oxidation of alcohols to carbonyl compounds; GP-2(method B)]: General procedure: In an oven dried Schlenk tube, were added alcohol 1 (69.0-199.5 mg, 0.5 mmol), CuI (10 mol%)and 1,10-Phenanthroline (20 mol%) and K3PO4 (2 mmol) followed by the addition of dioxane (2mL) at room temperature under open air atmosphere. The stirred reaction mixture was heated inan oil bath at 80 C for 7-48 h. Progress of the reaction was monitored by TLC till the reaction iscompleted. Then, the reaction mixture was cooled to room temperature, quenched with aqueousNH4Cl solution and then extracted with CH2Cl2 (3 10 mL). The organic layer was washed withsaturated NaCl solution, dried (Na2SO4), and filtered. Evaporation of the solvent under reducedpressure and purification of the crude material by silica gel column chromatography (petroleumether/ethyl acetate) furnished the aldehyde/ketone 2 (61-97%).
42%	With tert-butyl 1-hydroxy-2-methyl-6-trifluoromethyl-1H-indole-3-carboxylate; oxygen; copper(l) chloride In N,N-dimethyl-formamide at 50℃; for 24h; chemoselective reaction;	2.2 General procedure for aerobic oxidation of allylic and benzylic alcohols General procedure: To a 10 mL Schlenk tube, NHI-1 (0.2 mmol, 63 mg) and CuCl (0.2 mmol, 19.6 mg) and DMF (2 mL) were added and stirred at 50 °C for about 30 min to form a dark red solution. Alcohol 11 (2 mmol) was added, the mixture was left to stir at 50 °C under an oxygen balloon (1 atm). The reaction progress was monitored by TLC or GC. After completion, the mixture was allowed to cool to room temperature, quenched with 1M HCl and diluted with H2O (50 mL), extracted with EtOAc (EA) (10 mL × 3), the combined organic layer was washed with brine and dried over MgSO4, the crude was purified by flash column chromatography (EtOAc : hexane = 1 : 10 to 1: 3) to afford ketone or aldehyde 12.
35%	With 5-(2',4'-dinitrobenzylidene)-1,3-dimethylbarbituric acid In 1,4-dioxane for 72h; Heating;
88 % Spectr.	With trimethylamine-N-oxide; CHDFe-(CO)3 In benzene at 20℃; for 10h;
	With manganese(IV) oxide In dichloromethane for 24h;
31 %Chromat.	With tert.-butylhydroperoxide; Cs₅V₁₄As₈O₄₂Cl In water; acetone at 20℃; for 12h;
	With C₃₄H₃₇N₄O₆Ru₂⁽¹⁺⁾*Cl^(1-); potassium hydroxide In toluene at 70℃; for 24h; Schlenk technique; Inert atmosphere;
	With tert.-butylhydroperoxide; Cs₅V₁₄As₈O₄₂Cl In water; acetone at 20℃; for 48h; Sealed tube;
	With 2,2,6,6-tetramethyl-piperidine-N-oxyl; Trametes versicolor laccase; oxygen In aq. buffer at 30℃; for 32h; Enzymatic reaction;
	With sodium anthraquinone-2-sulfonate; oxygen In water at 30℃; for 8h; Irradiation;
	With fluorosulfonyl fluoride; potassium carbonate; dimethyl sulfoxide at 20℃; for 12h; chemoselective reaction;

Reference： [1]Location in patent: experimental part Landers, Brant; Berini, Christophe; Wang, Chao; Navarro, Oscar [Journal of Organic Chemistry, 2011, vol. 76, # 5, p. 1390 - 1397]
[2]Uyanik, Muhammet; Akakura, Matsujiro; Ishihara, Kazuaki [Journal of the American Chemical Society, 2009, vol. 131, p. 251 - 262]
[3]Arseniyadis, Stellios; Clavier, Louis; Copin, Chloé; Fournier, Jean; Giffard, Jean-François; Jean, Alexandre; Katsina, Tania; Macedo Portela Da Silva, Nayane; Tamion, Rodolphe [Organic process research and development, 2020, vol. 24, # 5, p. 856 - 860]
[4]Reddy, Alavala Gopi Krishna; Mahendar, Lodi; Satyanarayana, Gedu [Synthetic Communications, 2014, vol. 44, # 14, p. 2076 - 2087]
[5]Shen, Shu-Su; Kartika, Vita; Tan, Ying Shan; Webster, Richard D.; Narasaka, Koichi [Tetrahedron Letters, 2012, vol. 53, # 8, p. 986 - 990]
[6]Tanaka, Kiyoshi; Chen, Xing; Kimura, Teiji; Yoneda, Fumio [Chemical and pharmaceutical bulletin, 1988, vol. 36, # 1, p. 60 - 69]
[7]Pearson, Anthony J.; Kwak, Yoonhyun [Tetrahedron Letters, 2005, vol. 46, # 32, p. 5417 - 5419]
[8]Macaev; Vlad; Gudima [Chemistry of Natural Compounds, 2006, vol. 42, # 3, p. 301 - 303]
[9]Campbell, McKenzie L.; Sulejmanovic, Dino; Schiller, Jacqueline B.; Turner, Emily M.; Hwu, Shiou-Jyh; Whitehead, Daniel C. [Catalysis science and technology, 2016, vol. 6, # 9, p. 3208 - 3213]
[10]Dutta, Indranil; Sarbajna, Abir; Pandey, Pragati; Rahaman, S. M. Wahidur; Singh, Kuldeep; Bera, Jitendra K. [Organometallics, 2016, vol. 35, # 10, p. 1505 - 1513]
[11]Campbell, McKenzie L.; Sulejmanovic, Dino; Schiller, Jacqueline B.; Turner, Emily M.; Hwu, Shiou-Jyh; Whitehead, Daniel C. [Helvetica Chimica Acta, 2017, vol. 100, # 3]
[12]Martínez-Montero, Lía; Gotor, Vicente; Gotor-Fernández, Vicente; Lavandera, Iván [ACS Catalysis, 2018, vol. 8, # 3, p. 2413 - 2419]
[13]Zhang, Wuyuan; Fueyo, Elena Fernandez; Hollmann, Frank; Martin, Laura Leemans; Pesic, Milja; Wardenga, Rainer; Höhne, Matthias; Schmidt, Sandy [European Journal of Organic Chemistry, 2019, vol. 2019, # 1, p. 80 - 84]
[14]Zha, Gao-Feng; Fang, Wan-Yin; Leng, Jing; Qin, Hua-Li [Advanced Synthesis and Catalysis, 2019, vol. 361, # 10, p. 2262 - 2267]

8
[ 2244-16-8 ]
[ 56423-45-1 ]

Yield	Reaction Conditions	Operation in experiment
86.5%	With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0℃; for 13h;
67%	With 3-chloro-benzenecarboperoxoic acid In chloroform at 20℃; for 24h;

Reference： [1]Baldwin,J.F.; Broline,B.M. [Journal of the American Chemical Society, 1982, vol. 104, p. 2857]
[2]Kimbaris, Athanasios C.; González-Coloma, Azucena; Andrés, Maria Fe; Vidali, Veroniki P.; Polissiou, Moschos G.; Santana-Méridas, Omar [Chemistry and biodiversity, 2017, vol. 14, # 3]

9
[ 2244-16-8 ]
[ 677326-54-4 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium hydroxide; dihydrogen peroxide In methanol at 25℃; for 1h;
86%	With dihydrogen peroxide; potassium carbonate In methanol at 25℃; for 5h;
83%	With dihydrogen peroxide; sodium hydroxide In ethanol at 10℃;

40%	With L-arginine; dihydrogen peroxide In tert-Amyl alcohol; hexane; water at 25℃; for 24h;	A general method for the epoxidation is as follows General procedure: Method A: in a 4 mL vial, cyclohex-2-enone (0.5 mmol, 48 μL), internal standard (t-amyl alcohol, 0.05 mmol, 5.5 μL), amino acid (0.05 mmol), H2O2 (1.5 mmol, 155 μL of 30%) were added in water (791.5 μL). The reaction mixture was stirred at 25 °C. After 2 h, the reaction mixture (100 μL) was retrieved and extracted with hexane (1 mL). The hexane layer was analyzed by gas chromatography. Method B: in a 4 mL vial, cyclohex-2-enone (0.5 mmol, 48 μL), internal standard (t-amyl alcohol, 0.05 mmol, 5.5 μL), amino acid (0.05 mmol), H2O2 (1.5 mmol, 155 μL of 30%) were added in water (791.5 μL). After addition of hexane (1 mL), the reaction mixture was vigorously stirred at 25 °C. After 2 h, 100 μL of the hexane layer was retrieved for analysis by gas chromatography.
20%	With sodium percarbonate; N,N,N',N'-tetraacetylethylenediamine; sodium hydrogencarbonate In dichloromethane
	With gallium(III) nitrate; dihydrogen peroxide In water; ethyl acetate at 80℃; for 0.5h;	4. Experimental General procedure: The experiments on olefin oxidations were carried out in ace-tonitrile in thermostated Pyrex cylindrical vessels (total volume10 mL) with vigorous stirring. In a typical experiment, initially,a portion of the aqueous solution of H2O2(aqueous 70% hydro-gen peroxide, Solvay, solution was used as received) was addedto the solution of a substrate, catalyst 1 (gallium nitrate) in ace-tonitrile. Catalyst 1 was used in the form of stock solutions inH2O2. (CAUTION. The combination of air or molecular oxygen andH2O2with organic compounds at elevated temperatures may beexplosive). After certain periods, the reaction mixture wasanalyzed by GC using Shimadzu-HP 2010 gas chromato-graph equipped with a polyethylene glycol column (Innowax,25 m × 0.2 mm × 0.4 m) coupled to the flame ionization detectorand an automatic injector measuring concentrations of prod-ucts. Authentic samples of all oxygenated products were used toattribute the peaks in chromatograms (comparison of retentiontimes was carried out for different regimes of GC-analysis). Thequantification of products was accomplished by constructing cal-ibration curves for the products, by using standards of knownconcentrations knownconcentrations, and CH3NO2as internal standard. The productsformed from natural compounds were identified by using a gaschromatography coupled to a mass spectrometer (GC-MS) Shi-madzu 2010-plus. The turbidity of the system was monitored usinga turbidimeter PoliControl AP2000.

Reference： [1]Yang, Seung Gak; Hwang, Je Pil; Park, Min Young; Lee, Kieseung; Kim, Yong Hae [Tetrahedron, 2007, vol. 63, # 24, p. 5184 - 5188]
[2]McChesney, James D.; Thompson, Thomas N. [Journal of Organic Chemistry, 1985, vol. 50, # 19, p. 3473 - 3481]
[3]Plessis, Caroline [Chemistry and biodiversity, 2014, vol. 11, # 10, p. 1517 - 1539]
[4]Location in patent: experimental part Kim, Juhyun; Jung, Suhyun; Park, Seongsoon; Park, Sojung [Tetrahedron Letters, 2011, vol. 52, # 22, p. 2866 - 2868]
[5]Benitez, Ricardo B.; Bermudez, John H.; Franco, Jaime M.; Rojas, Giovanni [Journal of the Brazilian Chemical Society, 2020, vol. 31, # 5, p. 1086 - 1092]
[6]Mandelli, Dalmo; Kozlov, Yuriy N.; da Silva, Cezar A.R.; Carvalho, Wagner A.; Pescarmona, Paolo P.; Cella, Daniele de A.; de Paiva, Polyana T.; Shul'pin, Georgiy B. [Journal of Molecular Catalysis A: Chemical, 2016, vol. 422, p. 216 - 220]

10
[ 2244-16-8 ]
[ 36616-60-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium hydroxide; dihydrogen peroxide In methanol
100%	With dihydrogen peroxide; sodium hydroxide In methanol at -20 - 0℃; for 4h; Inert atmosphere;
98%	With sodium hydroxide; dihydrogen peroxide at 0℃;

98%	With sodium hydroxide; dihydrogen peroxide at 0℃; for 4h;
98%	With sodium hydroxide; dihydrogen peroxide at 0℃; for 3h;
98%	With sodium hydroxide; dihydrogen peroxide In methanol; water at 0℃; for 3h;	1 Preparation of (1R-(1α, 4α, 6α)-1-methyl-4-(1-methylethenyl)-7-oxabicyclo[4.1.0]heptan-2-one (compound 2): (R)-(-)-Carvone (compound 1) (60 g, 0.40 mol) was dissolved in 390 ml of methanol, 30% hydrogen peroxide solution (133 g, 1.17 mol) was added thereto, 6M NaOH (32.7g) was dropped thereinto under cooling with ice and the mixture was stirred at the same temperature for 3 hours. Water (1,170 ml) was added to the reaction solution, the mixture was extracted with tert-butyl methyl ether (500 ml) twice, the extract was washed with water and brine, dried over Na2SO4 and the solvent was evaporated in vacuo to give the title compound (compound 2) (62.5 g, yield 98%) as a colorless oily product. Its NMR data is shown below.1H-NMR (CDCl3) 4.77 (1H, brs), 4.70 (1H, brs), 3.43 (1H, dd, J=1.1, J=3.1), 2.70 (1H, m), 2.57 (1H, dd, J=6.1, J=17.6), 2.36 (1H, m), 2.01 (1H, dd, J=11.6, J=17.6), 1.89 (1H, m), 1.70(3H, s), 1.40(3H, s)
98%	With sodium hydroxide; dihydrogen peroxide In water
98%	With dihydrogen peroxide; sodium hydroxide In methanol; water at -20℃; stereoselective reaction;
96%	With dihydrogen peroxide; sodium hydroxide In methanol; water at 0℃; for 1h;	(1R,4R,6R)-1-methyl-4-(prop-1-en-2-yl)-7-oxa-bicyclo[4.1.0]heptan-2-one (11) To a 0 oC cooled solution of (R)-carvone (10, 1.0 g, 6.657 mmol) and NaOH (2.0 M, 0.35 mL, 0.666 mmol) in methanol (8 mL) was added H2O2 (35%, 2.4 mL, 26.60 mmol) in one portion and the reaction mixture was stirred at 0 oC for 1 h. Then the mixture was added sat. Na2SO3, diluted with CH2Cl2 and washed with sat. NaHCO3. The organic layer was concentrated under reduced pressure and purified by column chromatography with ethyl acetate and hexane (1:10) to afford the product 11 (1.06 g, 96 %) as colorless liquid, Rf 0.60 (ethyl acetate : hexane = 1:5). 1H-NMR (400 MHz; CDCl3): .. 1.38 (s, 3H), 1.69 (s, 3H), 1.87 (t, J = 12.8 Hz, 1H), 2.00 (dd, J = 15.6, 13.4 Hz, 1H), 2.33-2.36 (m, 1H), 2.56 (d, J = 17.6 Hz, 1H), 2.67-2.69 (m, 1H), 3.42 (bs, 1H), 4.69 (s, 1H), 4.76 (s, 1H); 13C-NMR (100 MHz; CDCl3): .. 15.1, 20.4, 28.5, 34.9, 41.6, 58.6, 61.1, 110.3, 146.2, 205.2; MS (EI) m/z 166 (M+, 6), 123 (100), 109 (67), 95 (82), 85 (86), 43 (97); HRMS (EI) calcd for C10H14O2 (M+) 166.0994; Found 166.0989.
95%	With sodium hydroxide; dihydrogen peroxide In methanol at 0℃; for 15h;
95%	With dihydrogen peroxide; sodium hydroxide In methanol at 0℃;
92%	With sodium hydroxide; dihydrogen peroxide In methanol at -10℃; for 3h;
92%	With sodium hydroxide; dihydrogen peroxide In methanol at -10℃; for 3h;
92%	With lithium hydroxide; dihydrogen peroxide In methanol at 0℃;
92%	With sodium hydroxide; water; dihydrogen peroxide In methanol at 0℃;
92%	With dihydrogen peroxide; sodium hydroxide In methanol Inert atmosphere;
92%	With dihydrogen peroxide; sodium hydroxide In methanol; water at -10℃; for 4h;	4.1.1 Preparation of carvone epoxide (+)-13 To a stirred solution of (-)-carvone 9 (23.5mL, 0.15mol) in MeOH (150mL) was added 30% H2O2 (33mL, 0.3mol) at -10°C. Freshly prepared 6N NaOH solution (15mL) was added drop wise to the reaction mixture over a period of 1h. The reaction mixture was stirred at the same temperature for 3h. The reaction mixture was diluted with water (200mL) and extracted with diethyl ether (ether) (3×100mL). The combined extract was washed with water (30mL), brine (30mL) and dried over anhydrous Na2SO4. The crude material was filtered through a silica gel pad to furnish 22.9g of carvone epoxide (+)-13 (92%) as a colorless liquid. [α]D24+47.7 (c 1.3, CHCl3); IR (neat): νmax 1709cm-1.
91%	With potassium hydroxide; 1,1-dihydroperoxycyclohexane In 1,4-dioxane at 20℃; for 2.5h;
90%	With sodium hydroxide; dihydrogen peroxide In methanol
90%	With sodium hydroxide; dihydrogen peroxide In methanol for 1h; Ambient temperature;
90%	With sodium hydroxide; dihydrogen peroxide In methanol
90%	With tert.-butylhydroperoxide; 1,8-diazabicyclo[5.4.0]undec-7-ene In 1,2-dichloro-ethane for 12h; Ambient temperature;
90%	Stage #1: (R)-Carvone With dihydrogen peroxide; sodium hydroxide In methanol; water for 1.5h; Inert atmosphere; Stage #2: With dihydrogen peroxide In methanol; water for 1h; Inert atmosphere;
85%	With potassium fluoride on basic alumina; t-BOOH In dichloromethane; acetonitrile for 10h; Ambient temperature;
85%	With tert.-butylhydroperoxide; aluminum oxide; potassium fluoride In 1,2-dichloro-ethane; acetonitrile for 10h; Ambient temperature;
85.86%	With dihydrogen peroxide; sodium hydroxide In methanol; water at 0℃; for 3h;	19 Compound (11) (30 g, 199.71 mmol, 31.28 mL, 1 eq.) was dissolved in MeOH (200 mL), H2O2 (65.67 g, 579.16 mmol, 55.65 mL, 30% purity, 2.9 eq.) was added, NaOH (6 M, 66.57 mL, 2 eq.) was dropped under 0 oC and the mixture was stirred at 0 °C for 3 hr. TLC (Petroleum ether / Ethyl acetate=3:1, Rf = 0.43) showed compound (11) was consumed. Water (300 mL) was added and extracted with MTBE (200 mL x 2), the combined organic was washed with sat. aq. Na2SO3 (100 mL) and sat. aq. NaHCO3, (100 mL), the organic was dried over Na2SO4, filtered and concentrated to get the crude. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=0/1 to 10/1) to get compound (12) (28.5 g, 171.46 mmol, 85.86% yield) as a colorless oil. 1HNMR (400MHz, CHLOROFORM-d): δ = 4.79 (s, 1H), 4.72 (s, 1H), 3.45 (d, J = 2.2 Hz, 1H), 2.77 - 2.67 (m, 1H), 2.59 (ddd, J = 1.1, 4.6, 17.6 Hz, 1H), 2.37 (td, J = 3.0, 14.8 Hz, 1H), 2.07 - 2.01 (m, 1H), 1.94 - 1.86 (m, 1H), 1.72 (s, 3H), 1.41 (s, 3H). TLC: (Petroleum ether / Ethyl acetate=3:1), Rf = 0.43.
84%	With lithium hydroxide monohydrate; dihydrogen peroxide In methanol at 0℃; for 0.5h; stereoselective reaction;
83%	With sodium hydroxide; dihydrogen peroxide In methanol; water at -15 - 0℃; for 4h;
82%	With sodium perborate In 1,4-dioxane for 0.05h; Irradiation;
80%	With sodium hydroxide; dihydrogen peroxide In methanol at 20℃; for 0.25h;
76%	With dihydrogen peroxide; potassium hydroxide In methanol at 0℃; for 4h;	3.2.4. Epoxidation of (-)-Carvone (1) and (+)-Carvone (2) General procedure: A solution of 1 or 2 g (5 g; 33.33 mmol) was dissolved in MeOH (35 mL), 30% H2O2 (1021 mL;9999 mmol) and 6 N KOH (16.64 mL; 99.99 mmol), and the mixture was stirred for 4 h at 0 °C.The two-phase system was vigorously stirred at room temperature, and the phases were separated;the aqueous layer was extracted with Et2O (3 20 mL). The organic phase was washed with water(3 x20 mL), and dried with Na2SO3. The solvent was evaporated and the residue chromatographedon silica gel, using a mixture of hexane and ethyl acetate (9:1) as eluent. (+)-cis-epoxycarvone(7) and (-)-cis-epoxycarvone (8) were obtained in 76% (25.33 mmol) and 69% (23.0 mmol) yield,respectively [29,30]. (7): [α]29D = +30.5 (CHCl3, c 0.03); IR (KBr) υmax: 2990, 2900, 1720, 1675, 880 cm-1; 1H-NMR(CDCl3)δ: 4.69 (2H, m), 3.38 (1H, d, J = 4.5), 2.48-2.60 (1H, m), 2.04-2.17 (1H, m), 1.95 (1H, dd,J = 11.6), 1.70 (3H, s), 1.63 (3H, s); 13C-NMR (CDCl3) δ: 206.2, 146.4, 111.2, 63.2, 58.5, 41.8, 35.2, 28.8,20.9, 15.7. CAS 36616-60-1.
75%	With sodium hydroxide; dihydrogen peroxide In methanol at 20℃; for 1.5h;
74%	With dihydrogen peroxide; dodecyltrimethylammonium bromide In n-heptane; water at 40℃; for 30h;
71%	With potassium hydroxide; water In methanol at 4℃; for 3h;
70%	With sodium hydroxide; dihydrogen peroxide In methanol at 0℃; for 2h;
	With sodium hydroxide; dihydrogen peroxide In methanol at 20 - 25℃;
	With sodium hydroxide; dihydrogen peroxide In methanol
	With lithium hydroxide; water; dihydrogen peroxide In methanol at 20℃;
	Stage #1: (R)-Carvone With sodium hydroxide; dihydrogen peroxide In methanol at 0 - 5℃; for 5h; Stage #2: With potassium dihydrogenphosphate; sodium sulfite In methanol; water at 25℃;	19A (1R,4R,6R)-4-Isopropenyl-1-methyl-7-oxabicyclo[4.1.0]heptan-2-one (R)-Carvone was epoxidized according to a modification of the method of E. Klein and G. Ohloff (Tetrahedron, 1963, 11, 1091-1099). Thus H2O2 (31%, 95 mL, 836 mmol, 1.3 equivalents) was added to a solution of (L)-carvone (100 mL, 640 mmol) in 650 mL of methanol at <5° C. After cooling to <0° C., 6N NaOH (10.5 mL, 63 mmol, 0.1 equivalents) was added. The reaction temperature was maintained at <5° C. After 5 hours, the reaction was diluted with 650 mL water, then quenched with 0.5 N KH2PO4 (250 mL) and 325 mL of 1 molal Na2SO3, keeping the temperature at <25° C. The reaction was extracted with 2×750 mL tert-butyl methyl ether. The combined tert-butyl methyl ether extracts were washed with 500 mL each of 20% aqueous NaCl then 10% then 25% to provide a clear organic layer which was dried over MgSO4, then filtered and concentrated, then chased with 100 mL of methanol. The resulting solution assayed (GC) at 101.3 g (96%) of the titled compound, which contained 5% of the minor isomer. 1H NMR (400 MHz, CDCl3) δ ppm 1.40 (s, 3 H) 1.70 (s, 3 H) 1.89 (ddd, J=14.75, 11.11, 1.17 Hz, 1 H) 2.02 (dd, J=17.56, 11.66 Hz, 1 H) 2.31 -2.41 (m, 1 H) 2.58 (ddd, J=17.56, 4.67, 1.37 Hz, 1 H) 2.65-2.76 (m, 1 H) 3.44 (dd, J=3.09, 1.03 Hz, 1 H) 4.70 (d, J=0.69 Hz, 1 H) 4.75-4.80 (m, 1 H).
	With dihydrogen peroxide; sodium hydroxide In methanol at 20℃;
	With dihydrogen peroxide; sodium hydroxide In methanol; water at 0 - 20℃;
	With dihydrogen peroxide; potassium carbonate In methanol
	With dihydrogen peroxide; sodium hydroxide In methanol; water at 0℃; for 1h; Inert atmosphere;
	With dihydrogen peroxide; sodium hydroxide In methanol; water at 0℃; for 2h; Inert atmosphere;

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11
[ 2244-16-8 ]
[ 116499-64-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	With nickel In tetrahydrofuran at 0℃; for 0.333333h;
86.2%	With water; potassium hydroxide; zinc In methanol at 65℃; Reflux;	1 (1) Synthesis of Compound 2 Under stirring, 40.8 kg of drinking water and 16.3 kg of potassium hydroxide were successively added until dissolved completely, and then 98.0 kg of methanol and 32.6 kg of zinc powder were sequentially added. The mixture was heated, refluxed and stirred, and L-carvone methanol solution was added slowly, then refluxed and stirred until the reaction is completed. Subsequently, the mixture was cooled, and filtered, and filter cake was rinsed with water. The temperature is controlled not to exceed 65° C., and the filtrate was decompressed and concentrated to remove methanol. The residue was stand and cooled, and then the oil layer was separated. The aqueous layer was extracted with n-hexane. The oil layer was combined with n-hexane, and washed with drinking water to near neutrality. Drying and filtering were performed, and the n-hexane was subjected to reduced pressure distillation. The remaining material was continuously subjected to reduced pressure rectification with a high vacuum pump to distill a fraction having a boiling point of 60° C.-70° C. (2-3 mmHg of fraction) to obtain the compound 2 (bp 74° C./2 mmHg, nd 1.470, yield: 86.2%).
84%	With potassium hydroxide; zinc In methanol for 9h; Heating;

50%	With phenylsilane; isopropyl alcohol at 23℃;
98.0 % Chromat.	With potassium bis(trimethylsilyl)amide In tetrahydrofuran at -78℃; for 8h;
	With aluminium tris(2,6-diphenylphenoxide); n-butyllithium; diisobutylaluminium hydride 1) toluene, -78 deg C; 2) toluene, THF, hexane, -78 deg C, 15 min; Yield given. Multistep reaction;
31 % Chromat.	With water In ethanol electrohydrogenation at pH 7 (phosphate buffer);
	Stage #1: (R)-Carvone With L-Selectride In tetrahydrofuran at -70℃; Stage #2: With dihydrogen peroxide; sodium hydroxide In tetrahydrofuran at 0℃;
	With hydrogen In methanol at 20℃; for 1h;
	With platinum(IV) oxide; hydrogen at 20℃; for 7h;	Synthesis of (1R,2S,5R)-2-(2-hydroxyethyl)-5-isopropyl-2-methylcyclohexan-1-ol(10j). A suspension of (R)-carvone (500 μL, 3.14 mmol) and PtO2 (0.7 mg, 3.14 μmol) wasvigorously stirred under a H2 atmosphere at room temperature for 7 h. The catalyst wasfiltered through a pad of celite, and the celite was washed with Et2O. The filtrate was concentrated in vacuo.
	With palladium on activated charcoal; hydrogen In ethyl acetate at 20℃;	General procedure: Authentic standards for each reduction product by stirring ethyl acetate solutions under an atmosphere of H2 in the presence of Pd/C. Reactions were stirred at room temp until GC/MS indicated complete consumption of starting materials, the solvent was removed by rotary evaporation.
	With D-glucose; glucose/glucose dehydrogenase; ene-reductase of the Old Yellow Enzyme 1; nicotinamide adenine dinucleotide phosphate In aq. phosphate buffer; dimethyl sulfoxide at 30℃;

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12
[ 2244-16-8 ]
[ 5524-05-0 ]

Yield	Reaction Conditions	Operation in experiment
95.6%	Stage #1: (R)-Carvone With sodium formate; NADH In aq. phosphate buffer for 2h; Stage #2: With recombinant Escherichia coli Loop 1,2a-FDH In aq. phosphate buffer at 25℃; for 5h;	4.5. Biotransformations of (R)-Carvone Biotransformations of (R)-carvone were carried out on two dierent scales: 15 mL for theevaluation of technical replicability and 0.7 L for the preparative biotransformation in the stirred-tankbio reactors. All biotrans formations were performed with 300 mM (R)-carvone and 450 mM sodium formate in 300 mM sodium phosphate buer (pH 7.0). Amberlite XAD4 with a wet mass ratio of 3:1to (R)-carvone was used for in situ substrate feeding and product removal. (R)-carvone and adsorbentresin (harmonic mean size 0.49-0.69 mm, uniformity coecient 2) were incubated for at least 2 hin buer (50% (v/v) of the total reaction volume) prior to the biotransformations. Reactions wereinitiated by the addition of the whole-cell biocatalysts resuspended in 300 mM sodium phosphatebuer and the samples were incubated at 25 °C.
90%	With glucose-6-phosphate; pentaerythritol tetranitrate reductase; nicotinamide adenine dinucleotide phosphate; glucose 6-phosphate dehydrogenase at 30℃; for 36h; aq. phosphate buffer; Enzymatic reaction; optical yield given as %ee;
89.5%	With cyanobacterial ene reductase 1 from Nostoc sp. PCC₇₁₂₀; NADH In aq. phosphate buffer at 30℃; for 24h; Enzymatic reaction; diastereoselective reaction;

83%	With (1,4-dimethyl-5,7-diphenyl-1,2,3,4-tetrahydro-6H-cyclopenta[b]pyrazin-6-one)(triphenylphosphine)(dicarbonyl)iron; caesium carbonate; isopropyl alcohol at 90℃; for 16h;
81%	With sodium dithionite; sodium hydrogencarbonate In water; toluene at 110℃; for 3h;
79%	With sodium dithionite; sodium hydrogencarbonate In water; toluene at 110℃; for 4h; stereoselective reaction;
71%	With sodium hydroxide; water; zinc In ethanol for 5.5h; Heating;
65.4%	With Gluconobacter oxydans old yellow enzyme family protein Gox0502 (a.a 1–315), recombinant, W66F mutant; NADPH In aq. phosphate buffer; ethanol at 30℃; for 1h; Enzymatic reaction; diastereoselective reaction;	Biocatalysis assay and data analysis. General procedure: Biotransformationswere typically performed in a standard reactionsystem containing 30 μg/mL enzyme, 2 mM substrate,2.1 mM NADPH, 100 mM PBS buffer pH 7.0, and10% (v/v) ethanol to a final volume of 0.5 mL. Themixtures were incubated in an orbital shaker at150 rpm at 30 °C for 1 h. Reactions were terminatedby extraction through chloroform (0.5 mL) containing0.15% (v/v) 2-octanone (as internal standard). Aftercentrifugation, the lower organic phase samples weretaken for GC (Gas chromatography) analysis.Concentrations and diastereomeric excesses (de) weredetermined by a GC-6890 N equipped with a30 m × 0.25 mm DB-5 column (Agilent Technologies).The injection volume was 1 μL with a split ratio of 10: 1.The following program was applied for GC analysis:40 °C for 3 min; 10 °C/min increase to 220 °C and maintainedat 220 °C for 3 min. For (S)-carvone’s catalysisexperiment, the corresponding retention times were asfollows: (S)-carvone 14.28 min, (1R, 4S)-dihydrocarvone13.60 min, and (1S, 4S)-dihydrocarvone 13.72 min. For(R)-carvone’s catalysis experiment, the correspondingretention times were as follows: (R)-carvone 14.28 min,(1R, 4R)-dihydrocarvone 13.72 min, and (1S, 4R)-dihydrocarvone13.60 min. The concentrations of the reactionproducts were calculated based on absorption. 2-Octanonewas used as an internal standard, which had beensubjected to chloroform during the extraction step.
65%	With 1-Benzyl-1,4-dihydronicotinamide In aq. phosphate buffer; acetone at 30℃; for 8h; Enzymatic reaction;
60%	With sodium hydroxide; zinc In ethanol
59%	With D-glucose 6-phosphate; glucose-6-phosphate dehydrogenease; Shewanella yellow enzyme 4; NADP In ethanol; water at 28℃; for 1h; Tris-HCl buffer; Enzymatic reaction; optical yield given as %de; diastereoselective reaction;	4.2. Typical screening procedure for bioreductions General procedure: Biotransformations were performed with SYE-4 protein (25 mg/mL) in sterile multi-well plates (500 μL each well) in the presence of Tris-HCl (50 mM, pH 8), NADP+ (200 μM), glucose-6-phosphate (4 mM), glucose-6-phosphate dehydrogenease (1 unit), and substrate 2 mM, 0.8 μL (stock solution in EtOH/H2O (2:1)) at 28 °C for 6 h. Samples were collected after 1 h, 3 h and 6 h. The reaction mixture was extracted with ethyl acetate containing the internal standard methyl benzoate and samples were analyzed by chiral GC and GC-MS (Table 1).
54%	With potassium tri-sec-butyl-borohydride In tetrahydrofuran
46%	With D-glucose; Saccharomyces cerevisiae old yellow enzyme 2; Pseudomonas sp. glucose dehydrogenase In aq. phosphate buffer at 37℃; for 24h; Enzymatic reaction;
	With tellurium; sodium tetrahydroborate 1.) EtOH, reflux, 2 h 2.) EtOH, rt, overnight; Yield given. Multistep reaction;
	With 1,4-dihydronicotinamide adenine dinucleotide; Triton X-100 at 30℃; for 24h; Na-Pi-buffer, reductase I from nicotiana tabacum cell cultures; Yield given;
1.4 mg	With 1,4-dihydronicotinamide adenine dinucleotide; enzyme preparation from Nicotiana tabacum; Triton X-100 In water at 30℃; for 20h;
	With potassium hydroxide; sodium methylate; zinc 1.) H₂O, EtOH, reflux, 7 h, 2.) CH₃OH, room temperature, 36 h.; Yield given. Multistep reaction;
	With 1,4-dihydronicotinamide adenine dinucleotide; water; Triton X-100 at 36℃; for 12h; reduction by reductase from Euglena gracilis Z; pH 6.0-8.3 (3-(N-morpholino)propane sulfonic acid buffer); further reagents: (4S)-<4-(2)H>NADH, (2)H2O; Yield given;
	With 1,4-dihydronicotinamide adenine dinucleotide at 30℃; for 24h; Na-Pi-buffer; reductase-I or reductase-II from nicotiana tabacum cell cultures; other enones;
99 % Chromat.	With sodium hydrogen telluride In ethanol for 4h; Ambient temperature;
	Multi-step reaction with 2 steps 1: Al(OC₃H₇)3 / propan-2-ol 2: cultured cells of Nicotiana tabacum / 144 h / 25 °C
	Multi-step reaction with 2 steps 1: H₂O / microbiological reduction, Tetramycena pyriformis strain GL 2: pyridinium chlorochromate
	Multi-step reaction with 2 steps 1: sodium; aqueous NH₃; benzene / 3 - 10 °C / Reinigung ueber das 3.5-Dinitro-benzoyl-Derivat 2: K₂cr2O₇; H₂SO₄; water
	With glucose-6-phosphate dehydrogenase; D-glucose 6-phosphate; Saccharomyces pastorianus old yellow enzyme W₁₁₆I; NADP at 20℃; Enzymatic reaction; diastereoselective reaction;
61 %Chromat.	With thermostable old yellow enzyme from Thermoanaerobacter pseudethanolicus E₃₉; NADH at 30℃; for 24h; aq. phosphate buffer; Enzymatic reaction; optical yield given as %de; diastereoselective reaction;
95 %Chromat.	With glucose-6-phosphate dehydrogenase; D-glucose 6-phosphate; pentaerythritol tetranitrate reductase T₂₆S mutant; NADPH In N,N-dimethyl-formamide at 30℃; for 24h; aq. phosphate buffer; Enzymatic reaction; optical yield given as %de;
76 %Chromat.	With glucose-6-phosphate dehydrogenase; β-D-glucose 6-phosphate; wild type pentaerythritol tetranitrate reductase; NADPH In N,N-dimethyl-formamide at 30℃; for 48h; phosphate buffer; Inert atmosphere; anaerobic; Enzymatic reaction; optical yield given as %de; diastereoselective reaction;
	With L-Cysteine In water at 30℃; for 4h; Potassium phosphate/citric acid buffer; Microbiological reaction; Enzymatic reaction; optical yield given as %de; diastereoselective reaction;
	With D-glucose; D-glucose dehydrogenase; Lactobacillus casei recombinant enoate reductase; NAD In dimethyl sulfoxide at 37℃; for 4h; aq. phosphate buffer; Enzymatic reaction; diastereoselective reaction;	4.3. Stepwise enzymatic reduction of (R)- and (S)-carvone to dihydrocarveol General procedure: The general experimental procedure was as follows: a (R)-carvone or (S)-carvone solution in DMSO (100 μL, 0.20 M) was mixed in a potassium phosphate buffer (0.9 mL, 100 mM, pH 8.0). Next, d-glucose (24 mg), d-glucose dehydrogenase (2 mg), NAD+ (1 mg), and the enoate reductase (LacER, 2 mg) were added. After the mixture was shaken at 37 °C for 4 h, d-glucose dehydrogenase (2 mg), NADP+ (1 mg), and the carbonyl reductase (2 mg) were added. The mixture was shaken at 37 °C for another 24 h. The mixture was extracted with methyl tert-butyl ether (1 mL). The organic extract was dried over anhydrous sodium sulfate and then subjected to chiral GC analysis to determine the diastereomeric excess. (2R,5R)-dihydrocarvone and (2R,5S)-dihydrocarvone were reduced by NaBH4 to give two sets of diastereomer mixtures, which served as the standard samples for GC analysis. Their retention times were as follows: (1S,2R,5R)-dihydrocarveol, 16.6 min; (1R,2R,5R)-dihydrocarveol, 17.2 min; (1S,2R,5S)-dihydrocarveol, 20.0 min; (1R,2R,5S)-dihydrocarveol, 19.3 min. The absolute configurations of the product alcohols were identified by comparing the chiral GC data with the standard samples and the 1H NMR spectra with those in the literature
99 % ee	With ene reductase from the cyanobacterium synechococcus species pcc 7942; NAD In aq. phosphate buffer; N,N-dimethyl-formamide at 30℃; for 24h; Enzymatic reaction; stereoselective reaction;	A Bioreduction on a mL-scale The bioreduction of alkenes was carried out in 1 mL sodium phosphate buffer (100 mM, pH 7.0) containing 5 mM substrates (added as a DMF solution, mM NADH and 85 μg mL-1 (2.1 μM) Syn7942ER. The reactions were agitated at 30 °C and 300 rpm (Thermomixer comfort, Eppendorf, Hamburg, Germany) for 24 h. The reduction of ketoisophorone with 5-20% (v/v) ethanol, iso-propanol or DMF was performed on a 1 mL-scale with 57 μg mL-1 (1.2 μM) NADP+-dependent MycFDH C145S/D221Q/C255V [37], 250 mM sodium formate, 0.5 mM NADP+, 10 mM ketoisophorone and 25 μg mL-1 (0.6 μM) Syn7942ER for 6 h at 30 °C and 150 rpm (WiseCube, Witeg Labortechnik, Wertheim, Germany). Reactions were stopped by extraction with ethyl acetate (1:1) containing 36 mM (R)-limonene as internal standard.
96 % de	With ene-reductase from Ralstonia metallidurans; NADH; sodium chloride In aq. buffer at 30℃; for 5h; Enzymatic reaction; stereoselective reaction;	2.4. Enzyme assays General procedure: Biotransformation for substrate scope and selectivity analysis were performed in 1 mL reaction volumes consisting of 2 mM NADH and 1 mM substrate, purified enzyme (20 μg) in 20 mM MOPS-NaOH (pH 7.4) with 0.1 M NaCl buffer at 30 °C. Conversions were determined after 5 h of incubation. For GC-MS analysis, reaction mixtures were extracted using an equal volume of ethyl acetate and samples separated on a FactorFour VF-5 ms column (30 m×0.25 mm×0.25 μm, Varian). Chiral separation of the reduction products of R- and S-carvone, 2-methylcyclopentenone and ketoisophorone were performed on a Astec Chiraldex G-TA column (30 m×0.25 mm×0.25 μm, Sigma-Aldrich) and compared to reference activities [37] or the MS fragmentation of diastereomers [38]. For HPLC analysis, reactions were stopped by the addition of 10 μL of concentrated HCl and samples separated on a Jupiter 5 μm C18 300 column (250 mm×4.6 mm, Phenomenex).
97 % de	With D-glucose; D-glucose dehydrogenase; Bacillus Old Yellow Enzyme 1, molecular mass: ca. 41 kDa; NADP In aq. buffer at 30℃; for 24h; Enzymatic reaction; enantioselective reaction;	2.8. Bioconversions General procedure: The bioconversion reactions for substrates S2, S3, S15, S16, S24 and S30 were performed in 1 mL of Tris-HCl buffer (50 mM, pH8.0). The reaction system contained d-glucose (11 g L-1), d-glucose dehydrogenase (1.5 g L-1), NADP+ (1 g L-1), OYE (2 g L-1) and substrate (20 mM). The mixtures were incubated at 30 °C, 200 rpm for 24 h and then extracted with an equal volume of ethyl acetate. The conversions and enantiomeric excess (ee)/diasteromeric excess(de) values of the reactions were measured by chiral GC analysis on an Agilent 7890 gas chromatography using CP ChiraSilDEX Column (25 m × 0.25 mm × 0.25 m, Varian, USA) for S2,S3, S16 and S24, and Gamma DEXTM 225 Capillary Column(30 m × 0.25 mm × 0.25 m, SUPELCO, Japan) for S15 and S30. Temperature programs were as follows: For S2: 10C min-1from 70to 100C, 100C for 10 min, 5C min-1to 120C, 60C min-1to180C, 180C for 3 min. For S3: 10C min-1from 70 to 100C,100C for 14 min, 60C min-1to 180C, 180C for 3 min. For S24:70C for 2 min, 5C min-1from 70 to 140C, 140C for 3 min,50C min-1to 180C, 180C for 3 min. For S16: 95C for 10 min,40C min-1from 95 to 160C, 160C for 3 min. For S15: 10C min-1from 70 to 100C, 100C for 7.2 min, 60C min-1to 180C, 180Cfor 3 min. For S30: 10C min-1from 80 to known enzymes, YqjM and morphinone reductase, which were performed at the same time [5,25,26]. For other substrates, the product configuration was determined as previously reported [16,27].170C, 170C for 15 min,10C min-1to 180C, 180C for 3 min. In order to determine the product configuration, the GC data were compared with those ofthe reduction products of S15, S16 and S30 catalyzed by known enzymes, YqjM and morphinone reductase, which were performedat the same time [5,25,26]. For other substrates, the product con-figuration was determined as previously reported [16,27].
95 % de	With D-glucose; ene-reductase 110; glucose dehydrogenase-105; nicotinamide adenine dinucleotide phosphate In aq. buffer at 30℃; for 6h; Enzymatic reaction; stereoselective reaction;
> 98 % de	With D-glucose; mutant of saccharomyces pastorianus OYE 1 with tyrosine at 116 position In aq. phosphate buffer at 20℃; for 24h; Enzymatic reaction; stereoselective reaction;
94 % de	With glucose-6-phosphate dehydrogenase; glucose-6-phosphate; enoate reductase from Shewanella oneidensis SYE-4; NAD In aq. buffer at 28℃; for 1h; Enzymatic reaction; stereoselective reaction;
94 % de	With glutamate dehydrogenase; D-glucose; NamA; nicotinamide adenine dinucleotide phosphate In aq. phosphate buffer; Petroleum ether at 25℃; for 12h; Enzymatic reaction; diastereoselective reaction;
> 99 % ee	With ene-reductase In acetonitrile at 20℃; Enzymatic reaction; enantioselective reaction;
91 % ee	With nicotinamide adenine dinucleotide phosphate; Paenibacillus polymyxa enzyme Ppo-ER₃ In aq. phosphate buffer; N,N-dimethyl-formamide at 30℃; for 1h; Enzymatic reaction; enantioselective reaction;
66 %Chromat.	With glucose-6-phosphate dehydrogenase; metagenomic ene-reductase from pQR₁₉₀₇; β-D-glucose-6-phosphate sodium salt; NADPH In dimethyl sulfoxide at 30℃; for 1h; Enzymatic reaction; stereoselective reaction;
	With D-glucose; Bacillus subtilis 168 glucose dehydrogenase E₁₇₀K/Q₂₅₂L; Thermus scotoductus SA-01 ene-reductase C₂₅G/I₆₇C; β-nicotinamide adenine dinucleotide phosphate sodium salt; cobalt(II) chloride In aq. phosphate buffer; ethanol at 30℃; for 1.5h; Enzymatic reaction; stereoselective reaction;	2.3. Biotransformations: screening scale General procedure: All reactants were mixed in 1.5 mL reaction tubes containing (final concentrations) 100 mM glucose, 10 μM enzyme, 0.1 mM CoCl2, 0.25 mM NADP+, GDH-60 (2.2 U mL 1) and 10 mM substrate (from 1 M stock in EtOH). The reactions were performed at least in triplicates in total reaction volume of 200 μL at 30 C and 700 rpm in a Thermomixer (Eppendorf). To stop the reaction, the aqueous solution was extracted with 200 μL ethyl acetate. Conversion and enantiomeric excess was determined by GC or HPLC. Peaks were assigned based on available authentic standards, by mass analysis or full characterisation. Precise ee determination for low conversion levels was performed as previously described [24]. The optical rotation of 2-methylcyclopentan-1-one (13b) was determined to assign chirality. All reactants were mixed in a 50 mL reaction containing 45 mL KPi buffer (100 mM, pH 7.4), glucose (87.5 mM), NADP+ (0.25 mM), BsGDH (2.2 U mL 1) and TsER C25G/I69T (20 μM). Reaction started upon addition of 50 mM 2-methylcyclopenten-1-one (13a) with 5 mL n-pentane and was performed at 30 C and 200 rpm. After completion the whole reaction mixture was extracted with n-pentane and the solvent was carefully evaporated under vacuum. The optical rotation was measured with a 20 mg mL 1 solution in chloroform in a 50 mm cuvette with a polarimeter P800-T, KRÜSS with λ =589 nm at 25 C and result in [∝]D25 -81 indicating that 2R-methylcyclopentanone is formed according to Shimoda et al.[35].
93 % ee	With pentaerythritol tetranitrate reductase; 1-butyl-5-methyl-1,4-dihydropyridine-3-carboxamide In dimethyl sulfoxide at 30℃; for 24h; Enzymatic reaction; enantioselective reaction;

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13
[ 2244-16-8 ]
[ 20549-48-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With D-glucose; D-glucose dehydrogenase; Candida magnolia carbonyl reductase; Lactobacillus casei recombinant enoate reductase; NAD; NADP In dimethyl sulfoxide at 37℃; for 24h; aq. phosphate buffer; Enzymatic reaction; optical yield given as %de; diastereoselective reaction;	4.5. Synthesis of (1S,2R,5R)-dihydrocarveol At first, d-glucose (110 g L-1), d-glucose dehydrogenase (2 g L-1), NAD+ (1 g L-1), NADP+ (1 g L-1), enoate reductase enzyme (2 g L-1), and carbonyl reductase (2 g L-1) were dissolved in potassium phosphate buffer (100 mM, pH 8.0, 27 mL). The resulting solution was mixed with 3 mL of (R)-carvone solution in DMSO (1.0 M). The reaction mixture was shaken at room temperature for 24 h. The reduction was completed as shown by GC analysis. The mixture was extracted with methyl tert-butyl ether (3 × 30 mL). The organic extract was dried over anhydrous sodium sulfate and removal of the solvent gave a yellow oil (429.5 mg, 93% yield), which was identified as (1S,2R,5R)-dihydrocarveol with >99% de.
87%	With Mn(CO)<SUB>3</SUB>Br(k<SUP>2</SUP>P,N-Ph<SUB>2</SUB>PN(H)Py); hydrogen; potassium hexamethylsilazane In toluene at 100℃; for 20h; Glovebox; Autoclave; Inert atmosphere; regioselective reaction;
10.7%	In various solvent(s) at 25℃; for 240h; rotary shaker (70 rpm), dark, suspension cells of Nicotiana tabacum;

	With tetracarbonylhydridoferrate In tetrahydrofuran at 60℃; for 216h; Yield given;
	With D-glucose; Trigonopsis variablis pH=7; Yield given;
	Multi-step reaction with 2 steps 1: 9 percent Chromat_. / Diplogelasinospora grovesii IMI 171018 cells / 72 h / 28 °C 2: 98 percent Chromat_. / Diplogelasinospora grovesii IMI 171018 / 72 h / 28 °C
	Multi-step reaction with 2 steps 1: 50 percent / Zn / ethanol 2: 90 percent / Li(s-Bu)3BH
	Multi-step reaction with 2 steps 1: Al(OC₃H₇)3 / propan-2-ol 2: cultured cells of Nicotiana tabacum / 144 h / 25 °C
	Multi-step reaction with 2 steps 1: glutamate dehydrogenase; D-glucose; nicotinamide adenine dinucleotide phosphate; OYE₁ W₁₁₆A, T₃₇A variant / aq. phosphate buffer; Petroleum ether / 12 h / 25 °C / pH 6 / Enzymatic reaction 2: glutamate dehydrogenase; D-glucose; nicotinamide adenine dinucleotide phosphate; LfSDR₁ V₁₈₆W variant / aq. phosphate buffer; ethanol / 12 h / 30 °C / pH 6 / Enzymatic reaction

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[5]Varie, David L.; Brennan, John; Briggs, Barbara; Cronin, Jason S.; Hay, David A.; Rieck III, John A.; Zmijewski, Milton J. [Tetrahedron Letters, 1998, vol. 39, # 46, p. 8405 - 8408]
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[7]Varie, David L.; Brennan, John; Briggs, Barbara; Cronin, Jason S.; Hay, David A.; Rieck III, John A.; Zmijewski, Milton J. [Tetrahedron Letters, 1998, vol. 39, # 46, p. 8405 - 8408]
[8]Hamada, Hiroki [Bulletin of the Chemical Society of Japan, 1988, vol. 61, p. 869 - 878]
[9]Guo, Jiyang; Zhang, Rui; Ouyang, Jingping; Zhang, Feiting; Qin, Fengyu; Liu, Guigao; Zhang, Wenhe; Li, Hengyu; Ji, Xiaohong; Jia, Xian; Qin, Bin; You, Song [ChemCatChem, 2018, vol. 10, # 23, p. 5496 - 5504]

14
[ 2244-16-8 ]
[ 294634-40-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With C₂₀H₂₆FeN₄⁽²⁺⁾*2CF₃O₃S^(1-); dihydrogen peroxide; acetic acid In acetonitrile at 0℃; for 0.166667h; regioselective reaction;
99%	With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 21℃; for 15h; Inert atmosphere; Schlenk technique;
96%	With [2,2']bipyridinyl 1,1'-dioxide; dihydrogen peroxide In dichloromethane; water for 24h; Ambient temperature;

94%	With (NC₅H₄CH(C₆H₅)N(CH₃)C₆H₁₀N(CH₃)CH(C₆H₅)C₅H₄N)Mn(CF₃SO₃)2; dihydrogen peroxide; acetic acid In acetonitrile at 0℃; for 0.583333h; Inert atmosphere; regioselective reaction;
92%	With [Mn(CF₃SO₃)2(H,MePyTACN)]; dihydrogen peroxide; acetic acid In acetonitrile at 0℃; for 0.583333h; regioselective reaction;
88%	Stage #1: (R)-Carvone With N-Bromosuccinimide; dimethyl sulfoxide at 10℃; for 0.416667h; Inert atmosphere; Stage #2: With 1,8-diazabicyclo[5.4.0]undec-7-ene In dimethyl sulfoxide at 0℃; for 0.5h; Inert atmosphere;
85%	With 3-chloro-benzenecarboperoxoic acid In diethyl ether
80%	With Oxone; 3,3-dimethyl-3,4-dihydroisoquinolinium tetrafluoroborate; sodium hydrogencarbonate In water; acetonitrile at 20℃; for 12h;
75%	With perfluoro-cis-2-n-butyl-3-n-propyloxaziridine In various solvent(s) at -40℃; for 0.5h;
74%	With Fe(bpmen)(OTf)2; dihydrogen peroxide; acetic acid In acetonitrile at 20℃;
70%	With trans-dioxo(5,10,15,20-tetramesitylporphirinato)ruthenium(VI); dichloropyridine N-oxide In benzene for 15h; Ambient temperature;
48%	With tert.-butylhydroperoxide for 30h; Ambient temperature;
	With peracetic acid; N,N’-dimethyl-N,N’-bis(2-pyridylmethyl)cyclohexane-1,2-diamine; acetic acid In acetonitrile at -20 - -10℃; for 0.216667h;
88 %Chromat.	With perchloric acid; dihydrogen peroxide In water; acetonitrile; <i>tert</i>-butyl alcohol at 59.84℃; for 1h; Inert atmosphere; regioselective reaction;
	With 2-pyrazylcarboxylic acid; gallium(III) nitrate; dihydrogen peroxide In water; ethyl acetate at 80℃;	4. Experimental General procedure: The experiments on olefin oxidations were carried out in ace-tonitrile in thermostated Pyrex cylindrical vessels (total volume10 mL) with vigorous stirring. In a typical experiment, initially,a portion of the aqueous solution of H2O2(aqueous 70% hydro-gen peroxide, Solvay, solution was used as received) was addedto the solution of a substrate, catalyst 1 (gallium nitrate) in ace-tonitrile. Catalyst 1 was used in the form of stock solutions inH2O2. (CAUTION. The combination of air or molecular oxygen andH2O2with organic compounds at elevated temperatures may beexplosive). After certain periods, the reaction mixture wasanalyzed by GC using Shimadzu-HP 2010 gas chromato-graph equipped with a polyethylene glycol column (Innowax,25 m × 0.2 mm × 0.4 m) coupled to the flame ionization detectorand an automatic injector measuring concentrations of prod-ucts. Authentic samples of all oxygenated products were used toattribute the peaks in chromatograms (comparison of retentiontimes was carried out for different regimes of GC-analysis). Thequantification of products was accomplished by constructing cal-ibration curves for the products, by using standards of knownconcentrations knownconcentrations, and CH3NO2as internal standard. The productsformed from natural compounds were identified by using a gaschromatography coupled to a mass spectrometer (GC-MS) Shi-madzu 2010-plus. The turbidity of the system was monitored usinga turbidimeter PoliControl AP2000.

Reference： [1]Spannring, Peter; Yazerski, Vital A.; Chen, Jianming; Otte, Matthias; Weckhuysen, Bert M.; Bruijnincx, Pieter C. A.; Klein Gebbink, Robertus J. M. [European Journal of Inorganic Chemistry, 2015, vol. 2015, # 21, p. 3462 - 3466]
[2]Kerschgens, Isabel; Rovira, Alexander R.; Sarpong, Richmond [Journal of the American Chemical Society, 2018, vol. 140, # 31, p. 9810 - 9813]
[3]Nakajima, Makoto; Sasaki, Yuka; Iwamoto, Hatsue; Hashimoto, Shun-Ichi [Tetrahedron Letters, 1998, vol. 39, # 1-2, p. 87 - 88]
[4]Location in patent: experimental part Yu, Songjie; Miao, Cheng-Xia; Wang, Daqi; Wang, Shoufeng; Xia, Chungu; Sun, Wei [Journal of Molecular Catalysis A: Chemical, 2012, vol. 353-354, p. 185 - 191]
[5]Garcia-Bosch, Isaac; Ribas, Xavi; Costas, Miquel [Advanced Synthesis and Catalysis, 2009, vol. 351, # 3, p. 348 - 352]
[6]Majetich, George; Shimkus, Joel; Li, Yang [Tetrahedron Letters, 2010, vol. 51, # 52, p. 6830 - 6834]
[7]Nishimura, Hiroyuki; Hiramoto, Shigeru; Mizutani, Junya; Noma, Yoshiaki; Furusaki, Akio; Matsumoto, Takeshi [Agricultural and Biological Chemistry, 1983, vol. 47, # 11, p. 2697 - 2700]
[8]Bohé, Luis; Kammoun, Majed [Tetrahedron Letters, 2002, vol. 43, # 5, p. 803 - 805]
[9]Arnone, Alberto; Desmarteau, Darryl D.; Novo, Barbara; Petrov, Viacheslav A.; Pregnolato, Massimo; Resnati, Giuseppe [Journal of Organic Chemistry, 1996, vol. 61, # 25, p. 8805 - 8810]
[10]Clemente-Tejeda, David; López-Moreno, Alejandro; Bermejo, Francisco A. [Tetrahedron, 2013, vol. 69, # 14, p. 2977 - 2986]
[11]Ohtake, Hiro; Higuchi, Tsunehiko; Hirobe, Masaaki [Heterocycles, 1995, vol. 40, # 2, p. 867 - 904]
[12]Fraile, Jose M.; Garcia, Jose I.; Mayoral, Jose A.; Menorval, Louis C. de; Rachdi, Ferid [Journal of the Chemical Society. Chemical communications, 1995, # 5, p. 539 - 540]
[13]Murphy, Andrew; Dubois, Geraud; Stack [Journal of the American Chemical Society, 2003, vol. 125, # 18, p. 5250 - 5251]
[14]Location in patent: scheme or table Kamata, Keigo; Sugahara, Kosei; Yonehara, Kazuhiro; Ishimoto, Ryo; Mizuno, Noritaka [Chemistry - A European Journal, 2011, vol. 17, # 27, p. 7549 - 7559]
[15]Mandelli, Dalmo; Kozlov, Yuriy N.; da Silva, Cezar A.R.; Carvalho, Wagner A.; Pescarmona, Paolo P.; Cella, Daniele de A.; de Paiva, Polyana T.; Shul'pin, Georgiy B. [Journal of Molecular Catalysis A: Chemical, 2016, vol. 422, p. 216 - 220]

15
[ 2244-16-8 ]
[ 127911-15-3 ]

Yield	Reaction Conditions	Operation in experiment
83%	With hydrogen In ethanol
	With hydrogen catalytic hydrogenation;
	With hydrogen In methanol at 20℃; for 4h; room pressure;

	Multi-step reaction with 2 steps 1: 98 percent / H₂ / [Rh(PPh₃)3Cl] / benzene / 40 h / 25 °C / 2280.15 Torr 2: 96 percent / H₂ / Pd/C / methanol / 6 h / 760.05 Torr
	With 10% palladium on carbon; hydrogen
	With hydrogen In methanol at 20℃; for 1h; Green chemistry;
	With nickel(II) chloride hexahydrate; water In 2-methoxy-ethanol at 30℃; Sonication;

Reference： [1]Takaki, Ken; Okada, Michikazu; Yamada, Michio; Negoro, Kenji [Journal of Organic Chemistry, 1982, vol. 47, # 7, p. 1200 - 1205]
[2]Takaki, Ken; Ohsugi, Masakatsu; Okada, Michikazu; Yasumura, Masateru; Negoro, Kenji [Journal of the Chemical Society. Perkin transactions I, 1984, # 4, p. 741 - 745]
[3]Kashima, Choji; Miwa, Yohei; Shibata, Saori; Nakazono, Hiroyuki [Journal of Heterocyclic Chemistry, 2002, vol. 39, # 6, p. 1235 - 1240]
[4]Fuerstner, Alois; Hannen, Peter [Chemistry - A European Journal, 2006, vol. 12, # 11, p. 3006 - 3019]
[5]Location in patent: scheme or table Ambrosini, Martino; Baricordi, Nikla; Benetti, Simonetta; De Risi, Carmela; Pollini, Gian P.; Zanirato, Vinicio [Tetrahedron Asymmetry, 2009, vol. 20, # 18, p. 2145 - 2148]
[6]Moreno-Marrodan, Carmen; Barbaro, Pierluigi; Catalano, Massimo; Taurino, Antonietta [Dalton Transactions, 2012, vol. 41, # 41, p. 12666 - 12669]
[7]Thompson, Samuel J.; Thach, Danny Q.; Dong, Guangbin [Journal of the American Chemical Society, 2015, vol. 137, # 36, p. 11586 - 11589]

16
[ 2244-16-8 ]
[ 82044-96-0 ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium chlorine monoxide; molybdenum pentachloride In dichloromethane; lithium hydroxide monohydrate at 20℃; for 0.5h;
86%	With chloro-trimethyl-silane; racemic methyl phenyl sulfoxide; dihydrogen peroxide In dichloromethane at 25℃; Flow reactor; regioselective reaction;
76%	With hypochlorous acid tert-butyl ester; mesoporous silica In hexane for 3h; Ambient temperature;

76%	With hypochlorous acid tert-butyl ester In hexane at 20℃; for 3h;
72%	With calcium hypochlorite In dichloromethane; lithium hydroxide monohydrate for 2h;
71%	With calcium hypochlorite In dichloromethane; lithium hydroxide monohydrate
67%	With calcium hypochlorite; carbon dioxide In dichloromethane; lithium hydroxide monohydrate at 0℃;
66%	With calcium hypochlorite In dichloromethane; lithium hydroxide monohydrate for 7h; Cooling with ice;
65%	With sodium chlorine monoxide; cerium(III) trichloride heptahydrate In dichloromethane; lithium hydroxide monohydrate for 0.583333h; regioselective reaction;	Compound 2 To a stirred solution of R-(-)-carvone (7.5 g, 50 mmol) in CH2Cl2/H2O (500mL, 1:1), CeCl3·7H2O (55.5 g, 150 mmol) was added. The mixture wasvigorously stirred and diluted NaClO (64 mL, 10-13% available chlorine,150 mmol) was added dropwise for 5 min. After 30 min, saturated aqueousNa2SO3 was added and the mixture was extracted with CH2Cl2. The combined organiclayers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo.The residue was purified by FCC (PE-EtOAc, 10:1) to give 2 (6.5 g, 65%) as a yellowliquid. 1H NMR (400 MHz, CDCl3) δ 6.70 (m, 1H), 5.20 (s, 1H), 4.99 (s, 1H), 4.05 (d,J = 12.0 Hz, 1H), 4.02 (d, J = 12.0 Hz, 1H), 2.90 (m, 1H), 2.59 (ddd, J = 16.0, 4.0, 1.2Hz, 1H), 2.50 (m, 1H), 2.31 (dd, J = 16.0, 13.0 Hz, 1H), 2.26 (m, 1H), 1.72 (s, 3H); 13CNMR (100 MHz, CDCl3) δ 198.8, 146.6, 143.9, 135.6, 115.1, 46.9, 43.0, 37.8, 31.4,15.6; HRMS(ESI) m/z calcd. for C10H14ClO (M+H)+ 185.0728, found 185.0733.
60%	With sodium chlorine monoxide; cerium(III) trichloride heptahydrate; lithium hydroxide monohydrate In dichloromethane at 0℃; for 3h;
	With N-chloro-succinimide; bis(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-ylmethyl)selenide; triethylamine In dichloromethane at 20℃; for 1h; chemospecific reaction;
	With sodium chlorine monoxide; cerium(III) chloride monohydrate In dichloromethane; lithium hydroxide monohydrate at 0℃; for 3h;	1 Take 500 ml of three necked flask, then R-Carvone (3g,20mmol) dissolved in 150ml of dichloromethane,then added water (100ml) of CeCl3.H2O(8.2g, 22mmol) solution, mechanical stirring, at 0°C aqueous NaClO solution(8%,160ml) was added dropwise with adropping funnel, Stirring was continued for 3 hours at 0 ° C until thin-layerchromatography to detect the disappearance of raw materials. Added diluted water , then slowly added SaturatedNa2S2O3 aqueous solution to quench thereaction, extracted thrice with dichloromethane.
	With hypochlorous acid tert-butyl ester; mesoporous silica In n-Pentane at 20℃; for 12h; Inert atmosphere; regioselective reaction;
	With hypochlorous acid tert-butyl ester; mesoporous silica In n-Pentane at 20℃; for 12h; Inert atmosphere;	1 Synthesis of Compound SI-Ol: (R)-5-(3-Chloroprop-1 -en-2-yI)-2-methylcyclohex-2-en-1 - one To a solution of (R)-(-)-carvone (10) (3.03 g, 20.14 mmol, 1.0 equiv) in pentane (60 mL) was added silica gel (5.0 g) and then tert-butyl hypochlorite (2.73 ml, 24.17 mmol, 1.2 equiv) at room temperature. The solution was stirred at room temperature for 12 hours before being filtrated through a pad of silica gel and washed with Et20/pentane = 1:4. The resulting solution was concentrated in vacuo to afford crude SI-Ol as a yellow oil, which was used in the next step without further purification. A small portion of crude product was purified by flash column chromatography (silica gel, Et20/pentane = 1:9) to afford SI-Ol as a colorless oil. All spectral data matched the reported values (Nakamura, E., et al. J. Am. Chem. Soc. 1987, 109: 8056-8066).Color and State: colorless oilRf = 0.48 (Et20/pentane = 1:4; UV, vanillin)jaj -41.5 (c = 0.45, CHCI3)1H NMR (600 MHz, CDCI3) 6 6.75-6.73 (m, 1 H), 5.25 (s, 1 H), 5.05 (s, I H), 4.09 (d, A of AB, JAB =12.0 Hz, 1 H), 4.07 (d, B of AB, JAB = 11.9 Hz, I H), 2.96 (app. tt, J = 11.9, 3.7 Hz, 1 H), 2.65 (ddd,J 16.0, 3.7, 1.3 Hz, IH), 2.55 (app. dtd, J 17.0, 5.5, 2.0 Hz, IH), 2.37(dd, J 16.0, 13.1 Hz,1H), 2.31 (ddt, J 17.9, 10.7, 2.4, 1H), 1.78 (d, J 1.0 Hz, 3H).IR (Neat) 2953, 2922, 2887, 1666, 1431, 1364, 1252, 1211, 1144, 1107, 1055, 1014, 962, 901,802, 748, 714, 686 cm-1.HRMS (ESI, [M+Na]) calcd for C10H13OCINa 207.0547, found 207.0541.
	With sodium chlorine monoxide; FeCl₃*10H₂O In dichloromethane; lithium hydroxide monohydrate at 25℃; for 0.5h;	2.2.1. General procedure for the preparationof compound 2 During 30 min at 25 °C, 40 mL of aqueous NaOCl (5.2%) wasadded dropwise to a stirred solution of (R)-carvone 1(2 mmol) and Fe(Cl3),10H2O (3 mmol) in 50mL of CH2Cl2/H2O(1/1). After 30 min stirring (TLC monitored the reaction) atroom temperature, the layers were separated, and the aqueouslayer was extracted with CH2Cl2 (310 mL). The combinedorganic extracts were dried over anhydrous Na2SO4and evaporated in vacuo. The residue was purified bycolumn chromatography using hexane/ethyl acetate mixture(95:5) as eluent.
	With sodium chlorine monoxide; potassium dihydrogen orthophosphate In dichloromethane; lithium hydroxide monohydrate at 0 - 20℃; for 7h;

Reference： [1]Location in patent: experimental part Boualy, Brahim; El Firdoussi, Larbi; Ali, Mustapha Ait; Karim, Abdellah [Journal of the Brazilian Chemical Society, 2011, vol. 22, # 7, p. 1259 - 1262]
[2]Iordanidis, Nicolaos S.; Zografos, Alexandros L.; Gallos, John K.; Koftis, Theocharis V.; Stathakis, Christos I. [European Journal of Organic Chemistry, 2021, vol. 2021, # 36, p. 5058 - 5062]
[3]Nakamura, Eiichi; Aoki, Satoshi; Sekiya, Kouichi; Oshino, Hiroji; Kuwajima, Isao [Journal of the American Chemical Society, 1987, vol. 109, # 26, p. 8056 - 8066]
[4]Chen, Jiaojiao; Lu, Min; Jing, Yongkui; Dong, Jinhua [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 19, p. 6539 - 6547]
[5]Hegde, Shridhar G.; Wolinsky, Joseph [Journal of Organic Chemistry, 1982, vol. 47, # 16, p. 3148 - 3150]
[6]Weinges, Klaus; Schwarz, Georg [Liebigs Annalen der Chemie, 1993, # 7, p. 811 - 814]
[7]Galstyan, Armen S.; Martiryan, Armen I.; Grigoryan, Karine R.; Ghazaryan, Armine G.; Samvelyan, Melanya A.; Ghochikyan, Tariel V.; Nenajdenko, Valentine G. [Molecules, 2018, vol. 23, # 11]
[8]Xuan, Mengyang; Paterson, Ian; Dalby, Stephen M. [Organic Letters, 2012, vol. 14, # 21, p. 5492 - 5495,4] Xuan, Mengyang; Paterson, Ian; Dalby, Stephen M. [Organic Letters, 2012, vol. 14, # 21, p. 5492 - 5495]
[9]Wang, Yang; Liu, Kang; Yu, Zhi-Xiang; Jia, Yanxing [Tetrahedron Letters, 2019, vol. 60, # 36]
[10]Huang, Bin; Zhang, Fengying; Yu, Gang; Song, Yan; Wang, Xintong; Wang, Meiliang; Gong, Zehui; Su, Ruibin; Jia, Yanxing [Journal of Medicinal Chemistry, 2016, vol. 59, # 8, p. 3953 - 3963]
[11]Boualy, Brahim; El Houssame, Soufiane; Sancineto, Luca; Santi, Claudio; Ait Ali, Mustapha; Stoeckli-Evans, Helen; El Firdoussi, Larbi [New Journal of Chemistry, 2016, vol. 40, # 4, p. 3395 - 3399]
[12]Current Patent Assignee: PEKING UNIVERSITY - CN102952072, 2016, B Location in patent: Paragraph 0056
[13]Chen, Dezhi; Evans, P. Andrew [Journal of the American Chemical Society, 2017, vol. 139, # 17, p. 6046 - 6049]
[14]Current Patent Assignee: QUEEN'S UNIVERSITY AT KINGSTON - WO2018/176133, 2018, A1 Location in patent: Page/Page column 47; 48
[15]Hachim, Mouhi Eddine; Oubella, Ali; Byadi, Said; Fawzi, Mourad; Laamari, Yassine; Bahsis, Lahoucine; Aboulmouhajir, Aziz; Morjani, Hamid; Podlipnik, Črtomir; Auhmani, Aziz; Ait Itto, My Youssef [Journal of Biomolecular Structure and Dynamics, 2021]
[16]Irie, Kazuhiro; Maki, Jumpei; Oshimura, Asami; Saito, Yutaka; Sakakibara, Yasubumi; Tsukano, Chihiro; Yanagita, Ryo C. [Chemical Communications, 2022, vol. 58, # 47, p. 6693 - 6696]

17
[ 2244-16-8 ]
[ 250647-16-6 ]

Yield	Reaction Conditions	Operation in experiment
98.0 % Chromat.	With potassium bis(trimethylsilyl)amide In tetrahydrofuran at 0℃; for 4h;
	With [(N,N′-bis(diisopropylphosphino)-2,6-diaminopyridine)Mn(CO)₃][Br]; potassium <i>tert</i>-butylate; hydrogen In toluene at 130℃; for 48h; Glovebox; Autoclave;	2.2. Typical catalytic hydrogenation General procedure: In a glove box, an autoclave was charged with the desired ketone (0.5 mmol), toluene (2 mL), Mn complex 1 (14 mg, 5 mol%) followed by t-BuOK (5.6 mg, 10 mol%), in this order. The autoclave is then closed and charged with H2 (50 bar).

Reference： [1]Kim, Kwan Eung; Park, Soo Bong; Yoon, Nung Min [Synthetic Communications, 1988, vol. 18, # 1, p. 89 - 96]
[2]Bruneau-Voisine, Antoine; Wang, Ding; Roisnel, Thierry; Darcel, Christophe; Sortais, Jean-Baptiste [Catalysis Communications, 2017, vol. 92, p. 1 - 4]

18
[ 2244-16-8 ]
[ 5044-52-0 ]
[ 72967-99-8 ]
[ 73036-61-0 ]
[ 73036-62-1 ]

Reference： [1]Journal of Organic Chemistry,1980,vol. 45,p. 1852 - 1863

19
(4R,6R)-carveol [ No CAS ]
[ 2244-16-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	With oxygen In 1,2-dichloro-ethane Ambient temperature;
86%	With tert-butyl 1-hydroxy-2-methyl-6-trifluoromethyl-1H-indole-3-carboxylate; oxygen; copper(l) chloride In N,N-dimethyl-formamide at 50℃; for 24h; chemoselective reaction;	2.2 General procedure for aerobic oxidation of allylic and benzylic alcohols General procedure: To a 10 mL Schlenk tube, NHI-1 (0.2 mmol, 63 mg) and CuCl (0.2 mmol, 19.6 mg) and DMF (2 mL) were added and stirred at 50 °C for about 30 min to form a dark red solution. Alcohol 11 (2 mmol) was added, the mixture was left to stir at 50 °C under an oxygen balloon (1 atm). The reaction progress was monitored by TLC or GC. After completion, the mixture was allowed to cool to room temperature, quenched with 1M HCl and diluted with H2O (50 mL), extracted with EtOAc (EA) (10 mL × 3), the combined organic layer was washed with brine and dried over MgSO4, the crude was purified by flash column chromatography (EtOAc : hexane = 1 : 10 to 1: 3) to afford ketone or aldehyde 12.
	With Tris-HCl buffer; NADP; Triton X-100 In water at 35℃; for 3h;

	With His-tagged Artemisia annua monoterpene alcohol dehydrogenase 2; NAD at 30℃; for 0.5h; aq. CHES buffer; Enzymatic reaction;
	With chromium(VI) oxide; acetic anhydride In dichloromethane at -55℃; for 0.333333h;

Reference： [1]Matsumoto, Masakatsu; Ito, Satoru [Journal of the Chemical Society. Chemical communications, 1981, # 17, p. 907 - 908]
[2]Shen, Shu-Su; Kartika, Vita; Tan, Ying Shan; Webster, Richard D.; Narasaka, Koichi [Tetrahedron Letters, 2012, vol. 53, # 8, p. 986 - 990]
[3]Hirata, Toshifumi; Tamura, Yoshitaka; Yokobatake, Naoyuki; Shimoda, Kei; Ashida, Yoshiyuki [Phytochemistry, 2000, vol. 55, # 4, p. 297 - 303]
[4]Location in patent: experimental part Polichuk, Devin R.; Zhang, Yansheng; Reed, Darwin W.; Schmidt, Janice F.; Covello, Patrick S. [Phytochemistry, 2010, vol. 71, # 11-12, p. 1264 - 1269]
[5]Location in patent: experimental part Hudlicky, Jason R.; Werner, Lukas; Semak, Vladislav; Simionescu, Razvan; Hudlicky, Tomas [Canadian Journal of Chemistry, 2011, vol. 89, # 5, p. 535 - 543]

20
[ 2244-16-8 ]
[ 141-78-6 ]
[ 138325-07-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: ethyl acetate With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1.16667h; Stage #2: (R)-Carvone In tetrahydrofuran at -78℃; for 2h;
	Yield given. Multistep reaction;

Reference： [1]Klahn, Philipp; Duschek, Alexander; Liebert, Clemence; Kirsch, Stefan F. [Organic Letters, 2012, vol. 14, # 5, p. 1250 - 1253]
[2]Liu, Hsing-Jang; Zhu, Bing-Yan [Canadian Journal of Chemistry, 1991, vol. 69, # 12, p. 2008 - 2013]

21
[ 2244-16-8 ]
[ 74-88-4 ]
[ 138812-34-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With lithium dipropan-2-ylazanide In tetrahydrofuran at 0 - 20℃; for 10h;
98%	Stage #1: (R)-Carvone With lithium dipropan-2-ylazanide In tetrahydrofuran; hexane at -10℃; for 2h; Stage #2: iodomethane In tetrahydrofuran; hexane at 20℃;
91%	Stage #1: (R)-Carvone With n-butyllithium; di-i-propyl amine In tetrahydrofuran; hexane at -10℃; for 4.16667h; Stage #2: iodomethane In tetrahydrofuran; hexane for 2h;	12 EXAMPLE 12; Preparation Of Compound Of Formula (33) To a stirred solution of diisopropylamine (11.7 g, 16.2 ml, 116 mmol) in dry THF (120 ml), was added n-BuLi (60 ml of 1.6 M solution in hexanes, 120 mmol) drop-wise at -10° C. over 1 h 40 minutes, under nitrogen atmosphere. The resulting yellowish solution was stirred for an additional 30 minutes at the same temperature; this was followed by drop-wise addition of a solution of (R)-(-)-carvone (30) (16.3 ml, 15.63 g, 104 mmol) in dry THF (80 ml) over 2 h at the same temperature. After stirring for another 30 minutes, CH3I (32.6 ml, 74.33 g, 523 mmol) was added rapidly to the reaction mixture and the stirring was continued for further 2 h. The reaction mixture was quenched with a saturated solution of NH4Cl and organic phase was separated. From the organic part THF was removed in a rotary evaporator to leave oil. The aqueous part was extracted with hexane (3*150 ml) and combined with the oil. The combined organic extract was washed with HCl (5%, 200 ml), water (200 ml), Na2S2O3 (5%, 200 ml), water (200 ml), brine (200 ml), dried over anhydrous Na2SO4. After evaporation of the solvent, the residual yellowish oil on short path distillation afforded the desired product (33) (15.56 g, 91%) as colourless oil. b.p. 120-122° C./10 mm Hg. IR (neat) 2975, 2930, 1668, 1449, 1375, 890 cm-1. 1H NMR (300 MHz in CDCl3):(mixture of two diastereoisomers epimeric at C-6) δ 0.92 and 1.04 (d, J 6 and 7 Hz, 3H in a ratio of ea 1:1) 1.78 and 1.73 br s, 6H), 2.1-2.85 (m, 8H), 4.82 (m, 2H), 6.70 (m, 1H).

90%	With lithium dipropan-2-ylazanide In tetrahydrofuran at -15℃; Inert atmosphere;
90%	Stage #1: (R)-Carvone With lithium dipropan-2-ylazanide In tetrahydrofuran; hexane at -78℃; for 1.75h; Inert atmosphere; Stage #2: iodomethane In tetrahydrofuran; hexane at -78 - 0℃; for 1h;	1 Dimethyl-Carvone (3) Formation A [0.33 M] solution of LDA in THF was formed by addition of nBuLi in hexanes [2.67 M] (1.2 equiv, 240.0 mmol, 90 mL) to a solution of diisopropylamine (distilled off CaH2) (1.5 equiv, 300.0 mmol, 42.0 ml) in THF (600 mL, [0.5 M] wrt HNiPr2) at -78° C. After addition, the solution was stirred at 0° C. for 30 minutes before cooling back to -78° C. To a flame-dried 500 mL round bottom flask containing a [0.33 M] solution of LDA in THF (1.2 equiv, 240.0 mmol, see above for preparation details) cooled to -78° C. in a dry ice/acetone bath under an argon atmosphere was added via cannula a [1M (ignoring carvone volume)] solution of (R)-carvone (SI-1) (1 equiv, 200.0 mmol, 30 g, 31.3 mL) in THF (200 mL). The addition took 10 minutes and the solution turned from clear and pale yellow to yellow over the course of the addition. The reaction was allowed to stir for 105 minutes, at which point methyl iodide (2.0 equiv, 200.0 mmol, 12.4 mL) was added neat in a slow but steady stream to the carvone enolate solution. The reaction was then stirred at 0° C. in an ice water bath and monitored by TLC (5% EtOAc/hex). Full consumption of can/one was observed after 60 minutes. After completion, the reaction was quenched by pouring the reaction onto a 1:1 mixture of saturated NH4Cl (aq.): H2O (500 mL). The aqueous layer was extracted with EtOAc (3* ˜250 mL). The organic layer was washed 1* each with Na2S2O3 (saturated, aq. ˜250 mL) and brine (saturated, aq. ˜250 mL), and then dried over MgSO4, filtered, and concentrated. A white precipitate crashed out of the solution during concentration on the rotovap (presumably a diisopropylamine HI salt). The solid was filtered off over a plug of celite, rinsing with hexanes. The yellow solution became increasingly yellow/orange upon concentration. Therefore, the solution was diluted in 500 mL of hexanes, washed 1* with Na2S2O3 (saturated, aq., 100 mL) which removed most of the yellow color, dried over MgSO4, filtered and concentrated. The crude residue was purified by fractional distillation on high vacuum. The desired mixture of α-methyl-carvone isomers was distilled over as a colorless to slightly pale-yellow oil at ˜125-130° C. (external temperature), ˜90-91° C. (internal temperature at distillation head) at a pressure of <5 torr. α-methyl-carvone (1:1 cis:trans) was obtained 90% yield (29.4 g, 180.0 mmol).
89%	Stage #1: (R)-Carvone With lithium dipropan-2-ylazanide In tetrahydrofuran at 0℃; Stage #2: iodomethane In tetrahydrofuran
88%	Stage #1: (R)-Carvone With lithium dipropan-2-ylazanide In tetrahydrofuran Stage #2: iodomethane In tetrahydrofuran
	With lithium dipropan-2-ylazanide 1) THF, hexane, 0 deg C; Yield given. Multistep reaction;
	With lithium dipropan-2-ylazanide 1) 0 degC; Multistep reaction;
	With lithium dipropan-2-ylazanide In tetrahydrofuran 1.) 0 deg C, 2 h, 2.) 0 deg C to r.t., 12 h;
	With lithium dipropan-2-ylazanide In tetrahydrofuran 1.) -10 deg C to r.t., 2.) 9 h;
	With lithium dipropan-2-ylazanide In tetrahydrofuran at -70 - 20℃; for 12h;
	With lithium dipropan-2-ylazanide In tetrahydrofuran
	With lithium dipropan-2-ylazanide In tetrahydrofuran at -25℃;
	Stage #1: (R)-Carvone With lithium dipropan-2-ylazanide In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #2: iodomethane In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere;
	With lithium dipropan-2-ylazanide

Reference： [1]Srikrishna; Ravi Kumar; Gharpure, Santosh J. [Tetrahedron Letters, 2001, vol. 42, # 23, p. 3929 - 3931] Srikrishna; Ravi Kumar [Tetrahedron Letters, 2002, vol. 43, # 6, p. 1109 - 1111]
[2]Srikrishna; Reddy; Kumar; Gharpure [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2001, vol. 40, # 10, p. 905 - 914]
[3]Current Patent Assignee: FRESENIUS SE & CO. KGAA - US2004/220197, 2004, A1 Location in patent: Page 17
[4]Location in patent: scheme or table Odani, Atsuki; Ishihara, Kaoru; Ohtawa, Masaki; Tomoda, Hiroshi; Omura, Satoshi; Nagamitsu, Tohru [Tetrahedron, 2011, vol. 67, # 42, p. 8195 - 8203]
[5]Current Patent Assignee: SCRIPPS RESEARCH - US2022/40147, 2022, A1 Location in patent: Paragraph 0087-0094
[6]Abad, Antonio; Agulló, Consuelo; Cuñat, Ana C.; García, Ana Belen [Tetrahedron Letters, 2002, vol. 43, # 44, p. 7933 - 7936]
[7]Location in patent: scheme or table Srikrishna; Babu, R. Ramesh; Beeraiah [Tetrahedron, 2010, vol. 66, # 4, p. 852 - 861]
[8]Cory, Robert M.; Bailey, Murray D.; Tse, Daniel W. C. [Tetrahedron Letters, 1990, vol. 31, # 47, p. 6839 - 6842]
[9]Cory, Robert M.; Renneboog, Richard M. [Journal of the Chemical Society. Chemical communications, 1980, # 22, p. 1081 - 1082]
[10]Srikrishna; Jagadeeswar Reddy; Praveen Kumar [Chemical Communications, 1996, # 11, p. 1369 - 1370]
[11]Srikrishna, Adusumilli; Reddy, Thumkunta Jagadeeswar [Journal of the Chemical Society. Perkin transactions I, 1997, # 22, p. 3293 - 3294]
[12]Srikrishna; Dethe, Dattatraya H. [Organic Letters, 2004, vol. 6, # 2, p. 165 - 168]
[13]Location in patent: scheme or table Srikrishna; Anebouselvy [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2009, vol. 48, # 3, p. 413 - 422] Location in patent: scheme or table Srikrishna; Anebouselvy [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2010, vol. 49, # 6, p. 776 - 788]
[14]Li, Tao; Wu, Guangmiao; Feng, Shangbiao; Wang, Zemin; Xie, Xingang; She, Xuegong [Organic and biomolecular chemistry, 2018, vol. 16, # 44, p. 8491 - 8494]
[15]Hu, Naifeng; Dong, Changming; Zhang, Cuifang; Liang, Guangxin [Angewandte Chemie - International Edition, 2019, vol. 58, # 20, p. 6659 - 6662][Angew. Chem., 2019, vol. 131, p. 6731 - 6734,4]
[16]Li, Tao; Wu, Guangmiao; Feng, Shangbiao; Hu, Xiaojun; Zhang, Weiwei; Tang, Shouchu; Xie, Xingang; She, Xuegong [Tetrahedron, 2019, vol. 75, # 29, p. 3939 - 3942]

22
[ 50-00-0 ]
[ 2244-16-8 ]
[ 172277-78-0 ]

Yield	Reaction Conditions	Operation in experiment
64%	With lithium diisopropyl amide In tetrahydrofuran at -78℃;
55%	With lithium diisopropyl amide In tetrahydrofuran at -78℃; Inert atmosphere; enantioselective reaction;
47%	With lithium diisopropyl amide In tetrahydrofuran at -84 - 20℃;

Reference： [1]Trost, Barry M.; Krische, Michael J. [Journal of the American Chemical Society, 1996, vol. 118, # 1, p. 233 - 234]
[2]Liu, Xin; Liu, Junyang; Wu, Jianlei; Li, Chuang-Chuang [Journal of Organic Chemistry, 2021, vol. 86, # 16, p. 11125 - 11139]
[3]Li, Yang; Feng, Jian-Peng; Wang, Wen-Hua; Chen, Jie; Cao, Xiao-Ping [Journal of Organic Chemistry, 2007, vol. 72, # 7, p. 2344 - 2350]

23
[ 2244-16-8 ]
[ 499-75-2 ]

Yield	Reaction Conditions	Operation in experiment
87%	With tert-butyldimethylsilyl 2-methylpropane-2-sulfonate; platinum(IV) chloride In toluene at 80℃; for 2h; Inert atmosphere; regioselective reaction;
67%	With triethylsilyl chloride; triethylamine; sodium iodide In acetonitrile at 4℃;
	With chloro-trimethyl-silane; water for 3h; Ambient temperature;

	In water Heating; Acidic conditions;	Another factor affecting the reaction rate and overall ease of purification of the product mixture was the identity and load of the catalyst. In conventional methods, a 1% v/v of cyclohex-2-en-1-one (2) has been reported for histidine decarboxylation2; however, others3 have reported difficulty in repeating these results without a substantially higher catalyst load. Significant impurities were also observed in the resulting reaction mixture by those authors, and in later attempts to reproduce the experiments. These authors alternatively used acetophenone (1) to modest success3 for the decarboxylation of histamine at 20 mol % in >40 hr. It was postulated that the greater the stability of the imine, the greater the reaction rate at a given catalyst load, and, indeed, cyclohex-2-en-1-one (2) proved to provide a greater catalytic effect at 20 mol % than acetophenone (1). On a belief that the enone functionality of cyclohex-2-ene-1-one provides some advantage over the benzyl ketone and given its toxicity and expense of, an alternative was selected for testing in the present examples. R-carvone (3), the natural product of spearmint oil, was selected for its potential to retain the catalytic advantage over acetophenone while providing an alternative method of removal of the catalyst based on the isomerization reaction of R-carvone (3) to carvacrol (4) (Scheme 1, FIG. 3).
	With aqueous acid Heating;

Reference： [1]Zheng, Shuyan; Zhang, Jinghua; Shen, Zhengwu [Advanced Synthesis and Catalysis, 2015, vol. 357, # 13, p. 2803 - 2808]
[2]Location in patent: experimental part Valeev; Bikzhanov; Selezneva; Gimalova; Miftakhov [Russian Journal of Organic Chemistry, 2011, vol. 47, # 9, p. 1287 - 1292]
[3]Boudjouk, Philip; Kim, Beon-Kyu; Han, Byung-Hee [Synthetic Communications, 1996, vol. 26, # 18, p. 3479 - 3484]
[4]Current Patent Assignee: UNIVERSITY SYSTEM OF GEORGIA - US2014/275569, 2014, A1 Location in patent: Paragraph 0060
[5]Jackson, Douglas M.; Ashley, Robert L.; Brownfield, Callan B.; Morrison, Daniel R.; Morrison, Richard W. [Synthetic Communications, 2015, vol. 45, # 23, p. 2691 - 2700]

24
[ 2244-16-8 ]
[ 308363-12-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium tetrahydridoborate In methanol at 0 - 20℃; for 5h;
96%	With sodium tetrahydridoborate; calcium trifluoromethane sulfonate In tetrahydrofuran; methanol at 20℃; for 0.5h; Inert atmosphere; regioselective reaction;
87%	With sodium tetrahydridoborate; cerium(III) trichloride In methanol for 1.5h; Ambient temperature;

	With sodium tetrahydridoborate
	With OsHCl(CO)[(tBu)2PNH(CH₂)2NHCH₂Py]; hydrogen; anhydrous sodium carbonate In tetrahydrofuran at 100℃; for 9h; Autoclave; regioselective reaction;	16 Table 5. Hydrogenation of substrates (S) of Figures 5 and 6 with Complex lb.’1
	With diisobutylaluminium hydride In dichloromethane at -78℃;
	With hydrogen In isopropanol at 60℃; for 24h; Autoclave;
	Stage #1: (R)-Carvone In toluene for 3h; Stage #2: With potassium hydroxide In lithium hydroxide monohydrate at 95℃;	4 a) General procedure to reduce Ketone/Aldehyde General procedure: Zinc catalyst solution as prepared in Example 1 (4.5 wt% Zn) was added to 1 eq of the ketone or aldehyde as reported in Table 1 in a solvent indicated in Table 1. The reaction mixture was heated at a temperature indicated in Table 1 and 1.1 to 2 eq. of PMHS was slowly added in 3 hours as reported in Table 1. The resulting reaction mixture was slowly added to an aqueous solution of potassium hydroxide 45 at 95°C and stirred for an extra hour. After removal of the basic aqueous layer, the organic layer was washed with water. The solvent was removed under vacuum and the crude was flash distilled leading to the desired product as reported in Table.

Reference： [1]Location in patent: scheme or table Fernandes, Rodney A.; Ingle, Arun B. [Tetrahedron Letters, 2011, vol. 52, # 3, p. 458 - 460]
[2]Forkel, Nina V.; Henderson, David A.; Fuchter, Matthew J. [Green Chemistry, 2012, vol. 14, # 8, p. 2129 - 2132]
[3]Mowery, Molly E.; DeShong, Philip [Journal of Organic Chemistry, 1999, vol. 64, # 2-5, p. 1684 - 1688]
[4]Myers, Andrew G.; Zheng, Bin [Tetrahedron Letters, 1996, vol. 37, # 28, p. 4841 - 4844]
[5]Current Patent Assignee: GOUSSEV; SPASYUK - WO2014/139030, 2014, A1 Location in patent: Page/Page column 39; 40; 41; 42
[6]Xu, Fan; Zhu, Lin; Zhu, Shaobin; Yan, Xiaomei; Xu, Hai-Chao [Chemistry - A European Journal, 2014, vol. 20, # 40, p. 12740 - 12744]
[7]Liu, Cheng; Luo, Wei; Liu, Junhua; Sun, Lei; Yang, Yue; Liu, Gui; Wang, Fang; Zhong, Wei; Guild, Curtis; Suib, Steven L. [Catalysis Letters, 2018, vol. 148, # 2, p. 555 - 563]
[8]Current Patent Assignee: Firmenich International SA - WO2022/112118, 2022, A1 Location in patent: Page/Page column 15-16

25
[ 2244-16-8 ]
[ 74-88-4 ]
[ 91781-46-3 ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: (R)-Carvone With lithium diisopropyl amide In tetrahydrofuran at -78 - 0℃; for 1.25h; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at 0℃; for 0.0833333h; Inert atmosphere; diastereoselective reaction;
52%	With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 8h;
	With 1,8-diazabicyclo[5.4.0]undec-7-ene; lithium diisopropyl amide 1.) THF, -10 deg C; 2.) CH₂Cl₂, 24 h, RT; Yield given. Multistep reaction;

With 1,8-diazabicyclo[5.4.0]undec-7-ene; lithium diisopropyl amide 1.) THF; 2.) CH₂Cl₂, r.t., 24 h; Multistep reaction;

Reference： [1]Chen, Yan; Ju, Tong [Organic Letters, 2011, vol. 13, # 1, p. 86 - 89]
[2]Zhao, Liang; Wang, Jinlian; Zheng, Hongyan; Li, Yun; Yang, Ke; Cheng, Bin; Jin, Xiaojie; Yao, Xiaojun; Zhai, Hongbin [Organic Letters, 2014, vol. 16, # 24, p. 6378 - 6381]
[3]Srikrishna; Vijaykumar [Tetrahedron Letters, 1998, vol. 39, # 27, p. 4901 - 4904]
[4]Srikrishna; Kumar, P. Praveen; Reddy, T. Jagadeeswar [Tetrahedron Letters, 1998, vol. 39, # 32, p. 5815 - 5818]

26
[ 7677-24-9 ]
[ 2244-16-8 ]
[ 332920-11-3 ]

Yield	Reaction Conditions	Operation in experiment
94%	With n-butyllithium; triethylene glucol monomethyl ether In tetrahydrofuran at 22℃; for 4h;
	With L-proline lithium salt at 20℃; for 24h;

Reference： [1]Wilkinson, H. Scott; Grover, Paul T.; Vandenbossche, Charles P.; Bakale, Roger P.; Bhongle, Nandkumar N.; Wald, Stephen A.; Senanayake, Chris H. [Organic Letters, 2001, vol. 3, # 4, p. 553 - 556]
[2]Location in patent: experimental part Hudlicky, Jason R.; Werner, Lukas; Semak, Vladislav; Simionescu, Razvan; Hudlicky, Tomas [Canadian Journal of Chemistry, 2011, vol. 89, # 5, p. 535 - 543]

27
[ 629-89-0 ]
[ 2244-16-8 ]
(5R)-(-)-1-hydroxy-5-isopropenyl-2-methyl-1-octadecynyl-2-cyclohexene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: 1-octadecyne With n-butyllithium In tetrahydrofuran; hexane for 1h; Stage #2: (R)-Carvone In tetrahydrofuran; hexane

Reference： [1]Dikusar; Kozlov; Moiseichuk; Potkin [Russian Journal of Organic Chemistry, 2002, vol. 38, # 8, p. 1093 - 1098]

28
[ 14070-51-0 ]
[ 2244-16-8 ]
[ 917-58-8 ]
[ 75-05-8 ]
(S)-5-(3-chloroprop-1-en-2-yl)-2-methylcyclohex-2-en-1-one [ No CAS ]
2-[2,4-dimethyl-4-(4-methyl-5-oxocyclohex-3-enyl)-4,5-dihydroimidazol-1-ylsulfonyl]benzoic acid ethyl ester [ No CAS ]

Reference： [1]Organic Letters,2003,vol. 5,p. 3313 - 3315

29
[ 120-72-9 ]
[ 2244-16-8 ]
[ 725252-07-3 ]

Yield	Reaction Conditions	Operation in experiment
53%	Stage #1: indole; (R)-Carvone With lithium hexamethyldisilazane In tetrahydrofuran; benzene at -78℃; for 0.5h; Stage #2: With copper(II) 2-ethylhexenoate In tetrahydrofuran; hexane at -78℃; for 12h;
53%	Stage #1: indole; (R)-Carvone With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Stage #2: With copper(II) 2-ethylhexanoate In tetrahydrofuran at -78 - 20℃; Further stages.;
53%	Stage #1: indole; (R)-Carvone With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: With copper(II) 2-ethylhexanoate In tetrahydrofuran at -78 - 23℃; for 0.333333h; Inert atmosphere;

Reference： [1]Baran, Phil S.; Richter, Jeremy M. [Journal of the American Chemical Society, 2004, vol. 126, # 24, p. 7450 - 7451]
[2]Richter, Jeremy M.; Whitefield, Brandon W.; Maimone, Thomas J.; Lin, David W.; Castroviejo, M. Pilar; Baran, Phil S. [Journal of the American Chemical Society, 2007, vol. 129, # 42, p. 12857 - 12869]
[3]Richter, Jeremy M.; Ishihara, Yoshihiro; Masuda, Takeshi; Whitefield, Brandon W.; Llamas, Tomas; Pohjakallio, Antti; Baran, Phil S. [Journal of the American Chemical Society, 2008, vol. 130, # 52, p. 17938 - 17954]

30
[ 37595-74-7 ]
[ 2244-16-8 ]
[ 730958-86-8 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: (R)-Carvone With L-Selectride In tetrahydrofuran at -78℃; for 1h; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran at -78 - 20℃;
	Stage #1: (R)-Carvone With L-Selectride In tetrahydrofuran at -78℃; for 1.5h; Stage #2: N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran at 20℃;	1 A solution of R-carvone (1 g, 6 66 mmol) in 50 m I tetrohydrofuran (THF) was cooled to -78°C, then L-selectride (7 mL of 1 M solution in THF) was added The reaction was then stirred for 1 5 hours after which N-phenylbisrϖflimide (2 5g, 6 99mmol) was added as a solid and the reaction was allowed to warm to room temperature overnight. The reaction was diluted with hexane and worked up with water and brine solution. The colorless oil was purified with chromatography using hexane. Product is not UV active.General palladium coupling and amide formation procedures were used to obtain Compound 4.1H NMR (300 MHz, CDCI3) δ 8.64(d, J=1.7, 1 H), 8.62 (d, J=5.4Hz, 1 H), 8.42 (bd, J=12.6Hz, 1 H), 8.01 (t, J=5.9Hz, 1 H), 7.60 (d, J=6.6Hz, 2H), 7.18 (d, J=6.6Hz, 1H), 4.74 (s, 2H)1 2.38-2.18 (m, 5H), 1.81-1.93 (m, 1 H), 1.77 (s, 3H), 1.23 (s, 3H)ppm. ESMS calcd. (C22H23FN2O): 350.2; found: 352.2 (M + H).

Reference： [1]Cai, Xiongwei; Snieckus, Victor [Organic Letters, 2004, vol. 6, # 14, p. 2293 - 2295]
[2]Current Patent Assignee: SYNTA PHARMACEUTICALS CORP. - WO2007/87443, 2007, A2 Location in patent: Page/Page column 109-110

31
[ 2244-16-8 ]
[ 127-65-1 ]
(5R)-2-methyl-5-(2-methyl-1-tosylaziridin-2-yl)cyclohex-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With phenyltrimethylammonium tribromide In acetonitrile at 28℃; for 12h;
72%	With trimethylphenylammonium tribromide In water; acetonitrile at 28℃; for 12h;	4.1. General procedure for sharpless aziridination General procedure: To a mixture of an appropriate olefin (3 mmol) and TsNClNa*3H2O (CAT) (0.930 g, 3.3 mmol) in CH3CN (15 mL), was added phenyltrimethylammonium tribromide, (PTAB) (0.113 g, 0.3 mmol) at 28 °C. After 12 h of vigorous stirring, the reaction mixture was concentrated and filtered through a short column of silica gel and eluted with 10% EtOAc in hexanes. After evaporation of solvent, the resultant solid was purified by flash column chromatography to yield the corresponding aziridines in good yield.

Reference： [1]Sureshkumar, Devarajulu; Koutha, Srinivasa Murthy; Chandrasekaran, Srinivasan [Journal of the American Chemical Society, 2005, vol. 127, # 37, p. 12760 - 12761]
[2]Sureshkumar, Devarajulu; Gunasundari, Thanikachalam; Chandrasekaran, Srinivasan [Tetrahedron, 2015, vol. 71, # 39, p. 7267 - 7281]

32
[ 2244-16-8 ]
[ 69226-51-3 ]
2-Methyl-2-((R)-4-methyl-5-oxo-cyclohex-3-enyl)-aziridine-1-sulfonic acid 2,2,2-trichloro-ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With [bis(acetoxy)iodo]benzene; magnesium oxide In chlorobenzene at -10 - 23℃; for 8h;

Reference： [1]Guthikonda, Kiran; Wehn, Paul M.; Caliando, Brian J.; Du Bois [Tetrahedron, 2006, vol. 62, # 49, p. 11331 - 11342]

33
[ 18282-40-1 ]
[ 2244-16-8 ]
1-(2-ethyl-phenyl)-5-isopropenyl-2-methyl-cyclohex-2-enol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: 1-ethyl-2-iodobenzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: (R)-Carvone In tetrahydrofuran; hexane at -78 - 20℃;

Reference： [1]Liu, Yongxiang; Lu, Kui; Dai, Mingji; Wang, Kai; Wu, Wanqing; Chen, Jiahua; Quan, Junmin; Yang, Zhen [Organic Letters, 2007, vol. 9, # 5, p. 805 - 808]

34
[ 2244-16-8 ]
[ 699119-05-6 ]
[ 931120-70-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: 1-bromo-4-iodo-2,5-dimethylbenzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: (R)-Carvone In tetrahydrofuran; hexane at -78 - 20℃;

Reference： [1]Liu, Yongxiang; Lu, Kui; Dai, Mingji; Wang, Kai; Wu, Wanqing; Chen, Jiahua; Quan, Junmin; Yang, Zhen [Organic Letters, 2007, vol. 9, # 5, p. 805 - 808]

35
[ 2244-16-8 ]
[ 31269-75-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: (R)-Carvone With platinum(IV) oxide; hydrogen In methanol Stage #2: With cerium(III) chloride heptahydrate In methanol at 0℃; for 0.166667h; Stage #3: With sodium tetrahydroborate In methanol at 0℃;
	Multi-step reaction with 2 steps 1: hydrogen / PtO₂ 2: LiAlH₄
	Multi-step reaction with 2 steps 1.1: platinum(IV) oxide; hydrogen / methanol / 5 h / 20 °C 2.1: cerium(III) chloride heptahydrate / methanol / 0.17 h / 0 °C / Inert atmosphere 2.2: 0.08 h / 0 °C / Inert atmosphere

Reference： [1]Dethe, Dattatraya H.; Dherange, Balu D.; Das, Saikat [Organic Letters, 2018, vol. 20, # 3, p. 680 - 683]
[2]Chen, Peiling; Chen, Yanping; Carroll, Patrick J.; Sieburth, Scott McN. [Organic Letters, 2006, vol. 8, # 15, p. 3367 - 3370]
[3]Dethe, Dattatraya H.; Dherange, Balu D. [Journal of Organic Chemistry, 2018, vol. 83, # 6, p. 3392 - 3396]

36
[ 2244-16-8 ]
[ 24120-79-4 ]

Yield	Reaction Conditions	Operation in experiment
50%	Stage #1: (R)-Carvone With sodium tetrahydroborate; cerium(III) chloride heptahydrate In methanol at 0℃; for 0.166667h; Stage #2: With tert.-butylhydroperoxide; bis(acetylacetonate)oxovanadium In water; toluene at 23℃; for 67h;
	Multi-step reaction with 2 steps 1: 75 percent / NaBH₄; CeCl₃ / methanol 2: 81 percent / MCPBA / CH₂Cl₂
	Multi-step reaction with 2 steps 1: NaBH₄, CeCl₃ / methanol 2: m-chloroperbenzoic acid, satd. aq. NaHCO₃ / CHCl₃

	Multi-step reaction with 2 steps 1.1: lithium aluminium tetrahydride / dichloromethane / 3 h / -78 - 20 °C / Inert atmosphere 1.2: 1 h / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 5 h / -40 - -30 °C
	Multi-step reaction with 2 steps 1: sodium tetrahydroborate; cerium(III) chloride / methanol / Inert atmosphere 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / Inert atmosphere
	Multi-step reaction with 2 steps 1: sodium tetrahydroborate; cerium(III) chloride heptahydrate / methanol / 0.25 h / 0 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3 h / 20 °C
	Multi-step reaction with 2 steps 1: sodium tetrahydroborate; cerium(III) chloride heptahydrate / methanol / 0.08 h / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / 0 °C
	Multi-step reaction with 2 steps 1: sodium tetrahydroborate; cerium(III) chloride heptahydrate 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 20 h / -36 °C

Reference： [1]Tanveer, Kashif; Kim, Seung-Joon; Taylor, Mark S. [Organic Letters, 2018, vol. 20, # 17, p. 5327 - 5331]
[2]Kirsch, Stefan; Bach, Thorsten [Synthesis, 2003, # 12, p. 1827 - 1836]
[3]Sarandeses, Luis A.; Mourino, Antonio; Luche, Jean-Louis [Journal of the Chemical Society. Chemical communications, 1991, # 12, p. 818 - 820]
[4]Chen, Yan; Ju, Tong [Organic Letters, 2011, vol. 13, # 1, p. 86 - 89]
[5]Fernández-Mateos; Herrero Teijón; Rubio González [Tetrahedron, 2013, vol. 69, # 5, p. 1611 - 1616]
[6]Tanveer, Kashif; Jarrah, Kareem; Taylor, Mark S. [Organic Letters, 2015, vol. 17, # 14, p. 3482 - 3485]
[7]Salgado, Paula Regina Rodrigues; Da Fonsêca, Diogo Vilar; Braga, Renan Marinho; De Melo, Cynthia Germoglio Farias; Andrade, Luciana Nalone; De Almeida, Reinaldo Nóbrega; De Sousa, Damião Pergentino [Molecules, 2015, vol. 20, # 11, p. 19660 - 19673]
[8]Santamarta, Francisco; Vilas, Miguel; Tojo, Emilia; Fall, Yagamare [RSC Advances, 2016, vol. 6, # 37, p. 31177 - 31180]

37
[ 1195-92-2 ]
[ 2244-16-8 ]

Yield	Reaction Conditions	Operation in experiment
		56 Preparation of R-(-)-carvone (One-pot Simultaneous Rearrangement of R-(+)-1,2-Limonene Oxide and Oppenauer Oxidation of R-(-)-carveol in the Presence of Magnesium Hydroxide-Carvacrol Catalyst System) The yield of R-(-)-carvone is 49.6 parts or 68.8% on reacted 1,2-limonene oxide. This mixture was further purified using conventional separation techniques to obtain flavor grade R-(-)-carvone.

Reference： [1]Current Patent Assignee: SYMRISE AG - US2003/65230, 2003, A1

38
[ 3189-13-7 ]
[ 2244-16-8 ]
[ 957373-12-5 ]

Yield	Reaction Conditions	Operation in experiment
49%	Stage #1: 6-methoxylindole; (R)-Carvone With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Stage #2: With copper(II) 2-ethylhexanoate In tetrahydrofuran at -78 - 20℃; Further stages.;

Reference： [1]Richter, Jeremy M.; Whitefield, Brandon W.; Maimone, Thomas J.; Lin, David W.; Castroviejo, M. Pilar; Baran, Phil S. [Journal of the American Chemical Society, 2007, vol. 129, # 42, p. 12857 - 12869]

39
[ 2244-16-8 ]
(1,3-dioxan-2-yl)ethylmagnesium bromide [ No CAS ]
[ 1013115-10-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: (R)-Carvone With cerium(III) chloride In tetrahydrofuran at 20℃; for 1h; Stage #2: (1,3-dioxan-2-yl)ethylmagnesium bromide In tetrahydrofuran at 23℃; for 3h; Stage #3: With pyridinium chlorochromate In dichloromethane at 20℃; for 2h; Further stages.;

Reference： [1]Nicolaou; Pappo, Doron; Tsang, Kit Y.; Gibe, Romelo; Chen, David Y.-K. [Angewandte Chemie - International Edition, 2008, vol. 47, # 5, p. 944 - 946]

40
[ 7751-38-4 ]
[ 2244-16-8 ]
[ 1093117-46-4 ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: (R)-Carvone With lithium diisopropyl amide In tetrahydrofuran at -78℃; Inert atmosphere; Stage #2: Diisopropylsilyl dichloride With triethylamine In tetrahydrofuran at -78 - 20℃; Inert atmosphere;
79%	Stage #1: (R)-Carvone With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Stage #2: Diisopropylsilyl dichloride With triethylamine In tetrahydrofuran at -78 - 20℃; for 3h;

Reference： [1]Avetta Jr., Christopher T.; Konkol, Leah C.; Taylor, Carla N.; Dugan, Karen C.; Stern, Charlotte L.; Thomson, Regan J. [Organic Letters, 2008, vol. 10, # 24, p. 5621 - 5624]
[2]Caravana, Aidan C.; Nagasing, Benjamin; Dhanju, Sandeep; Reynolds, Rebekah G.; Weiss, Emily A.; Thomson, Regan J. [Journal of Organic Chemistry, 2021, vol. 86, # 9, p. 6600 - 6611]

41
[ 50899-39-3 ]
[ 2244-16-8 ]
C₂₀H₂₃NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: (R)-Carvone With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: N-methoxymethylisatin In tetrahydrofuran at -78 - 20℃; for 0.5h; Inert atmosphere;

Reference： [1]Richter, Jeremy M.; Ishihara, Yoshihiro; Masuda, Takeshi; Whitefield, Brandon W.; Llamas, Tomas; Pohjakallio, Antti; Baran, Phil S. [Journal of the American Chemical Society, 2008, vol. 130, # 52, p. 17938 - 17954]

42
[ 60732-17-4 ]
[ 2244-16-8 ]
6-(2,5-dimethoxy-benzyl)-5-isopropenyl-2-methyl-cyclohex-2-enone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: (R)-Carvone With lithium diisopropyl amide In tetrahydrofuran; hexane at -10℃; for 3h; Stage #2: 2,5-dimethoxybenzyl bromide In tetrahydrofuran; hexane at -10 - 20℃; for 18.5h;	1 EXAMPLE 1; Preparation Of Compound Of Formula (31) To a stirred solution of LDA, prepared from diisopropylamine (3.44 g, 4.76 ml, 34 mmol) and n-BuLi (2.09 g, 16.3 ml of 2 M solution in hexanes, 32 mmol) in THF (30 ml) at -10° C. for 1 h, was added (R)-(-)-carvone (30) (3.78 g, 4 ml, 25 mmol) in dry THF (40 ml) drop-wise over 1 h at the same temperature under nitrogen atmosphere. The stirring was continued for further 2 h. At this temperature was added drop wise a solution of 2,5-dimethoxybenzylbromide (7.52 g, 32.5 mmol) in dry THF (20 ml) during 10 minutes. The reaction mixture was further stirred at -10° C. for 3 h and then the temperature was warmed to room temperature over 1.5 h and stirred for 14 h to complete the reaction (TLC monitored). The reaction mixture was quenched with saturated NH4Cl solution. The organic layer was separated and THF removed under reduced pressure in rotary evaporator to leave oil. The aqueous part was extracted with ether (200 ml) and the ether layer was combined with the residual oil. The combined ether layer was washed with brine (100 ml) and dried over anhydrous Na2SO4. After evaporation of the solvent, the residual brown liquid was chromatographed over silica gel (60-120 mesh) (3% ethyl acetate in petroleum ether as eluent) to afford the desired alkylated product (31) (6.4 g, 85%) as light yellow thick liquid.; IR: (neat) 2921, 2832, 1670, 1499, 1461, 1369, 1225, 1049, 895, 802, 710 cm-1. 1H NMR (300 MHz in CDCl3): δ 1.64 (3H, s), 1.76 (3H, s), 2.43-2.55 (3H, m), 2.79-2.90 (3H, m), 3.75 (6H, s), 4.71 (1H, s), 4.77 (1H, s), 6.60 (1H, bars), 6.61-6.70 (2H, m), 6.83 (1H, d, J 2.8 Hz).

Reference： [1]Current Patent Assignee: FRESENIUS SE & CO. KGAA - US2004/220197, 2004, A1 Location in patent: Page 15

43
[ 60732-17-4 ]
[ 2244-16-8 ]
6-(2,5-dimethoxy-benzyl)-5-isopropenyl-2,6-dimethyl-cyclohex-2-enone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: (R)-Carvone With lithium diisopropyl amide In tetrahydrofuran; hexane at -20℃; for 3.58333h; Stage #2: 2,5-dimethoxybenzyl bromide With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone In tetrahydrofuran; hexane at -70 - 0℃; for 4.25h;	13 EXAMPLE 13; Preparation Of Compound Of Formula (34) To a stirred solution of LDA, prepared from diisopropylamine (285 g, 4 ml, 30 mmol) and n-BuLi (1.73 g, 17 ml of 1.6 M solution in hexanes, 27 mmol) in THF (100 ml) at -20° C. for 1 h, was added methyl carvone (33) (4 g, 24 mmol) in dry THF (20 ml) drop-wise over 35 minutes at the same temperature under nitrogen atmosphere. The stirring was continued for further 2 h. The temperature of the reaction mixture was lowered to -78° C. and at this temperature was added at once a solution of 2,5-dimethoxybenzl bromide (5.95 g, 26.9 mmol) and DMPU (3.18 g, 3 ml, 25 mmol) in dry THF (20 ml). The reaction mixture was further stirred at -78° C. for 2 h and then the temperature was warmed to 0° C. over 1.5 h and stirred for 45 minutes to complete the reaction (TLC monitored). The reaction mixture was quenched with saturated NH4Cl solution. The organic layer was separated and THF removed under reduced pressure in rotary evaporator to leave oil. The aqueous part was extracted with ether (200 ml) and the ether layer was combined with the residual oil. The combined ether layer was washed with brine (100 ml) and dried over anhydrous Na2SO4. After evaporation of the solvent, the residual brown liquid was chromatographed over silica gel (60-120 mesh) (3% ethyl acetate in petroleum ether as eluent) to afford the desired alkylated product (34) (7 g, 90%) as solid.; m.p.: 52-55° C. IR (neat): 2955, 2910, 2834, 1665, 1500, 1444, 1221, 1051, 1024, 900 cm-1. 1H NMR (300 MHz in CDCl3): δ 0.94 (3H, s), 1.52 (3H,s), 1.83 (3H, s), 2.09-2.26 (1H, m), 2.73 (1H, d, J 6.5 Hz), 2.84 (1H, d, J 13.2 Hz), 2.99 (1H, d, J 13.3 Hz), 3.01-3.11 (1H, m), 3.71 (3H, s), 3.74 (3H, s), 4.61 (1H, s), 4.65 (1H, s).

Reference： [1]Current Patent Assignee: FRESENIUS SE & CO. KGAA - US2004/220197, 2004, A1 Location in patent: Page 17

44
(5R)-5-isopropenyl-2-methyl-2-cyclohexene-1-hydroperoxide [ No CAS ]
[ 99-48-9 ]
[ 2244-16-8 ]

Yield	Reaction Conditions	Operation in experiment
1: 70% 2: 30%	With meso-tetraphenylporphyrin iron(III) chloride at 25℃; for 1.66667h;

Reference： [1]Location in patent: body text Redeby, Theres; Nilsson, Ulrika; Altamore, Timothy M.; Ilag, Leopold; Ambrosi, Annalisa; Broo, Kerstin; Boerje, Anna; Karlberg, Ann-Therese [Chemical Research in Toxicology, 2010, vol. 23, # 1, p. 203 - 210]

45
[ 2244-16-8 ]
[ 3848-36-0 ]
[ 1293289-51-6 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium hypochlorite In dichloromethane; water at 0 - 20℃; for 0.166667h; diastereoselective reaction;	General procedure for the preparation of Isoxazoles (3a-e) General procedure: To a stirred solution of (R)-Carvone (1) (6.57 mmol) and p-substitutedbenzaldoximes (3.28 mmol) in CH2Cl2 (15 mL) was added dropwise(during 30min) at 0 °C 20mL of aqueous NaOCl (5.2%; 15,65 mmol).After 10 min stirring (the reaction was monitored by TLC) at roomtemperature, the layers were separated and the aqueous layer wasextracted with CH2Cl2 (3 x 10 mL). The combined organic extractswere dried over anhydrous Na2SO4 and evaporated in vacuo. Theresidue was purified by column chromatography using hexane/Ethylacetate mixture (88:12) as eluent.
70%	With sodium hypochlorite In chloroform; water at 0 - 20℃; for 52h;

Reference： [1]Oubella, Ali; Ait Itto, My Youssef; Auhmani, Aziz; Riahi, Abdelkhalek; Robert, Anthony; Daran, Jean-Claude; Morjani, Hamid; Parish, Carol A.; Esseffar, M'hamed [Journal of Molecular Structure, 2019, vol. 1198]
[2]Location in patent: experimental part El Mebtoul, Aziz; Rouani, Mohamed; Chammache, Malika; Bouidida, Houcine; Ilidrissi, Abdelkader [Helvetica Chimica Acta, 2011, vol. 94, # 3, p. 433 - 437]

46
[ 74-90-8 ]
[ 2244-16-8 ]
[ 16826-23-6 ]

Yield	Reaction Conditions	Operation in experiment
93.7%	With sodium methylate In water at 136 - 148℃; for 8h;	1 Example 1 Conversion of Carvone to Carvonenitrile1379.4 g (9 mol) of R-(-)-carvone (5-isoprenyl-2-methylcyclohex-2-enone) with a purity of 98% (5-isoprenyl-2-methylcyclohex-2-enone) were heated in a 4000 ml glass flask to approx. 150° C. with stirring. At 144° C., 18.4 g of 30% sodium methoxide in water (0.1 mol) were added and then a mixture of 1287.9 g (8.4 mol) of 98% R-(-)-carvone (5-isoprenyl-2-methylcyclohex-2-enone) and 330.5 g (12.15 mol) of hydrogen cyamide (HCN) was added dropwise at 136-148° C. with stirring within 8 h. The postreaction time was approx. one hour. Subsequently, the HCN conversion was checked, and was 99.5%. The entire raw output weighed 3014 g and had a dark red color. The raw output was distilled through a Vigreux column. The first fraction recovered was unconverted carvone (approx. 900 g), and, after a mixed fraction (147.5 g), 1809.8 g of carvonenitrile were obtained with a purity of 98-99% (gas chromatography).The yield including the product of value present in the mixed fraction was 93.7% based on HCN.

Reference： [1]Current Patent Assignee: BASF SE - US2011/124918, 2011, A1 Location in patent: Page/Page column 8

47
[ 2244-16-8 ]
[ 1062245-64-0 ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: (R)-Carvone With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 1.5h; Stage #2: With periodic acid In tetrahydrofuran; water for 6h;	(5R)-5-Acetyl-2-methylcyclohex-2-en-1-one (5). To a solution of 5.0 g (33.3 mmol) of R-(-)-carvone in 50 mL of CH2Cl2 was added 9.86 g (40.0 mmol) of 70% m-ClC6H4CO3H, the reaction mixture was stirred for 1.5 h at room temperature till disappearance of the initial compound (TLC monitoring). Then a saturated solution of Na2S2O3 was added, the mixture was stirred for 15 min, the organic layer was separated, washed with saturated NaHCO3 solution, dried over MgSO4, filtered, and evaporated. The residue was dissolved in 60 mL of a mixture THF-H2O, 5 : 1, 9.12 g (40.0 mmol) of H5IO6 was added, and the stirring was continued for 6 h. Then a saturated solution of Na2S2O3 was added, the mixture was stirred for 15 min, the organic layer was separated, washed with the saturated solution of NaHCO3, dried over MgSO4, filtered, evaporated, the residue was chromatographed on SiO2 (petroleum ether-EtOAc, 3 : 1). Yield 3.95 g (78%), yellow oil, [α]D20 -75.1° ( 1.24, CHCl3). IR spectrum, cm-1: 2925,1713, 1674, 1435, 1366, 1171, 1107. 1H NMR spectrum, δ, ppm: 1.79 s (3H, CH3), 2.19 s (3H, CH3), 2.51-2.56 m (2H, CH2), 2.69 d.d (2H, CH2, J 4.1, 16.4 Hz), 3.11 m (1H, CH), 6.70 m (1H, =CH). 13C NMR spectrum, δ, ppm: 15.7, 27.5, 27.8, 39.4, 48.1, 135.9, 142.6, 197.5, 207.8. Found, %: C 71.55; H 8.02. C9H12O2. Calculated, %: C 71.03; H 7.95.
69%	Stage #1: (R)-Carvone With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0℃; for 5h; Inert atmosphere; Stage #2: With periodic acid In diethyl ether at 0℃; Inert atmosphere;
69%	Stage #1: (R)-Carvone With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0℃; for 5h; Inert atmosphere; Stage #2: With periodic acid In diethyl ether at 0℃; Inert atmosphere;	2.2 Compound S9. This compound was prepared as reported by Miftakhov and coworkers.7 (R)-carvone ((R)-7) (3.0 g, 20.0 mmol, 1.0 equiv.) and DCM (200 mL, 0.1 M) were added to an oven-dried 500 mL round-bottom flask. The solution was cooled to 0° C. before adding mCPBA (5.2 g, 30.0 mmol, 1.5 equiv.) in three portions. Upon observed consumption of the starting material by TLC (after 5 hours), the reaction was quenched with saturated NaHCO3 and extracted with DCM. The combined organic layers were washed with brine, dried over MgSO4, and the solvent evaporated under reduced pressure. The crude epoxide was taken on to the next reaction, where it was diluted in ether (500 mL), cooled to 0° C., and H5IO6 (7.3 g, 32.0 mmol, 1.6 equiv.) was added in three portions. The reaction was left to stir overnight, after which it was diluted with saturated NaHCO3 and extracted with ether. The combined organic layers were washed with brine, dried with MgSO4, and the solvent evaporated under reduced pressure. The crude material was purified using flash chromatography on silica gel using 20% to 50% ether/pentanes yielding a yellow oil (2.1 g, 13.8 mmol, 69% over two steps): 1H NMR (500 MHz, Chloroform-d) δ 6.70 (ddq, J=4.8, 3.0, 1.5 Hz, 1H), 3.10 (dddd, J=12.1, 9.5, 5.4, 4.2 Hz, 1H), 2.69 (ddd, J=16.4, 4.2, 1.1 Hz, 1H), 2.58-2.45 (m, 3H), 2.19 (s, 3H), 1.78 (q, J=1.8 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 208.0, 197.6, 142.8, 136.0, 48.3, 39.6, 28.0, 27.6, 15.9; HRMS (ESI): Exact mass calc'd for C9H13O2 [M+H]+, 153.0916. Found 153.0910. All spectroscopic data for this compound agrees with previously reported values.7

60%	With pyridine; oxygen; ozone In dichloromethane Inert atmosphere;
	Multi-step reaction with 2 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 20 °C 2: periodic acid / diethyl ether / 0 - 20 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1: C₂₀H₂₆FeN₄⁽²⁺⁾*2CF₃O₃S^(1-); dihydrogen peroxide; acetic acid / acetonitrile / 0.17 h / 0 °C 2: sulfuric acid / water / 0.5 h / 50 °C 3: sodium hydrogencarbonate; sodium periodate / water / 0.5 h / 50 °C

Reference： [1]Valeev; Bikzhanov; Miftakhov [Russian Journal of Organic Chemistry, 2015, vol. 51, # 5, p. 660 - 663][Zh. Org. Khim., 2015, vol. 51, # 5, p. 660 - 663,4]
[2]Robinson, Emily E.; Thomson, Regan J. [Journal of the American Chemical Society, 2018, vol. 140, # 5, p. 1956 - 1965]
[3]Current Patent Assignee: NORTHWESTERN UNIVERSITY (ILLINOIS) - US2019/127306, 2019, A1 Location in patent: Paragraph 0225; 0258; 0259
[4]Myasoedova, Yuliya V.; Garifullina, Liliya R.; Belyaeva, Evelina R.; Ishmuratov, Gumer Yu [Journal of the Chinese Chemical Society, 2022, vol. 69, # 4, p. 744 - 749]
[5]Torosyan; Gimalova; Valeev; Miftakhov [Russian Journal of Organic Chemistry, 2011, vol. 47, # 5, p. 682 - 686]
[6]Spannring, Peter; Yazerski, Vital A.; Chen, Jianming; Otte, Matthias; Weckhuysen, Bert M.; Bruijnincx, Pieter C. A.; Klein Gebbink, Robertus J. M. [European Journal of Inorganic Chemistry, 2015, vol. 2015, # 21, p. 3462 - 3466]

48
[ 40018-26-6 ]
[ 2244-16-8 ]
[ 1350801-52-3 ]

Yield	Reaction Conditions	Operation in experiment
84%	In water Reflux;
45%	With triethylamine In dichloromethane at 20℃; for 16h; diastereoselective reaction;	4.3. General procedure for the preparation of compounds 13, 14, 15, 18, and 19 General procedure: A suspension of dithiane 6 (1.30 mmol), enone (2.60 mmol), and triethylamine (0.13 mmol) in CH2Cl2 (8 mL) was stirred at room temperature for 16 h. After this time, the reaction mixture was concentrated under reduced pressure and the residue obtained was purified by column chromatography (silica gel, EtOAc/cyclohexane 1:4).

Reference： [1]Current Patent Assignee: SOUTHWEST UNIVERSITY - CN104059051, 2016, B Location in patent: Paragraph 0055; 0056
[2]Location in patent: experimental part Baricordi, Nikla; Benetti, Simonetta; Bertolasi, Valerio; De Risi, Carmela; Pollini, Gian P.; Zamberlan, Francesco; Zanirato, Vinicio [Tetrahedron, 2012, vol. 68, # 1, p. 208 - 213]

49
[ 2244-16-8 ]
[ 308363-12-4 ]
[ 250647-16-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tetrahydroborate In methanol at 20℃; for 0.333333h; Inert atmosphere;
	With sodium tetrahydroborate In ethanol at 0 - 20℃; for 3h;	Chemical reduction of (R)-carvone To a solution of commercial (R)-carvone (1.0g, 6.67mmol) in EtOH (10.0mL), sodium borohydride (8equiv.) was slowly added at 0°C, and the reaction was stirred at room temperature for 3h. The reaction was quenched by the addition of H2O, and the products were extracted with EtOAc (3×10mL). The organic layer was dried over anhydride Na2SO4 and filtered. After solvent distillation under reduced pressure, the crude products (0.92mg) were coarsely purified on a silica gel column (silica gel 60, 230-240mesh; EtOAc/hexane as eluent) and analyzed by gas chromatography-mass spectrometry (GC-MS) recorded on a Shimadzu GCMS-QP5050A apparatus (Column OV5 [30m×0.25mm×0.25μm]). A mixture of carveol (4) and dihydrocarveol (5) was identified as the product of the chemical reduction of (R)-carvone (2).

Reference： [1]Forkel, Nina V.; Henderson, David A.; Fuchter, Matthew J. [Green Chemistry, 2012, vol. 14, # 8, p. 2129 - 2132]
[2]Nunes, Fátima M.; Dos Santos, Gabriel F.; Saraiva, Natália N.; Trapp, Marília A.; De Mattos, Marcos C.; Oliveira, Maria Da Conceição F.; Rodrigues-Filho, Edson [Applied Catalysis A: General, 2013, vol. 468, p. 88 - 94]

50
[ 2244-16-8 ]
[ 36919-03-6 ]
[ 123150-79-8 ]

Yield	Reaction Conditions	Operation in experiment
68%	With dmap; magnesium bromide ethyl etherate; N-ethyl-N,N-diisopropylamine In dichloromethane for 48h; Inert atmosphere; Reflux;

Reference： [1]Hale, Karl J.; Grabski, Milosz; Flasz, Jakub T. [Organic Letters, 2013, vol. 15, # 2, p. 370 - 373]

51
[ 2244-16-8 ]
C₁₀H₁₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	Stage #1: (R)-Carvone With 9-bora-bicyclo[3.3.1]nonane In tetrahydrofuran at 0 - 20℃; for 20h; Inert atmosphere; Stage #2: With dihydrogen peroxide; sodium hydroxide In tetrahydrofuran for 20h; Inert atmosphere; Reflux; Stage #3: With N-chloro-succinimide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetrabutyl-ammonium chloride In dichloromethane at 20℃; for 3h; Inert atmosphere;

Reference： [1]Ibrahim, Ahmad A.; Golonka, Alexander N.; Lopez, Alberto M.; Stockdill, Jennifer L. [Organic Letters, 2014, vol. 16, # 4, p. 1072 - 1075]

52
[ 2244-16-8 ]
[ 138-86-3 ]

Yield	Reaction Conditions	Operation in experiment
11%	With [NiNP^tBu₃]₄; phenylsilane In tetrahydrofuran at 60℃; for 16h; Sealed tube;	18 Catalytic Deoxygenation of Carvone Example 18 Catalytic Deoxygenation of Carvone A 100 mL Teflon-sealing glass reactor equipped with a Teflon-covered magnetic stir bar was charged with 8 mg (0.007 mmol) [NiNPtBu3]4, 100 mg (0.67 mmol) R-carvone, 73 mg (0.67 mmol) PhSiH3 and 1.5 mL tetrahydrofuran (THF). The reaction mixture was allowed to stir at a speed of 1200 rpm for 16 hours at 60° C. temperature. The reaction mixture was then filtered through a plug of Florisil and the THF-fraction was subjected to GC-MS analysis. The substrate was completely converted into a mixture of products identified to be the following: and the remaining fraction is a mixture of C=0 hydrosilylation products.

Reference： [1]Current Patent Assignee: UNIVERSITY OF ALBERTA - US2014/179954, 2014, A1 Location in patent: Paragraph 0190

53
L-(-)-carveol [ No CAS ]
[ 39903-76-9 ]
[ 2244-16-8 ]
2,3-epoxy-2-methyl-5-(1-methylethenyl)-cyclohexan-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dihydrogen peroxide In water; acetonitrile at 90℃; for 3h; Inert atmosphere; chemoselective reaction;	2.3 Catalytic tests General procedure: All catalysts were pre-treated under dry air at 500°C and cooled to room temperature under vacuum prior to use. The epoxidation tests on the alkenes, namely, cyclohexene (Aldrich 99%), 1-methyl-1-cyclohexene (Aldrich 97%), R-(+)-limonene (Aldrich 97%), (-)-carveol (Aldrich 97%), α-terpineol (Aldrich 90%), isopulegol (Aldrich techn.), carvotanacetol (prepared by selective hydrogenation of carveol, as previously described [44,45]), R-(-)-carvone (Aldrich 98%), isopulegyl acetate (Aldrich 96%) and squalene (Aldrich ≥98%) were carried out in a round-bottom glass batch reactor in an oil bath at 90°C equipped with magnetic stirring (ca. 800rpm) under inert atmosphere. The substrate (1.0mmol) was dissolved in acetonitrile (Aldrich, HPLC grade; 5.0mL) and aqueous hydrogen peroxide (H2O2; aq. 50% Aldrich; 2.0mmol) was used as oxidant. The samples were taken after reaction times of 1, 2 and 4h and analysed by gas-chromatography (Agilent 6890 Series; HP-5 column, 30m×0.25mm; FID detector). Mesitylene (Fluka, puriss. ≥99%) was used as internal standard. GC-peaks were identified by comparison with peaks of genuine samples of reference standards and/or by means of GC-MS analysis. In the tests of squalene epoxidation, the reaction was followed by 1H and 13C NMR analysis at room temperature (Bruker UXNMR, 400MHz) [46,47]. After all tests, the presence of residual hydrogen peroxide was checked and confirmed by iodometric assays and titrations. In none of the cases hydrogen peroxide was the limiting reagent. Specific activity, SA, of the catalyst is defined as the amount (moles) of converted alkene per amount (moles) of total Nb in the unit of time (1h).

Reference： [1]Tiozzo, Cristina; Bisio, Chiara; Carniato, Fabio; Guidotti, Matteo [Catalysis Today, 2014, vol. 235, p. 49 - 57]

54
[ 63-91-2 ]
[ 2244-16-8 ]
C₁₈H₂₃N [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: L-phenylalanine; (R)-Carvone In propan-1-ol at 190℃; for 0.0833333h; Microwave irradiation; Sealed tube; Stage #2: With water In propan-1-ol at 50℃; Acidic conditions;	It was also observed during these experiments that the rate of reaction significantly increased at the higher catalyst load, an effect maximizing at about 2 mole equivalents for both cyclo-hex-2-ene-1-one (2) and R-carvone (3). The reaction times in minutes of a series of microwave assisted decarboxylations of phenylalanine in n-propanol at 190° C., varying the load of R-carvone (3) catalyst, are given in FIG. 1. Table 1, below, compares several catalysts at the 2 equivalent load for performance on a series of decarboxylations. [0062] Considering that the reaction is thought to occur through a carboxylic acid imine intermediate and given the observed rise in impurities as a result of increasing the catalyst load from the Hashimoto procedure, the fate of the decarboxylated imine was then investigated as follows. A large excess of carvone was added to the reaction mixture to attempt to capture all product amine as an imine with carvone. The imine was then transferred into an aqueous acid mixture, excess carvone removed via ether wash, and then returned to an organic phase via neutralization with NaOH solution. A significant degree of hydrolysis was expected; however, in these observations, the imine of the decarboxylated product was quite stable and persisted as demonstrated by the GC-MS spectrum and gas chromatograph (FIGS. 2A and 2B) of the product mixture of decarboxylated phenylalanine. It was observed that only after heating in acid at >50° C. did the hydrolysis occur. Even after one pot reflux with many times the reaction volume of 2.0 M HCl, it proved difficult to adequately remove all traces of the imine at system equilibrium. Each conventional method of amino acid decarboxylation fails to account for the quantity of imine that may remain, thus lowering the yield and purity of the crude product and leading to further purification.
	In propan-1-ol at 20 - 190℃; Green chemistry;	General Decarboxylation Procedure General procedure: A magnetic stir bar, 3mL of n-PrOH, 10 mmol of R-carvone, and 5 mmol of amino acid were charged toa pressure vessel. The vessel was heated from room temperature to 190 °C over 5 min with stirring. If necessary the reaction vessel was maintained at 190 °C for an additional time until the slurry became clear. The vessel was allowed to cool to below the solvent boiling point, carefully vented to release evolved CO2, and analyzed via GC-MS to verify the presence of decarboxylated imine.

Reference： [1]Current Patent Assignee: UNIVERSITY SYSTEM OF GEORGIA - US2014/275569, 2014, A1 Location in patent: Page/Page column 0009; 0061; 0062; 0063; 0067
[2]Jackson, Douglas M.; Ashley, Robert L.; Brownfield, Callan B.; Morrison, Daniel R.; Morrison, Richard W. [Synthetic Communications, 2015, vol. 45, # 23, p. 2691 - 2700]

55
[ 6485-40-1 ]
[ 71-00-1 ]
C₁₅H₂₁N₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Another factor affecting the reaction rate and overall ease of purification of the product mixture was the identity and load of the catalyst. In conventional methods, a 1% v/v of cyclohex-2-en-1-one (2) has been reported for histidine decarboxylation2; however, others3 have reported difficulty in repeating these results without a substantially higher catalyst load. Significant impurities were also observed in the resulting reaction mixture by those authors, and in later attempts to reproduce the experiments. These authors alternatively used acetophenone (1) to modest success3 for the decarboxylation of histamine at 20 mol % in >40 hr. It was postulated that the greater the stability of the imine, the greater the reaction rate at a given catalyst load, and, indeed, cyclohex-2-en-1-one (2) proved to provide a greater catalytic effect at 20 mol % than acetophenone (1). On a belief that the enone functionality of cyclohex-2-ene-1-one provides some advantage over the benzyl ketone and given its toxicity and expense of, an alternative was selected for testing in the present examples. R-carvone (3), the natural product of spearmint oil, was selected for its potential to retain the catalytic advantage over acetophenone while providing an alternative method of removal of the catalyst based on the isomerization reaction of R-carvone (3) to carvacrol (4) (Scheme 1, FIG. 3).It was also observed during these experiments that the rate of reaction significantly increased at the higher catalyst load, an effect maximizing at about 2 mole equivalents for both cyclo-hex-2-ene-1-one (2) and R-carvone (3). The reaction times in minutes of a series of microwave assisted decarboxylations of phenylalanine in n-propanol at 190 C., varying the load of R-carvone (3) catalyst, are given in FIG. 1. Table 1, below, compares several catalysts at the 2 equivalent load for performance on a series of decarboxylations. [0062] Considering that the reaction is thought to occur through a carboxylic acid imine intermediate and given the observed rise in impurities as a result of increasing the catalyst load from the Hashimoto procedure, the fate of the decarboxylated imine was then investigated as follows. A large excess of carvone was added to the reaction mixture to attempt to capture all product amine as an imine with carvone. The imine was then transferred into an aqueous acid mixture, excess carvone removed via ether wash, and then returned to an organic phase via neutralization with NaOH solution. A significant degree of hydrolysis was expected; however, in these observations, the imine of the decarboxylated product was quite stable and persisted as demonstrated by the GC-MS spectrum and gas chromatograph (FIGS. 2A and 2B) of the product mixture of decarboxylated phenylalanine. It was observed that only after heating in acid at >50 C. did the hydrolysis occur. Even after one pot reflux with many times the reaction volume of 2.0 M HCl, it proved difficult to adequately remove all traces of the imine at system equilibrium. Each conventional method of amino acid decarboxylation fails to account for the quantity of imine that may remain, thus lowering the yield and purity of the crude product and leading to further purification.
	In propan-1-ol; at 20 - 190℃;Green chemistry;	General procedure: A magnetic stir bar, 3mL of n-PrOH, 10 mmol of R-carvone, and 5 mmol of amino acid were charged toa pressure vessel. The vessel was heated from room temperature to 190 C over 5 min with stirring. If necessary the reaction vessel was maintained at 190 C for an additional time until the slurry became clear. The vessel was allowed to cool to below the solvent boiling point, carefully vented to release evolved CO2, and analyzed via GC-MS to verify the presence of decarboxylated imine.

Reference： [1]Patent: US2014/275569,2014,A1 .Location in patent: Page/Page column 0060; 0061; 0062; 0067
[2]Synthetic Communications,2015,vol. 45,p. 2691 - 2700

56
[ 2244-16-8 ]
[ 60-18-4 ]
C₁₈H₂₃NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (R)-Carvone; L-tyrosine In propan-1-ol at 190℃; for 0.333333h; Microwave irradiation; Sealed tube; Stage #2: With water In propan-1-ol at 50℃; Acidic conditions;	Another factor affecting the reaction rate and overall ease of purification of the product mixture was the identity and load of the catalyst. In conventional methods, a 1% v/v of cyclohex-2-en-1-one (2) has been reported for histidine decarboxylation2; however, others3 have reported difficulty in repeating these results without a substantially higher catalyst load. Significant impurities were also observed in the resulting reaction mixture by those authors, and in later attempts to reproduce the experiments. These authors alternatively used acetophenone (1) to modest success3 for the decarboxylation of histamine at 20 mol % in >40 hr. It was postulated that the greater the stability of the imine, the greater the reaction rate at a given catalyst load, and, indeed, cyclohex-2-en-1-one (2) proved to provide a greater catalytic effect at 20 mol % than acetophenone (1). On a belief that the enone functionality of cyclohex-2-ene-1-one provides some advantage over the benzyl ketone and given its toxicity and expense of, an alternative was selected for testing in the present examples. R-carvone (3), the natural product of spearmint oil, was selected for its potential to retain the catalytic advantage over acetophenone while providing an alternative method of removal of the catalyst based on the isomerization reaction of R-carvone (3) to carvacrol (4) (Scheme 1, FIG. 3).It was also observed during these experiments that the rate of reaction significantly increased at the higher catalyst load, an effect maximizing at about 2 mole equivalents for both cyclo-hex-2-ene-1-one (2) and R-carvone (3). The reaction times in minutes of a series of microwave assisted decarboxylations of phenylalanine in n-propanol at 190° C., varying the load of R-carvone (3) catalyst, are given in FIG. 1. Table 1, below, compares several catalysts at the 2 equivalent load for performance on a series of decarboxylations. [0062] Considering that the reaction is thought to occur through a carboxylic acid imine intermediate and given the observed rise in impurities as a result of increasing the catalyst load from the Hashimoto procedure, the fate of the decarboxylated imine was then investigated as follows. A large excess of carvone was added to the reaction mixture to attempt to capture all product amine as an imine with carvone. The imine was then transferred into an aqueous acid mixture, excess carvone removed via ether wash, and then returned to an organic phase via neutralization with NaOH solution. A significant degree of hydrolysis was expected; however, in these observations, the imine of the decarboxylated product was quite stable and persisted as demonstrated by the GC-MS spectrum and gas chromatograph (FIGS. 2A and 2B) of the product mixture of decarboxylated phenylalanine. It was observed that only after heating in acid at >50° C. did the hydrolysis occur. Even after one pot reflux with many times the reaction volume of 2.0 M HCl, it proved difficult to adequately remove all traces of the imine at system equilibrium. Each conventional method of amino acid decarboxylation fails to account for the quantity of imine that may remain, thus lowering the yield and purity of the crude product and leading to further purification.
	In propan-1-ol at 20 - 190℃; Green chemistry;	General Decarboxylation Procedure General procedure: A magnetic stir bar, 3mL of n-PrOH, 10 mmol of R-carvone, and 5 mmol of amino acid were charged toa pressure vessel. The vessel was heated from room temperature to 190 °C over 5 min with stirring. If necessary the reaction vessel was maintained at 190 °C for an additional time until the slurry became clear. The vessel was allowed to cool to below the solvent boiling point, carefully vented to release evolved CO2, and analyzed via GC-MS to verify the presence of decarboxylated imine.

Reference： [1]Current Patent Assignee: UNIVERSITY SYSTEM OF GEORGIA - US2014/275569, 2014, A1 Location in patent: Page/Page column 0060; 0061; 0062; 0067
[2]Jackson, Douglas M.; Ashley, Robert L.; Brownfield, Callan B.; Morrison, Daniel R.; Morrison, Richard W. [Synthetic Communications, 2015, vol. 45, # 23, p. 2691 - 2700]

57
[ 2244-16-8 ]
[ 71-00-1 ]
C₁₅H₂₁N₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Another factor affecting the reaction rate and overall ease of purification of the product mixture was the identity and load of the catalyst. In conventional methods, a 1% v/v of cyclohex-2-en-1-one (2) has been reported for histidine decarboxylation2; however, others3 have reported difficulty in repeating these results without a substantially higher catalyst load. Significant impurities were also observed in the resulting reaction mixture by those authors, and in later attempts to reproduce the experiments. These authors alternatively used acetophenone (1) to modest success3 for the decarboxylation of histamine at 20 mol % in >40 hr. It was postulated that the greater the stability of the imine, the greater the reaction rate at a given catalyst load, and, indeed, cyclohex-2-en-1-one (2) proved to provide a greater catalytic effect at 20 mol % than acetophenone (1). On a belief that the enone functionality of cyclohex-2-ene-1-one provides some advantage over the benzyl ketone and given its toxicity and expense of, an alternative was selected for testing in the present examples. R-carvone (3), the natural product of spearmint oil, was selected for its potential to retain the catalytic advantage over acetophenone while providing an alternative method of removal of the catalyst based on the isomerization reaction of R-carvone (3) to carvacrol (4) (Scheme 1, FIG. 3).It was also observed during these experiments that the rate of reaction significantly increased at the higher catalyst load, an effect maximizing at about 2 mole equivalents for both cyclo-hex-2-ene-1-one (2) and R-carvone (3). The reaction times in minutes of a series of microwave assisted decarboxylations of phenylalanine in n-propanol at 190 C., varying the load of R-carvone (3) catalyst, are given in FIG. 1. Table 1, below, compares several catalysts at the 2 equivalent load for performance on a series of decarboxylations. [0062] Considering that the reaction is thought to occur through a carboxylic acid imine intermediate and given the observed rise in impurities as a result of increasing the catalyst load from the Hashimoto procedure, the fate of the decarboxylated imine was then investigated as follows. A large excess of carvone was added to the reaction mixture to attempt to capture all product amine as an imine with carvone. The imine was then transferred into an aqueous acid mixture, excess carvone removed via ether wash, and then returned to an organic phase via neutralization with NaOH solution. A significant degree of hydrolysis was expected; however, in these observations, the imine of the decarboxylated product was quite stable and persisted as demonstrated by the GC-MS spectrum and gas chromatograph (FIGS. 2A and 2B) of the product mixture of decarboxylated phenylalanine. It was observed that only after heating in acid at >50 C. did the hydrolysis occur. Even after one pot reflux with many times the reaction volume of 2.0 M HCl, it proved difficult to adequately remove all traces of the imine at system equilibrium. Each conventional method of amino acid decarboxylation fails to account for the quantity of imine that may remain, thus lowering the yield and purity of the crude product and leading to further purification.

Reference： [1]Patent: US2014/275569,2014,A1 .Location in patent: Page/Page column 0060; 0061; 0062; 0063; 0067

58
[ 75-52-5 ]
[ 2244-16-8 ]
C₁₁H₁₇NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%	With L-lysine In ethanol; water at 25℃; for 48h; Green chemistry;	A General Method for Michael Addition with Cyclohex-2-enone. General procedure: Method B: In a 4-mL vial, cyclohex-2-enone (0.5 mmol, 48 μL), internal standard (t-amyl alcohol, 0.05 mmol, 5.5μL), amino acid (625 μL of 400 mM), nitromethane (0.55 mmol, 30 μL) were added in water (311.5 μL). After addition of ethanol (1 mL), the reaction mixture was stirred at 25 °C. After 24 or 48 h, the reaction mixture (100 μL) was retrieved and extracted with MTBE (1 mL). The organic layer was analyzed by gas chromatography.

Reference： [1]Park, Seongsoon [Bulletin of the Korean Chemical Society, 2014, vol. 35, # 12, p. 3671 - 3674]

59
[ 2244-16-8 ]
[ 5524-05-0 ]
(+)-isodihydrocarvone [ No CAS ]
[ 127911-15-3 ]

Yield	Reaction Conditions	Operation in experiment
	With methanol; hydrogen at 100℃; for 13h; Autoclave; stereoselective reaction;	Catalytic experiment General procedure: The reactions were carried out in a stainless steel reactor(150 ml) equipped with an electromagnetic stirrer (1100 rpm)and the sampling system. In a typical experiment, a mixtureof the substrate (10 mmol), solvent (36 ml) and the solid cata-lyst (336 mg of TiO2or Au/TiO2, Au 0.3 mol % to substrate) wasintensively stirred at 100C under H2atmosphere (9 bar). (-)-Carvone, d-(+)-dihydrocarvone (mixture cis- and trans-isomers,cis-/trans- = 20:80), l-(-)-carveol (mixture cis- and trans-isomers,cis-/trans- = 54:46) and (-)-limonene were used as substrates,while methanol, ethanol and 2-propanol were applied as solvents.Reagents and solvents were purchased from commercial suppliersand used as received except for the solvents, which were dried prior to experiments. At appropriate time intervals aliquots were taken and ana-lyzed by gas chromatography (Tzvet-500) using a Carbowax-20M 20M column (length 50 m, inner diameter 0.2 mm and film thick-ness 0.5 m) at 160C and a flame ionization detector operatingat 250C. Additionally the product structures were confirmed byanalysis with a gas chromatograph-mass spectrometer (AgilentTechnologies 7000 GC/MS Triple Quad, HP-5MS column) as wellas by nuclear magnetic resonance (NMR) spectroscopy. The chemi-cal shifts of the cis- and trans-dihydrocarvones were determined inaccordance with [36].1H NMR spectra were recorded by Bruker AV-400 spectrometer (400.13 MHz (1H)) in the CDCl3solutions of thereaction mixture. To estimate reproducibility of GC analysis of thereaction mixture some withdrawn samples were analyzed twiceboth by GC/MS and NMR in a parallel way. To judge reproducibil-ity of the catalytic data some experiments were carried out threetimes. As a result, the measurement errors calculated for carvonehydrogenation, e.g., in methanol at 100C after 1 h were found tobe 4.7 ± 2.1% and 1.7 ± 0.1 for carvone conversion and the trans- tocis-dihydrocarvone ratio, respectively.

Reference： [1]Demidova; Suslov; Simakova; Simakova; Volcho; Salakhutdinov; Murzin [Catalysis Today, 2015, vol. 241, # PB, p. 189 - 194]

60
[ 2244-16-8 ]
[ 300-38-9 ]
C₁₈H₂₁Br₂NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In propan-1-ol at 20 - 190℃; Green chemistry;	General Decarboxylation Procedure General procedure: A magnetic stir bar, 3mL of n-PrOH, 10 mmol of R-carvone, and 5 mmol of amino acid were charged toa pressure vessel. The vessel was heated from room temperature to 190 °C over 5 min with stirring. If necessary the reaction vessel was maintained at 190 °C for an additional time until the slurry became clear. The vessel was allowed to cool to below the solvent boiling point, carefully vented to release evolved CO2, and analyzed via GC-MS to verify the presence of decarboxylated imine.

Reference： [1]Jackson, Douglas M.; Ashley, Robert L.; Brownfield, Callan B.; Morrison, Daniel R.; Morrison, Richard W. [Synthetic Communications, 2015, vol. 45, # 23, p. 2691 - 2700]

61
[ 2244-16-8 ]
[ 6636-22-2 ]
C₂₀H₂₅NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In propan-1-ol at 20 - 190℃; Green chemistry;	General Decarboxylation Procedure General procedure: A magnetic stir bar, 3mL of n-PrOH, 10 mmol of R-carvone, and 5 mmol of amino acid were charged toa pressure vessel. The vessel was heated from room temperature to 190 °C over 5 min with stirring. If necessary the reaction vessel was maintained at 190 °C for an additional time until the slurry became clear. The vessel was allowed to cool to below the solvent boiling point, carefully vented to release evolved CO2, and analyzed via GC-MS to verify the presence of decarboxylated imine.

Reference： [1]Jackson, Douglas M.; Ashley, Robert L.; Brownfield, Callan B.; Morrison, Daniel R.; Morrison, Richard W. [Synthetic Communications, 2015, vol. 45, # 23, p. 2691 - 2700]

62
(1S,2S,4R)-2-bromo-1-methyl-4-(prop-1-en-2-yl)cyclohexanol [ No CAS ]
[ 2244-16-8 ]

Yield	Reaction Conditions	Operation in experiment
52%	With zinc sulfide; dimethyl sulfoxide In neat (no solvent) at 100℃; for 1.25h; Microwave irradiation; Green chemistry;	2.3 Synthesis of Carvone (1a) and Compounds 2a-5a General procedure: In a pear shaped flask 1 g of substrate (1-5) was takenwith 1 mL DMSO and charged with one equivalent ofZnS. The mixture was stirred under microwave irradiationin an open vessel (Milestone START S microwavelaboratory system operated at 70-100C, temperaturemonitored by built-in infrared sensor). The reactionswere monitored using worked up aliquot by TLC (5%EtOAc in hexane) for disappearance of starting material.On completion of reaction, it was poured into water(20 ml) and extracted using CH2Cl2 (3 × 5 mL). Thecombined organic layer was dried over Na2SO4 andconcentrated to afford crude product. It was purified bycolumn chromatography over silica gel (200-400 mesh)by eluting with mixture of EtOAc and petroleum ether(60-80C) to afford pure products (1a, 2a, 3a, 4a and 5a).

Reference： [1]Kannan, Nandini; Rangaswamy, Manjunatha Javagal; Kemapaiah, Bettadaiah Bheemanakere [Journal of Chemical Sciences, 2015, vol. 127, # 8, p. 1405 - 1410]

63
[ 637-53-6 ]
[ 2244-16-8 ]
2-[(1S,5R)-1-hydroxy-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-yl]-N-phenylethanethioamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	Stage #1: thioacetanilide With N,N,N,N,N,N-hexamethylphosphoric triamide; n-butyllithium In tetrahydrofuran at -5 - 5℃; for 1.5h; Inert atmosphere; Stage #2: (R)-Carvone In tetrahydrofuran at -15 - -5℃; Inert atmosphere; stereoselective reaction;	Synthesis of β-hydroxythioamides 4,6,8,10,12. General procedure General procedure: Thioacetanilide 0.75 g (5 mmol) was dissolved in 12 mL dryTHF/HMPA (5:1) under argon and n-butyllithium (7.5 mL,1.6 M solution, 12 mmol) was added slowly while maintainingthe solution at ca. (-5°C). The mixture was stirred at 0-5°C for 1.5 h recooled to (-15°C) and a solution of 7 mmol ofthe appropriate terpenone in 5 mL THF was then added whilemaintaining the solution at ca. (-5)°C. Stirring at the sametemperature was continued for 1.5-2 h and the reaction mixturepoured onto saturated aqueous NH4Cl solution. The productwas extracted with ethyl acetate, the organic layer washedwith water and dried with MgSO4, filtered, and concentrated invacuo. The crude product was purified on silica gel chromatographiccolumn (hexane/ethyl acetate 4/1) and finally recrystallizedfrom hexane.

Reference： [1]Jagodziński, Tadeusz S.; Sos̈nicki, Jacek G.; Struk, Łukasz [Phosphorus, Sulfur and Silicon and the Related Elements, 2016, vol. 191, # 2, p. 290 - 296]

64
[ 2244-16-8 ]
8,9-epoxicarvone-1,2-olide [ No CAS ]
[ 294634-40-5 ]

Yield	Reaction Conditions	Operation in experiment
1: 70% 2: 12%	With hydrotalcite; 3-chloro-benzenecarboperoxoic acid In dichloromethane at 40℃; for 5h; Green chemistry; regioselective reaction;	3.3. General procedure for the reaction with hydrotalcite and m-CPBA In a round-bottom flask equipped with a reflux condenser, carvone 1 (505 mg, 3.4 mmol), hydrotalcite (39.0 mg), MCPBA (782 mg, 4.5 mmol) and DCM (15.0 mL) were heated at 40 Cwhile stirring. The progress of the reaction was monitored by TLC. After 5 h, the reaction was extracted with DCM, washed with water, dried and the solvent evaporated. Finally, the pure compound was obtained by flash column chromatography on silica gel, 2 (70.0%), 4(4.0%) and 6 (12.0%).

Reference： [1]Rodilla, Jesus M.; Neves, Patricia P.; Pombal, Sofia; Rives, Vicente; Trujillano, Raquel; Díez, David [Natural Product Research, 2016, vol. 30, # 7, p. 834 - 840]

65
[ 2244-16-8 ]
(4R,5R)-5-(hydroxymethyl)-5-methyl-4-(3-oxobutyl)dihydrofuran-2(3H)-one [ No CAS ]
(4R,5S)-5-(hydroxymethyl)-5-methyl-4-(3-oxobutyl)dihydrofuran-2(3H)-one [ No CAS ]
[ 294634-40-5 ]

Yield	Reaction Conditions	Operation in experiment
1: 28% 2: 10% 3: 6%	With aluminum (III) chloride; dihydrogen peroxide In ethanol at 75℃; for 48h; regioselective reaction;	3.1. General procedure for the reaction with AlCl3 In a round-bottom flask equipped with a reflux condenser, carvone 1 (300 mg, 2 mmol), AlCl3 (60 mg, 0.45 mmol), H2O2 30% (0.12 mL, ~2 eq) and 50 mL of EtOH were heated at 75°C while stirring. The progress of the reaction was monitored TLC. After 48 h, the reaction wasextracted with DCM, washed with water, dried and the solvent evaporated. Finally, the pure compound was obtained by flash chromatography on silica gel (hexane/EtOAc 8 : 2) to obtain 1 (39.0%), 2 (25.0%), 7 (15.0%) and 8 (12.0%).
1: 18% 2: 6% 3: 5%	With hydrotalcite; dihydrogen peroxide; sodium dodecyl-sulfate In ethanol; benzonitrile at 50℃; for 96h; Green chemistry; regioselective reaction;	3.2. General procedure for the reaction with hydrotalcite and H2O2 General procedure: In a round-bottom flask equipped with a reflux condenser, Carvone 1 (300 mg, 2 mmol), benzonitrile (0.82 mL, 8 mmol), H2O2 30% (0.12 mL, 4 mmol), hydrotalcite Mg4/Al-CO3 (17.0 mg),SDS (35 mg, 0.10 mmol) and EtOH (0.87 mL) were heated at 40-60 °C while stirring. The progress of the reaction was monitored by TLC. After 50-250 h, the reaction was extracted with DCM, washed with water, dried and the solvent evaporated. Finally, the pure compound was obtained by flash column chromatography on silica gel, 1 (15.0%), 2 (25.0%), 4 (12.0%)7 (27.0%) and 8 (26.0%).

Reference： [1]Rodilla, Jesus M.; Neves, Patricia P.; Pombal, Sofia; Rives, Vicente; Trujillano, Raquel; Díez, David [Natural Product Research, 2016, vol. 30, # 7, p. 834 - 840]
[2]Rodilla, Jesus M.; Neves, Patricia P.; Pombal, Sofia; Rives, Vicente; Trujillano, Raquel; Díez, David [Natural Product Research, 2016, vol. 30, # 7, p. 834 - 840]

66
[ 2244-16-8 ]
[ 466679-48-1 ]
(4R,5R)-5-(hydroxymethyl)-5-methyl-4-(3-oxobutyl)dihydrofuran-2(3H)-one [ No CAS ]
(4R,5S)-5-(hydroxymethyl)-5-methyl-4-(3-oxobutyl)dihydrofuran-2(3H)-one [ No CAS ]
[ 294634-40-5 ]

Yield	Reaction Conditions	Operation in experiment
1: 60% 2: 30% 3: 6% 4: 5.3%	With hydrotalcite; dihydrogen peroxide; sodium dodecyl-sulfate In ethanol; benzonitrile at 40℃; for 400h; Green chemistry; regioselective reaction;	3.2. General procedure for the reaction with hydrotalcite and H2O2 General procedure: In a round-bottom flask equipped with a reflux condenser, Carvone 1 (300 mg, 2 mmol), benzonitrile (0.82 mL, 8 mmol), H2O2 30% (0.12 mL, 4 mmol), hydrotalcite Mg4/Al-CO3 (17.0 mg),SDS (35 mg, 0.10 mmol) and EtOH (0.87 mL) were heated at 40-60 °C while stirring. The progress of the reaction was monitored by TLC. After 50-250 h, the reaction was extracted with DCM, washed with water, dried and the solvent evaporated. Finally, the pure compound was obtained by flash column chromatography on silica gel, 1 (15.0%), 2 (25.0%), 4 (12.0%)7 (27.0%) and 8 (26.0%).
1: 31% 2: 25% 3: 19.5% 4: 10%	With hydrotalcite; dihydrogen peroxide; sodium dodecyl-sulfate In ethanol; benzonitrile at 40℃; for 200h; Green chemistry; regioselective reaction;	3.2. General procedure for the reaction with hydrotalcite and H2O2 General procedure: In a round-bottom flask equipped with a reflux condenser, Carvone 1 (300 mg, 2 mmol), benzonitrile (0.82 mL, 8 mmol), H2O2 30% (0.12 mL, 4 mmol), hydrotalcite Mg4/Al-CO3 (17.0 mg),SDS (35 mg, 0.10 mmol) and EtOH (0.87 mL) were heated at 40-60 °C while stirring. The progress of the reaction was monitored by TLC. After 50-250 h, the reaction was extracted with DCM, washed with water, dried and the solvent evaporated. Finally, the pure compound was obtained by flash column chromatography on silica gel, 1 (15.0%), 2 (25.0%), 4 (12.0%)7 (27.0%) and 8 (26.0%).
1: 27% 2: 26% 3: 25% 4: 12%	With hydrotalcite; dihydrogen peroxide; sodium dodecyl-sulfate In ethanol; benzonitrile at 60℃; for 100h; Green chemistry; regioselective reaction;	3.2. General procedure for the reaction with hydrotalcite and H2O2 General procedure: In a round-bottom flask equipped with a reflux condenser, Carvone 1 (300 mg, 2 mmol), benzonitrile (0.82 mL, 8 mmol), H2O2 30% (0.12 mL, 4 mmol), hydrotalcite Mg4/Al-CO3 (17.0 mg),SDS (35 mg, 0.10 mmol) and EtOH (0.87 mL) were heated at 40-60 °C while stirring. The progress of the reaction was monitored by TLC. After 50-250 h, the reaction was extracted with DCM, washed with water, dried and the solvent evaporated. Finally, the pure compound was obtained by flash column chromatography on silica gel, 1 (15.0%), 2 (25.0%), 4 (12.0%)7 (27.0%) and 8 (26.0%).

Reference： [1]Rodilla, Jesus M.; Neves, Patricia P.; Pombal, Sofia; Rives, Vicente; Trujillano, Raquel; Díez, David [Natural Product Research, 2016, vol. 30, # 7, p. 834 - 840]
[2]Rodilla, Jesus M.; Neves, Patricia P.; Pombal, Sofia; Rives, Vicente; Trujillano, Raquel; Díez, David [Natural Product Research, 2016, vol. 30, # 7, p. 834 - 840]
[3]Rodilla, Jesus M.; Neves, Patricia P.; Pombal, Sofia; Rives, Vicente; Trujillano, Raquel; Díez, David [Natural Product Research, 2016, vol. 30, # 7, p. 834 - 840]

67
[ 5989-27-5 ]
[ 2244-16-8 ]
[ 57717-97-2 ]
[ 185329-56-0 ]

Yield	Reaction Conditions	Operation in experiment
	With dihydrogen peroxide In water at 70℃; for 24h;	General procedure: In the oxidation of limonene the following reactants were used:R(+)-limonene (97%, Sigma), hydrogen peroxide (60 wt% watersolution, Chempur), t-butyl hydroperoxide-TBHP (5.5 M solutionin decane, Fluka) and methanol (analytical grade, Chempur).The oxidation of limonene was carried out at the tempera-ture of 70C and in the range of the reaction time from 0.5 h to48 h. The other parameters were as follows: the molar ratio oflimonene/H2O2or limonene/TBHP = 1:2 (for hydrogen peroxidethe concentrations of the reactants in the reaction mixture were asfollows: limonene - about 2.8 wt%, and hydrogen peroxide about1.6 wt% and for TBHP: limonene - about 2.9 wt%, and TBHP 1.5 wt%,respectively), methanol concentration 95 wt% and the catalystcontent in the reaction mixture of 2.45 wt%. The process wascarried out in a glass reactor with the capacity of 25 cm3, equippedwith a reflux condenser, a thermometer and a magnetic stirrer.The raw materials were introduced into the glass reactor in thefollowing order: catalyst, limonene, methanol and 60 wt% watersolution of hydrogen peroxide (or TBHP). The temperature of 70Cwas achieved with help of a silicon oil bath. The progress of thereaction was examined after the following reaction time: 30 min,1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 5 h, 24 h and 48 h. During the studies also studiesalso blank experiment was done and it shows that hydrogenperoxide and TBHP did not oxidize limonene without the catalyst.

Reference： [1]Mlodzik, Jacek; Wrblewska, Agnieszka; Makuch, Edyta; Wrbel, Rafal J.; Michalkiewicz, Beata [Catalysis Today, 2016, vol. 268, p. 111 - 120]

68
[ 2244-16-8 ]
[ 69361-41-7 ]
C₁₄H₂₀O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: 4-bromo-1-trimethylsilylbut-1-yne With magnesium In tetrahydrofuran; ethylene dibromide at 50℃; for 1.5h; Inert atmosphere; Schlenk technique; Stage #2: With copper(I) bromide dimethylsulfide complex In tetrahydrofuran; ethylene dibromide at -78℃; for 0.25h; Inert atmosphere; Schlenk technique; Stage #3: (R)-Carvone Further stages;

Reference： [1]Hartrampf, Felix W. W.; Furukawa, Takayuki; Trauner, Dirk [Angewandte Chemie - International Edition, 2017, vol. 56, # 3, p. 893 - 896][Angew. Chem., 2016, vol. 129, # 3, p. 912 - 915]

69
[ 7677-24-9 ]
[ 2244-16-8 ]
β-cyanocarvone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: trimethylsilyl cyanide; (R)-Carvone With L-proline lithium salt at 20℃; for 24h; Stage #2: With hydrogenchloride; water In tetrahydrofuran at 20℃; for 1h; Stage #3: With chromium(VI) oxide; acetic anhydride In dichloromethane at -55℃; for 0.5h;	6 The raw material (R) - carvone (10.0 g, 66.6 mmol) readily obtained from natural sources as starting material and lithium salt of L-proline (810 mg, 6.66 mmol) were placed in a round bottom flask, and TMSCN (8.86 ml * 2, 66.6 mmol * 2) was slowly added thereto. The resulting suspension was stirred for 12 hours at room temperature and then 1 eq of TMSCN was added and the mixture was stirred for another 12 hours at room temperature. When the raw material was almost exhausted as shown by TLC, the mixture was diluted with 100 ml of THF and 100 ml of 1 M hydrochloric acid, and the mixture was stirred for 1 h at room temperature. Subsequently, the mixture was diluted with water, extracted with ether, and the organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated to give intermediate 177, which was directly subjected to the next step. Chromium trioxide (13.9 g, 139.2 mmol) was slowly added to acetic anhydride (54 ml) and the mixture was stirred at room temperature until completely dissolved. The resulting chromic acid reagent was then added dropwise to a solution of intermediate 177 in dichloromethane at -55 °C , the resulting mixture was maintained at this temperature and stirred for half an hour. When the raw material was exhausted as shown by TLC, the reaction was quenched with methanol, and the resultant was diluted with water, extracted with dichloromethane. The organic phase was washed with saturated sodium bicarbonate aqueous solution and concentrated. The resultant was isolated by column chromatography (petroleum ether/ethyl acetate (v/v) = 10/1) to give the product 15-1 as yellow oil (7.59 g, yield 65% in two steps): 1H NMR (CDCl3, 300 MHz) δ4.87 (s, 1H), 4.77 (s, 1H), 2.78-2.32 (m, 5H), 2.06 (s, 3H), 1.68 (s, 3H).

Reference： [1]Current Patent Assignee: Shanghai Institute of Materia Medica (in: CAS); CHINESE ACADEMY OF SCIENCES - EP3272755, 2018, A1 Location in patent: Paragraph 0068; 0069

70
[ 2244-16-8 ]
[ 39904-03-5 ]

Yield	Reaction Conditions	Operation in experiment
67%	Stage #1: (R)-Carvone With dihydrogen peroxide; potassium hydroxide In methanol; water at -5 - 15℃; for 2.91667h; Stage #2: With sodium hydroxide In water for 1h; Reflux;	1 40 ml of a methanol solution containing 40.0 g (0.266 mol) of (R)-carvone was cooled to 0 °C, and then a mixed solution of 40 ml of water and 120 ml of methanol containing 32.0 g (0.57 mol) of KOH was added. The resulting mixture was cooled to -5 °C, and then 30 ml of 30% H2O2 was added. After 10 minutes, the temperature was elevated to 15 °C. The mixture was stirred for 25 minutes and then cooled to -3 °C. Another 35 ml of 30% H2O2 was added to the mixture, and the resulting mixture was stirred for 2.5 hours at 0 °C. After the reaction was complete which was monitored by TLC, the reaction was quenched with a lot of crushed ice. Then the resultant was extracted with ethyl acetate, washed with brine, dried and concentrated. After adding 1L 1 mol/l aqueous sodium hydroxide solution to the crude product in an ice bath, the resultant was heated under reflux for 1 hour, then cooled to room temperature, and 20% hydrochloric acid was added thereto under low temperature to adjust the pH to be acidic, followed by filtration, to give a light yellow solid as product 2-1 (total 29.8 g , 67%): 1H NMR (CDCl3, 300 MHz) δ 4.8 (dd, J = 13.8, 15.3 Hz, 2H), 2.74-2.41 (m, 5H), 1.74 (s, 3H), 1.69 (s, 3H).
	With dihydrogen peroxide; potassium hydroxide

Reference： [1]Current Patent Assignee: Shanghai Institute of Materia Medica (in: CAS); CHINESE ACADEMY OF SCIENCES - EP3272755, 2018, A1 Location in patent: Paragraph 0035; 0036
[2]Ding, Yi-Xuan; Zhu, Zhou-Hao; Wang, Han; Yu, Chang-Bin; Zhou, Yong-Gui [Science China Chemistry, 2021, vol. 64, # 2, p. 232 - 237]

71
[ 2244-16-8 ]
C₁₀H₁₄N₆O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With tert-Butyl peroxybenzoate; iron(II) bis((trifluoromethyl)sulfonyl)amide; trimethylsilylazide; 2,6-bis[4’,4’-dimethyloxazolin-2’-yl]pyridine; isopropyl alcohol In dichloromethane; acetonitrile at 22℃; Inert atmosphere;

Reference： [1]Shen, Shou-Jie; Zhu, Cheng-Liang; Lu, Deng-Fu; Xu, Hao [ACS Catalysis, 2018, vol. 8, # 5, p. 4473 - 4482]

72
[ 201230-82-2 ]
[ 2244-16-8 ]
3-(4-methylcyclohex-4-en-3-onyl)butanal [ No CAS ]
1,5-dimethylhexahydro-1H-inden-4(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dicarbonyl(acetylacotonato)rhodium(I); hydrogen; pyridinium p-toluenesulfonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 120℃; for 24h; Autoclave;	3.1 General procedure for the synthesis of 1,5-dimethylhexahydro-1H-inden-4(2H)-one General procedure: In a typical experiment, a 100 mL high-pressure reactor charged with (R)-carvone (750 mg, 5 mmol), Rh(CO)2(acac) (2.58 mg 0.01mmol), dppp (16.50 mg, 0.04 mmol, L/Rh 4:1), PPTS (0.02 mmol in 1mL toluene) in 9 mL toluene. Was pressurized to 650 psi CO/H2 (1:1) and heated to 120°C for 22 h with a stirring speed of 700 rpm. After completion of the reaction, the heater was stopped and reactor allowed cool to room temperature and existing synthesis gas was carefully vented. The crude reaction product mixture was analyzed by gas chromatography and mass spectrometry, concentrated under vacuum washed three times with 50mL water and extracted with pet-ether. Column chromatography with pet ether and ethyl acetate (99:1) as running phase turn out to be excellent to obtain pure compound (1d).