* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Chemistry - A European Journal, 1999, vol. 5, # 4, p. 1320 - 1330
[2] Chemistry - A European Journal, 1999, vol. 5, # 4, p. 1320 - 1330
[3] Angewandte Chemie - International Edition, 2001, vol. 40, # 7, p. 1235 - 1238
[4] Angewandte Chemie - International Edition, 2008, vol. 47, # 5, p. 894 - 897
2
[ 445-27-2 ]
[ 171032-87-4 ]
[ 162427-79-4 ]
Yield
Reaction Conditions
Operation in experiment
100%
With RuBr2[(S,S)-2,4-bis(diphenylphosphino)pentane](2-picolylamine); potassium <i>tert</i>-butylate; hydrogen In ethanol at 40℃; for 19 h; Inert atmosphere; Autoclave
General procedure: In an autoclave, 1.32 mg of RuBr2[(S,S)-xylskewphos] (3,5-Me2pica) (1.29×10−3 mmol, S/C=10000) and 5.79 mg of potassium tert-butoxide (5.16×10−2 mmol) are placed, and replaced with argon gas. Under argon gas flow, 1.5 mL of acetophenone (12.9 mmol) and 2.9 mL of ethanol was added while measuring by a syringe, pressurized with hydrogen to 10 atm, stirred at 40° C. for 19 hours, then the reduction of the hydrogen pressure was confirmed and phenylethanol was obtained at 100percent yield. The optical purity was 88.0percent ee as measured by GC (CP-Chirasil-DEX CB (0.25 mml. D×25 m, DF=0.25 μm, from VARIAN), constant at 110° C., pressure: 102.0 kPa, column flow: 1.18 mL/min, vaporizing chamber temperature: 250° C., detector temperature: 275° C., the retention time of each enantiomer was: (R): 11.7 min, (S): 12.4 min), and (S) isomer has predominantly been generated.The reaction was carried out in similar way as Working Example 1 except that the complex was changed to RuBr2 [(S,S)-xylskewphos](pica), and the reaction solvent and substrate were changed as indicated in the Table below. The results are summarized in the Table below, which also describes the results from Comparative Example 1. Analysis conditions indicated in the Table is the same as the Table provided from Working Examples ito 6. From the results, it is clear that RuBr2[(S,S)-xylskewphos] (3,5-Me2pica) has a better enantioselectivity as compared to RuBr2[(S,S)-xyl- skewphos] (pica) complex.
83.7 % ee
With dodecacarbonyl-triangulo-triruthenium; (S,S)-N-{1,2-diphenyl-2-[(pyridin-2-ylmethyl)amino]ethyl}-4-methylbenzenesulfonamide In isopropyl alcohol at 80℃; for 48 h; Inert atmosphere; Schlenk technique
General procedure: A mixture of catalyst (2 molpercent) and Ru3 (CO)12 (0.67 molpercent) in IPA (10 cm3) was stirred at 80 °C under an inert atmosphere in a schlenk tube for 30 min. To this solution, ketone (1 mmol) was added and the resulting mixture was stirred at 80 °Cfor 48 h. The reaction mixture was filtered through a short column of silica using (EtOAc:hexane 1:1), a small amount of the filtrate was dilluted in EtOAc and then injected on the GC to determine the conversion and enantiomeric excess.
89.8 % ee
at 60℃; for 5 h; Schlenk technique
General procedure: As Examples 20 to 35, hydrogen transfer reactions to ketones shown in Tables 1, 2, and 3 below were conducted by the same operation as in Examples 16 and 18. In these reactions, the catalyst ratios (S/C) were as shown in the tables, the reaction temperature was 60° C., and a formic acid-triethylamine (5:2) azeotrope was used as a hydrogen source in such an amount that the concentration of the substrate was 2 mol/L. The conversions and the optical purities were determined by analyzing the reaction liquids by GC after predetermined periods.; In addition, as Comparative Examples, results of reactions in which RuCl ((S,S)-Tsdpen) (mesitylene) was used in the same manner are also shown in each table. Note that, in these tables, conv. represents the conversion of the ketone substrate, selec. represents the selectivity for the target product, percent ee represents the optical purity, and S/C represents a value represented by the number of moles of the ketone substrate/the number of moles of the catalyst.
73 % ee
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; C26H29N4O3S(1+)*Cl(1-); sodium formate In water at 20℃; for 5 h;
General procedure: To a solution of ligand 5d (2.1 mg, 0.004 mmol) in water (1 mL) was added [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), HCO2Na (41 mg, 3.0 mmol), and ketone (2.0 mmol). The reaction mixture was stirred at room temperature for the time as indicated in Tables 1 and 2 . The reaction mixture was extracted by ethyl ether. The conversion was determined by 1H NMR analysis of the crude product. After concentration, the crude product was purified by chromatography on silica gel to give the pure product.
73 % ee
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; C26H29N4O3S(1+)*Cl(1-); sodium formate In water at 20℃; for 5 h; Green chemistry
General procedure: To a solution of ligand 5d (2.1 mg, 0.004 mmol) in water (1 mL) was added [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), HCO2Na (41 mg, 3.0 mmol), and ketone (2.0 mmol). The reaction mixture was stirred at room temperature for the time as indicated in Tables 1 and 2. The reaction mixture was extracted by ethyl ether. The conversion was determined by 1H NMR analysis of the crude product. After concentration, the crude product was purified by chromatography on silica gel to give the pure product.
81 % ee
Stage #1: With dimethylsulfide borane complex; 3-(5-((3R,5S)-5-(hydroxydiphenylmethyl)pyrrolidin-3-yloxy)-5-oxopentyl)-1-methyl-1H-imidazol-3-ium hexafluorophosphate In tetrahydrofuran at 70℃; for 0.5 h; Inert atmosphere; Schlenk technique Stage #2: With hydrogenchloride In waterInert atmosphere; Schlenk technique
General procedure: In a schlenk tube, BH3·SMe2(0.55 mmol, 275 L) was added inthe solution of IL 5 (28 mg, 10 molpercent) dissolved in THF (1 mL), undernitrogen atmosphere. The homogenous mixture was stirred andheated at 70C for 30 min. Later, a solution of ketone (0.5 mmolin THF (0.5 mL)) was added within 30 min. After the addition wascompleted, the solvent was evaporated under vacuum. An aqueoussolution of 1M HCl (5 mL) was added and the product was extractedwith DCM. The solvent was dried on anhydrous sodium sulfateand evaporated under reduced pressure. Crude residue was furtherpurified by column chromatography on silica gel using hexane-ethyl acetate as eluent. Enantiomeric excesses of all alcohols weredetermined by HPLC analysis using Chiralcel OD–H/AD–H chiralcolumn, isopropanol-n-hexane as mobile phase and HPLC condi-tions are given in SI.
74 % ee
at 82℃; for 0.5 h; Inert atmosphere; Schlenk technique
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction: a solution of the Ru(II)-complexes 17–24 (0.005 mmol), KOH (0.025mmol) and the corresponding ketone (0.5 mmol) in degassed 2-propanol (5 mL) was refluxed until the reaction was completed. Periodically samples taken from the reaction medium were passed through acetone silica gel column and conversion rates were observed in gas chromatography, which were calculated based on unreacted ketone.
Reference：
[1] Patent: US2015/31920, 2015, A1, . Location in patent: Page/Page column 0167
[2] Tetrahedron, 1996, vol. 52, # 2, p. 589 - 598
[3] Journal of Organic Chemistry, 1999, vol. 64, # 7, p. 2186 - 2187
[4] European Journal of Inorganic Chemistry, 2000, # 8, p. 1687 - 1692
[5] Tetrahedron: Asymmetry, 2003, vol. 14, # 6, p. 710 - 716
[6] Organic Letters, 2004, vol. 6, # 2, p. 169 - 172
[7] European Journal of Organic Chemistry, 2005, # 15, p. 3221 - 3227
[8] Advanced Synthesis and Catalysis, 2005, vol. 347, # 9, p. 1193 - 1197
[9] Organic Letters, 2006, vol. 8, # 14, p. 3025 - 3027
[10] Tetrahedron Asymmetry, 2006, vol. 17, # 8, p. 1179 - 1185
[11] Angewandte Chemie - International Edition, 2006, vol. 45, # 9, p. 1432 - 1435
[12] Chemical Communications, 2005, # 32, p. 4039 - 4041
[13] Chemical Communications, 2004, # 18, p. 2070 - 2071
[14] Journal of Organic Chemistry, 2002, vol. 67, # 15, p. 5301 - 5306
[15] Tetrahedron Letters, 2004, vol. 45, # 12, p. 2603 - 2605
[16] Advanced Synthesis and Catalysis, 2007, vol. 349, # 17-18, p. 2556 - 2562
[17] Chemistry - A European Journal, 2006, vol. 12, # 12, p. 3218 - 3225
[18] European Journal of Organic Chemistry, 2008, # 5, p. 934 - 940
[19] Angewandte Chemie - International Edition, 2008, vol. 47, # 48, p. 9240 - 9244
[20] Angewandte Chemie - International Edition, 2008, vol. 47, # 48, p. 9240 - 9244
[21] Tetrahedron Asymmetry, 2009, vol. 20, # 13, p. 1521 - 1525
[22] Tetrahedron Letters, 2009, vol. 50, # 46, p. 6321 - 6324
[23] Chirality, 2010, vol. 22, # 1, p. 173 - 181
[24] Catalysis Letters, 2010, vol. 137, # 1-2, p. 104 - 109
[25] Catalysis Communications, 2010, vol. 11, # 7, p. 584 - 587
[26] Catalysis Communications, 2010, vol. 11, # 5, p. 373 - 377
[27] Chinese Chemical Letters, 2010, vol. 21, # 5, p. 576 - 579
[28] Journal of Molecular Catalysis A: Chemical, 2010, vol. 333, # 1-2, p. 20 - 27
[29] Dalton Transactions, 2011, vol. 40, # 10, p. 2338 - 2347
[30] Monatshefte fur Chemie, 2009, vol. 140, # 10, p. 1189 - 1194
[31] Organic and Biomolecular Chemistry, 2012, vol. 10, # 25, p. 4864 - 4877
[32] Tetrahedron Letters, 2012, vol. 53, # 30, p. 3839 - 3842
[33] Organometallics, 2012, vol. 31, # 11, p. 4241 - 4250
[34] Tetrahedron Asymmetry, 2012, vol. 23, # 11-12, p. 834 - 837
[35] Organic Letters, 2012, vol. 14, # 20, p. 5230 - 5233,4
[36] Organic Letters, 2012, vol. 14, # 20, p. 5230 - 5233
[37] Tetrahedron Letters, 2013, vol. 54, # 32, p. 4250 - 4253
[38] Patent: US2014/51871, 2014, A1, . Location in patent: Paragraph 0129; 0130; 0138; 0139; 0140
[39] ChemistryOpen, 2013, vol. 2, # 2, p. 50 - 54
[40] ChemCatChem, 2014, vol. 6, # 5, p. 1368 - 1374
[41] Applied Organometallic Chemistry, 2014, vol. 28, # 7, p. 517 - 522
[42] Catalysis Communications, 2014, vol. 57, p. 111 - 114
[43] Catalysis Communications, 2012, vol. 28, p. 5 - 8
[44] Catalysis Communications, 2014, vol. 57, p. 111 - 114
[45] European Journal of Organic Chemistry, 2006, # 16, p. 3606 - 3616
[46] Journal of Molecular Catalysis A: Chemical, 2015, vol. 398, p. 184 - 189
[47] Applied Organometallic Chemistry, 2015, vol. 29, # 11, p. 764 - 770
[48] Applied Organometallic Chemistry, 2015, vol. 29, # 11, p. 764 - 770
[49] ChemCatChem, 2016, vol. 8, # 6, p. 1199 - 1207
[50] Organometallics, 2016, vol. 35, # 21, p. 3781 - 3787
[51] Inorganica Chimica Acta, 2018, vol. 471, p. 430 - 439
[52] ChemCatChem, 2017, vol. 9, # 10, p. 1744 - 1748
[53] Applied Organometallic Chemistry, 2018, vol. 32, # 1,
[54] European Journal of Inorganic Chemistry, 2018, vol. 2018, # 12, p. 1383 - 1393
3
[ 445-27-2 ]
[ 171032-87-4 ]
Yield
Reaction Conditions
Operation in experiment
98%
With dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran at 20℃; for 2 h;
To anhydrous tetrahydrofuran (20 mL) was added (R)-2-methyl-CBS-oxazaborolidine (1.0 M, 2.9 mL) and borane dimethyl sulfide complex (10.0 M, 1.88 mL) and the mixture was stirred at ambient temperature for 1 h. To this mixture was then added dropwise a solution of 1-(2-fluorophenyl)ethanone (2.00 g, 14.5 mmol, 1.75 mL) in anhydrous tetrahydrofuran (5 mL). The reaction mixture was stirred at ambient temperature for 2 h. The mixture was quenched by addition of methanol (20 mL) and concentrated in vacuo to afford the title compound as a colorless oil (2.00 g, 98percent yield) that was used without further purification: 1H NMR (400 MHz, CDCl3) δ 7.53-7.49 (m, 1H), 7.28-7.24 (m, 1H), 7.20-7.16 (m, 1H), 7.04 (ddd, J=10.8, 8.2, 1.2 Hz, 1H), 5.23 (q, J=6.4 Hz, 1H), 1.54 (d, J=6.4 Hz, 3H), OH not observed.
92%
With (R)-methyl oxazaborolidine; N,N-diethylaniline; diborane In <i>tert</i>-butyl alcohol at 45℃; for 1 h;
First Step Synthesis of (S)-1-(2-Fluorophenyl)ethanol To a solution (60 mL) of (R)-methyl oxazaborolidine (0.32 g, 1.2 mmol) in tert-butyl alcohol, N,N-diethylaniline borane (2.6 g, 16 mmol) was added, and a solution (150 mL) of 1-(2-fluorophenyl)ethanone (2.0 g, 14 mmol) in tert-butyl alcohol was then added thereto at 45° C., and the resulting mixture was stirred. One hour later, the reaction solution was cooled to room temperature, methanol was added thereto and the resultant was concentrated. After 1.0 N hydrochloric acid was added thereto, the resultant was extracted with ethyl acetate, and the organic layer was washed with brine, then dried over anhydrous sodium sulfate and concentrated. The obtained crude product was purified by silica gel column chromatography (hexane alone to hexane/ethyl acetate=85/15) to obtain the title compound (1.9 g; 92percent) as a colorless liquid. 1H-NMR (400 MHz, CDCl3) δ: 1.52 (3H, d, J=6.8 Hz), 5.17-5.24 (1H, m), 6.98-7.05 (1H, m), 7.15 (1H, ddd, J=1.2, 7.6, 7.6 Hz), 7.21-7.28 (1H, m), 7.49 (1H, ddd, J=1.6, 7.6, 7.6 Hz).
74%
at 35℃; for 36 h; Tris buffer; Microbiological reaction; Enzymatic reaction
General procedure: The preparative scale (large scale) production of (S)-1-phenylethanol 1b from acetophenone 1a by immobilized C. laurentii EBK-19 cells was also achieved. The reduction of 1a was carried out in a 1000-mL Erlenmeyer flask using beads prepared as described in Section 4.4. The cells were activated by suspending the beads in 300 mL tris buffer containing 4percent glucose. After cell activation (3 h), acetophenone 1a (6 mM) was directly added to the mixture. During the 36 h reaction period, the beads were regularly separated by filtration, resuspended in tris buffer and glucose and reused for the same reaction without washing. At regular time intervals (36 h), the conversion and enantiomeric excess (ee) of the product were determined and the yields calculated. The run time of the beads was optimized for the production of 1b and found to be 27 days.
90.7 % ee
With hydrogen; lithium hydroxide; (8R,9R)-9-amino(9-deoxy)epicinchonin In methanol at 25℃; for 3 h; Autoclave
General procedure: Asymmetric hydrogenation of aromatic ketones was performed in a 60mL stainless steel autoclave with a magnetic stirred bar at room temperature, by using 9-amino(9-deoxy)epicinchonine as modifier, which is derived from cinchonine. In a typical run, the catalyst, chiral diamine, solvent, base and acetophenone were placed in the autoclave, followed by five purges hydrogen. The hydrogen pressure was thereafter increased to desired level. The mixture was stirred at room temperature for the appropriate duration.
99 % ee
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C49H67FeN2O2PS; hydrogen; lithium tert-butoxide In isopropyl alcohol at 20℃; for 12 h; Inert atmosphere; Autoclave
In a high-purity argon atmosphere,[Ir(COD)Cl]2 (3.4 mg, 0.005 mmol)The chiral ligand L6 (9.2 mg, 0.011 mmol) was dissolved in isopropanol (1 mL).Stirring for 3 hours at room temperature gives an orange clear solution.20 μL (0.001 molpercent) of this orange solution was taken with a microinjector.Add to a mixed system of o-fluoroacetophenone (2 mmol), isopropyl alcohol (2 mL) and lithium tert-butoxide (1 mol percent).The reaction system was placed in an autoclave and stirred at room temperature under H2 (20 atm) for 12 hours.The solvent was removed under reduced pressure and the column was separated by chromatography (silica gel, eluent: ethyl acetate).The pure product 1-o-fluorophenylethanol was analyzed by HPLC and the ee value was found to be 99percent.
Reference：
[1] Journal of the American Chemical Society, 1998, vol. 120, # 51, p. 13529 - 13530
[2] Tetrahedron: Asymmetry, 2003, vol. 14, # 6, p. 710 - 716
[3] Patent: US2018/162868, 2018, A1, . Location in patent: Paragraph 1572-1573
[4] Tetrahedron Asymmetry, 2002, vol. 13, # 13, p. 1347 - 1349
[5] Tetrahedron Letters, 2006, vol. 47, # 27, p. 4619 - 4622
[6] Journal of Organic Chemistry, 1998, vol. 63, # 24, p. 8957 - 8964
[7] Patent: US2014/128606, 2014, A1, . Location in patent: Paragraph 0174; 0175; 0176; 0177
[8] Organic Letters, 2018, vol. 20, # 4, p. 1110 - 1113
[9] Tetrahedron Asymmetry, 2008, vol. 19, # 19, p. 2272 - 2275
[10] Advanced Synthesis and Catalysis, 2016, vol. 358, # 24, p. 4006 - 4018
[11] Chemical Communications, 2000, # 15, p. 1367 - 1368
[12] Tetrahedron Asymmetry, 2007, vol. 18, # 19, p. 2332 - 2335
[13] Chirality, 2010, vol. 22, # 9, p. 849 - 854
[14] Organic and Biomolecular Chemistry, 2016, vol. 14, # 13, p. 3404 - 3408
[15] ACS Catalysis, 2018, vol. 8, # 9, p. 8020 - 8026
[16] Tetrahedron Letters, 2009, vol. 50, # 34, p. 4934 - 4936
[17] Tetrahedron Asymmetry, 2011, vol. 22, # 3, p. 345 - 350
[18] Tetrahedron Asymmetry, 2008, vol. 19, # 16, p. 1992 - 1997
[19] Tetrahedron, 2006, vol. 62, # 26, p. 6143 - 6149
[20] Helvetica Chimica Acta, 2011, vol. 94, # 8, p. 1506 - 1514
[21] Tetrahedron Letters, 2000, vol. 41, # 35, p. 6799 - 6802
[22] Chemical Communications, 2003, # 10, p. 1198 - 1199
[23] Tetrahedron: Asymmetry, 2003, vol. 14, # 6, p. 710 - 716
[24] Tetrahedron Asymmetry, 2009, vol. 20, # 13, p. 1521 - 1525
[25] Chinese Chemical Letters, 2011, vol. 22, # 2, p. 155 - 158
[26] Organometallics, 2012, vol. 31, # 11, p. 4241 - 4250
[27] Catalysis Communications, 2014, vol. 54, p. 27 - 30
[28] RSC Advances, 2018, vol. 8, # 27, p. 14829 - 14832
[29] Patent: CN107722068, 2018, A, . Location in patent: Paragraph 0079; 0080; 0081; 0082
[30] Chinese Journal of Chemistry, 2018, vol. 36, # 9, p. 851 - 856
4
[ 394-46-7 ]
[ 50919-06-7 ]
[ 171032-87-4 ]
[ 162427-79-4 ]
Reference：
[1] Chemistry - A European Journal, 1999, vol. 5, # 4, p. 1320 - 1330
[2] Chemistry - A European Journal, 1999, vol. 5, # 4, p. 1320 - 1330
[3] Angewandte Chemie - International Edition, 2001, vol. 40, # 7, p. 1235 - 1238
[4] Angewandte Chemie - International Edition, 2008, vol. 47, # 5, p. 894 - 897
5
[ 934226-04-7 ]
[ 171032-87-4 ]
Yield
Reaction Conditions
Operation in experiment
99.3 % ee
With sodium hydroxide; water In toluene at 60℃; for 1 h;
520mL (3.12mol, 5.00eq) of 6.0N sodium hydroxide was added to the toluene solution, followed by stirring at 60°C for 1hr. Conversion of the hydrolysis was 100percent by determination by 19F-NMR. The organic layer of the reaction-terminated liquid was separated. The recovered organic layer was washed with 500mL of 1.0N sodium hydroxide, followed by washing with 500mL of 10percent brine, drying with anhydrous sodium sulfate, concentration under reduced pressure, and vacuum drying, thereby obtaining (S)-1-(2-fluorophenyl)ethyl alcohol represented by the following formula [Show Image] The alcohol was subjected to a fractional distillation (58°C/530Pa), thereby obtaining 63.5g of a distillation purified product of (S)-1-(2-fluorophenyl)ethyl alcohol represented by the above formula. Optical purity of the purified product was 99.3percent ee by determination by chiral chromatography. Chemical purity of the purified product was 99.9percent by determination by gas chromatography. The total yield from the recrystallization purification of the diastereomer salt of (S)-1-(2-fluorophenyl)ethyl alcohol phthalate half ester-(S)-1-phenylethylamine was 65.3percent. 1H-NMR and 19F-NMR spectrums of the obtained (S)-1-(2-fluorophneyl)ethyl alcohol are shown in the following. 1H-NMR (standard substance: (CH3)4Si, deuterated solvent: CDCl3), δ ppm: 1.53 (d, 6.8Hz, 3H), 1.80 (br, 1H), 5.21 (q, 6.8Hz, 1H), 6.95-7.55 (Ar-H, 4H). 19F-NMR (standard substance: C6F6, deuterated solvent: CDCl3), δ ppm: 41.67 (m, 1F).
With RuBr2[(S,S)-2,4-bis(diphenylphosphino)pentane](2-picolylamine); potassium tert-butylate; hydrogen; In ethanol; at 40℃; under 7600.51 Torr; for 19h;Inert atmosphere; Autoclave;
General procedure: In an autoclave, 1.32 mg of RuBr2[(S,S)-xylskewphos] (3,5-Me2pica) (1.29×10-3 mmol, S/C=10000) and 5.79 mg of potassium tert-butoxide (5.16×10-2 mmol) are placed, and replaced with argon gas. Under argon gas flow, 1.5 mL of acetophenone (12.9 mmol) and 2.9 mL of ethanol was added while measuring by a syringe, pressurized with hydrogen to 10 atm, stirred at 40 C. for 19 hours, then the reduction of the hydrogen pressure was confirmed and phenylethanol was obtained at 100% yield. The optical purity was 88.0% ee as measured by GC (CP-Chirasil-DEX CB (0.25 mml. D×25 m, DF=0.25 mum, from VARIAN), constant at 110 C., pressure: 102.0 kPa, column flow: 1.18 mL/min, vaporizing chamber temperature: 250 C., detector temperature: 275 C., the retention time of each enantiomer was: (R): 11.7 min, (S): 12.4 min), and (S) isomer has predominantly been generated.The reaction was carried out in similar way as Working Example 1 except that the complex was changed to RuBr2 [(S,S)-xylskewphos](pica), and the reaction solvent and substrate were changed as indicated in the Table below. The results are summarized in the Table below, which also describes the results from Comparative Example 1. Analysis conditions indicated in the Table is the same as the Table provided from Working Examples ito 6. From the results, it is clear that RuBr2[(S,S)-xylskewphos] (3,5-Me2pica) has a better enantioselectivity as compared to RuBr2[(S,S)-xyl- skewphos] (pica) complex.
With (S,S)-DPENDS; C36H24Cl2O18P2RuS6(6-)*6Na(1+); hydrogen; potassium hydroxide; In water; at 30℃; under 37503.8 Torr; for 3h;Autoclave;
General procedure: To a 60 mL stainless autoclave with a glass liner and magnetic stirrer were added PEG-400, H2O, RuCl2(TPPTS)2, (S,S)-DPENDS, KOH, and reactant. Hydrogen was introduced to the desired pressure after the reaction mixture had been purged with H2 five times. The products were extracted by n-hexane and analyzed by GC-960 with a FID detector and beta-DEX120 capillary column (30 m × 0.25 mm, 0.25 mum film) at 115 C. The enantiomeric excess (ee value) was calculated from the equation: ee (%) = 100 × (R - S)/(R + S).
With dodecacarbonyl-triangulo-triruthenium; (S,S)-N-{1,2-diphenyl-2-[(pyridin-2-ylmethyl)amino]ethyl}-4-methylbenzenesulfonamide; In isopropyl alcohol; at 80℃; for 48h;Inert atmosphere; Schlenk technique;
General procedure: A mixture of catalyst (2 mol%) and Ru3 (CO)12 (0.67 mol%) in IPA (10 cm3) was stirred at 80 C under an inert atmosphere in a schlenk tube for 30 min. To this solution, ketone (1 mmol) was added and the resulting mixture was stirred at 80 Cfor 48 h. The reaction mixture was filtered through a short column of silica using (EtOAc:hexane 1:1), a small amount of the filtrate was dilluted in EtOAc and then injected on the GC to determine the conversion and enantiomeric excess.
With formic acid; (S,S)-RuCl(eta6-CH3C6H4CH2CH2CH2CH2NHCH(C6H5)CH(C6H5)NSO2Ts); C32H35ClN2O2RuS; triethylamine; at 60℃; for 5h;Schlenk technique;Catalytic behavior;
General procedure: As Examples 20 to 35, hydrogen transfer reactions to ketones shown in Tables 1, 2, and 3 below were conducted by the same operation as in Examples 16 and 18. In these reactions, the catalyst ratios (S/C) were as shown in the tables, the reaction temperature was 60 C., and a formic acid-triethylamine (5:2) azeotrope was used as a hydrogen source in such an amount that the concentration of the substrate was 2 mol/L. The conversions and the optical purities were determined by analyzing the reaction liquids by GC after predetermined periods.; In addition, as Comparative Examples, results of reactions in which RuCl ((S,S)-Tsdpen) (mesitylene) was used in the same manner are also shown in each table. Note that, in these tables, conv. represents the conversion of the ketone substrate, selec. represents the selectivity for the target product, % ee represents the optical purity, and S/C represents a value represented by the number of moles of the ketone substrate/the number of moles of the catalyst.
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; C26H29N4O3S(1+)*Cl(1-); sodium formate; In water; at 20℃; for 5h;Catalytic behavior;
General procedure: To a solution of ligand 5d (2.1 mg, 0.004 mmol) in water (1 mL) was added [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), HCO2Na (41 mg, 3.0 mmol), and ketone (2.0 mmol). The reaction mixture was stirred at room temperature for the time as indicated in Tables 1 and 2 . The reaction mixture was extracted by ethyl ether. The conversion was determined by 1H NMR analysis of the crude product. After concentration, the crude product was purified by chromatography on silica gel to give the pure product.
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; C26H29N4O3S(1+)*Cl(1-); sodium formate; In water; at 20℃; for 5h;Green chemistry;
General procedure: To a solution of ligand 5d (2.1 mg, 0.004 mmol) in water (1 mL) was added [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), HCO2Na (41 mg, 3.0 mmol), and ketone (2.0 mmol). The reaction mixture was stirred at room temperature for the time as indicated in Tables 1 and 2. The reaction mixture was extracted by ethyl ether. The conversion was determined by 1H NMR analysis of the crude product. After concentration, the crude product was purified by chromatography on silica gel to give the pure product.
General procedure: In a schlenk tube, BH3·SMe2(0.55 mmol, 275 L) was added inthe solution of IL 5 (28 mg, 10 mol%) dissolved in THF (1 mL), undernitrogen atmosphere. The homogenous mixture was stirred andheated at 70C for 30 min. Later, a solution of ketone (0.5 mmolin THF (0.5 mL)) was added within 30 min. After the addition wascompleted, the solvent was evaporated under vacuum. An aqueoussolution of 1M HCl (5 mL) was added and the product was extractedwith DCM. The solvent was dried on anhydrous sodium sulfateand evaporated under reduced pressure. Crude residue was furtherpurified by column chromatography on silica gel using hexane-ethyl acetate as eluent. Enantiomeric excesses of all alcohols weredetermined by HPLC analysis using Chiralcel OD-H/AD-H chiralcolumn, isopropanol-n-hexane as mobile phase and HPLC condi-tions are given in SI.
With (2R)-2-[benzyl([6-({benzyl[(1R)-2-[(diphenylphosphanyl)oxy]-1-phenylethyl]amino}methyl)pyridin-2-yl]methyl})amino]-2-phenylethyl diphenylphosphinite bis(dichloro-eta6-p-cymeneruthenium(II)); isopropyl alcohol; potassium hydroxide; at 82℃; for 0.5h;Inert atmosphere; Schlenk technique;Catalytic behavior;
General procedure: Typical procedure for the catalytic hydrogen-transfer reaction: a solution of the Ru(II)-complexes 17-24 (0.005 mmol), KOH (0.025mmol) and the corresponding ketone (0.5 mmol) in degassed 2-propanol (5 mL) was refluxed until the reaction was completed. Periodically samples taken from the reaction medium were passed through acetone silica gel column and conversion rates were observed in gas chromatography, which were calculated based on unreacted ketone.
With [(1S,2S)-N-(p-toluensulfonyl)-1,2-diphenylethanediamine](p-cymene)ruthenium (I); sodium formate; In methanol; water; at 50℃; for 12h;Green chemistry;
0.5 mmol of 1-(2-fluorophenyl)ethanol was added to the test tube, 1.5 mmol of dipropylene glycol dimethyl ether was added to the oxygen balloon, and the reaction was completed at 120 C for 12 hours until the reaction was completed, and sodium formate was added to the reaction system, 2.5 mmol. Then add 0.0025 mmol of catalyst B, add 4 mL of methanol:water (3:1), replace with nitrogen three times, react at 50 C for 12 h, wash with water after the reaction, extract the aqueous phase with ethyl acetate three times, and concentrate the organic phase to dry Column chromatography (petroleum ether: ethyl acetate = 10:1) gave (S)-1-(2-fluorophenyl)ethanol (61.6 mg), yield 88%, ee value 86%. HPLC separation conditions: chiral column OD-H column, mobile phase: n-hexane / isopropanol = 98: 2 (volume ratio), flow rate: 1.0 ml / min, wavelength: 254 nm, temperature, 25 C, t1 = 11.82min, t2=12.72min;
With glucose dehydrogenase; D-glucose; NAD; acetophenone reductase from Geotrichum candidum NBRC 4597 (Trp288Ala mutant); In aq. buffer; at 30℃; for 14h;pH 7.2;Enzymatic reaction;Kinetics;
General procedure: Reductions were performed in 50 mL of 100 mM HEPES-NaOH buffer (pH 7.2) consisting of1.4 mM NAD+, 0.23-0.39 mmol of 2a-13a, cofactor regeneration reagent written in Table S1, and purified GcAPRD with the amount written in Table S1. Reactions were done for 14 h at 30C with a rotational speed of 130 rpm. The product was extracted with diethyl ether, dried over MgSO4, and evaporated under reduced pressure. Silica gel column chromatography (hexane:ethyl acetate 4:1) were performed to give the corresponding chiral alcohols 2b-13b.
With dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole; In tetrahydrofuran; at 20℃; for 2h;
To anhydrous tetrahydrofuran (20 mL) was added (R)-2-methyl-CBS-oxazaborolidine (1.0 M, 2.9 mL) and borane dimethyl sulfide complex (10.0 M, 1.88 mL) and the mixture was stirred at ambient temperature for 1 h. To this mixture was then added dropwise a solution of 1-(2-fluorophenyl)ethanone (2.00 g, 14.5 mmol, 1.75 mL) in anhydrous tetrahydrofuran (5 mL). The reaction mixture was stirred at ambient temperature for 2 h. The mixture was quenched by addition of methanol (20 mL) and concentrated in vacuo to afford the title compound as a colorless oil (2.00 g, 98% yield) that was used without further purification: 1H NMR (400 MHz, CDCl3) delta 7.53-7.49 (m, 1H), 7.28-7.24 (m, 1H), 7.20-7.16 (m, 1H), 7.04 (ddd, J=10.8, 8.2, 1.2 Hz, 1H), 5.23 (q, J=6.4 Hz, 1H), 1.54 (d, J=6.4 Hz, 3H), OH not observed.
92%
With (R)-methyl oxazaborolidine; N,N-diethylaniline; diborane; In tert-butyl alcohol; at 45℃; for 1h;
First Step Synthesis of (S)-1-(2-Fluorophenyl)ethanol To a solution (60 mL) of (R)-methyl oxazaborolidine (0.32 g, 1.2 mmol) in tert-butyl alcohol, N,N-diethylaniline borane (2.6 g, 16 mmol) was added, and a solution (150 mL) of 1-(2-fluorophenyl)ethanone (2.0 g, 14 mmol) in tert-butyl alcohol was then added thereto at 45 C., and the resulting mixture was stirred. One hour later, the reaction solution was cooled to room temperature, methanol was added thereto and the resultant was concentrated. After 1.0 N hydrochloric acid was added thereto, the resultant was extracted with ethyl acetate, and the organic layer was washed with brine, then dried over anhydrous sodium sulfate and concentrated. The obtained crude product was purified by silica gel column chromatography (hexane alone to hexane/ethyl acetate=85/15) to obtain the title compound (1.9 g; 92%) as a colorless liquid. 1H-NMR (400 MHz, CDCl3) delta: 1.52 (3H, d, J=6.8 Hz), 5.17-5.24 (1H, m), 6.98-7.05 (1H, m), 7.15 (1H, ddd, J=1.2, 7.6, 7.6 Hz), 7.21-7.28 (1H, m), 7.49 (1H, ddd, J=1.6, 7.6, 7.6 Hz).
77%
With acetophenone reductase from Geotrichum candidum NBRC 4597; NAD; isopropyl alcohol; In aq. buffer; at 30℃; for 14h;pH 7.2;Enzymatic reaction;Kinetics;
General procedure: Reductions were performed in 50 mL of 100 mM HEPES-NaOH buffer (pH 7.2) consisting of1.4 mM NAD+, 0.23-0.39 mmol of 2a-13a, cofactor regeneration reagent written in Table S1, and purified GcAPRD with the amount written in Table S1. Reactions were done for 14 h at 30C with a rotational speed of 130 rpm. The product was extracted with diethyl ether, dried over MgSO4, and evaporated under reduced pressure. Silica gel column chromatography (hexane:ethyl acetate 4:1) were performed to give the corresponding chiral alcohols 2b-13b.
74%
With D-glucose; at 35℃; for 36h;pH 7.5;Tris buffer; Microbiological reaction; Enzymatic reaction;
General procedure: The preparative scale (large scale) production of (S)-1-phenylethanol 1b from acetophenone 1a by immobilized C. laurentii EBK-19 cells was also achieved. The reduction of 1a was carried out in a 1000-mL Erlenmeyer flask using beads prepared as described in Section 4.4. The cells were activated by suspending the beads in 300 mL tris buffer containing 4% glucose. After cell activation (3 h), acetophenone 1a (6 mM) was directly added to the mixture. During the 36 h reaction period, the beads were regularly separated by filtration, resuspended in tris buffer and glucose and reused for the same reaction without washing. At regular time intervals (36 h), the conversion and enantiomeric excess (ee) of the product were determined and the yields calculated. The run time of the beads was optimized for the production of 1b and found to be 27 days.
With hydrogen; lithium hydroxide; (8R,9R)-9-amino(9-deoxy)epicinchonin; In methanol; at 25℃; under 45004.5 Torr; for 3h;Autoclave;
General procedure: Asymmetric hydrogenation of aromatic ketones was performed in a 60mL stainless steel autoclave with a magnetic stirred bar at room temperature, by using 9-amino(9-deoxy)epicinchonine as modifier, which is derived from cinchonine. In a typical run, the catalyst, chiral diamine, solvent, base and acetophenone were placed in the autoclave, followed by five purges hydrogen. The hydrogen pressure was thereafter increased to desired level. The mixture was stirred at room temperature for the appropriate duration.
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C49H67FeN2O2PS; hydrogen; lithium tert-butoxide; In isopropyl alcohol; at 20℃; under 15201.0 Torr; for 12h;Inert atmosphere; Autoclave;
In a high-purity argon atmosphere,[Ir(COD)Cl]2 (3.4 mg, 0.005 mmol)The chiral ligand L6 (9.2 mg, 0.011 mmol) was dissolved in isopropanol (1 mL).Stirring for 3 hours at room temperature gives an orange clear solution.20 muL (0.001 mol%) of this orange solution was taken with a microinjector.Add to a mixed system of o-fluoroacetophenone (2 mmol), isopropyl alcohol (2 mL) and lithium tert-butoxide (1 mol %).The reaction system was placed in an autoclave and stirred at room temperature under H2 (20 atm) for 12 hours.The solvent was removed under reduced pressure and the column was separated by chromatography (silica gel, eluent: ethyl acetate).The pure product 1-o-fluorophenylethanol was analyzed by HPLC and the ee value was found to be 99%.
With RuBr2[(S,S)-2,4-bis(diphenylphosphino)pentane](2-aminomethyl-3,5-dimethylpyridine); potassium tert-butylate; hydrogen; In ethanol; at 40℃; under 7600.51 Torr; for 19h;Inert atmosphere; Autoclave;
General procedure: In an autoclave, 1.32 mg of RuBr2[(S,S)-xylskewphos] (3,5-Me2pica) (1.29×10-3 mmol, S/C=10000) and 5.79 mg of potassium tert-butoxide (5.16×10-2 mmol) are placed, and replaced with argon gas. Under argon gas flow, 1.5 mL of acetophenone (12.9 mmol) and 2.9 mL of ethanol was added while measuring by a syringe, pressurized with hydrogen to 10 atm, stirred at 40 C. for 19 hours, then the reduction of the hydrogen pressure was confirmed and phenylethanol was obtained at 100% yield. The optical purity was 88.0% ee as measured by GC (CP-Chirasil-DEX CB (0.25 mml. D×25 m, DF=0.25 mum, from VARIAN), constant at 110 C., pressure: 102.0 kPa, column flow: 1.18 mL/min, vaporizing chamber temperature: 250 C., detector temperature: 275 C., the retention time of each enantiomer was: (R): 11.7 min, (S): 12.4 min), and (S) isomer has predominantly been generated.
10
[ 171032-87-4 ]
[ 911716-00-2 ]
Yield
Reaction Conditions
Operation in experiment
65%
With N-chloro-succinimide; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃;
General Method C; Triphenyl phosphine (1.3 equiv.) in THF was added at 0 C to NCS (1.3 equiv.) in THF under an argon atmosphere. The resulting mixture was stirred at ambient temperature for EPO <DP n="24"/>30 min. Cl or C2 (1 equiv.) was added at 0 C and the reaction mixture was stirred at ambient temperature until the reaction was complete (monitored by LC-MS, HPLC or TLC). The solvent was evaporated off followed by addition of hexane and removal of the precipitate by filtration. The filtrate was concentrated in vacuo and the crude product was, if necessary, purified using preparative HPLC or by flash column chromatography.; Example 1; (2RV2-r('2-Amino-5-(rri^-l-r2-fluorophenvnethyllthioUl,31thiazolo|'4.5-J1pyrimidin-7- vDaminolpentan- 1 -ol; a) l-[(lR)-l-Chloroethyll-2-fluorobenzene; The title compound was obtained in 65% yield with 93% enantiomeric excess using general method C starting from (15)-l-(2-fluorophenyl)ethanol (3.56.g, 25 mmol). 1H NMR (CDCl3) delta 7.53 (td, IH), 7.28 (m, IH), 7.16 (m, IH), 7.04 (m, IH), 5.42 (q, IH), 1.84 (d, 3H); MS (ESI+) m/z 158 [M+H]+.
With sodium hydroxide; water; In toluene; at 60℃; for 1h;
520mL (3.12mol, 5.00eq) of 6.0N sodium hydroxide was added to the toluene solution, followed by stirring at 60C for 1hr. Conversion of the hydrolysis was 100% by determination by 19F-NMR. The organic layer of the reaction-terminated liquid was separated. The recovered organic layer was washed with 500mL of 1.0N sodium hydroxide, followed by washing with 500mL of 10% brine, drying with anhydrous sodium sulfate, concentration under reduced pressure, and vacuum drying, thereby obtaining (S)-1-(2-fluorophenyl)ethyl alcohol represented by the following formula [Show Image] The alcohol was subjected to a fractional distillation (58C/530Pa), thereby obtaining 63.5g of a distillation purified product of (S)-1-(2-fluorophenyl)ethyl alcohol represented by the above formula. Optical purity of the purified product was 99.3%ee by determination by chiral chromatography. Chemical purity of the purified product was 99.9% by determination by gas chromatography. The total yield from the recrystallization purification of the diastereomer salt of (S)-1-(2-fluorophenyl)ethyl alcohol phthalate half ester-(S)-1-phenylethylamine was 65.3%. 1H-NMR and 19F-NMR spectrums of the obtained (S)-1-(2-fluorophneyl)ethyl alcohol are shown in the following. 1H-NMR (standard substance: (CH3)4Si, deuterated solvent: CDCl3), delta ppm: 1.53 (d, 6.8Hz, 3H), 1.80 (br, 1H), 5.21 (q, 6.8Hz, 1H), 6.95-7.55 (Ar-H, 4H). 19F-NMR (standard substance: C6F6, deuterated solvent: CDCl3), delta ppm: 41.67 (m, 1F).
Second Step Synthesis of Imidazole-1-carboxylic acid (S)-1-(2-fluorophenyl)ethyl ester To a solution (16 mL) of 1,1'-carbonyldiimidazole (3.3 g, 20 mmol) in tetrahydrofuran, a solution (4.0 mL) of (S)-1-(2-fluorophenyl)ethanol (1.9 g, 13 mmol) in tetrahydrofuran was gently added at 50 C., and the resulting mixture was stirred. Four hours later, distilled water was added thereto and the resultant was extracted with ethyl acetate. The organic layer was washed with brine, then dried over anhydrous sodium sulfate and concentrated. The obtained crude product was purified by silica gel column chromatography (hexane/ethyl acetate=90/10 to 70/30) to obtain the title compound (3.1 g; 99%) as a colorless liquid. 1H-NMR (400 MHz, CDCl3) delta: 1.75 (3H, d, J=6.4 Hz), 6.33 (1H, q, J=6.4 Hz), 7.06-7.13 (2H, m), 7.18 (1H, ddd, J=1.2, 7.2, 7.6 Hz), 7.31-7.46 (3H, m), 8.16 (1H, s).MS (ESI) [M+H]+235
(S)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-4-(1-(2-fluorophenyl)ethoxy)-N-(thiazol-2-yl)benzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
99%
With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0 - 20℃; for 2h;
To a mixture of <strong>[171032-87-4](S)-1-(2-fluorophenyl)ethan-1-ol</strong> (0.14 g, 1.0 mmol) and N-(2,4-dimethoxybenzyl)-2,4,5-trifluoro-N-(thiazol-2-yl)benzenesulfonamide (0.49 g, 1.1 mmol) in anhydrous N,N-dimethylformamide (10 mL) was added sodium hydride (60% dispersion in mineral oil, 0.08 g, 2.0 mmol) at 0 C. The mixture was stirred at ambient temperature for 2 h, cooled to 0 C., and quenched by addition of saturated ammonium chloride solution (20 mL). The mixture was ethyl acetate (3×30 mL). The combined organic layers were washed with water (40 mL), brine (40 mL), dried over anhydrous magnesium sulfate, and filtered. Concentration of the filtrate in vacuo and purification of the residue by column chromatography, eluting with 0% to 50% of ethyl acetate in hexanes, afforded the title compound as a colorless solid (0.56 g, 99% yield): MS (ES+) m/z 565.1 (M+1).
(S)-5-chloro-2-fluoro-4-(1-(2-fluorophenyl)ethoxy)-N-(thiazol-4-yl)benzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
20%
With caesium carbonate; In dimethyl sulfoxide; at 75℃; for 17h;
To a solution of <strong>[171032-87-4](S)-1-(2-fluorophenyl)ethan-1-ol</strong> (0.102 g, 0.730 mmol) and tert-butyl ((5-chloro-2,4-difluorophenyl)sulfonyl)(thiazol-4-yl)carbamate (0.30 g, 0.730 mmol) in anhydrous dimethyl sulfoxide (3 mL) was added cesium carbonate (0.571 g, 1.75 mmol) and the reaction mixture was heated at 75 C. for 17 h. The reaction mixture was diluted with ethyl acetate (5 mL) and water (5 mL), and the aqueous phase was extracted with ethyl acetate (2×5 mL). The combined organic layers were washed with brine (5 mL), dried over anhydrous magnesium sulfate, and filtered. Concentration of the filtrate in vacuo and purification of the residue by preparative reverse phase HPLC using acetonitrile in water containing 0.1% of trifluoroacetic acid as eluent afforded the title compound as a colorless solid (0.062 g, 20% yield): 1H NMR (300 MHz, DMSO-d6) delta11.34 (s, 1H), 8.88 (d, J=2.2 Hz, 1H), 7.80 (d, J=7.5 Hz, 1H), 7.51-7.33 (m, 2H), 7.30-7.18 (m, 3H), 7.06 (d, J=2.2 Hz, 1H), 5.97 (q, J=6.4 Hz, 1H), 1.63 (d, J=6.4 Hz, 3H); MS (ES+) m/z 431.0 (M+1), 432.9 (M+1).
3-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(thiazol-2-yl)benzenesulfonamide[ No CAS ]
[ 171032-87-4 ]
(S)-3-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-(1-(2-fluorophenyl) ethoxy)-N-(thiazol-2-yl)benzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0 - 20℃; for 2h;
To a solution of 3-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(thiazol-2-yl)benzenesulfonamide (0.250 g, 0.56 mmol) and <strong>[171032-87-4](S)-1-(2-fluorophenyl)ethan-1-ol</strong> (0.075 g, 0.540 mmol) in anhydrous N,N-dimethylformamide (5 mL) was added sodium hydride (60% dispersion in mineral oil, 0.043 g, 1.08 mmol) at 0 C. The reaction was allowed to warm to ambient temperature and stirred for 2 h. The reaction was diluted with ethyl acetate (50 mL) and saturated aqueous ammonium chloride solution (30 mL), and the aqueous phase was extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with brine (3×20 mL), dried over anhydrous sodium sulfate, and filtered. Concentration of the filtrate in vacuo and purification of the residue by column chromatography eluting with a gradient of 0 to 40% of ethyl acetate in hexanes provided the title compound as a yellow oil (0.250 g, 80% yield): 1H NMR (300 MHz, CDCl3) delta 7.65-7.59 (m, 1H), 7.41-7.36 (m, 2H), 7.33-7.25 (m, 2H), 7.18-7.04 (m, 2H), 6.95 (dd, J=3.6, 1.4, 1H), 6.60-6.57 (m, 1H), 6.37-6.31 (m, 2H), 5.79-5.72 (m, 1H), 5.18 (s, 2H), 3.75 (d, J=1.3 Hz, 3H), 3.69 (d, J=1.2 Hz, 3H), 1.72 (d, J=6.4 Hz, 3H); MS (ES+) m/z 581.1 (M+1), 583.1 (M+1).
(S)-tert-butyl (2,6-difluoro-4-(1-(2-fluorophenyl)ethoxy)phenyl)sulfonyl(thiazol-4-yl)carbamate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
51%
With caesium carbonate; In dimethyl sulfoxide; at 20℃; for 12h;
To a solution of tert-butyl thiazol-4-yl((2,4,6-trifluorophenyl)sulfonyl)carbamate (0.150 g, 0.380 mmol) in anhydrous dimethyl sulfoxide (2 mL) was added (S)-1-(2-fluorophenyl)ethanol (0.106 g, 0.760 mmol) and cesium carbonate (0.248 g, 0.760 mmol). The reaction mixture was stirred at ambient temperature for 12 h. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous sodium sulfate, and filtered. Concentration of the filtrate in vacuo and purification of the residue by preparative thin layer chromatography, eluting with 20% of ethyl acetate in petroleum ether, afforded the title compound as a yellow oil (0.100 g, 51% yield): MS (ES+) m/z 414.9 (M-99).
Stage #1: With C36H28FeMnN2O3P(1+)*Br(1-); potassium carbonate In ethanol at 20℃; for 0.0833333h; Glovebox;
Stage #2: With hydrogen In ethanol at 50℃; for 16h; Glovebox; Autoclave;
16 Example 11 Asymmetric hydrogenation of acetophenone with Mn-PNN catalyst
General procedure: In the glove box, add Mn-Cat.1 catalyst (3.8mg, 0.005mmol) and substrate acetophenone (120mg, 1mmol) into a 5mL clear glass vial, then potassium carbonate (1.4 mg, 0.01 mmol) and absolute ethanol (3 mL) were added, and the mixture was stirred at room temperature for 5 min. Finally, the hydrogenation bottle was put into the autoclave, the hydrogen was replaced three times and then filled with 30 bar H2, and reacted at 50°C for 16h. After the reaction is completed, the hydrogen is released carefully, the solvent is spin-dried under reduced pressure, and the hydrogenated product (R)-1-phenylethanol is purified by silica gel column, a colorless and transparent liquid, >99% conversion, 95% yield, 77% ee,
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
