* 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.
With tetrabutylammomium bromide; toluene-4-sulfonic acid hydrazide; sodium hydroxide In water at 80℃; for 10 h; Air atmosphere
General procedure: A Schlenk tube with a magnetic stir bar charged with α,β-unsaturated carbonyl compounds (0.5 mmol, 1 equiv), tosyl hydrazide (0.6 mmol, 1.2 equiv), NaOH (1.5 equiv), (n-Bu)4NBr (1.5 equiv). The reaction vessel was placed in an 80 °C oil bath, and then stirring at this temperature for 10 h. The reaction mixture was then allowed to cool to ambient temperature, and diluted with 20 mL of ethyl acetate, and washed with brine (15 mL), water (15 mL), and then the organic layer was dried over Na2SO4. After concentrated in vacuo, the crude product was purified by column chromatography. The identity and purity of the known product was confirmed by 1H NMR, 13C NMR, and GC-MS.
Reference：
[1] Angewandte Chemie - International Edition, 2001, vol. 40, # 4, p. 763 - 766
[2] Synthetic Communications, 2011, vol. 41, # 2, p. 206 - 218
[3] RSC Advances, 2013, vol. 3, # 42, p. 19455 - 19466
[4] European Journal of Organic Chemistry, 2012, # 29, p. 5655 - 5659
[5] Tetrahedron Letters, 2014, vol. 55, # 30, p. 4095 - 4097
[6] Journal of Molecular Catalysis A: Chemical, 2016, vol. 411, p. 87 - 94
4
[ 75-07-0 ]
[ 1122-91-4 ]
[ 49678-04-8 ]
Reference：
[1] Journal of the Indian Chemical Society, 2010, vol. 87, # 9, p. 1145 - 1148
[2] Organic Letters, 2016, vol. 18, # 1, p. 4 - 7
[3] Angewandte Chemie - International Edition, 2015, vol. 54, # 6, p. 1885 - 1887[4] Angew. Chem., 2014, vol. 54-126, # 6, p. 1905 - 1907,3
[5] European Journal of Organic Chemistry, 2017, vol. 2017, # 25, p. 3631 - 3634
5
[ 1124-14-7 ]
[ 49678-04-8 ]
[ 90712-56-4 ]
Yield
Reaction Conditions
Operation in experiment
70.5 %Spectr.
With trifluoroacetic acid; sodium nitrite In chloroform at 0 - 20℃;
General procedure: Sodium nitrite, 0.69 g (0.01 mol), was added in portions over a period of 10–15 min to a mixture of 0.01 mol of arylcyclopropane 1a–1l, 5.2 g of trifluoroacetic acid, and 15 mL of chloroform, cooled to 0–5 °C.The mixture was allowed to warm up to 20 °C, kept for1 h at that temperature, and poured into 100 mL of cold water. The organic phase was separated, the aqueousphase was extracted with chloroform (2 × 10 mL), the extracts were combined with the organic phase,washed with water (2 × 30 mL), and dried over MgSO4, the solvent was removed, and the residue was analyzed by 1H NMR. Compound 2l was isolated by crystallization. The compositions of the reaction mixtures are given in Table 1. The physical constants and spectral characteristics of 2a [16], 2b [30], and 2l [28] coincided with published data.
Reference：
[1] Russian Journal of Organic Chemistry, 2016, vol. 52, # 3, p. 397 - 403[2] Zh. Org. Khim., 2016, vol. 52, # 3, p. 417 - 423,7
6
[ 2039-82-9 ]
[ 75-27-4 ]
[ 49678-04-8 ]
Reference：
[1] Chemical Science, 2018, vol. 9, # 11, p. 2986 - 2990
With aluminum oxide; dipyridinium dichromate; In dichloromethane; at 20℃; for 24h;
General procedure: To a solution of arylaldehyde 12c-e (35.0 mmol) inbenzene was added methoxycarbonyl methylidene triphenylphosphorane (15.2 g, 45.5 mmol). Afterstirring for overnight at 90 C, the solution was cooled to rt and concentrated in vacuo. The residue wasthen washed with Et2O to remove precipitate and the combined organic layers were concentrated in vacuo.The crude was then purified by short column chromatography on silica gel using benzene to give desiredester 13c-e. The product was used without further purification.To a cool (0 C) solution of 13c-e (10.0 mmol) in CH2Cl2 (80 mL) was added slowly DIBAL (inn-hexane, 20.8 mL, 20.0 mmol). After stirring for 2 h at 0 C, the mixture was warmed up to rt and thenquenched by saturated aqueous potassium sodium tartrate solution (100 mL). After 1 h, the solution wasextracted with CH2Cl2 (100 mL × 3) and the combined organic layers were dried over Na2SO4. Thesolution was concentrated in vacuo to give desired alcohol 14c-e as a crude product. The product wasused for the next reaction without further purification.To a suspended solution of PDC (11.3 g, 30.0 mmol) and aluminium oxide (neutral, 11.3 g, 110 mmol)in CH2Cl2 (50 mL) was added the solution of 14c-e (crude, 10.0 mmol) in CH2Cl2 (40 mL). After stirringfor 24 h at rt, the solution was concentrated in vacuo and filtered through silica gel (5 cm) usinghexane/AcOEt (1:1) until all aldehyde had been removed from silica gel. The combined filtrate wasconcentrated in vacuo and the crude was purified by column chromatography on silica gel usinghexane/AcOEt to give desired cinnamaldehyde derivative 2c-e (56-79%).
With gold; dihydrogen peroxide; In methanol; water; at 55℃; for 8h;Inert atmosphere;
General procedure: The liquid-phase oxidation reactions were performed usinground bottom flask equipped with water condenser and a mag-netic stirrer. In a typical alcohol oxidation reaction, 0.67 g (5 mmol)of cinnamyl alcohol was mixed with 5 mL of methanol and 0.56 g(5 mmol) of dilute H2O2(30 wt% aqueous solution) in a 25 mL two-necked round bottom flask followed by addition of 5 wt% catalystwith respect to substrate. Cycloheptanone was used as an inter-nal standard to quantify the reaction product. The reaction wasperformed at 328 K while effectively circulation ice-cold waterthrough the condenser and the mixture was maintained under N2atmosphere using a N2balloon. The progress of the reaction wasmade by analyzing the products with a capillary gas chromato-graph (Agilent 13G, OV-1 column with flame ionization detector,FID). The quantification of products has been performed with spe-cial care using internal standard and response factor of reactantand products. For catalyst reusability study, the catalyst was recov-ered through centrifugation followed by activation under 5% H2(remaining N2) atmosphere at 180C. It is pertinent to mention thatlow-temperature activation was carried out to remove the physi-cally adsorbed organic reactant, product or solvent molecules fromthe metal surface of the used catalyst
With tert.-butylhydroperoxide;C18H11F12N*C50H57O4P; In 1,4-dioxane; at 35℃; for 72h;Product distribution / selectivity;
Asymmetric EpoxidationIt is also possible to catalyze epoxidations in a manner analogous to Scheme 2. For example, cinnamaldehyde can be converted using tert-butyl hydroperoxide enantioselectively to the corresponding epoxide when the catalysts used are the salts 11 bw (Scheme 16). Scheme 16. Inventive highly enantioselective epoxidation R Yield dr ee (a) Ph 75% >99:1 91% (b) 2-naphthyl 76% >99:1 95% (c) 1-naphthyl 70% 98:2 91% (d)4-Ph-C6H4 78% >99:1 91% (e)4-Me-C6H4 65% >99:1 92% (f)3-Me-C6H4 68% >99:1 92% (g)2-Me-C6H4 62% 97:3 90% (h)4-cyclohexyl-C6H4 60% >99:1 90% (i)4-F-C6H4 78% >99:1 93% (j)3-F-C6H4 82% >99:1 84% (k)2-F-C6H4 69% 98:2 91% (l)4-Cl-C6H4 84% >99:1 87% (m)4-Br-C6H4 80% >99:1 87% (n) n-hexyl 92% 95:5 70%
General procedure: To a mixture of catalyst 9 (0.01 mmol, 0.1 equiv) and benzoic acid (0.01 mmol, 0.1 equiv) in DCM (0.2 mL) was added beta-ketoamide 8 (0.1 mmol, 1 equiv) under an atmosphere of N2. Followed by the addition of alpha,beta-unsaturated aldehyde 1 (0.15 mmol, 1.5 equiv). The reaction was stirred at 20 C and followed by TLC. After full consumption of beta-ketoamide 8, the reaction mixture was diluted with DCM (0.3 mL). Then TFA (0.1 mmol, 1 equiv) was added. The reaction mixture was stirred at 20 C for 0.5 h. The reaction mixture was diluted with DCM (5 mL) and washed with saturated NaHCO3 (3 mL). The aqueous phase was extracted with DCM (2×5 ml). The combined organic phases were dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a petroleum ether and ethyl acetate mixture to give pure compounds 10.
General procedure: To a mixture of catalyst 9 (0.01 mmol, 0.1 equiv) and benzoic acid (0.01 mmol, 0.1 equiv) in DCM (0.2 mL) was added beta-ketoamide 8 (0.1 mmol, 1 equiv) under an atmosphere of N2. Followed by the addition of alpha,beta-unsaturated aldehyde 1 (0.15 mmol, 1.5 equiv). The reaction was stirred at 20 C and followed by TLC. After full consumption of beta-ketoamide 8, the reaction mixture was diluted with DCM (0.3 mL). Then TFA (0.1 mmol, 1 equiv) was added. The reaction mixture was stirred at 20 C for 0.5 h. The reaction mixture was diluted with DCM (5 mL) and washed with saturated NaHCO3 (3 mL). The aqueous phase was extracted with DCM (2×5 ml). The combined organic phases were dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a petroleum ether and ethyl acetate mixture to give pure compounds 10.
(2R,3S)-3-(4-bromophenyl)oxirane-2-carbaldehyde[ No CAS ]
[ 1020746-20-6 ]
Yield
Reaction Conditions
Operation in experiment
General procedure: Catalyst 10 (22.8mg, 0.06mmol) was added at rt to a solution of the alpha,beta-unsaturated aldehyde (0.3mmol) in MeOH (1.0mL). The mixture was stirred for 10min at rt followed by the addition of H2O2 (30% in H2O, 92muL, 0.9mmol). The reaction was stirred for 48h under argon. After completion, the reaction was cooled to 0C (ice bath) followed by the addition of NaBH4 (45.6mg, 1.2mmol). The reaction mixture was then stirred for a further 30min at 0C, and quenched with a pH=7.0 phosphate buffer solution. The aqueous phase was extracted with CH2Cl2 (3×5mL) and the combined organic extracts were dried over anhydrous MgSO4 and concentrated in vacuo after filtration. The crude product was purified by column chromatography (silica gel; petroleum ether/AcOEt=8:1) to give target compounds 2a-h
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; triethylamine; In dichloromethane; at 20℃; for 24h;
To a solution of CH2Cl2 (0.6 mL) were added alpha, beta-unsaturated aldehydes 1 (0.3 mmol), chloroacetophenones 2 (0.9 mmol), catalyst I (0.06 mmol) and triethylamine (0.3 mmol). The reaction mixture was stirred at room temperature for 24 h and then the solvent was removed under vacuum. The residue was added 1 M hydrochloric acid (5.0 mL) and extracted with CH2Cl2 for three times. The combined organic phases were dried over anhydrous Na2SO4, filtered and evaporated under vacuum. The residue was purified by silica gel chromatography to yield the desired product.
2-(4-bromophenyl)-3-(4-methylbenzoyl)cyclopropanecarbaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
81%
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; triethylamine; In dichloromethane; at 20℃; for 24h;
To a solution of CH2Cl2 (0.6 mL) were added alpha, beta-unsaturated aldehydes 1 (0.3 mmol), chloroacetophenones 2 (0.9 mmol), catalyst I (0.06 mmol) and triethylamine (0.3 mmol). The reaction mixture was stirred at room temperature for 24 h and then the solvent was removed under vacuum. The residue was added 1 M hydrochloric acid (5.0 mL) and extracted with CH2Cl2 for three times. The combined organic phases were dried over anhydrous Na2SO4, filtered and evaporated under vacuum. The residue was purified by silica gel chromatography to yield the desired product.
ethyl 4-(4-bromophenyl)-6-hydroxy-1-methyl-2-oxopiperidine-3-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; potassium acetate; In 2,2,2-trifluoroethanol; at 20℃; for 14h;
General procedure: In a round bottom flask, unsaturated aldehyde 2 (0.25 mmol, 1 equiv), amidomalonate 1 (0.3 mmol, 1.2 equiv), catalyst (0.05 mmol, 20% mol), and KOAc (0.3 mmol, 1.2 equiv) were added sequentially in 1 mL of 2,2,2-trifluoroethanol. The reaction was stirred at room temperature overnight. Then the crude was purified by column chromatography to furnish piperidine adducts 3.
ethyl 1-benzyl-4-(4-bromophenyl)-6-hydroxy-2-oxopiperidine-3-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; potassium acetate; In 2,2,2-trifluoroethanol; at 20℃;
General procedure: In a round bottom flask, unsaturated aldehyde 2 (0.25 mmol, 1 equiv), amidomalonate 1 (0.3 mmol, 1.2 equiv), catalyst (0.05 mmol, 20% mol), and KOAc (0.3 mmol, 1.2 equiv) were added sequentially in 1 mL of 2,2,2-trifluoroethanol. The reaction was stirred at room temperature overnight. Then the crude was purified by column chromatography to furnish piperidine adducts 3.
With tetrabutylammomium bromide; toluene-4-sulfonic acid hydrazide; sodium hydroxide; In water; at 80℃; for 10h;Air atmosphere;
General procedure: A Schlenk tube with a magnetic stir bar charged with alpha,beta-unsaturated carbonyl compounds (0.5 mmol, 1 equiv), tosyl hydrazide (0.6 mmol, 1.2 equiv), NaOH (1.5 equiv), (n-Bu)4NBr (1.5 equiv). The reaction vessel was placed in an 80 C oil bath, and then stirring at this temperature for 10 h. The reaction mixture was then allowed to cool to ambient temperature, and diluted with 20 mL of ethyl acetate, and washed with brine (15 mL), water (15 mL), and then the organic layer was dried over Na2SO4. After concentrated in vacuo, the crude product was purified by column chromatography. The identity and purity of the known product was confirmed by 1H NMR, 13C NMR, and GC-MS.
With oxygen; 1,8-diazabicyclo[5.4.0]undec-7-ene; 1,3-bis(mesityl)imidazolium chloride; In tetrahydrofuran; at 25℃; for 16h;
General procedure: to a stirred solution of N-heterocyclic carbene precursor (10 mol %), DBU (6 mmol), and aldehyde (5 mmol) in anhydrous THF (5 ml), tri-n-butyltin chloride (6 mmol) was added under an O2 atmosphere. The reaction mixture was then stirred at 25 C for 16 h. After completion of the reaction (monitored by TLC), the reaction mixture was concentrated, followed by the addition of H2O (50 mL). It was extracted with EtOAc (3 × 50 ml) and the combined organic layers dried over anhydrous Na2SO4. Removal of solvent gave organotin carboxylates, which were purified by column chromatography over silica gel using pet ether/EtOAc (1/19) as eluent to obtain pure tri-n-butyltin(IV) carboxylates in high purity
General procedure: To a solution of the aldehyde (4) (0.4 mmol) and the catalyst (10 mol %, 40 mumol) in MeOH (0.5 ml) were added CsOAc (60 mol %, 0.24 mmol) and 3-(2-(1H-indol-3-yl)ethylamino)-3-oxopropanoate (7) (1.2 eq., 0.48 mmol) in MeOH (0.5 ml) at 0C. The reaction mixture was stirred at 0C for 20-40 hr, cooled to -80 C, and TFA (10 eq) was added. The reaction mixture was warmed to room temperature, passed through a short plug of silica, and concentrated under reduced pressure. Purification by column chromatography on silica gel (ethyl acetate/dichloromethane = 1/5?1/2) yielded the product.
With C27H29F12NOSi; sodium hydrogencarbonate; In toluene; at 20℃;
General procedure: alpha,beta-unsaturated aldehyde 8 (0.40 mmol), 3-chlorooxindole 6 (0.20 mmol), amine 12 (26 mg, 20 mol %, 0.04 mmol), and NaHCO3 (1.1 equiv, 18 mg, 0.22 mmol) were suspended in a 5 mL round bottomed flask and toluene (2 mL) was added. Resulting heterogeneous mixture was stirred at RT until TLC indicated full conversion. Upon completion, the mixture was diluted with MeOH (2 mL) and cooled in an ice bath. NaBH4 (2 equiv, 15 mg, 0.40 mmol) was added and the reaction stirred for 30 min. The mixture was poured into 10 mL of sat. NH4Cl aqueous solution, extracted with DCM (3x10 mL). The organics were combined, concentrated and directly purified by silica gel column chromatography using a mixture of heptane - EtOAc as an eluent. Diastereomeric ratios were determined from the crude reaction mixture by 1H NMR and enantiomeric purity by chiral HPLC analysis.
With 4-methyl-morpholine; titanium tetrachloride; In tetrahydrofuran; tetrachloromethane; at 0 - 20℃;Inert atmosphere;
General procedure: alpha,beta-Unsaturated aldehyde (5.0 mmol) and tetraethyl bisphosphonate (5.0 mmol) wereadded into a solution of TiCl4 (10 mmol) in CCl4 (2.5 mL) at 0 C, Then, N-methylmorpholine (1.61 mL, 14.6 mmol) in THF (3 mL) was added dropwisely over 1 h.The resulting mixture was stirred at room temperature overnight. After quenched withwater, the mixture was extracted with ethyl acetate, dried over Na2SO4, filtered andconcentrated under vacuum. The residue was purified by silica gel chromatographywith CH2Cl2/MeOH = 50/1 to afford the product.
6,7-bis(4-bromophenyl)-3-phenyl-1,3-diazepane-2,4-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
86%
General procedure: A flame-dried round-bottom flask was charged with imidazolium salt 4b (0.034 g, 0.1 mmol, 10 mol%), alpha,beta-unsaturated aldehyde (1 mmol) and CH2Cl2 (4 mL) under a positive pressure of nitrogen, followed by addition of DBU (0.0152 g, 0.1 mmol, 10 mol%) by using a syringe, and the resulting orange solution was stirred for 30 min at room temperature. To this solution, aromatic aldehyde (1.0 mmol) and N-phenyl urea/thiourea (1.0 mmol) was added by using a syringe and the reaction mixture was stirred for a further 2.5 h (completion of reaction was confirmed by TLC analysis). Subsequently, water (5 mL) was added and the reaction mixture was extracted with EtOAc. The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was then purified by column chromatography (silica gel; Merck, 60-120 mesh; EtOAc-hexane, 3:22) to afford the pure product.
6-(4-bromophenyl)-7-(4-nitrophenyl)-3-phenyl-2-thioxo-1,3-diazepane-4-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
General procedure: A flame-dried round-bottom flask was charged with imidazolium salt 4b (0.034 g, 0.1 mmol, 10 mol%), alpha,beta-unsaturated aldehyde (1 mmol) and CH2Cl2 (4 mL) under a positive pressure of nitrogen, followed by addition of DBU (0.0152 g, 0.1 mmol, 10 mol%) by using a syringe, and the resulting orange solution was stirred for 30 min at room temperature. To this solution, aromatic aldehyde (1.0 mmol) and N-phenyl urea/thiourea (1.0 mmol) was added by using a syringe and the reaction mixture was stirred for a further 2.5 h (completion of reaction was confirmed by TLC analysis). Subsequently, water (5 mL) was added and the reaction mixture was extracted with EtOAc. The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was then purified by column chromatography (silica gel; Merck, 60-120 mesh; EtOAc-hexane, 3:22) to afford the pure product.
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; benzoic acid; In chloroform; at 20℃; for 20h;
General procedure: To a solution of alpha,beta-unsaturated aldehyde 2a (0.1 mmol) and 4-acetyl-5-oxohexanal (3, 0.12 mmol) in 0.4 mL of chloroform, catalyst 1b (0.02 mmol) and benzoic acid (0.02 mmol) were added. The mixture was stirred at room temperature for 20 h, and the crude product was purified directly by column chromatography on silica gel (hexane/ethyl acetate = 2:1) to afford the corresponding product 4a as a white solid in 76% yield and 96% ee.
(4S)-4,6-bis(4-bromophenyl)-2-hydroxy-3,4-dihydro-2H-pyran-5-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
With (S)-2-{bis(3,5-dimethylphenyl)[(trimethylsilanyl)oxy]methyl}pyrrolidine; 3,5-dinitrobenzoic acid; In toluene; at 0℃; for 48h;
General procedure: To a solution of catalyst 4 (0.01mmol), 3,5-(NO2)2C6H3CO2H (0.02mmol), and alpha,beta-unsaturated aldehyde 2 (0.10mmol) in toluene (1.0mL) was added alpha-cyanoketones 1 (0.15mmol) at 0C. The resulting solution was then stirred for 48h. After complete consumption of the aldehyde (as monitored by TLC), the reaction mixture was evaporated and then loaded onto silica gel (ethyl acetate/petroleumether=1:10 to 1:7) and the products 3a-n were obtained by column chromatography. The title compound was obtained according to the general procedure (85% yield) as mixture of two diastereoisomers (major and minor). Yellow solid; [alpha]D30=+8.7 (c 1.75, CHCl3); mp=176-178C; 1H NMR (400MHz,CDCl3): delta 7.65 (d, J=8.4Hz, 2H; both diastereoisomers), 7.56 (d, J=8.4Hz, 2H; both diastereoisomers), 7.51 (d, J=8.0Hz, 2H; both diastereoisomers), 7.18 (d, J=8.4Hz, 2H; both diastereoisomers), 5.64 (s, 1H; major), 5.56 (s, 1H; minor), 3.91 (dd, J=10.4, 6.4Hz, 1H; major), 3.85 (dd, J=9.6, 6.4Hz, 1H; minor), 3.69 (s, 1H; major), 3.64 (s, 1H; minor), 2.48-2.43 (m, 1H; minor), 2.28-2.22 (m, 1H; major), 2.04-1.96 (m, 1H; both diastereoisomers); 13C NMR (100MHz, CDCl3): delta 162.2, 139.9, 139.5, 132.2, 131.9, 131.8, 131.7, 129.7, 129.6, 129.3, 125.5, 121.7, 118.9, 95.7, 92.4, 87.8, 39.8, 37.1, 36.0, 35.1ppm; (additional peaks are observed due to diastereoisomers). IR (KBr): nu 3366.1, 2206.6, 1606.9, 1588.2, 1487.1, 1143.5, 1073.0, 1010.0, 868.9, 826.7, 734.3cm-1; d.r.: trans/cis=3.92/1; ESI-MS (m/z): 431.8 (M-H)-; HRMS(ESI): calcd for ([C18H12Br2NO2]): 431.9235. Found: 431.9241; enantiomeric excess: 94%, determined by HPLC (Chiralcel OD-H column, hexane/ i-PrOH 80:20, flow rate 0.7mL/min; lambda=254nm, tmajor=13.3min, tminor=10.6min).
(4S)-1,4-bis(4-bromophenyl)-3-methyl-1,4,5,6-tetrahydropyrano[2,3-c]pyrazol-6-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
With (S)-2-{bis[3,5-bis(trifluoromethyl)phenyl][(trimethylsilanyl)oxy]methyl}pyrrolidine; benzoic acid; In 1,2-dichloro-ethane; at 0℃; for 5h;
To a solution of trans-cinnamaldehyde 1i (26.0 mg, 0.2 mmol, 1.0 equiv) and 3-methyl-1-phenyl-pyrazol-5-one 2a (35.0 mg, 0.2 mmol, 1.0 equiv) in 1,2-dichloroethane (1 mL) was added catalyst (S)-2-(bis(3,5-bis(trifluoromethyl)phenyl) ((trimethylsilyl)oxy)methyl)pyrrolidine (6) (12.0 mg, 0.02 mmol, 0.1 equiv) and benzoic acid (2.4 mg, 0.02 mmol, 0.1 equiv) at 0 C. The resulting mixture was stirred for 5 h at the same temperature. Then the solvent was removed under vacuum, and the residue was directly purified through flash column chromatography on silica gel (hexane/EtOAc = 15:1-10:1) to afford 3i as pale purple solid (60.0 mg, yield 86%). The synthetic procedures for compound 3a, 3c, 3e, 3g, 3k were similar to those used for the synthesis of compound 3i. The racemates 3b, 3d, 3f, 3h, 3j, 3l were prepared with the same procedure except for the racemate catalyst diphenylprolinol trimethyl silyl ether.
With Cp*Ir(6,6'-dionato-2,2'-bipyridine)(H2O); isopropyl alcohol; at 100℃; for 12h;Inert atmosphere; Green chemistry;
4-bromocinnamaldehyde (211 mg, 1.0 mmol), cat. [Ir] (1.1 mg, 0.002 mmol, 0.2 mol%) and isopropanol (5 mL) were sequentially added to a 25 mL Kelvin tube, N2 protected, 100 C Reaction for 12 h. Cool to room temperature and remove the solvent by rotary evaporation.The pure target compound was obtained by column chromatography (developing solvent: petroleum ether / ethyl acetate), yield: 97%
80%
With formic acid; C13H14ClIrN3(1+)*Cl(1-); In ethanol; water; at 95℃; for 2h;pH 2;
In a 25 ml test tube reaction flask, 1.0 mmol of 4-bromocinnamaldehyde, 0.001 mmol of bisazide chelate 1 (R1 is a hydrogen group, R2 is a hydrogen group), 5.0 mmol of formic acid,2 ml of water and ethanol (5:1 by volume) mixed solvent, adjust the pH of the solution to about 2.0,The reaction system was stirred at 95 C for 2.0 hours, the heating and stirring were stopped, and the mixture was cooled to room temperature. The reaction solution was extracted with ethyl acetate. The solvent was evaporated under reduced pressure, and then purified and purified by column chromatography to give the desired product. The column chromatography eluent was used as a petroleum ether: ethyl acetate mixed solvent in a volume ratio of 5:1. The yield is 80% and the semi-complete reduction is >99%.
With formic acid; bis(acetato)bis(triphenylphosphine)palladium(0); triethylamine; In acetonitrile; at 80℃; for 3h;Inert atmosphere;
General procedure: Under argon protection, cinnamaldehyde (1.36 g, 10.0 mmol) was allowed to react withexcessive amounts of the 4-iodophenol (4.40 g, 20.0 mmol), triethylamine (3.03 g, 30.0mmol) and formic acid (1.15 g, 25.0 mmol), and a catalytic amount ofbis(triphenylphosphine)palladium diacetate (37.5 mg, 0.05 mmol) in acetonitrile (4 mL)at 80 C with stirring for 3 h. The mixture was then diluted with CH2Cl2 (20 mL),washed with water, and the CH2Cl2 layer was dried (MgSO4), then concentrated underreduced pressure. The residue was subjected to column chromatography (CH2Cl2) toprovide 12 (1.09 g, 48 %) as an orange oil.
(R)-2-(4-bromophenyl)-1,2-dihydroquinoline-3-carbaldehyde[ No CAS ]
(S)-2-(4-bromophenyl)-1,2-dihydroquinoline-3-carbaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With pepsin from porcine gastric mucosa [EC 3.4.23.1]; water; In N,N-dimethyl-formamide; at 40℃; for 118h;Enzymatic reaction;
General procedure: To a mixture of 2-aminobenzaldehyde (0.30 mmol), alpha,beta-unsaturated aldehyde (0.26 mmol), pepsin (12.3 kU) and DMF (0.5 mL), deionized water (0.3 mL) was added. The resultant mixture was stirred for the specified time at 40 C, and monitored by TLC analysis. The reaction was terminated by filtering the enzyme. Ethyl acetate was employed to wash the residue on the filter paper to assure that products obtained were all dissolved in the filtrate. The filtrate was washed with saturated brine three times, and the combined organic layers were dried over anhydrous Na2SO4, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel using a mixture of petroleum ether and ethyl acetate ratio 3:1-20:1 as eluent.
With trifluoroacetic acid; sodium nitrite; In chloroform; at 0 - 20℃;
General procedure: Sodium nitrite, 0.69 g (0.01 mol), was added in portions over a period of 10-15 min to a mixture of 0.01 mol of arylcyclopropane 1a-1l, 5.2 g of trifluoroacetic acid, and 15 mL of chloroform, cooled to 0-5 C.The mixture was allowed to warm up to 20 C, kept for1 h at that temperature, and poured into 100 mL of cold water. The organic phase was separated, the aqueousphase was extracted with chloroform (2 × 10 mL), the extracts were combined with the organic phase,washed with water (2 × 30 mL), and dried over MgSO4, the solvent was removed, and the residue was analyzed by 1H NMR. Compound 2l was isolated by crystallization. The compositions of the reaction mixtures are given in Table 1. The physical constants and spectral characteristics of 2a [16], 2b [30], and 2l [28] coincided with published data.
ethyl 4-(4-bromophenyl)-1-phenyl-1,4-dihydropyridine-3-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
With copper(II) bis(trifluoromethanesulfonate); In toluene; at 70℃; for 6h;Schlenk technique; Inert atmosphere;
General procedure: 3. Typical Procedure for N-substituted 1, 4-dihydropyridines via three-component reaction Ethyl propiolate 3a (0.6 mmol, 60 muL), alpha-methyl cinnamaldehyde 1a (0.3 mmol, 42 S3 muL), aniline 2a (0.36 mmol, 33 muL), Cu(OTf)2 (0.015 mmol, 5.4 mg) and 2.0 mL toluene were added to a Schlenk tube in argon atmosphere. Then the mixture was stirred at 70 oC under argon atmosphere with TLC monitoring until the complete consumption of 1a. The reaction mixture was washed with brine, and then extracted with ethyl acetate three times. The organic layers were combined, dried over Na2SO4, and concentrated in vacuo, the residue was purified by triethylamine treated silica gel column chromatography to afford the desired product 4aaa (88.1 mg, 92% yield).
With 4-nitro-phenol; 1,8-diazabicyclo[5.4.0]undec-7-ene; In toluene; at 100℃; for 4h;Inert atmosphere;
General procedure: Aldehyde 16 (1.5 mmol), alcohol 17 (3.0 mmol), and 6 (20 mol %) were mixed in toluene (1 mL)in a reaction vial. The vial was flushed with N2. DBU (25 mol %) was then added slowly dropwiseinto the reaction vial and the reaction mixture, followed by the addition of 4-nitrophenol (100 mol %),the reaction mixture was then stirred at 100 C. The reaction was monitored by TLC and stirred for time indicated in Table 5. The mixture was then cooled to room temperature and the reaction wasquenched by a solution of HCl in 1,4-dioxane (4.0 M, 0.2 mL). Ethyl acetate (20 mL) was dropwise intothe vial to precipitate the polymeric catalyst. The precipitate was filtered and the filtrate was washedwith additional ethyl acetate (10 mL). The combined organic phase was concentrated under vaccumand purified by column chromatography (SiO2; hexanes: ethyl acetate). Characterization details foreach compound are shown below. See Supplementary Materials for NMR spectra.
ethyl 2-(4-bromophenyl)-1-cyano-3-formyl-4-vinylcyclopentane-1-carboxylate[ No CAS ]
ethyl 2-(4-bromophenyl)-1-cyano-3-formyl-4-vinylcyclopentane-1-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; tris-(dibenzylideneacetone)dipalladium(0); In ethyl acetate; at 20℃; for 16h;
General procedure: To a closed vial were added the secondary amine catalyst 2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine (I) (0.04 mmol, 0.2 equiv), vinylcyclopropane 1 (0.24 mmol, 1.2 equiv), enal 2 (0.2 mmol, 1equiv), Pd2(dba)3 (0.01 mmol, 0.05 equiv) and EtOAc (1 mL). The reaction was stirred at room temperature for 16 h. After completion, the mixture was concentrated in vacuo and purified by flash column chromatography (EtOAc/n-hexane) to afford the desired product 3.
With 18-crown-6 ether; sodium hydride; In tetrahydrofuran; at 20℃; for 2h;Inert atmosphere;
To a stirred solution of 4-bromobenzaldehyde (2000mg, 10.81mmol), 18-crown-6 (25mg) and (1,3-dioxolan-2-ylmethyl)-triphenylphosphoniumbromide (7000mg, 16.3mmol) in THF (90mL) under N2, NaH (1038mg, 86.5mmol) was added in one portion. After 2-h stirring at room temperature, the reaction mixture was quenched with water and extracted with EtOAc. After evaporation of EtOAc, the residue was dissolved in the mixture of THF (90mL) and 20% hydrochloric acid, and stirred for 2h at room temperature. After the mixture was turned basic with 2N NaOHaq and aqueous saturated solution of NaHCO3, the organic solvent was evaporated, and the mixture extracted with EtOAc. The combined EtOAc extracts were washed with brine and dried over Na2SO4.The solvent was removed, and the residue was purified by silica gel chromatography (EtOAc/hexane=17/83) to give 2 (1568mg, 68.8%). 1H NMR (400MHz, CDCl3) delta 9.71 (d, J=8.4Hz, 1H), 7.58 (d, J=7.6Hz, 2H), 7.44 (d, J=8.4Hz, 2H), 7.42 (d, J=16.0Hz, 1H), 6.71 (dd, J1=8.0Hz, J2=16.8Hz, 1H). MS (ESI) m/z 211 and 213 [MH+].
46.8%
4-Bromobenzaldehyde (925 mg, 5.00 mmol) and(1,3-dioxolan-2-ylmethyl) triphenylphosphonium bromide (4.29 g, 10.0 mmol)Was suspended in tetrahydrofuran (50.0 mL)Sodium hydride (480 mg, 20.0 mmol) and 18-crown-6 (20.0 mg) were added,And the mixture was stirred at room temperature for 2 hours.Sodium hydride (480 mg, 20.0 mmol) was further added,And the mixture was stirred at room temperature for 12 hours.Distilled water was added,After stopping the reaction,And extracted with ethyl ether (50 mL × 3).After distilling off the organic layer under reduced pressure,Was dissolved in tetrahydrofuran (50.0 mL)A 10% hydrochloric acid aqueous solution (20.0 mL) was added and the mixture was stirred at room temperature for 6 hours.The mixture was extracted with dichloromethane (100 mL × 2) and 1 mol / L sodium hydroxide aqueous solution,And washed with saturated brine.After dehydration with anhydrous magnesium sulfate,The solvent was distilled off under reduced pressure,The residue was subjected to silica gel column chromatography using ethyl acetate / hexane (1/1 (volume ratio)) as an elution solvent,Compound 1 was obtained in a yield of 491 mg (46.8%).
1.65 g (1.1 equivalents) of potassium t-butoxide was suspended in 50 mL of anhydrous THF at 0 C. (in ice) to obtain a suspension. This suspension was slowly added dropwise to a solution of 5.0 g (1.0 equivalent) of a Wittig reagent represented by Formula (5?) in 30 mL of anhydrous THF, to produce a reaction active species solution, The reaction active species solution was slowly added dropwise to a solution of 2.83 g (1.0 equivalent) of <strong>[49678-04-8]4-bromocinnamoyl aldehyde</strong> in 30 mL of anhydrous THF at 0 C. (in ice), stirred at 0 C. (in ice) for 30 minutes, and then heated to 40 C. to 50 C. to terminate reaction. Once the reaction was complete, concentrating of THF, extracting with a separatory funnel within water and ethyl acetate, and drying and concentrating an extracted organic layer were carried out to obtain a crude product using a conventional method. This crude product was recrystallized using a mixed solvent of methanol and ethyl acetate to obtain 5.76 g of a powder-form compound.The obtained powder-form compound was analyzed using LC-MS. As a result, the compound was identified as a butadiene-based intermediate (A?) represented by Formula (7?) with different halogen atoms substituted at specific sites, which had a calculated molecular weight of 461.14 and exhibited a peak of proton-added molecular ions [M+H]+ at 462.7 (Yield: 93.3%)
93.3%
With potassium tert-butylate; In tetrahydrofuran; at 0℃; for 0.5h;
(0220) 1.65 g (1.1 equivalents) of potassium t-butoxide was suspended in 50 mL of anhydrous THF at 0 C. (in ice) to obtain a suspension. This suspension was slowly added dropwise to a solution of 5.0 g (1.0 equivalent) of a Wittig reagent represented by Formula (5?) in 30 mL of anhydrous THF, to produce a reaction active species solution: (0221) The reaction active species solution was slowly added dropwise to a solution of 2.83 g (1.0 equivalent) of <strong>[49678-04-8]4-bromocinnamoyl aldehyde</strong> in 30 mL of anhydrous THF at 0 C. (in ice), stirred at 0 C. (in ice) for 30 minutes, and then heated to 40 C. to 50 C. to terminate reaction. Once the reaction was complete, concentrating of THF, extracting with a separatory funnel within water and ethyl acetate, and drying and concentrating an extracted organic layer were carried out to obtain a crude product using a conventional method. This crude product was recrystallized using a mixed solvent of methanol and ethyl acetate to obtain 5.76 g of a powder-form compound. (0222) The obtained powder-form compound was analyzed using LC-MS. As a result, the compound was identified as a butadiene-based intermediate (A?) represented by Formula (7?) with different halogen atoms substituted at specific sites, which had a calculated molecular weight of 461.14 and exhibited a peak of proton-added molecular ions [M+H]+ at 462.7 (Yield: 93.3%): (0223) As a result of the LC-MS analysis, it was found that the butadiene-based intermediate (A?) had a purity of 99.5%.
With pyridine; titanium tetrachloride; In tetrahydrofuran; tetrachloromethane; at 0 - 20℃;Inert atmosphere; Schlenk technique;
General procedure: alpha,beta-Unsaturated aldehyde (3.0 mmol) and malonate (3.0 mmol) were added into asolution of TiCl4 (6.0 mmol) in CCl4 (2.0 mL) and THF (10 mL) at 0 C, Then, pyridine (0.96 mL, 12.0 mmol) in THF (2 mL) was added dropwisely over 1 h. The resulting mixture was stirred at room temperature overnight. After quenched with water, the mixture was extracted with ethyl acetate, dried over Na2SO4, filtered and concentrated under vacuum. The residue was purified by silica gel chromatography with hexane/ethyl acetate = 20/1 to afford the product.
The reaction tube of 10mL, benzaldehyde were added sequentially 212mg (2mmol), VB190mg (0.3mmol), in 2mL acetonitrile as solvent, aqueous sodium hydroxide solution was added dropwise to adjust the pH to 9-10, and stirred at 60 , thin tracking, after the reaction reached equilibrium (about 1.5h), bromine was added directly cinnamaldehyde 147.7mg (0.7 mmol), diphenyl prolinol silyl ether 65mg (0.2mmol), benzoic acid 212mg (1.8mmol) of toluene and 2mL, heating the reaction was continued to 120 , thin tracking, after completion of the reaction, the reaction solvent was removed by rotary evaporation under reduced pressure - toluene and acetonitrile, the residue on silica gel, petroleum ether: ethyl acetate = 15: 1 as eluent to give the first step The crude product was 138mg (0.4mmol). The obtained reaction product was dissolved in 2mL of dichloromethane was added pyridinium chlorochromate 172mg (0.8mmol), the reaction mixture was stirred at 50 , until the end of the oxidation reaction was filtered, spin-dry the liquid part of the methylene chloride solvent, the residue was purified by silica gel column petroleum ether: ethyl acetate = 50: 1 as eluent the compound of formula Il.
ethyl 2-[(2S,3S,4S)-1-benzyl-2-(4-bromophenyl)-3-formylpiperidin-4-yl]acetate[ No CAS ]
ethyl 2-[(2R,3R,4R)-1-benzyl-2-(4-bromophenyl)-3-formylpiperidin-4-yl]acetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
General procedure: A mixture of alpha,beta-unsaturated aldehyde 2a (0.2 mmol), catalyst I (13.0 mg, 0.04 mmol, 20 mol%) and co-catalyst 4-nitrophenol (5.6 mg, 0.04 mmol, 20 mol%) in toluene (1 mL) was stirred at r.t. for 5 min. Then 5-aminopentenoate 1a (51 mg, 0.22 mmol) was added in one portion. After stirring for 24 h, the reaction mixture was concentrated and directly purified by silica gel column chromatography (PE/EtOAc, 20:1to 5:1) to afford the product 4a as a single diastereoisomer (64 mg, 77%).
(1R,2R,3R,5S)-3-(4-bromophenyl)-1-hydroxy-2-methyl-6-phenyl-8-oxa-6-azabicyclo[3,2,1]octan-7-one[ No CAS ]
3-(4-bromophenyl)-1-hydroxy-2-methyl-6-phenyl-8-oxa-6-azabicyclo[3,2,1]octan-7-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
79%
With (S)-2-(((tert-butyldimethylsilyl)oxy)diphenylmethyl)pyrrolidine; triethylamine; In toluene; at 0℃; for 48h;
2-carbonyl-N-phenylbutanamide (0.0354 g, 0.2 mmol), 4-bromocinnamaldehyde (0.0504 g,0.24mmol) and 0.5mL toluene, chiral secondary amine catalysts (VI) (0.017g, 0.04mmol) and triethylamine (0.004g, 0.04Mmol) at 0 C for 48 h, extracted with ethyl acetate (3 x 2 mL) and the solvent removed by distillation of the extract,The concentrate was separated by column chromatography using 200-300 mesh silica gel. The eluent was a 1: 3 mixture of ethyl acetate and petroleum ether, And the eluate containing the target compound was collected and concentrated to dryness to give the title compound (0.0613 g, yield 79%, Ee value 99%96%, dr value 3.7: 1)
(S)-methyl 4-(4-bromostyryl)-6-isopropyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
General procedure: The precatalysts trans-4,5-methano-L-proline 5 (3.18 mg,0.025 mmol, and 5 mol%), quinidine thiourea 6 (14.86 mg,0.025 mmol, and 5 mol%) and DCM (2.0 mL) were addedto a capped sample vial at room temperature. After themixture had been stirred for 10 min, a solution of aldehyde1 (0.5 mmol and 1.0 equiv.) and thiourea 2 (57 mg, 0.75mmol, and 1.5 equiv.) in DCM mL) were added and thestirring was continued for 3 h at room temperature. Then beta-dicarbonyl compound 3 (0.55 mmol and 1.1 equiv.) wasadded, the reaction mixture was stirred at 50 C for 15 h asmonitored by TLC. After the reaction was completed, themixture was purified through flash CC on a silica gel using(PE/EA = 4/1) as eluent to afford pure products.
92%
General procedure: The precatalysts trans-4,5-methano-L-proline 5a (3.18 mg,0.025 mmol, 5 mol %), quinidine thiourea 6a (14.86 mg,0.025 mmol, 5 mol %) and DCM (2.0 mL) were added to a capped sample vial at room temperature. After the mixture had been stirred for 10 min, a solution of aldehyde 1 (0.5 mmol, 1.0 equiv) and thiourea 2 (57 mg, 0.75 mmol, 1.5 equiv) in DCM (1.0 mL) wasadded and stirring was continued for 3 h at room temperature. Next, beta-dicarbonyl compound 3 (0.55 mmol, 1.1 equiv) was added, and the reaction mixture was stirred at 50 C for 15 h monitored byTLC. After the reaction was completed, the mixture was purified through flash column chromatography on a silica gel using (PE/EA = 4/1) as eluent to afford pure products.
92%
General procedure: The precatalysts trans-4,5-methano-l-proline 5a (3.18 mg, 0.025 mmol, 5 mol %), quinidine thiourea 6a (14.86 mg, 0.025 mmol, 5 mol %) and DCM (2.0 mL) were added to a capped sample vial at room temperature. After the mixture had been stirred for 10 min, a solution of aldehyde 1a (0.5 mmol, 1.0 equiv) and thiourea 2 (57 mg, 0.75 mmol, 1.5 equiv) in 111DCM (1.0 mL) was added and stirring was continued for 3 h at room temperature. Next, beta-dicarbonyl compound 3 (0.55 mmol, 1.1 equiv) was added, and the reaction mixture was stirred at 50 C for 15 h monitored by TLC. After the reaction was completed, the mixture was purified through flash column chromatography on a silica gel using (PE/EA = 4/1) as eluent to afford pure products 4a. Compounds 4b~4v were synthesized by similar methods (the purity of all compounds > 90%).
(S)-methyl 4-(4-bromostyryl)-6-(tert-butyl)-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
General procedure: The precatalysts trans-4,5-methano-L-proline 5 (3.18 mg,0.025 mmol, and 5 mol%), quinidine thiourea 6 (14.86 mg,0.025 mmol, and 5 mol%) and DCM (2.0 mL) were addedto a capped sample vial at room temperature. After themixture had been stirred for 10 min, a solution of aldehyde1 (0.5 mmol and 1.0 equiv.) and thiourea 2 (57 mg, 0.75mmol, and 1.5 equiv.) in DCM mL) were added and thestirring was continued for 3 h at room temperature. Then beta-dicarbonyl compound 3 (0.55 mmol and 1.1 equiv.) wasadded, the reaction mixture was stirred at 50 C for 15 h asmonitored by TLC. After the reaction was completed, themixture was purified through flash CC on a silica gel using(PE/EA = 4/1) as eluent to afford pure products.
92%
General procedure: The precatalysts trans-4,5-methano-L-proline 5a (3.18 mg,0.025 mmol, 5 mol %), quinidine thiourea 6a (14.86 mg,0.025 mmol, 5 mol %) and DCM (2.0 mL) were added to a capped sample vial at room temperature. After the mixture had been stirred for 10 min, a solution of aldehyde 1 (0.5 mmol, 1.0 equiv) and thiourea 2 (57 mg, 0.75 mmol, 1.5 equiv) in DCM (1.0 mL) wasadded and stirring was continued for 3 h at room temperature. Next, beta-dicarbonyl compound 3 (0.55 mmol, 1.1 equiv) was added, and the reaction mixture was stirred at 50 C for 15 h monitored byTLC. After the reaction was completed, the mixture was purified through flash column chromatography on a silica gel using (PE/EA = 4/1) as eluent to afford pure products.
92%
General procedure: The precatalysts trans-4,5-methano-l-proline 5a (3.18 mg, 0.025 mmol, 5 mol %), quinidine thiourea 6a (14.86 mg, 0.025 mmol, 5 mol %) and DCM (2.0 mL) were added to a capped sample vial at room temperature. After the mixture had been stirred for 10 min, a solution of aldehyde 1a (0.5 mmol, 1.0 equiv) and thiourea 2 (57 mg, 0.75 mmol, 1.5 equiv) in 111DCM (1.0 mL) was added and stirring was continued for 3 h at room temperature. Next, beta-dicarbonyl compound 3 (0.55 mmol, 1.1 equiv) was added, and the reaction mixture was stirred at 50 C for 15 h monitored by TLC. After the reaction was completed, the mixture was purified through flash column chromatography on a silica gel using (PE/EA = 4/1) as eluent to afford pure products 4a. Compounds 4b~4v were synthesized by similar methods (the purity of all compounds > 90%).
(S)-ethyl 4-(4-bromostyryl)-6-isopropyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
93%
General procedure: The precatalysts trans-4,5-methano-L-proline 5 (3.18 mg,0.025 mmol, and 5 mol%), quinidine thiourea 6 (14.86 mg,0.025 mmol, and 5 mol%) and DCM (2.0 mL) were addedto a capped sample vial at room temperature. After themixture had been stirred for 10 min, a solution of aldehyde1 (0.5 mmol and 1.0 equiv.) and thiourea 2 (57 mg, 0.75mmol, and 1.5 equiv.) in DCM mL) were added and thestirring was continued for 3 h at room temperature. Then beta-dicarbonyl compound 3 (0.55 mmol and 1.1 equiv.) wasadded, the reaction mixture was stirred at 50 C for 15 h asmonitored by TLC. After the reaction was completed, themixture was purified through flash CC on a silica gel using(PE/EA = 4/1) as eluent to afford pure products.
93%
General procedure: The precatalysts trans-4,5-methano-L-proline 5a (3.18 mg,0.025 mmol, 5 mol %), quinidine thiourea 6a (14.86 mg,0.025 mmol, 5 mol %) and DCM (2.0 mL) were added to a capped sample vial at room temperature. After the mixture had been stirred for 10 min, a solution of aldehyde 1 (0.5 mmol, 1.0 equiv) and thiourea 2 (57 mg, 0.75 mmol, 1.5 equiv) in DCM (1.0 mL) wasadded and stirring was continued for 3 h at room temperature. Next, beta-dicarbonyl compound 3 (0.55 mmol, 1.1 equiv) was added, and the reaction mixture was stirred at 50 C for 15 h monitored byTLC. After the reaction was completed, the mixture was purified through flash column chromatography on a silica gel using (PE/EA = 4/1) as eluent to afford pure products.
93%
General procedure: The precatalysts trans-4,5-methano-l-proline 5a (3.18 mg, 0.025 mmol, 5 mol %), quinidine thiourea 6a (14.86 mg, 0.025 mmol, 5 mol %) and DCM (2.0 mL) were added to a capped sample vial at room temperature. After the mixture had been stirred for 10 min, a solution of aldehyde 1a (0.5 mmol, 1.0 equiv) and thiourea 2 (57 mg, 0.75 mmol, 1.5 equiv) in 111DCM (1.0 mL) was added and stirring was continued for 3 h at room temperature. Next, beta-dicarbonyl compound 3 (0.55 mmol, 1.1 equiv) was added, and the reaction mixture was stirred at 50 C for 15 h monitored by TLC. After the reaction was completed, the mixture was purified through flash column chromatography on a silica gel using (PE/EA = 4/1) as eluent to afford pure products 4a. Compounds 4b~4v were synthesized by similar methods (the purity of all compounds > 90%).
General procedure: Catalyst 10 (22.8mg, 0.06mmol) was added at rt to a solution of the alpha,beta-unsaturated aldehyde (0.3mmol) in MeOH (1.0mL). The mixture was stirred for 10min at rt followed by the addition of H2O2 (30% in H2O, 92muL, 0.9mmol). The reaction was stirred for 48h under argon. After completion, the reaction was cooled to 0C (ice bath) followed by the addition of NaBH4 (45.6mg, 1.2mmol). The reaction mixture was then stirred for a further 30min at 0C, and quenched with a pH=7.0 phosphate buffer solution. The aqueous phase was extracted with CH2Cl2 (3×5mL) and the combined organic extracts were dried over anhydrous MgSO4 and concentrated in vacuo after filtration. The crude product was purified by column chromatography (silica gel; petroleum ether/AcOEt=8:1) to give target compounds 2a-h
ethyl (1R,2S,3S,5S)-2-(4-bromophenyl)-1'-methyl-2',7-dioxo-6-oxaspiro[bicyclo[3.2.0]heptane-3,3'-indoline]-5-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
With (5aS,10bR)-5a,10b-dihydro-2-(2,4,6-trimethylphenyl)-4H,6H-indeno[2,1-b]-1,2,4-triazolo[4,3-d]-1,4-oxazinium chloride; In 1,3,5-trimethyl-benzene; at 0℃; for 24h;Molecular sieve;
The reaction flask was successively added with nitrogen heterocyclic carbene(3.7 mg, 0.01 mmol) as a catalyst, and 1 g (31.3 mg, 0.15(12 mg, 0.1 mmol), 4A molecular sieve (10 mg), 0.5 mL of mesitylene was added and reacted at 0 C24 hours, the reaction system through a simple column chromatography (eluent for ethyl acetate: petroleum ether = 1: 10) to get the target product3 g (28.1 mg) as a white solid in 60% yield,> 99/1 dr, 90% ee.
(2S,4S)-4-(4-bromophenyl)-2-hydroxy-3,4,5,6-tetrahydrocyclopenta[b]pyran-7(2H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
82%
With (S)-2-(((tert-butyldimethylsilyl)oxy)diphenylmethyl)pyrrolidine; In dichloromethane; at 20℃;
General procedure: 2-Hydroxycyclopent-2-en-1-one (1, 23.5 mg, 0.24 mmol), aldehyde 2(25.2 muL, 0.2 mmol), and aminocatalyst 4e (7.3 mg, 0.02 mmol) weredissolved in CH2Cl2 (0.7 mL). The mixture was stirred at r.t. until completionof the reaction (TLC monitoring). The mixture was purified bycolumn chromatography (CH2Cl2/EtOAc 25:1) to yield the product.
(rac)-(2S,4S)-4-(4-bromophenyl)-2-hydroxy-3,4,5,6-tetrahydrocyclopenta[b]pyran-7(2H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With pyrrolidine; In dichloromethane; at 20℃;
General procedure: 2-Hydroxycyclopent-2-en-1-one (1, 23.5 mg, 0.24 mmol), aldehyde 2(25.2 muL, 0.2 mmol), and aminocatalyst 4e (7.3 mg, 0.02 mmol) weredissolved in CH2Cl2 (0.7 mL). The mixture was stirred at r.t. until completionof the reaction (TLC monitoring). The mixture was purified bycolumn chromatography (CH2Cl2/EtOAc 25:1) to yield the product.
40 mg of the substance (III) was added to a 100 ml round bottom flask,20 ml of hydrochloric acid and 1.8 g of tin powder were added and then reacted at 130 C for 8 h,After the consumption of tin powder, 36.22mg of cinnamaldehyde derivatives were added for 4h,And then extracted with ethyl acetate, the material was obtained by using a column of petroleum ether: ethyl acetate = 15: 1(VI) (2-styrylbenzothiazole derivative) in a yield of 13.4%.
With 18-crown-6 ether; sodium hydride; In tetrahydrofuran; at 20℃; for 2h;Inert atmosphere;
General procedure: To a stirred solution of 4-bromobenzaldehyde (2000mg, 10.81mmol), 18-crown-6 (25mg) and (1,3-dioxolan-2-ylmethyl)-triphenylphosphoniumbromide (7000mg, 16.3mmol) in THF (90mL) under N2, NaH (1038mg, 86.5mmol) was added in one portion. After 2-h stirring at room temperature, the reaction mixture was quenched with water and extracted with EtOAc. After evaporation of EtOAc, the residue was dissolved in the mixture of THF (90mL) and 20% hydrochloric acid, and stirred for 2h at room temperature. After the mixture was turned basic with 2N NaOHaq and aqueous saturated solution of NaHCO3, the organic solvent was evaporated, and the mixture extracted with EtOAc. The combined EtOAc extracts were washed with brine and dried over Na2SO4.The solvent was removed, and the residue was purified by silica gel chromatography (EtOAc/hexane=17/83) to give 2 (1568mg, 68.8%).
2-(4-bromophenethyl)quinazoline-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77%
With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In toluene; at 120℃; for 12h;Inert atmosphere;
Under nitrogen atmosphere, 2-aminobenzamide (136 mg, 1 mmol), [Cp*IrCl2]2 (8 mg, 0.01 mmol, 1 mol%), toluene (2.0 mL), p-bromocinnamaldehyde (211 mg, 1 mmol) were added in order.Into 25mL Schlenk reaction flask.The mixture was reacted at 120C for 12 hours and then cooled to room temperature.The solvent was removed in vacuo under reduced pressure and then purified by column chromatography (developer: ethyl acetate/petroleum ether) to give the pure target compound in a yield of 77%
2-(4-bromo-phenyl)-2<i>H</i>-chromene-3-carbaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
General procedure: To a stirred solution of (S)-N-((3-methylpyridin-2-yl)carbamothioyl) pyrrolidine-2-carboxamide (0.10 mmol), alpha,beta-unsaturated aldehyde (1.0 mmol) and 4 A MS (0.1 g) in CH2Cl2 (20 mL) were added and stirred at room temperature for 10 min. Next, O-nitrobenzoic acid (0.10 mmol) and the salicylaldehyde derivative (1.20 mmol) were added slowly over 10 min. The mixture was stirred for indicated time at room temperature. The corresponding 2-aryl-2H-chromenes-3-carbaldehyde was separated and purified by silica gel chromatography. The ee value of the product was determined by specific rotation and chiral HPLC analysis.
4-bromo-3-((2-oxo-2-phenylethyl)thio)-2H,3H-indol-2-one[ No CAS ]
6′-benzoyl-4-bromo-3′-(4-bromophenyl)-5′-hydroxy-3′,4′,5′,6′-tetrahydrospiro[indoline-3,2′-thiopyran]-2-one[ No CAS ]
6'-benzoyl-4-bromo-3'-(4-bromophenyl)-3',4'-dihydrospiro[indoline-3,2'- thiopyran]-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
25%
With pyrrolidine; acetic acid; In dichloromethane; at 20℃; for 72h;
General procedure: A solution of catalyst/additive pyrrolidine (20 mol%) and AcOH (20 mol%), substrate 1 (0.10 mmol) and alpha,beta unsaturated aldehyde 2 (0.12 mmol, 1.2 eq) in DCM (2.0 mL) was stirred at room temperature for 3d. After reaction, the solvent was evaporated and the crude product was purified using flash column chromatography (silica gel, DCM) to afford the product 3 and desired 4.
3-((2-oxo-2-phenylethyl)thio)indolin-2-one[ No CAS ]
6'-benzoyl-3'-(4-bromophenyl)-3',4'-dihydrospiro[indoline-3,2'-thiopyran] -2-one[ No CAS ]
C25H20BrNO3S[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
29%
With pyrrolidine; acetic acid; In dichloromethane; at 20℃; for 72h;
General procedure: A solution of catalyst/additive pyrrolidine (20 mol%) and AcOH (20 mol%), substrate 1 (0.10 mmol) and alpha,beta unsaturated aldehyde 2 (0.12 mmol, 1.2 eq) in DCM (2.0 mL) was stirred at room temperature for 3d. After reaction, the solvent was evaporated and the crude product was purified using flash column chromatography (silica gel, DCM) to afford the product 3 and desired 4.
4-bromo-3-((2-(4-methoxyphenyl)-2-oxoethyl)thio)indolin-2-one[ No CAS ]
C26H19Br2NO3S[ No CAS ]
C26H21Br2NO4S[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
21%
With pyrrolidine; acetic acid; In dichloromethane; at 20℃; for 72h;
General procedure: A solution of catalyst/additive pyrrolidine (20 mol%) and AcOH (20 mol%), substrate 1 (0.10 mmol) and alpha,beta unsaturated aldehyde 2 (0.12 mmol, 1.2 eq) in DCM (2.0 mL) was stirred at room temperature for 3d. After reaction, the solvent was evaporated and the crude product was purified using flash column chromatography (silica gel, DCM) to afford the product 3 and desired 4.
With tert.-butylhydroperoxide; Ru(2,4,13,15-tetraphenyl-1,5,12,16-tetraaza-tricyclo[14.2.2.06,11]eicosa-4,6(11),7,9,12-pentaene)Cl2; In acetonitrile; at 20℃; for 3h;Irradiation;
General procedure: To a solution of Zn(II)/Ru(II) complex (1.25mumol), methylstyrenes (0.5mmol) and TBHP (1.0mmol) in 10mL of acetonitrile was added at room temperature. After the reaction was stirred under visible light for three hours, (monitored the reaction by LC-MS) solvent was distilled under reduced pressure. Purification of crude products by column chromatography with hexane/dichloromethane (9:1, v/v) as eluent to an afforded pure product (Scheme 2).
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; 1,4-diaza-bicyclo[2.2.2]octane; In toluene; at 20℃; for 168h;
General procedure: Add bifunctional oxidized indole-chromone synthon 1a to the reaction tube in sequence(0.10 mmol),Cinnamaldehyde 2a (0.15 mmol), chiral diphenylprolinol silyl ether C3(20mol%, 0.02mmol) and 1.0mL toluene,After stirring the reaction at room temperature for 2 days, DABCO6H2O was added(20mol%, 0.02mmol),The reaction was continued for 5 days, and the basic reaction was detected by TLC. The sample was directly loaded and subjected to column chromatography.(Eluent: V (petroleum ether): V (ethyl acetate) = 4: 1)Purified to obtain compound 3a,White solid,
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; 1,4-diaza-bicyclo[2.2.2]octane; In toluene; at 20℃; for 168h;
General procedure: Add bifunctional oxidized indole-chromone synthon 1a to the reaction tube in sequence(0.10 mmol),Cinnamaldehyde 2a (0.15 mmol), chiral diphenylprolinol silyl ether C3(20mol%, 0.02mmol) and 1.0mL toluene,After stirring the reaction at room temperature for 2 days, DABCO6H2O was added(20mol%, 0.02mmol),The reaction was continued for 5 days, and the basic reaction was detected by TLC. The sample was directly loaded and subjected to column chromatography.(Eluent: V (petroleum ether): V (ethyl acetate) = 4: 1)Purified to obtain compound 3a,White solid,
With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; 1,4-diaza-bicyclo[2.2.2]octane; In toluene; at 20℃; for 168h;
General procedure: Add bifunctional oxidized indole-chromone synthon 1a to the reaction tube in sequence(0.10 mmol),Cinnamaldehyde 2a (0.15 mmol), chiral diphenylprolinol silyl ether C3(20mol%, 0.02mmol) and 1.0mL toluene,After stirring the reaction at room temperature for 2 days, DABCO6H2O was added(20mol%, 0.02mmol),The reaction was continued for 5 days, and the basic reaction was detected by TLC. The sample was directly loaded and subjected to column chromatography.(Eluent: V (petroleum ether): V (ethyl acetate) = 4: 1)Purified to obtain compound 3a,White solid,
With caesium carbonate; copper(ll) bromide; In 1,4-dioxane; water; at 100℃; for 0.25h;
In the first step, 105.5 mg (0.5 mmol) of p-bromocinnamaldehyde 1f, 139.7 mg (0.55 mmol) of pinacol diborate, 1.1 mg (0.005 mmol) of copper bromide, and 8.1 mg (0.025 mmol) of carbonic acid Cesium and 18.0 mg (1 mmol) of deionized water were added to 1.5 mL of dioxane and reacted at 100 C for 15 minutes. The reaction was followed by TLC, the reaction was completed, washed with water, extracted with ethyl acetate and dried over anhydrous MgSO4, and removed under reduced pressure. The solvent and the obtained crude product were separated by column chromatography to obtain a pure intermediate 2f with a yield of about 76%.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
