| 97% |
|
34 EXAMPLE 34 Enantioselective Reduction of Various Substrates
The procedure was the same as in Examples 1 to 9, the catalyst used being diethylzinc (1 mol %, based on the substrate) and N,N'-bis-(1-(R)-phenylethyl)-1,2-ethylene-(1 mol %), but the acetophenone was replaced by one of the prochiral ketones or dietones shown in Table V. In all cases, a greater proportion of the (S) enantiomer was obtained, with the ee between 65 and 80%. |
| 97% |
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; (R)-N-(3-methylpyridine-2-methyl)-7-bis-(3,5-di-tert-butylphenyl)phosphino-7′-amino-1,1′-spirodihydroindane; potassium <i>tert</i>-butylate; hydrogen In ethanol at 25 - 30℃; for 0.5h; Autoclave; optical yield given as %ee; enantioselective reaction; |
|
| 97% |
With (mer-[(S,S)-1,5-dimethyl-2,4-bis(4-phenyl-1,3-oxazolin-2-yl)benzene(1-)]Ru(CO)Cl)2(ZnCl2); hydrogen; sodium methylate; (-)-(S)-1-Anthracen-9-ylethanol In isopropyl alcohol at 40℃; for 24h; Inert atmosphere; Autoclave; optical yield given as %ee; enantioselective reaction; |
|
| 97% |
With sodium t-butanolate; <i>tert</i>-butyl alcohol; (S)-2,2',6,6'-tetramethoxy-4,4'-bis(di(3,5-xylyl)phosphino)-3,3'-bipyridine In toluene at 20℃; for 14h; enantioselective reaction; |
|
| 96% |
With sodium hydroxide; Boc-L-alanine(2S)-hydroxypropylamide In isopropyl alcohol at 20℃; for 1.5h; |
|
| 96% |
With formic acid; N-[(1S,2S)-1,2-diphenyl-2-(3-phenylpropylamino)ethyl]-4-methylbenzene sulfonamide ammonium chloride ruthenium; triethylamine In dichloromethane at 35℃; for 48h; Inert atmosphere; |
|
| 96% |
With succinylated alginate yeast cells In aq. phosphate buffer at 30 - 35℃; for 24h; Enzymatic reaction; enantioselective reaction; |
2.3 Synthesis of chiral alcohols using functionalized alginate immobilized yeast cells
General procedure: The fermentation medium, in a total volume of 1L, consists of 20gL-1 glucose, 20gL-1 peptone and 10gL-1 yeast extract, to this yeast cells were inoculated, followed by incubation at 28-30°C for 48h. After optimal growth, the medium was centrifuged to isolate fermented yeast cells, which were then washed with sterile distilled water. These fermented yeast cells were immobilized different alginate matrix i.e. a) Calcium alginate immobilized yeast beads and b) Succinyl modified alginate immobilized beads as described in our earlier studies [14]. The degree of succinylation was determined by the titration method as described by Wurzburg [15]. To the 4% sodium alginate/succinylated alginate solution, 2% (v/v) of fermented S.cerevisiae cells were added and the resultant cell suspension (107cfu/cm3) was extruded through a needle with diameter-0.5mm injector added as droplets into 2% calcium chloride solution under continuous stirring to get the calcium alginate/succinylated alginate-immobilized beads. Beads having a diameter in the range of 1.5-2.5mm were selected for subsequent fermentation experiments. Cell viability was determined by plate counts. The stability of yeast entrapped in the succinyl alginate matrix (beads) was measured as described in [14]. The binding efficiency of yeast cells in the alginate/functionalized alginate matrix has been confirmed by SEM studies (Fig. 1 ). To the above immobilized yeast cells (10gm in 250mL of phosphate buffer, pH 7.5), the pro-chiral ketones 1a-9a or azido ketones 10a-12a, (100mg/mL) each were added and incubated at 30-37°C. The progress of the reactions at different time intervals was monitored by TLC and HPLC. After optimal biotransformation of ketones to respective chiral alcohols the immobilized beads containing yeast cells were separated and reused up to 7 cycles without much loss enzyme activity. Thus collected reaction medium containing products was extracted with equal amounts of ethyl acetate and the products obtained were isolated and purified by column chromatography. The spectral data of all the chiral products synthesized has confirmed by literature [9,10,17-23]. Further the chiral azido alcohols 10b-12b obtained were subjected to hydrogenation by using Pd nanoparticles to obtain chiral amino alcohols. |
| 95% |
With C36H40Cl2N2P2Ru; potassium <i>tert</i>-butylate In dichloromethane; isopropyl alcohol at 23℃; for 2h; enantioselective reaction; |
|
| 93% |
Stage #1: methyl 2-naphthyl ketone With 1-((1R,2R)-2-(benzylamino)cyclohexyl)-3-(3,5-bis(trifluoromethyl)phenyl)thiourea; benzo[1,3,2]dioxaborole In toluene at -46℃; for 24h; Molecular sieve; Inert atmosphere;
Stage #2: With methanol; sodium hydroxide In toluene at -46 - 20℃; optical yield given as %ee; enantioselective reaction; |
|
| 92% |
Stage #1: methyl 2-naphthyl ketone With copper acetylacetonate; (S)-Xyl-P-Phos In toluene at -20℃; for 12h;
Stage #2: With sodium hydroxide In water; toluene for 3h; optical yield given as %ee; stereoselective reaction; |
|
| 92% |
With borane-THF In tetrahydrofuran; toluene at 25℃; for 12h; Inert atmosphere; enantioselective reaction; |
|
| 90% |
With diisopinocamphenylchloroborane In tetrahydrofuran at -25℃; for 7h; |
|
| 90% |
With C30H32ClN2O2RuS; hydrogen; potassium hydroxide In 2,2,2-trifluoroethanol at 40℃; for 24h; Autoclave; enantioselective reaction; |
|
| 89% |
With [(1S,2S)-N-(p-toluensulfonyl)-1,2-diphenylethanediamine](p-cymene)ruthenium (I); sodium formate In methanol; water at 50℃; for 12h; Green chemistry; enantioselective reaction; |
13 Example 13: (S)-1-(naphthalen-2-yl)ethanol
0.5 mmol of 1-(naphthalen-2-yl)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 carried out at 120 ° C for 12 hours until the reaction was completed, and sodium formate 2.5 mmol was added to the reaction system. 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-(naphthalen-2-yl)ethanol (76.5 mg),yield: 89%, ee value: 90%. HPLC separation conditions: chiral column competition AD-H column, mobile phase: n-hexane / isopropanol = 90:10 (volume ratio), flow rate: 1.0 ml / min, wavelength: 215 nm, temperature, 25 ° C, t1 = 30.37min, t2=43.52min; |
| 88% |
Stage #1: methyl 2-naphthyl ketone With C32H41CrN3O2Si; C7H14O4Si In toluene at -40 - 20℃; for 2h;
Stage #2: With potassium carbonate In methanol for 1h; enantioselective reaction; |
|
| 88% |
With hydrogenchloride In aq. buffer at 30℃; for 48h; Enzymatic reaction; |
General procedure for microbial bioreduction
General procedure: 50 mg of dry L. paracasei BD87E6 was transferred to a 250mL Erlenmeyer flask bearing100 ml MRS broth. The suspension was stirred on an orbital shaker at 30 C and150 rpm for 2 h. Then, the pH of the medium was adjusted to 5.5 with 1M HCl andafter 2 h, 1 mmol of substrate was added into the suspension and incubated for 48 h at30 C under agitation speed at 150 rpm. On completion of the reaction, the cell wasremoved by centrifugation and the liquid phase was saturated by sodium chloride, theaqueous phases were extracted with CH2Cl2. The organic phase was washed with saturatedNaCl and then dried with anhydrous Na2SO4. The solvent was removed; finalproduct was analyzed using NMR after it was purified by column chromatography. Theconversion of substrates was determined by HPLC analysis comparing the alcohol peakswith the ketone peak after filtering the crude products with a column containing a littlesilica gel. Configurations of products were assigned on the comparison of the rotationsign with literature data (supporting information). |
| 85% |
Stage #1: methyl 2-naphthyl ketone With copper (II)-fluoride; 1,2,4,5-tetra[(4'S)-isopropyloxazolin-2'-yl]benzene; diphenylsilane In dichloromethane at -5℃; for 16h; Air atmosphere;
Stage #2: With hydrogenchloride In methanol; dichloromethane; water optical yield given as %ee; enantioselective reaction; |
|
| 85% |
Stage #1: methyl 2-naphthyl ketone With chloro(1,5-cyclooctadiene)rhodium(I) dimer; (+)-3,4-dihydroxy-2,5-bis[4-(S)-benzyloxazolin-2-yl]furan In tetrahydrofuran at 20℃; for 1h; Inert atmosphere;
Stage #2: With diphenylsilane In tetrahydrofuran at -5℃; for 72h; Inert atmosphere;
Stage #3: With hydrogenchloride In tetrahydrofuran; methanol; water at 0℃; optical yield given as %ee; enantioselective reaction; |
|
| 83% |
Stage #1: methyl 2-naphthyl ketone With (1R,2R)-N,N’-bis(3,5-di-tert-butylbenzyl)-1,2-diphenylethane-1,2-diamine; diethoxymethylane; zinc diacetate In tetrahydrofuran at 25℃; for 24h; Inert atmosphere;
Stage #2: With hydrogenchloride; water In tetrahydrofuran for 1h; enantioselective reaction; |
|
| 82% |
With (S)-(-)-α,α-bis[3,5-bis(trifluoromethyl)phenyl]-2-pyrrolidinemethanol; Trimethyl borate; dimethylsulfide borane complex In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; |
|
| 81% |
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; C31H40N2O8S; sodium isopropylate; lithium chloride In tetrahydrofuran; isopropyl alcohol at 20℃; for 3h; Inert atmosphere; Schlenk technique; enantioselective reaction; |
|
| 79% |
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; formic acid; (αR,2S)-(-)-1-(2-diphenylphosphinobenzyl)-α-(2,2-dimethylpropynyl)-2-pyrrolidinemethanol; potassium carbonate at 25℃; for 6h; Inert atmosphere; Sealed tube; enantioselective reaction; |
|
| 70% |
With carbonyl reductase from Candida parapsilosis; formate dehydrogenase from Candida boidinii; triethanolamine buffer pH=7; NAD; heptakis(2,6-di-O-methyl)cyclomaltoheptaose; sodium formate; diothiothreitol for 336h; Ambient temperature; |
|
| 70% |
With Daucus carota root In water at 20℃; for 49h; |
|
| 70% |
In water at 37 - 40℃; for 49h; Enzymatic reaction; Aqueous phosphate buffer; |
1.9
The General Methodology for the Reduction of the Substituted Acetophenones; 100 mg of each of the compounds in Table 1 entry No. 1-10 and other similarly related compounds were added to a crude extract of 2 gm Daucas carota (protein 1 gm/ml) in 50 ml of 0.1 M sodium phosphate buffer pH 6.5 to 7.5. The reactions were incubated in a shaking incubator for 30 to 50 hours. The product formed was isolated and purified by flash chromatography and the product obtained was confirmed by standard spectral data. |
| 70% |
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; N-(tert-butoxycarbonyl)-L-valine-(6-amido-1-O-benzyl-6-deoxy-2,3-O-isopropylidene-α-D-mannofuranose); potassium <i>tert</i>-butylate; lithium chloride In tetrahydrofuran; isopropyl alcohol at 20℃; for 3h; enantioselective reaction; |
|
| 56% |
With dimethylsulfide borane complex; 5,5-dimethyl-2-pyrrolidinyl-diphenylphosphine oxide In toluene at 110℃; for 0.5h; |
|
| 41% |
With Rhodotorula glutinis 16740 In various solvent(s) |
|
|
(microbiological transformation); |
|
|
With 2,2'-iminobis[ethanol]; (-)-diisopinocamphenylborane chloride 1) THF, -25 deg C, 7 h; 2) ethyl ether, 2 h; Yield given. Multistep reaction; |
|
| 93 % Chromat. |
With potassium hydroxide; <RuCl2(mesitylene)>2 (1S,2S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine In isopropyl alcohol for 16h; Ambient temperature; |
|
|
With [(1S,2S)-N-(p-toluensulfonyl)-1,2-diphenylethanediamine](p-cymene)ruthenium (I); formic acid; triethylamine at 28℃; for 22h; Yield given; |
|
| 12 mg |
With Na-Pi buffer In acetone for 48h; tubers of Helianthus tuberosus presence, pH 5.9; other biologically active material: tubers of Solanum tuberosum cv. Saturna; |
|
|
With whole cells of Rhodococcus ruber DSM 44541; isopropyl alcohol In phosphate buffer at 24℃; for 22h; |
|
| 100 % Chromat. |
With roots of Daucus carota L In phosphate buffer; acetone for 48h; |
|
| 98 % Chromat. |
With ((S)-Xyl-SDP)Ru((R,R)DPEN)Cl2; potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 20℃; for 4h; |
|
|
With Zr[Ru((R)L1)(DPEN)Cl2]*4H2O; potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol for 20h; |
|
|
With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 20℃; for 2h; |
|
|
With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 20℃; for 20h; |
|
|
With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol for 24h; |
|
|
With borane Ν,Ν-diethylaniline complex; Trimethyl borate; chiral 2-(diphenylhydroxymethyl)pyrrolidine In toluene at 23℃; |
|
|
With sodium isopropylate; isopropyl alcohol; Boc-L-alanine(2S)-hydroxypropylamide at 20℃; for 1h; |
|
|
With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol; <i>tert</i>-butyl alcohol at 18 - 20℃; for 1h; |
|
|
With lyophilized cells of Rhodococcus ruber DSM 44541; isopropyl alcohol In phosphate buffer at 24℃; for 22h; |
|
|
With lyophilized cells of Rhodococcus ruber DSM 44541; isopropyl alcohol In phosphate buffer at 24℃; for 22h; |
|
|
Multi-step reaction with 2 steps
1: AgBF4 / (S)-[RhBr(nbd)(oxazolinyl-carbene)] / CH2Cl2 / 10 h / -60 °C
2: K2CO3 / methanol / 4 h / 20 °C |
|
| 92 % ee |
Stage #1: methyl 2-naphthyl ketone With phenylsilane In toluene at -20℃; for 24h;
Stage #2: With hydrogenchloride In water; toluene |
Reaction conditions: 100 mg-42 g substrate, substrate concentration = 0.6-1 M toluene, >99% conversion is observed in all cases. |
|
With [(R,RR)-Ru(2,2'-bis(di-3,5-xylylphosphino)-BINAP)(N-(3-(trihydroxysilyl)propyl)-1,2-cyclohexanediamine)Cl2]; potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 20℃; for 24h; Autoclave; optical yield given as %ee; |
|
|
With C55H69ClFeN2O2P2Ru; sodium isopropylate; isopropyl alcohol at 60℃; for 0.0833333h; Inert atmosphere; |
|
| 99 % ee |
With potassium <i>tert</i>-butylate; hydrogen In toluene; <i>tert</i>-butyl alcohol at 25 - 30℃; for 2h; Autoclave; |
24
Accurately weighed amounts of (S5,S)-9 (0.9 mg, 1 μmol), solid KO-^-C4H9 (6 mg, 0.05 mmol) and sometimes derivatives [eg. PPh3 (0.3 mg, 1 μmol)] were placed in a pre-oven-dried (120 0C) 350-mL autoclave containing a magnetic stirring bar, and placed under high vacuum for at least 20 min before purging with argon. Freshly distilled solvent (toluene, 2.7 mL; t-BuOH, 0.3 mL) and purified ketones (1 mmol, S/C = 1,000) were placed into a pre-dried Schlenk and degassed by 3 cycles of freeze-and-thaw and then added to the autoclave under an Ar atmosphere. H2 was introduced under 20 atm pressure with several quick release-fill cycles before being set to 8 atm. The solution was vigorously stirred at 25 0C and H2 consumption monitored. The H2 was carefully released after a period of time, the solution passed through a short pad of silica gel and solvent removed under reduced pressure. The crude product mixture was analyzed by 1H NMR to determine conversion and chiral GC or HPLC to determine ee of the chiral alcohol products. The hydrogenation results are given in Table 5. |
| 97.1 % ee |
With hydrogen In isopropyl alcohol for 20h; |
|
| 82.1 % ee |
With hydrogen In isopropyl alcohol for 20h; |
|
|
With C66H64Cl2N2OsP2; hydrogen; sodium ethanolate In ethanol at 60℃; for 0.3h; optical yield given as %ee; enantioselective reaction; |
|
|
With C50H54ClFeN2OsP2; potassium <i>tert</i>-butylate; hydrogen In methanol; ethanol at 40℃; for 0.5h; optical yield given as %ee; chemoselective reaction; |
|
|
With tris hydrochloride In water at 30℃; optical yield given as %ee; enantioselective reaction; |
|
| 91.8 % ee |
With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol; <i>tert</i>-butyl alcohol at 20℃; for 4.5h; Heating / reflux; |
11
Dichlorotris(triphenylphosphine)ruthenium(II) (14.4 mg; 0.015 mmol) and ligand 1a (7.9 mg; 0.018 mmol; 1.2 equiv based on Ru) were combined in a flask and purged with argon for 15 min. Argon-degassed isopropanol (3 mL) was added and the mixture was heated to reflux for 30 min and then cooled to ambient temperature to afford a rose-red 5.0 mM solution of the ruthenium complex of 1a. 2-Acetonaphthone (5c) (170 mg; 1.0 mmol) was added to a pressure vessel, a pressure head was attached, and the vessel was evacuated and filled with argon ten times. Argon-degassed isopropanol (3.0 mL) was added and the vessel was evacuated and filled with argon five times. 1.0 mL of the solution of the ruthenium complex of 1a (0.005 mmol; 0.005 equiv) was added, the vessel was evacuated and filled with argon five times, and the mixture was stirred for 5 min. A 1.0 M solution of potassium tert-butoxide in tert-butanol (50 uL; 0.05 mmol; 0.05 equiv) was added affording an immediate color change from pale red to orange, and the vessel was evacuated and filled with argon ten times, then with hydrogen five times and pressurized to 40 psig (2.72 barg) hydrogen. The vessel was sealed and stirred vigorously for 2 h, during which time slow hydrogen uptake was noted. The vessel was sampled and analyzed by chiral GC and HPLC to indicate 90.6% conversion and 92.8% ee for (S)-1-(2-naphthyl)ethanol (S-6c). The reaction was stopped after 4 h by evacuating and filling with argon five times and the solution was stripped to afford 164 mg, which analyzed at 92.1% conversion, 91.8% ee S-6c. 1H NMR (CDCl3) δ 7.84-7.81 (m, 4H); 7.51-7.46 (m, 3H); 5.067 (q, 1H, J=6.32 Hz); 1.579 (d, 3H, J=6.32 Hz). Chiral GC [Cyclosil-B (J&W Scientific), 165° C., hold for 15 min, 165 to 200° C. at 15° C./min, hold at 200° C. for 15 minutes]: tR=20.5 min (5d), tR=22.7 min (R-6d), tR=22.8 min (S-6d). |
|
With water; sodium acetate at 40℃; for 10h; optical yield given as %ee; enantioselective reaction; |
|
|
With potassium <i>tert</i>-butylate; hydrogen In isopropyl alcohol at 20℃; for 24h; Autoclave; optical yield given as %ee; enantioselective reaction; |
|
| 100 %Chromat. |
With RuCl2[(S,S)-diop][(S)-Me-bima]; potassium <i>tert</i>-butylate; hydrogen; triphenylphosphine In toluene; <i>tert</i>-butyl alcohol at 25℃; for 2h; Autoclave; optical yield given as %ee; enantioselective reaction; |
|
|
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; lithium chloride; sodium t-butanolate; Boc-L-alanine(2S)-hydroxypropylamide In tetrahydrofuran; ethanol; water at 40℃; for 4h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; |
General procedure for the ATH of aryl alkyl ketones
General procedure: To a 10 ml vial equipped with a septum and stirring bar, [Ru(p-cymene)Cl2)2 (0.0024 g, 0.004 mmol), ligand 1 (0.0028 g, 0.0088 mmol), and LiCl (0.0034 g, 0.08 mmol) were added. The vial was sealed and the atmosphere exchanged via 3 × vacuum/N2 cycles. The vial was placed in an oil bath at 40 °C and dry THF (0.8 ml), 99% EtOH (0.4 ml) and the substrate (0.8 mmol) were added. The mixture was allowed to stir for 20 min, after which NaOtBu (0.0046 g, 0.048 mmol) dissolved in 99% EtOH (0.4 ml) was added. Aliquots were removed and filtered through a small plug of silica before analysis on chiral GC. Solid substrates were added to the vial at the same time as the metal precursor and the ligand. |
|
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; sodium formate In water at 20℃; optical yield given as %ee; enantioselective reaction; |
|
|
With RuCl2(1,1'-bis(diphenyphosphino)ferrocene)[(1S,1'S)-6,6'-dibromo-1,1'-biisoindoline]; potassium <i>tert</i>-butylate; hydrogen In propan-1-ol at 20℃; for 12h; Inert atmosphere; Autoclave; optical yield given as %ee; enantioselective reaction; |
|
| 99 % ee |
With potassium <i>tert</i>-butylate; hydrogen; triphenylphosphine In toluene; <i>tert</i>-butyl alcohol at 25 - 30℃; for 2h; |
24
Accurately weighed amounts of (SS,S)-9 (0.9 mg, 1 μmol), solid KO-t-C4H9 (6 mg, 0.05 mmol) and sometimes derivatives [e.g. PPh3 (0.3 mg, 1 μmol)] were placed in a pre-oven-dried (120° C.) 350-mL autoclave containing a magnetic stirring bar, and placed under high vacuum for at least 20 min before purging with argon. Freshly distilled solvent (toluene, 2.7 mL; t-BuOH, 0.3 mL) and purified ketones (1 mmol, S/C=1,000) were placed into a pre-dried Schlenk and degassed by 3 cycles of freeze-and-thaw and then added to the autoclave under an Ar atmosphere. H2 was introduced under 20 atm pressure with several quick release-fill cycles before being set to 8 atm. The solution was vigorously stirred at 25° C. and H2 consumption monitored. The H2 was carefully released after a period of time, the solution passed through a short pad of silica gel and solvent removed under reduced pressure. The crude product mixture was analyzed by 1H NMR to determine conversion and chiral GC or HPLC to determine ee of the chiral alcohol products. The hydrogenation results are given in Table 5. TABLE 5 Screening of aromatic substrates using complex (SS,S)-9a Entry subPPh3b t/h Conv. % Ee % (S) 1 acetophenone 1 100 96 2 acetophenone 3eq 1 62 98 3 acetophenone 1eq 1 100 98 4 2-Me-acetophenone 13.5 87 90 5 2-Me-acetophenone 1eq 8.5 74 97 6 4-MeO-acetophenone 5 99 97 7 4-MeO-acetophenone 1eq 3 99 99.6 8 4-Br-acetophenone 15 100 93 9 4-Br-acetophenone 1eq 6 99 98 10 4-F-acetophenone 1eq 9.5 100 98 11 4-Me-acetophenone 1eq 12 99 98 12 3-Br-acetophenone 1eq 1.5 99 98 133,5-CF3-acetophenone 1eq 3 100 92 14 1eq 5 100 99 15 1eq 2 99 99 16 1eq 10 90 98 17 1eq 3 97 91 18c 1eq 8 99 99 aConditions: Substrate/Catalyst/Base = 1000/1/50; VT = 3 mL, 25-30° C.bCompared to catalyst;cThe H2 pressure was 20 atm and the configuration of the product was R. |
|
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; C27H42N2O8; sodium isopropylate; isopropyl alcohol; lithium chloride In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; |
|
|
With phenylsilane; copper diacetate; (S)-2,2',6,6'-tetramethoxy-4,4'-bis(di(3,5-xylyl)phosphino)-3,3'-bipyridine In toluene at -20℃; for 4h; stereoselective reaction; |
|
| 98 % ee |
With sodium formate In water at 40℃; for 4h; |
2.3 General procedure for asymmetric transfer hydrogenation
General procedure: For asymmetric transfer hydrogenation of ketones, the catalyst 5 (15.0 mg, 4.0 μmol of Ru based on the ICP analysis), HCO2Na (0.27 g, 10.0 mmol), ketone (0.40 mmol), and 2.0 mL of water were added in a 10 mL round bottom flask in turn. The mixture was allowed to react at 40 °C for 3.0-9.0 h. [For asymmetric transfer hydrogenation of quinolines, the catalyst 5 (15.0 mg, 4.0 μmol of Ru based on the ICP analysis), HCO2Na (0.27 g, 10.0 mmol), quinolines (0.40 mmol), and 2.0 mL (2.0 M HCOOH/HCOONa buffer solution, pH = 5.0) were added in a 10 mL round bottom flask in turn. The mixture was allowed to react at 40 °C for 10.0-24 h.] During that time, the reaction was monitored constantly by TLC. After completion of the reaction, the catalyst was separated via centrifuge (10,000 r/min) for the recycle experiment. The aqueous solution was extracted by Et2O (3 × 3.0 mL). The combined Et2O was washed with brine twice and dehydrated with Na2SO4. After the evaporation of Et2O, the residue was purified by silica gel flash column chromatography to afford the desired product. The conversion could be determined by an external standard method, and the ee value could be determined by chiral GC using a Supelco β-Dex 120 chiral column (30 m × 0.25 mm (i.d.), 0.25 μm film) or a HPLC analysis with a UV-Vis detector using a Daicel OJ-H/OD-H/OB-H chiralcel column (Φ 0.46 × 25 cm). |
| 92 % ee |
With RuCl2(PPh3)2{(1S,1’S)-1,1’-biisoindoline}; potassium <i>tert</i>-butylate; hydrogen; triphenylphosphine In isopropyl alcohol at 20℃; for 12h; Autoclave; enantioselective reaction; |
|
| 93 % ee |
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; C33H44N2O8S; sodium isopropylate; lithium chloride In tetrahydrofuran; isopropyl alcohol at 20℃; for 91h; Inert atmosphere; Schlenk technique; enantioselective reaction; |
|
| 91 % ee |
With [Ru-Cl(bis(2-diphenylphosphanylphenyl)methanone)((R,R)-DPEN)]Cl; potassium <i>tert</i>-butylate; hydrogen In ethanol at 25℃; for 6h; Autoclave; enantioselective reaction; |
|
| 96 % ee |
With triethylammonium formate In ethyl acetate at 40℃; for 10h; enantioselective reaction; |
|
|
Multi-step reaction with 2 steps
1: (1R,2R)-N,N’-bis(3,5-di-tert-butylbenzyl)-1,2-diphenylethane-1,2-diamine; zinc diacetate / neat (no solvent) / 6 h / 25 °C / Inert atmosphere; Sealed tube
2: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.08 h / 0 °C / Inert atmosphere |
|
| 90 % ee |
With C35H42ClFeNOP2; potassium <i>tert</i>-butylate; hydrogen In tetrahydrofuran at 50℃; for 1.5h; Autoclave; enantioselective reaction; |
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Multi-step reaction with 2 steps
1: <SUP>Ph</SUP>boxmi-MnCH<SUB>2</SUB>SiMe<SUB>3</SUB> / toluene / 2 h / -40 - 20 °C / Schlenk technique; Inert atmosphere; Glovebox
2: silica gel |
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| 94 % ee |
With trans-1,2-(1S,2S)-1,2-diaminocyclohexane-N,N’-bis(2’-diphenylphosphinobenzoyl); rhodium(III) chloride hydrate; hydrogen; sodium carbonate In methanol at 20℃; for 22h; Autoclave; enantioselective reaction; |
|
| > 99 % ee |
With halophilic alcohol dehydrogenase ADH2 from Haloferax volcanii; NADPH In ethanol; acetonitrile at 25℃; Enzymatic reaction; enantioselective reaction; |
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| 95 %Chromat. |
With C50H47Cl2N6O5PRuS2; potassium isopropoxide; isopropyl alcohol at 28℃; for 0.0833333h; Inert atmosphere; enantioselective reaction; |
|
| > 99 % ee |
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C49H67FeN2O2PS; hydrogen; lithium tert-butoxide In isopropyl alcohol at 25 - 30℃; for 12h; Autoclave; enantioselective reaction; |
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With dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran; toluene at -40℃; for 12h; |
|
| 90 % ee |
With hydrogen; C32H12BF24(1-)*C39H43IrN2P(1+) In isopropyl alcohol at 20℃; for 0.5h; enantioselective reaction; |
|
| 76.6 mg |
With sodium formate; C31H36N2O2RuS In methanol; water at 50℃; for 12h; Inert atmosphere; enantioselective reaction; |
3. General procedure for the one-pot synthesis of chiral alcohol
General procedure: The corresponding 1-phenylethanol (rac)-1 (0.5 mmol), and bis(methoxypropyl)ether (1.5 mmol, 243.3 mg) were put into a 10 mL of glass tube. The mixture was stirred at 120 °C for 12 h under oxygen balloon atmosphere. After the reaction was complete monitored by GC, removing the oxygen balloon and cooling down, (S,S)-2b (0.025 mmol, 16 mg), HCOONa (2.5 mmol, 170 mg) and 4 mL of MeOH/H2O (v/v = 3/1) were added. The mixture was degassed 3 times by nitrogen gas, and stirred at 50 °C for 12 h under nitrogen atmosphere. After the reaction was complete monitored by GC, 5.0 mL of H2O was added, the mixture was extracted with ethyl acetate (3 × 10 mL). The combined organic layer was dried over Na2SO4 and evaporated in vacuo. The residue was purified by silica gel column chromatography to give the corresponding chiral 1-phenylethanol (S)-1. |
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Multi-step reaction with 3 steps
1: sodium tetrahydroborate; methanol / 0.67 h / 0 - 20 °C / Inert atmosphere
2: (OC-6-23)-[2-[6-[(amino-κN)methyl]-2-pyridinyl-κN]-5-methylphenyl-κC][1,1'-(1,4-butanediyl)bis[1,1-diphenylphosphine-κP]]chlororuthenium(II); copper(l) chloride; sodium t-butanolate; (R,R)-1,2-bis(2,5-diphenylphospholanyl)ethane / toluene / 14 h / 20 °C / Glovebox; Inert atmosphere
3: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere |
|
| 98 % ee |
With formic acid; C31H36ClN2O3RuS; triethylamine at 50℃; for 5h; Schlenk technique; enantioselective reaction; |
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Multi-step reaction with 4 steps
1: (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole; borane-THF / tetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere
2: sodium hydride / mineral oil / 0 - 20 °C / Inert atmosphere
3: tricyclohexylphosphine; silver fluoride; nickel(II) bromide diethylene glycol dimethyl ether / tetrahydrofuran; toluene / 7 h / 0 °C / Inert atmosphere; Schlenk technique
4: boron trifluoride diethyl etherate / dichloromethane / 16 h / 20 °C / Inert atmosphere; Schlenk technique |
|
| 51 %Spectr. |
With phenylsilane In aq. buffer at 20℃; for 3h; Enzymatic reaction; enantioselective reaction; |
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Multi-step reaction with 2 steps
1: (S,E)-3-methyl-N-phenyl-2-((pyridin-2-ylmethylene)amino)butanamide-UiO-Fe metal-organic framework / tetrahydrofuran / 2 h / 25 °C / Inert atmosphere; Glovebox
2: potassium carbonate / methanol / 0.5 h / 25 °C / Inert atmosphere |
|
| 71 %Chromat. |
With hydrogen; C36H40MnNO2P2 In toluene at 80℃; for 6h; enantioselective reaction; |
|
| 92 % ee |
With sodium formate at 40℃; for 18h; enantioselective reaction; |
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Multi-step reaction with 2 steps
1: L-valinol-functionalized UiO-68 MOF with 71percent iron / tetrahydrofuran / 0.17 h / 25 °C / Green chemistry
2: potassium carbonate / formic acid |
|
| 98 % ee |
With tris(2,2'-bipyridyl)ruthenium dichloride; D-glucose; NAD; Bacillusa myloliquefaciens flavin-dependent nitroreductase BaNTR1 In dimethyl sulfoxide for 16h; Irradiation; Enzymatic reaction; enantioselective reaction; |
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