(2S)-4-phenylbutan-2-ol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenyl ring-containing 2-butanone derivatives were reduced to the corresponding (S)-alcohols with excellent stereoselectivities and moderate to excellent yields (Table 4). 4-Phenyl-2-butanone (1a) was reduced stereoselectively to produce (S)-4-phenyl-2-butanol ((S)-1b) with excellent chemical and optical yields. The â-diketone 1-phenyl-1,3-butadione (2a) was reduced regio- and stereoselectively to furnish the monohydroxy ketone (S)-3-hydroxy-1-phenyl-1-butanone ((S)-2b) with excellent yield and ee, leaving the other keto group at C-1 intact. (E)-4-Phenyl-3-butene-2-one (3a) was reduced with moderate yield and excellent optical purity to produce the allylic alcohol (S)-4-phenyl-3-butene-2-ol ((S)-3b). The presence of the methoxy group at the para position of the phenyl ring in 4-(4-methoxyphenyl)-2-butanone (4a) affected the ee of the produced (S)-4-(4-methoxyphenyl)-2-butanol ((S)-4-b) (91% ee), which was lower than for (S)-1b. Phenoxy-2-propanone (5a) was reduced with very high yield and optical purity to produce the corresponding (S)-phenoxy-2-propanol ((S)-5b). When the R-chloroketone, 3-chloro-4-(4-chlorophenyl)-2-butanone (6a), was reduced with W110A TESADH, (+)-(2S,3R)-3-chloro-4-(4-chlorophenyl)-2-butanol ((+)-(2S,3R)-6b) was produced with high enantioselectivity (>99% ee) and diastereoselectivity (92:8 mixture of anti- and syn-R-chlorohydrins). moderate to excellent yields (Table 4)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenyl ring-containing 2-butanone derivatives were reduced to the corresponding (S)-alcohols with excellent stereoselectivities and moderate to excellent yields (Table 4). 4-Phenyl-2-butanone (1a) was reduced stereoselectively to produce (S)-4-phenyl-2-butanol ((S)-1b) with excellent chemical and optical yields. The â-diketone 1-phenyl-1,3-butadione (2a) was reduced regio- and stereoselectively to furnish the monohydroxy ketone (S)-3-hydroxy-1-phenyl-1-butanone ((S)-2b) with excellent yield and ee, leaving the other keto group at C-1 intact. (E)-4-Phenyl-3-butene-2-one (3a) was reduced with moderate yield and excellent optical purity to produce the allylic alcohol (S)-4-phenyl-3-butene-2-ol ((S)-3b). The presence of the methoxy group at the para position of the phenyl ring in 4-(4-methoxyphenyl)-2-butanone (4a) affected the ee of the produced (S)-4-(4-methoxyphenyl)-2-butanol ((S)-4-b) (91% ee), which was lower than for (S)-1b. Phenoxy-2-propanone (5a) was reduced with very high yield and optical purity to produce the corresponding (S)-phenoxy-2-propanol ((S)-5b). When the R-chloroketone, 3-chloro-4-(4-chlorophenyl)-2-butanone (6a), was reduced with W110A TESADH, (+)-(2S,3R)-3-chloro-4-(4-chlorophenyl)-2-butanol ((+)-(2S,3R)-6b) was produced with high enantioselectivity (>99% ee) and diastereoselectivity (92:8 mixture of anti- and syn-R-chlorohydrins). moderate to excellent yields (Table 4)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chemicals. The racemic (rac), (S)-, and (R)-forms of 1-phenyl-2-propanol, racemic 4-phenyl-2-butanol, NaIO4, Na2Cr2O7.2H2O, and isopropenyl acetate were purchased from Aldrich (St. Louis, Mo.). Benzylacetone was purchased from ACROS Organics (Morris Plains, N.J.). Candida Antarctica lipase immobilized on acrylic resin was purchased from Sigma (L4777). Phenylacetone Synthesis. Phenylacetone was synthesized from (rac)-1-phenyl-2-propanol as described Vondervoot et al., (2002) Synlett, 2:243-246, herein incorporated by reference, with a modification were the reaction was performed at room temperature instead of 4° C. as previously published. An exemplary yield was 33%. 1H NMR spectra were recorded on a Varian Mercury Plus 400 spectrometer at 400 MHz 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.7 (s, 2H), δ 2.2 (s, 3H). In brief, phenylacetone was synthesized from (rac)-1-phenyl-2-propanol as described Vondervoot et al., (2002) Synlett, 2:243-246, herein incorporated by reference), with a modification were the reaction was performed at room temperature instead of 4° C. as previously published. An exemplary yield was 33%. 1H NMR spectra were recorded on a Varian Mercury Plus 400 spectrometer at 400 MHz 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.7 (s, 2H), δ 2.2 (s, 3H). In brief, distilled water (25 ml), 70% aq HNO3 (0.080 g, 0.88 mmol), and Na2Cr2O7.2H2O (0.048 g, 0.16 mmol) were mixed in a 100 ml-flask equipped with a mechanical stirrer. NaIO4 (3.76 g, 17.6 mmol) was added at maximum speed of mechanical stirring. Subsequently, a solution of (rac)-1-phenyl-2-propanol (2.18 g, 16 mmol) in CHCl3 (25 ml) was added in one portion. The mixture was vigorously stirred for 24 h at room temperature. The organic layer was separated from the aqueous layer, which was subsequently extracted with CH2Cl2 (2×25 ml). The combined organic layer was dried over Na2SO4, and the solvent was evaporated under reduced pressure to produce oil. The residual oil was purified by chromatography on a silica gel column (ethyl acetate/n-hexane=1/8) to give pure phenylacetone. An exemplary phenylacetone yield was 33%. 1H NMR spectra were recorded on a Varian Mercury Plus 400 spectrometer at 400 MHz 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.7 (s, 2H), δ 2.2 (s, 3H). (S)-4-phenyl-2-butanol synthesis and kinetic resolution of 4-phenyl-2-butanol. (S)-4-Phenyl-2-butanol was produced from (rac)-4-phenyl-2-butanol by kinetic resolution as described (Choi et al., 2004), with the exception that the ruthenium catalyst and tert-butoxide were omitted. (S)-4-Phenyl-2-butanol and (R)-1-methyl-3-phenylpropyl acetate were produced in exemplary quantitative yields after a 5-day reaction at room temperature. In brief, racemic 4-phenyl-2-butanol (2.10 g, 14.0 mmol), isopropenyl acetate (2.10 g, 21.0 mmol), and lipase (42 mg) in toluene (50 ml) were mixed together in a 100-ml flask equipped with a mechanical stirrer. The reaction mixture was stirred at room temperature for 5 days. The reaction was monitored by GC to check the complete conversion of (R)-4-phenyl-2-butanol to the corresponding acetate. Capillary GC was performed on a Varian 3300 gas chromatograph with FI detection (Superco β-Dex 120 chiral column, 30m×0.250 mm id, 0.25 μm film thickness) programmed between 110° C. and 115° C. (1.5° C./min). The reaction mixture was filtered and concentrated at 50° C. under reduced pressure. The residue was chromatographed on a silica gel column (ethyl acetate/hexane=⅛) to give (S)-4-phenyl-2-butanol and (R)-1-methyl-3-phenylpropyl acetate in exemplary quantitative yields. (S)-4-Phenyl-2-butanol [α]D+13.5 (c=3.9, CHCl3) 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.8 (m, 1H), δ 2.8 (m, 2H), δ 1.80 (m, 3H), δ 1.3 (d, 3H). (R)-1-Methyl-3-phenylpropyl acetate 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 4.9 (m, 1H), δ 2.7 (m, 2H). δ 2.1 (s, 3H), δ 1.8 (m, 2H), δ 1.3 (d, 3H). Preparation of (R)-4-phenyl-2-butanol. (R)-4-phenyl-2-butanol was then produced from (R)-1-methyl-3-phenylpropyl acetate by saponification. In brief, (R)-4-phenyl-2-butanol was then produced from (R)-1-methyl-3-phenylpropyl acetate by saponification. In brief, (R)-1-Methyl-3-phenylpropyl acetate (1.00 g, 5.20 mmol) and NaOH (0.31 g, 7.8 mmol) were dissolved in methanol/water (1:1) (40 ml) in a 100-ml flask equipped with a mechanical stirrer. The reaction mixture was refluxed for 1.5 hours then extracted with CH2Cl2 (3×20 ml). The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure to produce (R)-4-phenyl-2-butanol. An exemplary yield was 90%. [α]D-14.9 (c=3.9, CHCl3) 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.8 (m, 1H), δ 2.7 (m, 2H). δ 1.8 (m, 2H), δ 1.6 (s, 1H), δ 1.3 (d, 3H). Modeling. Modeling was done manually in InsightII (Accelrys, San Diego, Calif.) on a Silicon Graphics Octane 2 computer. Protein structures were obtained at the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB) (Berman, et al., (2003) Nature Structural Biology 10 (12):980) website (www.pdb.org/; herein incorporated by reference). quantitative yields after a 5-day reaction at room temperature equipped with a mechanical stirrer programmed between 110° C. and 115° C. The reaction mixture was filtered concentrated at 50° C. under reduced pressure The residue was chromatographed on a silica gel column (ethyl acetate/hexane=⅛)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chemicals. The racemic (rac), (S)-, and (R)-forms of 1-phenyl-2-propanol, racemic 4-phenyl-2-butanol, NaIO4, Na2Cr2O7.2H2O, and isopropenyl acetate were purchased from Aldrich (St. Louis, Mo.). Benzylacetone was purchased from ACROS Organics (Morris Plains, N.J.). Candida Antarctica lipase immobilized on acrylic resin was purchased from Sigma (L4777). Phenylacetone Synthesis. Phenylacetone was synthesized from (rac)-1-phenyl-2-propanol as described Vondervoot et al., (2002) Synlett, 2:243-246, herein incorporated by reference, with a modification were the reaction was performed at room temperature instead of 4° C. as previously published. An exemplary yield was 33%. 1H NMR spectra were recorded on a Varian Mercury Plus 400 spectrometer at 400 MHz 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.7 (s, 2H), δ 2.2 (s, 3H). In brief, phenylacetone was synthesized from (rac)-1-phenyl-2-propanol as described Vondervoot et al., (2002) Synlett, 2:243-246, herein incorporated by reference), with a modification were the reaction was performed at room temperature instead of 4° C. as previously published. An exemplary yield was 33%. 1H NMR spectra were recorded on a Varian Mercury Plus 400 spectrometer at 400 MHz 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.7 (s, 2H), δ 2.2 (s, 3H). In brief, distilled water (25 ml), 70% aq HNO3 (0.080 g, 0.88 mmol), and Na2Cr2O7.2H2O (0.048 g, 0.16 mmol) were mixed in a 100 ml-flask equipped with a mechanical stirrer. NaIO4 (3.76 g, 17.6 mmol) was added at maximum speed of mechanical stirring. Subsequently, a solution of (rac)-1-phenyl-2-propanol (2.18 g, 16 mmol) in CHCl3 (25 ml) was added in one portion. The mixture was vigorously stirred for 24 h at room temperature. The organic layer was separated from the aqueous layer, which was subsequently extracted with CH2Cl2 (2×25 ml). The combined organic layer was dried over Na2SO4, and the solvent was evaporated under reduced pressure to produce oil. The residual oil was purified by chromatography on a silica gel column (ethyl acetate/n-hexane=1/8) to give pure phenylacetone. An exemplary phenylacetone yield was 33%. 1H NMR spectra were recorded on a Varian Mercury Plus 400 spectrometer at 400 MHz 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.7 (s, 2H), δ 2.2 (s, 3H). (S)-4-phenyl-2-butanol synthesis and kinetic resolution of 4-phenyl-2-butanol. (S)-4-Phenyl-2-butanol was produced from (rac)-4-phenyl-2-butanol by kinetic resolution as described (Choi et al., 2004), with the exception that the ruthenium catalyst and tert-butoxide were omitted. (S)-4-Phenyl-2-butanol and (R)-1-methyl-3-phenylpropyl acetate were produced in exemplary quantitative yields after a 5-day reaction at room temperature. In brief, racemic 4-phenyl-2-butanol (2.10 g, 14.0 mmol), isopropenyl acetate (2.10 g, 21.0 mmol), and lipase (42 mg) in toluene (50 ml) were mixed together in a 100-ml flask equipped with a mechanical stirrer. The reaction mixture was stirred at room temperature for 5 days. The reaction was monitored by GC to check the complete conversion of (R)-4-phenyl-2-butanol to the corresponding acetate. Capillary GC was performed on a Varian 3300 gas chromatograph with FI detection (Superco β-Dex 120 chiral column, 30m×0.250 mm id, 0.25 μm film thickness) programmed between 110° C. and 115° C. (1.5° C./min). The reaction mixture was filtered and concentrated at 50° C. under reduced pressure. The residue was chromatographed on a silica gel column (ethyl acetate/hexane=⅛) to give (S)-4-phenyl-2-butanol and (R)-1-methyl-3-phenylpropyl acetate in exemplary quantitative yields. (S)-4-Phenyl-2-butanol [α]D+13.5 (c=3.9, CHCl3) 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.8 (m, 1H), δ 2.8 (m, 2H), δ 1.80 (m, 3H), δ 1.3 (d, 3H). (R)-1-Methyl-3-phenylpropyl acetate 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 4.9 (m, 1H), δ 2.7 (m, 2H). δ 2.1 (s, 3H), δ 1.8 (m, 2H), δ 1.3 (d, 3H). Preparation of (R)-4-phenyl-2-butanol. (R)-4-phenyl-2-butanol was then produced from (R)-1-methyl-3-phenylpropyl acetate by saponification. In brief, (R)-4-phenyl-2-butanol was then produced from (R)-1-methyl-3-phenylpropyl acetate by saponification. In brief, (R)-1-Methyl-3-phenylpropyl acetate (1.00 g, 5.20 mmol) and NaOH (0.31 g, 7.8 mmol) were dissolved in methanol/water (1:1) (40 ml) in a 100-ml flask equipped with a mechanical stirrer. The reaction mixture was refluxed for 1.5 hours then extracted with CH2Cl2 (3×20 ml). The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure to produce (R)-4-phenyl-2-butanol. An exemplary yield was 90%. [α]D-14.9 (c=3.9, CHCl3) 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.8 (m, 1H), δ 2.7 (m, 2H). δ 1.8 (m, 2H), δ 1.6 (s, 1H), δ 1.3 (d, 3H). Modeling. Modeling was done manually in InsightII (Accelrys, San Diego, Calif.) on a Silicon Graphics Octane 2 computer. Protein structures were obtained at the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB) (Berman, et al., (2003) Nature Structural Biology 10 (12):980) website (www.pdb.org/; herein incorporated by reference). quantitative yields after a 5-day reaction at room temperature equipped with a mechanical stirrer programmed between 110° C. and 115° C. The reaction mixture was filtered concentrated at 50° C. under reduced pressure The residue was chromatographed on a silica gel column (ethyl acetate/hexane=⅛)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chemicals. The racemic (rac), (S)-, and (R)-forms of 1-phenyl-2-propanol, racemic 4-phenyl-2-butanol, NaIO4, Na2Cr2O7.2H2O, and isopropenyl acetate were purchased from Aldrich (St. Louis, Mo.). Benzylacetone was purchased from ACROS Organics (Morris Plains, N.J.). Candida Antarctica lipase immobilized on acrylic resin was purchased from Sigma (L4777). Phenylacetone Synthesis. Phenylacetone was synthesized from (rac)-1-phenyl-2-propanol as described Vondervoot et al., (2002) Synlett, 2:243-246, herein incorporated by reference, with a modification were the reaction was performed at room temperature instead of 4° C. as previously published. An exemplary yield was 33%. 1H NMR spectra were recorded on a Varian Mercury Plus 400 spectrometer at 400 MHz 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.7 (s, 2H), δ 2.2 (s, 3H). In brief, phenylacetone was synthesized from (rac)-1-phenyl-2-propanol as described Vondervoot et al., (2002) Synlett, 2:243-246, herein incorporated by reference), with a modification were the reaction was performed at room temperature instead of 4° C. as previously published. An exemplary yield was 33%. 1H NMR spectra were recorded on a Varian Mercury Plus 400 spectrometer at 400 MHz 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.7 (s, 2H), δ 2.2 (s, 3H). In brief, distilled water (25 ml), 70% aq HNO3 (0.080 g, 0.88 mmol), and Na2Cr2O7.2H2O (0.048 g, 0.16 mmol) were mixed in a 100 ml-flask equipped with a mechanical stirrer. NaIO4 (3.76 g, 17.6 mmol) was added at maximum speed of mechanical stirring. Subsequently, a solution of (rac)-1-phenyl-2-propanol (2.18 g, 16 mmol) in CHCl3 (25 ml) was added in one portion. The mixture was vigorously stirred for 24 h at room temperature. The organic layer was separated from the aqueous layer, which was subsequently extracted with CH2Cl2 (2×25 ml). The combined organic layer was dried over Na2SO4, and the solvent was evaporated under reduced pressure to produce oil. The residual oil was purified by chromatography on a silica gel column (ethyl acetate/n-hexane=1/8) to give pure phenylacetone. An exemplary phenylacetone yield was 33%. 1H NMR spectra were recorded on a Varian Mercury Plus 400 spectrometer at 400 MHz 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.7 (s, 2H), δ 2.2 (s, 3H). (S)-4-phenyl-2-butanol synthesis and kinetic resolution of 4-phenyl-2-butanol. (S)-4-Phenyl-2-butanol was produced from (rac)-4-phenyl-2-butanol by kinetic resolution as described (Choi et al., 2004), with the exception that the ruthenium catalyst and tert-butoxide were omitted. (S)-4-Phenyl-2-butanol and (R)-1-methyl-3-phenylpropyl acetate were produced in exemplary quantitative yields after a 5-day reaction at room temperature. In brief, racemic 4-phenyl-2-butanol (2.10 g, 14.0 mmol), isopropenyl acetate (2.10 g, 21.0 mmol), and lipase (42 mg) in toluene (50 ml) were mixed together in a 100-ml flask equipped with a mechanical stirrer. The reaction mixture was stirred at room temperature for 5 days. The reaction was monitored by GC to check the complete conversion of (R)-4-phenyl-2-butanol to the corresponding acetate. Capillary GC was performed on a Varian 3300 gas chromatograph with FI detection (Superco β-Dex 120 chiral column, 30m×0.250 mm id, 0.25 μm film thickness) programmed between 110° C. and 115° C. (1.5° C./min). The reaction mixture was filtered and concentrated at 50° C. under reduced pressure. The residue was chromatographed on a silica gel column (ethyl acetate/hexane=⅛) to give (S)-4-phenyl-2-butanol and (R)-1-methyl-3-phenylpropyl acetate in exemplary quantitative yields. (S)-4-Phenyl-2-butanol [α]D+13.5 (c=3.9, CHCl3) 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.8 (m, 1H), δ 2.8 (m, 2H), δ 1.80 (m, 3H), δ 1.3 (d, 3H). (R)-1-Methyl-3-phenylpropyl acetate 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 4.9 (m, 1H), δ 2.7 (m, 2H). δ 2.1 (s, 3H), δ 1.8 (m, 2H), δ 1.3 (d, 3H). Preparation of (R)-4-phenyl-2-butanol. (R)-4-phenyl-2-butanol was then produced from (R)-1-methyl-3-phenylpropyl acetate by saponification. In brief, (R)-4-phenyl-2-butanol was then produced from (R)-1-methyl-3-phenylpropyl acetate by saponification. In brief, (R)-1-Methyl-3-phenylpropyl acetate (1.00 g, 5.20 mmol) and NaOH (0.31 g, 7.8 mmol) were dissolved in methanol/water (1:1) (40 ml) in a 100-ml flask equipped with a mechanical stirrer. The reaction mixture was refluxed for 1.5 hours then extracted with CH2Cl2 (3×20 ml). The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure to produce (R)-4-phenyl-2-butanol. An exemplary yield was 90%. [α]D-14.9 (c=3.9, CHCl3) 1H NMR (CDCl3): δ 7.2-7.4 (m, 5H), δ 3.8 (m, 1H), δ 2.7 (m, 2H). δ 1.8 (m, 2H), δ 1.6 (s, 1H), δ 1.3 (d, 3H). Modeling. Modeling was done manually in InsightII (Accelrys, San Diego, Calif.) on a Silicon Graphics Octane 2 computer. Protein structures were obtained at the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB) (Berman, et al., (2003) Nature Structural Biology 10 (12):980) website (www.pdb.org/; herein incorporated by reference). quantitative yields after a 5-day reaction at room temperature equipped with a mechanical stirrer programmed between 110° C. and 115° C. The reaction mixture was filtered concentrated at 50° C. under reduced pressure The residue was chromatographed on a silica gel column (ethyl acetate/hexane=⅛)