Lipase-mediated resolution of substituted 2-aryl-propanols: application to the enantioselective synthesis of phenolic sesquiterpenes

A comprehensive study of the lipase-mediated resolution of substituted 2-aryl-propanols is reported. The latter alcohols were submitted to the irreversible acetylation catalyzed either by PPL, CRL, or lipase PS. The enantioselectivity of these transformations was dependent on the type of lipase used. The type of substituents and particularly their position on the aromatic ring strongly affected the selectivity of the reaction. The experiments described prove that PPL is the more versatile lipase catalyzing the acetylation with an enantiomeric ratio (E) value that ranges from 1 up to 144, depending on the substrate used. Conversely, the same transformations were catalyzed by CRL and lipase PS with an enantiomeric ratio value, which is always less than 5. The remarkable behavior of PPL was exploited in the large scale resolution of some substituted 2-aryl-propanols whose enantiomeric forms are relevant building blocks in the enantioselective synthesis of phenolic sesquiterpenes. By these means, the synthesis of (S)-turmeronol B and the formal syntheses of (R)-curcumene, (R)-curcuphenol, (R)-xanthorrhizol, and (R)-curcuhydroquinone were accomplished.

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(S)-2-Phenylpropan-1-ol acetateC11H14O2Ee = 78%[α]D20=-1.4 (c 3.5, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(R)-2-Phenylpropan-1-olC9H12OEe = 66%[α]D20=+8.7 (c 3.2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(S)-2-(2-Methoxy-4-methyl-phenyl)-propan-1-ol acetateC13H18O3Ee = 99%[α]D20=+27.2 (c 2.5, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(R)-2-(2-Methoxy-4-methyl-phenyl)-propan-1-olC11H16O2Ee = 95%[α]D20=-2.8 (c 2.5, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(S)-2-(2,4-Dichloro-phenyl)-propan-1-ol acetateC11H12Cl2O2Ee = 83%[α]D20=+13.3 (c 3, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(R)-2-(2,4-Dichloro-phenyl)-propan-1-olC9H10Cl2OEe = 52%[α]D20=-1.4 (c 3, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(S)-2-(2-Bromo-phenyl)-propan-1-ol acetateC11H13BrO2Ee = 25%[α]D20=+8.6 (c 8, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(R)-2-(2-Bromo-phenyl)-propan-1-olC9H11BrOEe = 22%[α]D20=-2.5 (c 3.5, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(S)-2-(2-Iodo-phenyl)-propan-1-ol acetateC11H13IO2Ee = 26%[α]D20=+9.6 (c 3, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(R)-2-(2-Iodo-phenyl)-propan-1-olC9H11IOEe = 10%[α]D20=-1.8 (c 5, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(R)-2-(2-Nitro-phenyl)-propan-1-ol acetateC11H13NO4Ee = 49%[α]D20=-82.8 (c 6, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(S)-2-(2-Nitro-phenyl)-propan-1-olC9H11NO3Ee = 38%[α]D20=+2.1 (c 6, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(R)-2-(2-Methyl-phenyl)-propan-1-ol acetateC12H16O2Ee = 43%[α]D20=-9.2 (c 6, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(R)-2-(2-Methyl-phenyl)-propan-1-olC10H14OEe = 43%[α]D20=+2.4 (c 3, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(R)-2-(2-Ethyl-phenyl)-propan-1-ol acetateC13H18O2Ee = 54%[α]D20=-11.7 (c 3, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(S)-2-(2-Methyl-phenyl)-propan-1-olC11H16OEe = 18%[α]D20=-1.0 (c 4, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(S)-2-(4-Methoxy-phenyl)-propan-1-ol acetateC12H16O3Ee = 97%[α]D20=-9.5 (c 3, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(R)-2-(4-Methoxy-phenyl)-propan-1-olC10H14O2Ee = 89%[α]D20=+16.6 (c 3, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(S)-2-(4-Methyl-phenyl)-propan-1-ol acetateC12H16O2Ee = 98%[α]D20=-8.0 (c 3.5, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(R)-2-(4-Methyl-phenyl)-propan-1-olC10H14OEe = 96%[α]D20=+18.0 (c 3.5, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(S)-2-(3-Methoxy-4-methyl-phenyl)-propan-1-ol acetateC13H18O3Ee = 95%[α]D20=-4.6 (c 3.5, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(R)-2-(3-Methoxy-4-methyl-phenyl)-propan-1-olC11H16O2Ee = 96%[α]D20=+15.7 (c 3.5, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(S)-2-(2,5-Dimethoxy-4-methyl-phenyl)-propan-1-ol acetateC14H20O4Ee = 93%[α]D20=+4.2 (c 3, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(S)-2-(2,5-Dimethoxy-4-methyl-phenyl)-propan-1-olC12H18O3Ee = 99%[α]D20=-13.9 (c 2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(R)-3-(4-Methyl-phenyl)-butan-1-olC11H16O2Ee = 98%[α]D20=-32.1 (c 3, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (3R)

(R)-3-(2-Methoxy-4-methyl-phenyl)-butan-1-olC12H18O2Ee = 99%[α]D20=-22.9 (c 2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (3R)

(R)-3-(3-Methoxy-4-methyl-phenyl)-butan-1-olC12H18O2Ee = 95%[α]D20=-25.6 (c 3, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (3R)

(R)-3-(2,5-Dimethoxy-4-methyl-phenyl)-butan-1-olC13H20O3Ee = 99%[α]D20=-41.9 (c 2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (3R)

(S)-3-(2-Methoxy-4-methyl-phenyl)-butyric acidC12H16O3Ee >95%[α]D20=+16.6 (c 2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (3S)

(S)-4,7-Dimethyl-chroman-2-oneC11H12O2Ee >95%[α]D20=-16.9 (c 2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (4S)

(S)-6-(2-Hydroxy-4-methyl-phenyl)-2-methyl-hept-2-en-4-oneC15H20O2Ee >95%[α]D20=+80.5 (c 2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (6S)