Highly enantioselective dynamic kinetic resolution of alkyl aryl carbinols carrying a trimethylsilyl group with a highly active lipoprotein lipase preparation

The kinetic and dynamic kinetic resolution of alkyl aryl carbinols carrying a trimethylsilyl group with a highly active lipase preparation containing lipoprotein lipase, dextrin, and ionic surfactant 1 has been explored. It was found that all the trimethylsilyl-containing substrates were accepted by lipoprotein lipase–dextrin 1 (LPL–D1) with perfect enantioselectivity (E = >200). As a result, the dynamic kinetic resolution of these substrates with LPL–D1 in the presence of a Ru-based racemization catalyst provided single enantiomeric products (>99% ee) with good yields. Furthermore, the dynamic kinetic resolution products were readily desilylated or halodesilylated to yield enantiopure alkyl aryl carbinols. Thus a useful protocol for the highly enantioselective synthesis of alkyl aryl carbinols, particularly those carrying a long alkyl chain (C6–C10) has been established.

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(R)-1-(4-(Trimethylsilyl)phenyl)propyl acetateC14H22O2SiEe = >99%[α]D25 = +93.8 (c 0.8, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-(Trimethylsilyl)phenyl)propyl acetateC14H22O2SiEe = >99%[α]D25 = +93.8 (c 0.8, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-(Trimethylsilyl)phenyl)butyl acetateC15H24O2SiEe = >99%[α]D25 = +86.8 (c 0.7, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-(Trimethylsilyl)phenyl)pentyl acetateC16H26O2SiEe = >99%[α]D25 = +83.6 (c 0.75, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-(Trimethylsilyl)phenyl)heptyl acetateC18H30O2SiEe = >99%[α]D25 = +67.4 (c 1.2, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-(Trimethylsilyl)phenyl)nonyl acetateC20H34O2SiEe = >99%[α]D22 = +59.9 (c 1.5, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-(Trimethylsilyl)phenyl)undecyl acetateC22H38O2SiEe = >99%[α]D24 = +53.4 (c 0.7, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(3-(Trimethylsilyl)phenyl)ethyl acetateC13H20O2SiEe = >99%[α]D25 = +66.9 (c 0.65, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(3-(Trimethylsilyl)phenyl)propyl acetateC14H22O2SiEe = >99%[α]D25 = +73.5 (c 1.1, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(3-(Trimethylsilyl)phenyl)butyl acetateC15H24O2SiEe = >99%[α]D25 = +69.0 (c 0.8, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(3-(Trimethylsilyl)phenyl)pentyl acetateC16H26O2SiEe = 97%[α]D25 = +64.8 (c 1.0, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(3-(Trimethylsilyl)phenyl)heptyl acetateC18H30O2SiEe = >99%[α]D25 = +32.3 (c 1.0, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-Phenylheptan-1-olC13H20OEe = >99%[α]D25 = +31.8 (c 1.1, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-Phenylnonan-1-olC15H24OEe = >99%[α]D21 = +29.2 (c 0.55, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-Phenylundecan-1-olC17H28OEe = >99%[α]D23 = +23.7 (c 0.5, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-Chlorophenyl)heptan-1-olC13H19ClOEe = >99%[α]D25 = +26.1 (c 0.3, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-Chlorophenyl)nonan-1-olC15H23ClOEe = >99%[α]D22 = +23.9 (c 0.6, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-Chlorophenyl)undecan-1-olC17H27ClOEe = >99%[α]D21 = +20.5 (c 1.3, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-Bromophenyl)heptan-1-olC13H19BrOEe = >99%[α]D25 = +23.3 (c 0.6, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-Bromophenyl)nonan-1-olC15H23BrOEe = >99%[α]D25 = +20.5 (c 0.8, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)

(R)-1-(4-Bromophenyl)undecan-1-olC17H27BrOEe = >99%[α]D23 = +19.0 (c 1.0, CHCl3)Source of chirality: metalloenzymatic dynamic kinetic resolutionAbsolute configuration: (R)