Influence of the position of the substituent on the efficiency of lipase-mediated resolutions of 3-aryl alkanoic acids

Hydrolase-catalysed kinetic resolutions to provide enantioenriched α-substituted 3-aryl alkanoic acids are described. (S)-2-Methyl-3-phenylpropanoic acid (S)-1a was prepared in 96% ee by Pseudomonas fluorescens catalysed ester hydrolysis, while, Candida antarctica lipase B (immob) resolved the α-ethyl substituted 3-arylalkanoic acid (R)-1b in 82% ee. The influence of the position of the substituent relative to the ester site on the efficiency and enantioselectivity of the biotransformation is also explored; the same lipases were found to resolve both the α- and β-substituted alkanoic acids. Furthermore, the steric effect of substituents at the C2 stereogenic centre relative to that for their C3 substituted counterparts on the efficiency and stereoselectivity is discussed.

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(S)-2-Methyl-3-phenylpropanoic acidC10H12O296% ee[α]D20=+28.0 (c 0.82, CHCl3)Source of chirality: Lipase mediated hydrolysisAbsolute configuration: (S)

Ethyl (R)-2-methyl-3-phenylpropanoateC12H16O2>98% ee[α]D20=-36.4 (c 1.0, CHCl3)Source of chirality: Lipase mediated hydrolysisAbsolute configuration: (R)

(R)-2-Benzylbutanoic acidC11H14O282% ee[α]D20=-43.8 (c 1.0, CH2Cl2)Source of chirality: Lipase mediated hydrolysisAbsolute configuration: (R)

Ethyl (S)-2-benzylbutanoateC13H18O226% ee[α]D20=+6.8 (c 1.0, CH2Cl2)Source of chirality: Lipase mediated hydrolysisAbsolute configuration: (S)