Enzyme-catalyzed resolution of aromatic ring fused cyclic tertiary alcohols

An efficient chemoenzymatic route for the synthesis of optically active aromatic ring fused cyclic tertiary alcohols (S)-(−)-1-methyl-1,2,3,4-tetrahydronaphthalen-1-ol (−)-1b and (S)-(+)-1-methyl-2,3-dihydro-1H-inden-1-ol (+)-1a has been developed. Different lipases have been tested in the transesterification of these tertiary alcohols; CAL-A (Candida antarctica Lipase A) was found to be the best biocatalyst for 1b and CAL-A-CLEA (Lipase A, C. antarctica, cross-linked enzyme aggregate) for 1a, obtained with ee values of 20% and 45%, respectively, and the corresponding esters 2b and 2a with the ee values of 99% and 71%, respectively.

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(R)-(−)-1-Methyl-2,3-dihydro-1H-inden-1-yl acetateC12H14O2[α]D26=-5.0 (c 0.25, CHCl3)ee = 71%Source of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-(−)-1-Methyl-1,2,3,4-tetrahydronaphthalen-1-yl-acetateC13H16O2[α]D26=-14.3 (c 0.60, CHCl3)ee = 99%Source of chirality: enzymatic resolutionAbsolute configuration: (R)