Recognition of the remote chiral center in lipase-catalyzed kinetic resolution of [2-methyl-2-(2′-naphthyl)-1,3-benzodioxol-4-yl]methyl acetate, the precursor of 2-methyl-2-(2′-naphthyl)-1,3-benzodioxole-4-carboxylic acid (MNB carboxylic acid)

To access the enantiomers of 2-methyl-2-(2′-naphthyl)-1,3-benzodioxole-4-carboxylic acid (MNB carboxylic acid), lipase-catalyzed kinetic resolution of racemic [2-methyl-2-(2′-naphthyl)-1,3-benzodioxol-4-yl]methyl acetate was examined with Burkholderia cepacia lipase (Amano PS-IM) and Candida antarctica lipase B (Novozym 435) under transesterification conditions. Enantioselectivity of B. cepacia lipase (E = 72) was higher than that of C. antarctica lipase B (E = 1.7), and these lipases showed a reversal of enantiopreference in the recognition of a remote chiral center. The computational study showed that the tetrahedral intermediate complex of B. cepacia lipase with (R)-4a, the fast isomer, was more stable than that with (S)-4a, the slow isomer. The repetitive use of B. cepacia lipase and further chemical transformation provided both enantiomers [(R)-: 99.4% ee and (S)-: 99.4% ee] of MNB carboxylic acid as methyl esters.