Enantioselective synthesis of 4,5,6,7-tetrahydro-4-oxo-benzofuran-5-yl acetate and 1-benzyl-4,5,6,7-tetrahydro-4-oxo-1(H)-indol-5-yl acetate using chemoenzymatic methods

Abstract

The chemoenzymatic synthesis of both of the enantiomers of pharmacologically interesting compounds such as 4,5,6,7-tetrahydro-4-oxo-benzofuran-5-yl acetate ( 2a), 4,5,6,7-tetrahydro-4-oxo-6,6-dimethylbenzofuran-5-yl acetate ( 2b), and their hydroxy derivatives 3a, 3b, 1-benzyl-4,5,6,7-tetrahydro-4-oxo-1(H)-indol-5-yl acetate ( 5), starting from 6,7-dihydrobenzofuran-4(5H)-one ( 1a), 6,7-dihydro-6,6-dimethylbenzofuran-4(5H)-one ( 1b), and 1-benzyl-6,7-dihydro-1H-indol-4(5H)-one ( 4) are reported. Manganese(III) acetate-mediated acetoxylation followed by the enzyme-mediated kinetic resolution of α′-acetoxy enone provides acetoxy and hydroxy derivatives in good yields and high enantiomeric excesses.