Biocatalytic conversion of cyclic ketones bearing α-quaternary stereocenters to lactones in an enantioselective radical approach to medium-sized carbocycles

Cyclic ketones bearing α-quaternary stereocenters undergo efficient kinetic resolution using cyclohexanone monooxygenase (CHMO) from Acinetobacter calcoaceticus. Lactones possessing tetrasubstituted stereocenters are obtained with high enantioselectivity (up to >99% ee) and complete chemoselectivity. Preparative scale biotransformations were exploited in conjunction with a SmI2-mediated cyclization process to access complex, enantiomerically enriched cycloheptan- and cycloctan-1,4-diols. In a parallel approach to structurally distinct products, enantioenriched ketones from the resolution bearing an α- all carbon quaternary stereocenter were used in a SmI2-mediated cyclization process to give cyclobutanol products (up to >99% ee).