Biocatalytic Conversion of Cyclic Ketones Bearing α-Quaternary Stereocenters into Lactones in an Enantioselective Radical Approach to Medium-Sized Carbocycles.

Cyclic ketones bearing α-quaternary stereocenters underwent efficient kinetic resolution using cyclohexanone monooxygenase (CHMO) from Acinetobacter calcoaceticus. Lactones possessing tetrasubstituted stereocenters were 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, enantiomerically enriched ketones from the resolution with an α-quaternary stereocenter were used in a SmI2 -mediated cyclization process to give cyclobutanol products (up to >99 % ee).