Enzymatic Baeyer-Villiger Oxidation of Benzo-Fused Ketones: Formation of Regiocomplementary Lactones

Baeyer-Villiger monooxygenases (BVMOs) are enzymes that are known to catalyse the Baeyer-Villiger oxidation of ketones in aqueous media using O-2 as oxidant. Herein, we describe the oxidation of a set of diverse benzo-fused ketones by three different BVMOs in both aqueous and non-conventional reaction media. Most of the tested ketones, for example, 1-tetralone and 1- and 2-indanone, were converted by one of the employed biocatalysts. The catalytic efficiency could be improved by performing the oxidation reactions at a relatively high pH and by adding organic cosolvents. One striking observation is that absolute and complementary regioselectivities were obtained when oxidizing a range of 1-indanones using two different BVMOs. The conversion of 1-indanone by 4-hydroxyacetophenone monooxygenase (HAPMO) results in the formation of the expected lactone, 3,4-dihydrocoumarin. In contrast, by using a phenylacetone monooxygenase mutein (M-PAMO), conversion of 1-indanone leads to the formation of only the unexpected lactone, 1-isochromanone. This illustrates that by the appropriate choice of BVMO as biocatalyst, the effective and regioselective conversion of a wide range of benzo-fused ketones is feasible. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)