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

Abstract

AbstractBaeyer–Villiger monooxygenases (BVMOs) are enzymes that are known to catalyse the Baeyer–Villiger oxidation of ketones in aqueous media using O2 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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)