Asymmetric Baeyer–Villiger Reactions Using Whole‐Cell Biocatalysts

Abstract

Many organic syntheses are very dependent on oxidation reactions, sometimes as a means of introducing asymmetry, but in all cases to increase the functionality of molecules. However, achieving effective large-scale oxidations in a synthetic scheme is not easy. In many cases hazardous oxidants are required. Indeed, the combination of high-energy oxidants together with flammable solvents (which are often required as a reaction medium for poorly water-soluble molecules) is a major safety concern for large-scale industrial production [1]. In addition,many oxidations are not particularly selective, leading to low yields and difficult product recovery problems. An alternative approach is to use oxygen as the oxidant, water as the solvent, and a biocatalyst to carry out the oxidation. Biocatalytic methods for the introduction of oxygen afford synthetic chemistry with safe and green methods of oxidation (via molecular oxygen or air) in addition to the possibility of regioor stereoselective conversions. This powerful combination means that they are an attractive step in many potential pharmaceutical synthetic schemes and also for the synthesis of some lower value compounds. Furthermore, the mild conditions of biological catalysis will protect existing functionality. A range of biocatalysts, including monoand dioxygenases, exist to introduce one or two oxygen atoms of the oxygen molecule in an asymmetric way [2]. One of the most useful groups of oxygen-introducing enzymes are the Baeyer–Villiger monooxygenases (BVMOs), which permit the introduction of oxygen into a linear or cyclic ketone to create an ester or a lactone, respectively, in an analogous way to the well-established chemical Baeyer–Villiger reaction. Heteroatom oxidations (such as sulfoxidation) can also be carried out using BVMOs. Today, around 30 different types of BVMOs have been identified, which can be used to carry out useful synthetic chemistry to introduce oxygen undermild and aqueous conditions. An increasing number of substrates have been shown to undergo biocatalytic asymmetric Baeyer–Villiger oxidationwith excellent enantioselectivity [3, 4]. BVMO biocatalysts are still themost advantageous catalysts for asymmetric Baeyer–Villiger