Enzymatic Anti-Markovnikov Oxidations of Styrenes

Key words

anti-Markovnikov - monooxygenase - alkenes - oxidation - styrenes - homobenzylic alcohols

Significance

The Arnold group reports an ­enzyme-catalyzed anti-Markovnikov oxidation of styrenes for the synthesis of homobenzylic alcohols with molecular oxygen as the oxidant. Several mutations of an iron-heme-dependent cytochrome P450 monooxygenase from the rhodobacterium Labrenzia aggregata were necessary to obtain a highly selective alkene anti-Markovnikov oxygenase (aMOx) that is also compatible with α- and β-substituted styrenes. Furthermore, synthetically useful scale-up experiments using 0.05 mol% aMOx resulted in high yields. Control experiments suggest that the reaction occurs through an anti-Markovnikov oxo transfer followed by 1,2-hydride shift and that it competes with the commonly observed epoxidation.

Comment

Anti-Markovnikov oxidations of alkenes are a great synthetic challenge because the corresponding epoxide formation is highly kinetically favored. However, due to their intrinsic properties, enzymes can be evolved toward new reaction pathways. The obtained products are highly valuable and, because combination with other enzymes is possible, further synthetic applications of this system can be envisioned.