Synfacts 2018; 14(01): 0083
DOI: 10.1055/s-0036-1592052
Organo- and Biocatalysis
© Georg Thieme Verlag Stuttgart · New York

Enzymatic Anti-Markovnikov Oxidations of Styrenes

Benjamin List
Grigory A. Shevchenko
Hammer SC. Kubik G. Watkins E. Huang S. Mingens H. Arnold FH. * California Institute of Technology, Pasadena, USA
Anti-Markovnikov Alkene Oxidation by Metal-Oxo-Mediated Enzyme Catalysis.

Science 2017;
358: 215-218
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15. Dezember 2017 (online)



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.



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.