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
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.
