Stereocomplementary Unspecific Peroxygenases for Asymmetric Anti-Markovnikov Wacker-Type Oxidation and Epoxidation of Styrenes

The Wacker reaction
gives access to carbonyls from olefins and
is traditionally relying on metals, mostly palladium. Here, unspecific
peroxygenases (UPOs) are spotlighted as palladium-free biocatalysts
for asymmetric anti-Markovnikov Wacker-type oxidation of styrenes,
moving them beyond their traditional role in C–H oxidation
and stereoselective epoxidation. Screening 53 wild-type UPOs for the
oxidation of styrene and derivatives revealed examples of high reaction
selectivity leading mostly to the epoxide with an epoxide selectivity
of up to >99%. For selected UPOs and styrene derivatives, aldehyde
formation was found with an aldehyde selectivity of up to 86%. Conversions
of up to 89% were reached (preferring epoxidation). Stereocomplementary
UPOs were identified for the epoxidation, giving access to the (R)- and (S)-epoxides with ee values of
up to 94%. Also, for the anti-Markovnikov Wacker-type oxidation of
α-methylstyrene, stereocomplementary enzymes were identified,
leading to an excess of either the (R)- or (S)-enantiomer of 2-phenylpropanal. Most interestingly, it
was found that the absolute configuration of the aldehyde formed does
not necessarily correlate with the absolute configuration of the epoxide;
thus, aldehyde and epoxide may have the same or the opposite absolute
configurations.