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

• Published in: ACS catalysis Vol. 14; no. 17; pp. 13334 - 13342
• Main Authors: Swoboda, Alexander, Duhović, Zerina, Kroschel, Isabella E. E., Bürgler, Moritz, Ebner, Katharina, Glieder, Anton, Kroutil, Wolfgang
• Format: Journal Article
• Language: English
• Published: American Chemical Society 06.09.2024
• Subjects: Wacker oxidation; epoxidation; anti-Markovnikov oxidation; biocatalysis; unspecific peroxygenases
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.4c02169

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.