A Simple Access to γ‐ and ε‐Keto Arenes via Enzymatic Divergent C─H Bond Oxyfunctionalization

Abstract

Abstract Performing divergent C─H bond functionalization on molecules with multiple reaction sites is a significant challenge in organic chemistry. Biocatalytic oxyfunctionalization reactions of these compounds to the corresponding ketones/aldehydes are typically hindered by selectivity issues. To address these challenges, the catalytic performance of oxidoreductases is explored. The results show that combining the peroxygenase‐catalyzed propargylic C─H bond oxidation with the Old Yellow Enzyme‐catalyzed reduction of conjugated C─C triple bonds in one‐pot enables the regio‐ and chemoselective oxyfunctionalization of sp3 C─H bonds that are distant from benzylic sites. This enzymatic approach yielded a variety of γ‐keto arenes with diverse structural and electronic properties in yields of up to 99% and regioselectivity of 100%, which are difficult to achieve using other chemocatalysis and enzymes. By adjusting the C─C triple bond, the carbonyl group's position can be further tuned to yield ε‐keto arenes. This enzymatic approach can be combined with other biocatalysts to establish new synthetic pathways for accessing various challenging divergent C─H bond functionalization reactions.

Keywords

• biocatalysis
• cascades
• C─H bond oxyfunctionalization
• keto arenes
• peroxygenases