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

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.