Bio-inspired iron-catalyzed oxidation of alkylarenes enables late-stage oxidation of complex methylarenes to arylaldehydes.

Abstract

It is a long-standing challenge to achieve efficient and highly selective aerobic oxidation of methylarenes to benzaldehydes, owing to overoxidation problem stemming from the oxidizability of benzaldehyde far higher than the toluene under usual aerobic conditions. Herein we report a bio-inspired iron-catalyzed polymethylhydrosiloxane-promoted aerobic oxidation of methylarenes to benzaldehydes with high yields and selectivities. Notably, this method can tolerate oxidation-labile and reactive boronic acid group, which is normally required to be transformed immediately after its introduction, and represents a significant advance in the area of the chemistry of organoboronic acids, including the ability to incorporate both aldehyde and ketone functionalities into unprotected arylboronic acids, a class that can be difficult to access by current means. The robustness of this protocol is demonstrated on the late-stage oxidation of complex bioactive molecules, including dehydroabietic acid, Gemfibrozil, Tocopherol nicotinate, a complex polyol structure, and structurally complex arylboronic acids.