A bio-inspired synthesis of oxindoles by catalytic aerobic dual C–H functionalization of phenols

Abstract

Nitrogen-containing heterocycles are fundamentally important to the function of pharmaceuticals, agrochemicals and materials. Herein, we report a bio-inspired approach to the synthesis of oxindoles, which couples the energetic requirements of dehydrogenative C-N bond formation to the reduction of molecular oxygen (O₂). Our method is inspired by the biosynthesis of melanin pigments (melanogenesis), but diverges from the biosynthetic polymerization. Mechanistic analysis reveals the involvement of Cu^II-semiquinone radical intermediates, which enable dehydrogenative carbon-heteroatom bond formation that avoids a catechol/quinone redox couple. This mitagates the deleterious polarity reversal that results from phenolic dearomatization, and enables a high-yielding phenolic C-H functionalization under catalytic aerobic conditions. Our work highlights the broad synthetic utility and efficiency of forming C-N bonds <i>via</i> a catalytic aerobic dearomatization of phenols, which is currently an underdeveloped transformation.