C-centered radical-initiated cyclization by directed C(sp3)–H oxidative functionalization

Abstract

The development of C(sp³)–H functionalization has been proved to be challenging and therefore is attracting constant attention. This provides an opportunity to obviate the requirement of a preexisting functional handle with high atom- and step-economy, which are often complementary to traditional methods. The C-centered radical strategy with considerable potential has been established as a powerful toolbox for chemists to construct molecules with comprehensive value from various organic functional groups via oxidation, avoiding the difficulty of removing or converting directing groups and the limitations of utilizing metals or harsh temperature. The selection of an oxidation system requires the cooperation of multiple parameters, which provides great freedom for the application of substrates and the optimization of conditions. Based on our long-term interest in radical oxidative cyclization, herein, we focus on C-centered radical-initiated cyclization strategies by directed C(sp³)–H oxidative functionalization since 2012. The typical routes are intramolecular and intermolecular cyclization, where intermolecular cyclization is further classified according to the type of addition to the unsaturated bonds of alkenes, acrylamides, alkynes, eneynes, isonitriles and C(sp) or C(sp²) bonds in other substrates. These studies not only pave the way to C(sp³)–H oxidative functionalization but also provide insight into the exploration of new reaction modes for radical chemistry.