Expeditious diastereoselective synthesis of elaborated ketones via remote Csp(3)–H functionalization

The quest for selective C–H functionalization reactions, able to provide new strategic opportunities for the rapid assembly of molecular complexity, represents a major focus of the chemical community. Examples of non-directed, remote Csp(3)–H activation to forge complex carbon frameworks remain scarce due to the kinetic stability and thus intrinsic challenge associated to the chemo-, regio- and stereoselective functionalization of aliphatic C–H bonds. Here we describe a radical-mediated, directing-group-free regioselective 1,5-hydrogen transfer of unactivated Csp(3)–H bonds followed by a second Csp(2)–H functionalization to produce, with exquisite stereoselectivity, a variety of elaborated fused ketones. This study demonstrates that aliphatic acids can be strategically harnessed as 1,2-diradical synthons and that secondary aliphatic C–H bonds can be engaged in stereoselective C–C bond-forming reactions, highlighting the potential of this protocol for target-oriented natural product and pharmaceutical synthesis.