Expeditious diastereoselective synthesis of elaborated ketones via remote Csp3–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 C sp 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 C sp 3 –H bonds followed by a second C sp 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. C-H activation is a powerful method to form functionalised molecules, but is particularly challenging for unactivated sp 3 sites. Here the authors report a directing-group-free radical cascade process for converting vinyl azides and carboxylic acids to tetralone derivatives in high diastereoselectivity.