Generation of Heteroatom Stereocenters by Enantioselective C-H Functionalization

C-H functionalization has been established as an efficient way to generate molecular complexity. The formation of stereogenic carbon atoms by asymmetric C-H functionalization has seen tremendous progress over the past decade. More recently, the direct catalytic modification of C-H bonds has been powerfully applied to the formation of noncarbon stereogenic centers, which constitute a key design element of biologically active molecules and chiral ligands for asymmetric catalysis. This area was opened by a seminal report describing enantioselective C-H functionalization for the formation of a silicon stereocenter. It rapidly expanded with advances in the enantioselective formation of phosphorus(V) centers. Moreover, enantioselective routes to chiral sulfur atoms in the oxidation states IV (sulfoxides) and VI (sulfoximines) have been disclosed. Herein, we discuss methods of using selective functionalization of C-H bonds to generate a remote heteroatom stereogenic center via an inner-sphere C-H activation mechanism.