Stereospecific Rhodium-Catalyzed Allylic Substitution with Alkenyl Cyanohydrin Pronucleophiles: Construction of Acyclic Quaternary Substituted α,β-Unsaturated Ketones

A highly regio- and stereospecific rhodium-catalyzed allylic alkylation of tertiary allylic carbonates with alkenyl cyanohydrin pronudeophiles is described. This protocol offers a fundamentally novel approach toward the synthesis of acyclic quaternary-substituted alpha,beta-unsaturated ketones and thereby provides a new cross-coupling strategy for target directed synthesis. A particularly attractive feature with this process is the ability to directly couple di-, tri- and tetrasubstituted alkenyl cyanohydrin pronucleophiles to prepare the corresponding alpha,beta-unsaturated ketone derivatives in a highly selective manner. Additionally, the chemoselective 1,4-reduction of the enone products provides rapid access to acyclic enantiomerically enriched alpha,alpha'-dialkyl-substituted ketones, which are challenging motifs to prepare using conventional enolate alkylation.