Gamma-hydroxy-alpha,beta-alkenenitriles: chelation-controlled conjugate additions.

Temporarily anchoring Grignard and organolithium reagents to gamma-hydroxy-alpha,beta-alkenenitriles promotes efficient conjugate additions to what are otherwise recalcitrant Michael acceptors. Sequential deprotonation and addition of a modest excess of a second Grignard reagent allows effective conjugate delivery of alkyl groups to cyclic and acyclic alkenenitriles. Mechanistically, conjugate additions proceed through alkylmagnesium alkoxide complexes for all but the more substituted alkenenitriles that require alkyl transfers from the more reactive ate complexes. Synthetically, chelation-controlled conjugate additions rapidly, and stereoselectively, assemble substituted nitriles, installing up to two new stereocenters in a single synthetic operation.