Metalated Nitriles: Internal 1,3‐Asymmetric Induction

Stereoselective alkylations of acyclic, metalated nitriles are intimately controlled by a remote stereocenter. Probing the optimal steric demand through alkylations with a series of substituted pentanenitriles reveal the fundamental requirements for 1,3‐asymmetric induction. Relaying these requirements into a predictive model suggests that the stereoselectivity arises from a preferential electrophilic attack on the more stable diamond lattice conformation of the metalated nitrile. Using this strategy a series of metalated alkanenitriles selectively intercept a diverse range of electrophiles in alkylations that efficiently install new quaternary centers. The metalated nitrile alkylations provide fundamental insight for remote stereoinduction and a solid foundation for further advances in stereoselective alkylations of flexible nucleophiles having a defined shape.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)