Metalated nitriles: Diastereoselective internal asymmetric induction

Metalated nitriles are exceptional nucleophiles for a diverse range of alkylation reactions. A survey of metalated nitrile crystallographic structures reveals several unusual features that help understand the reactivity of metalated nitriles. The range of geometries at the formally anionic carbon and the potential for metal co-ordination to the nitrile nitrogen or the adjacent carbon, imply facile loss of stereochemistry for metalated nitrile. Conversely this implies that an efficient means of stereoselectively alkylating metlated nitriles is through the alkylation of nitriles containing an appropriately positioned chiral center.; Stereoselective alkylations of acyclic nitriles are challenging. The difficulty lies partly in the inherent bonding of metalated nitriles which precludes direct attachment of a chiral auxiliary to the CN group and partly in the coordination mode. Exceptional levels of diastereoselectivity are observed in metalated nitriles containing vicinal methyl groups embedded in an alkyl chain containing a trisubstituted alkene or a benzene ring. Extensive alkylations with C and N-metalated nitriles implicate a reactive conformation in which one methyl group effectively projects over the plane of the metalated nitrile. Alkylations of these metalated nitriles are exceptionally stereoselective for diverse electrophiles and efficiently provides for a synthetically valuable method for installing hindered quaternary centers.