γ- and δ-Hydroxynitriles: diastereoselective electrophile-dependent alkylations

Deprotonating γ- and δ-hydroxynitriles with i-PrMgCl allows highly diastereoselective alkylations controlled by the asymmetry of the remote carbinol stereocenter. Mechanistic experiments are consistent with γ-hydroxynitriles alkylating via a chelated magnesiated nitrile whereas δ-hydroxynitriles favor alkylation from acyclic magnesiated nitriles. Collectively these alkylations; are the first electrophile-dependent alkylations of acyclic nitriles, exhibit a unique influence on the nature of the Grignard used for the deprotonation, and address the challenge of installing quaternary centers in conformationally mobile, acyclic nitriles.