Cyclic Nitriles: Diastereoselective Alkylations

Diastereoselective alkylations of metalated conformationally locked 4-tert-butylcyclohexanecarbonitrile are highly diastereoselective with magnesium and copper counterions but only modestly
diastereoselective with lithium as the counterion. Selective generation of diverse metalated nitriles
is readily achieved through bromine−magnesium, −copper, and −lithium exchange reactions of
the corresponding bromonitrile or, for lithium, by deprotonating the parent nitrile with lithium
diethylamide. Collectively, high alkylation stereoselectivities correlate with the retentive alkylations
of C-metalated nitriles, whereas N-lithiated nitriles alkylate with modest selectivity, reflecting
minimal steric differences in the corresponding axial and equatorial electrophile trajectories.