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Cyclic Nitriles:  Diastereoselective Alkylations

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posted on 13.05.2005, 00:00 by Fraser F. Fleming, Subrahmanyam Gudipati, Zhiyu Zhang, Wang Liu, Omar W. Steward
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.