Cyclization of zincated α-N-homoallylamino nitriles: a new entry to enantiopure 2,3-methanopyrrolidines.

Stereoselective cyclization of zincated α-N-homoallylamino nitriles has been developed. Following treatment with lithium diisopropylamide (LDA) and transmetalation with zinc bromide, α-N-(1-phenylethyl)-N-homoallylamino nitriles lead to 2,3-methanopyrrolidines in moderate to good yields (up to 66 %) and excellent selectivities (up to >98:2). With substrates derived from α-branched homoallylic amines, a stereospecific inversion of the homoallylic stereogenic center was observed. To account for this, a mechanistic rationale involving the formation of zincioiminium ions from zincated α-amino nitriles is put forward. 2,3-Methanopyrrolidines should then arise from a sequence involving an aza-Cope rearrangement providing a configurationally stable (2-azoniaallyl)zinc species that then undergoes a [3+2] cycloaddition reaction.