Metalated nitriles: stereodivergent cation-controlled cyclizations

Stereodivergent cyclizations of γ-hydroxy cyclohexanecarbonitriles are controlled simply through judicious choice of cation in the alkylmetal base. Deprotonating a series of cyclic γ-hydroxy nitriles with i-PrMgBr generates C-magnesiated nitriles that cyclize under stereoelectronic control to cis-fused hydrindanes, decalins, and bicyclo[5.4.0]undecanes. An analogous deprotonation with BuLi triggers cyclization to trans-fused hydrindanes, decalins, and bicyclo[5.4.0]undecanes consistent with a sterically controlled electrophilic attack on an equatorial nitrile anion. Using cations to control the geometry of metalated nitriles provides a versatile, stereodivergent cyclization to cis- and trans-hydrindanes, decalins, and [5.4.0]undecanes, and reveals the key geometric requirements for intramolecular SN2 and SN2′ displacements.