Cyclic Alkenenitriles: Synthesis, Conjugate Addition, and Stereoselective Annulation

O-Alkylation of unsaturated silyl cyanohydrins with DMSO−Ac2O triggers a rearrangement to
methylthiomethyl-protected hydroxyalkenenitriles that are easily hydrolyzed for subsequent
annulations with ω-chloroalkyl Grignard reagents. Deprotonating the γ-hydroxyalkenenitriles with
t-BuMgCl followed by addition of ω-chloroalkyl Grignard reagents triggers a conjugate addition−alkylation sequence leading exclusively to cis-octalins, hydrindanes, and decalins. Stereoelectronic
control favors an axial conjugate addition leading to a particularly reactive conformer that rapidly
cyclizes to cis-fused bicyclic nitriles, whereas generating the ring-flipped conformer, through a
stepwise sequence, allows access to the diastereomeric trans-decalin. Collectively, the rearrangement−annulation sequence represents the first general annulation of alkenenitriles to assemble
diverse bicyclic nitriles with complete control over the two newly installed stereocenters.