Cyclic alkenenitriles: Synthesis, conjugate addition, and stereoselective annulation

Article abstract of DOI:10.1021/jo0345291

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.