title: Cyclic alkenenitriles: synthesis, conjugate addition, and stereoselective annulation.
abstract: O-Alkylation of unsaturated silyl cyanohydrins with DMSO-Ac2O triggers a rearrangement to methylthiomethyl-protected hydroxyalkenenitriles that are easily hydrolyzed for subsequent annulations with omega-chloroalkyl Grignard reagents. Deprotonating the gamma-hydroxyalkenenitriles with t-BuMgCl followed by addition of omega-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.
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000478:Alkylation; D002614:Chelating Agents / Q000737:chemistry; D003500:Cyclization; D006844:Hydrocarbons, Cyclic / Q000138:chemical synthesis*; D008274:Magnesium / Q000737:chemistry; D009570:Nitriles / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D002614:Chelating Agents; D006844:Hydrocarbons, Cyclic; D009570:Nitriles; C430593:cyanohydrin; D008274:Magnesium