Stereoselective formal [3 + 3] cycloaddition approach to cis-1-azadecalins and synthesis of (-)-4a,8a-diepi-pumiliotoxin C. Evidence for the first highly stereoselective 6π-electron electrocyclic ring closures of 1-azatrienes

Evidence is described here to support that a highly stereoselective 6π-electron electrocyclic ring closure of 1-azatrienes is a key step in formal [3 + 3] cycloaddition or annulation reactions of chiral vinylogous amides with α,β-unsaturated iminium salts. This would represent the first highly stereoselective 6π-electron electrocyclic ring closure of 1-azatrienes. We have also unambiguously demonstrated that these specific ring closures are reversible, leading to the major diastereomer that is also thermodynamically more stable, and that a rotation preference likely also plays a role. A synthetic application is illustrated here to stereoselectively transform the resulting dihydropyridines to cis-1-azadecalins with unique anti relative stereochemistry at C2 and C2a, leading to synthesis of epi isomers of (−)-pumiliotoxin C.