Asymmetric [5+3] formal cycloadditions with cyclic enones through cascade dienamine-dienamine catalysis

Abstract

A few aminocatalytic modes, such as iminium ions and different dienamines, have provided versatile tools for the functionalization of cyclic enones at various sites. Described here is a previously unreported cascade dienamine/dienamine catalytic pathway for β-substituted 2-cyclopentenones, and even 2-cyclohexenone. It involves domino α'-regioselective Michael addition and a γ-regioselective Mannich reaction with 3-vinyl-1,2-benzoisothiazole-1,1-dioxides to give fused or bridged architectures, which incorporate a spirocyclic skeleton, in excellent stereocontrol, thus furnishing unusual [5+3] formal cycloaddition reactions. Moreover, preliminary biological assays showed that some of the chiral products exhibited promising activity against some cancer cell lines, thus indicating that such skeletons might serve as leads in drug discovery.

Keywords: cancer; cycloaddition; organocatalysis; regioselectivity; synthetic metehods.