Enantioselective synthesis of tetra-substituted tetralines and tetrahydro-indolizines by NHC-catalyzed azolium-enolate cascade

NHC-catalyzed cascade reaction of enals with suitably substituted beta-(hetero)aryl enones allowing the enantioselective synthesis of tetra-substituted tetralines and tetrahydro indolizines is presented. The catalytically generated chiral alpha,beta-unsaturated acylazoliums from enals under oxidative conditions reacted in a Michael-Michael-lactonization sequence to form the tricyclic delta-lactone products bearing four contiguous stereocentres.

Automated summary

The NHC-catalyzed cascade reaction allows for the enantioselective synthesis of tetra-substituted tetralines and tetrahydro indolizines from enals and beta-(hetero)aryl enones. The catalytically generated chiral alpha,beta-unsaturated acylazoliums from enals under oxidative conditions reacted in a Michael-Michael-lactonization sequence to form tricyclic delta-lactone products with four contiguous stereocentres.