A Stereoselective Michael-Mannich Annelation Strategy for the Construction of Novel Tetrahydrocarbazoles

A novel annelation strategy has been devised for stereoselective synthesis of tetrahydrocarbazoles. The pathway features a regio- and stereocontrolled condensation of indole and its substituted derivatives with electron-deficient 1,3-dienes via a Michael-Mannich reaction sequence. An extension of this method to include cross-conjugated allenes as substrates also results in a Michael-Mannich-Michael cascade, incorporating 2 equiv of indole with increasing product complexity. The formal 4π + 2π cyclization describes a concise route to polycyclic alkaloids of this family.