Cu(I)-Mediated [3+3] Cycloaddition Reaction Delivering Tricyclic Alkaloid Scaffolds

Significance

A new, extremely valuable method for the preparation of fused tricyclic alkaloid scaffolds is presented in this article. The desired tricyclic amino alcohols are synthesized in two steps via a novel CuBr×SMe₂-mediated formal [3+3] cycloaddition reaction between cyclic enamines and enones and a subsequent reduction of the resulting imine with NaBH₄. The addition proceeds with complete diastereoselectivity via a chair-like transition state which allows the simultaneous control of up to five stereocenters. An asymmetric organocatalytic variant is also proposed.