Two Decades of Progress in the Asymmetric Intramolecular aza-Michael Reaction.

The asymmetric intramolecular aza-Michael reaction (IMAMR) is a very convenient strategy for the generation of heterocycles bearing nitrogen-substituted stereocenters. Due to the ubiquitous presence of these skeletons in natural products, the IMAMR has found widespread applications in the total synthesis of alkaloids and biologically relevant compounds. The development of asymmetric versions of the IMAMR are quite recent, most of them reported in this century. The fundamental advances in this field involve the use of organocatalysts. Chiral imidazolidinones, diaryl prolinol derivatives, Cinchone-derived primary amines and quaternary ammonium salts, and BINOL-derived phosphoric acids account for the success of those methodologies. Moreover, the use of N-sulfinyl imines with a dual role, as nitrogen nucleophiles and as chiral auxiliaries, appeared as a versatile mode of performing the asymmetric IMAMR.