Bifunctional Iminophosphorane Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated |á,|?-Unsaturated Amides

The first metal-free catalytic intermolecular enantioselective sulfa-Michael addition to unactivated |á,|?- unsaturated amides is described. Consistently high enantiomeric excesses, and yields were obtained over a wide range of alkyl thiol pronucleophiles and electrophiles under mild reaction conditions, enabled by a novel squaramide-based bifunctional iminophosphorane (BIMP) catalyst. Low catalyst loadings (2 mol%) were achieved on a decagram scale, demonstrating the scalability of the reaction. Computational analysis revealed the origin of the high enantiofacial selectivity, corresponding transition states, and provided substantial evidence for specific non-covalent activation of the carbonyl group of the |á,|?-unsaturated amide by the catalyst.