Bisphosphine-Catalyzed Mixed Double-Michael Reactions:  Asymmetric Synthesis of Oxazolidines, Thiazolidines, and Pyrrolidines

Bisphosphine-catalyzed mixed double-Michael reactions have been developed to afford β-amino carbonyl derivatives of oxazolidines, thiozolidines, and pyrrolidines in excellent yields and with high diastereoselectivities. Efficient reactions between amino-acid-derived pronucleophiles, such as β-amino alcohols, β-amino thiols, and γ-amino diesters, as Michael donors and electron-deficient acetylenes, such as propiolates, acetylacetylene, and tosylacetylene, as Michael acceptors provided access to azolidines containing both diversity of substituents and asymmetry. This methodologythe first examples of mixed double-Michael reactions of acetylenesis operationally simple and involves mild conditions. Mechanistically, it constitutes a rare example of the anchimeric assistance of bisphosphines in organocatalysis.