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

摘要

Five-membered nitrogen-atom-containing heterocycles are structural components of many natural products and Pharmaceuticals; in addition, many of them—for example, enantiopure azolidine derivatives—have been employed as synthetic intermediates, auxiliaries, ligands, and catalysts for asymmetric synthesis. Consequently, there is a high demand for new methods for the efficient construction of optically active azolidine derivatives. As part of a program aimed at developing phosphine-mediated annulation reactions, we sought a novel route toward highly substituted and functionalized five-membered-ring nitrogen-atom-containing heterocycles. In light of recent reports on the phosphine-catalyzed conjugate additions of electron-deficient olefins and acetylenes with alcohols,5 herein we report a bisphosphine-catalyzed mixed double-Michael process6 that generates azolidines (2; eq 1). Use of amino-acid-derived pronucleophiles (1) as Michael donors and electron-deficient acetylenes as Michael acceptors provides efficient access to azolidines containing both diversity and asymmetry.