Asymmetric Organocatalytic Thio-Diels–Alder Reactions via Trienamine Catalysis

We report a new process to access highly enantioenriched sulfur-based heterocycles by an asymmetric catalytic thio-Diels–Alder reaction. Thiocarbonyls are challenging heterodienophiles in enantioselective Diels–Alder reactions, due to their inherent high reactivity and their poor ability to coordinate to chiral catalysts. We successfully circumvented these problems by employing a different strategy, which explores the use of in situ generated catalyst-bound dienes. Synthetically useful dihydrothiopyrans as well as other bi- and tricyclic sulfur-containing heterocycles are formed in high yields and high to excellent selectivities. DFT calculations were performed to examine the mechanism of the developed reaction. Furthermore, a series of synthetic transformations of the optically active sulfur-based heterocycles are presented.