Asymmetric Carbene Insertion into Se‐S Bonds by Synergistic Rh(II)/Guanidine Catalysis Involving Chalcogen‐Bond Assistance

The efficient construction of chalcogen‐atom‐based chiral compounds remains a challenge, despite the importance of organoselenium and organosulfur compounds in life and materials science. Chalcogen atoms can form net attractive interactions called chalcogen bonds, but it is an undeveloped tool to assist asymmetric catalysis. Herein, we report an enantioselective insertion platform to install a stereogenic center bearing selanyl and thiocyano functional groups. Our method operates by synergistic catalysis by a chiral guanidine and an achiral dirhodium complex in a three‐component or four‐component reaction, through Se‐S bond insertion into carbene species, competing successfully with the spontaneous racemic process and showing high regioselectivity. As elucidated by spectroscopic experiments and computational studies, a unique mechanism involving chalcogen as well as hydrogen bonding was established to account for the enantiocontrol. The high stereoselectivity holds for a broad array of selanylthiocyanatopropanoates, which showed excellent anti‐inflammatory toward IL‐1β and low cytotoxicity.