Origins of Regio- and Enantiocontrol in Rhodium-Catalyzed Synthesis of Alkylidene Dihydrothiophenes from 1,2,3-Thiadiazoles and Allenes

With cumulated experimental and theoretical evidence, we herein disclose the origins of the regio-, enantio-, and geometric control in our previous Rh-catalyzed and ligand-controlled asymmetric synthesis of 2- and 3-alkylidene 2,3-dihydrothiophenes from 1,2,3-thiadiazoles and allenes. Control experiments reveal the key intermediates and identify the involvement of the dynamic kinetic resolution of allenes. Hammett analysis and density functional theory (DFT) calculations give migratory insertion as the rate-, enantio-, regio-, and Z/E-geometry-determining step. In detail, the C–H···π interaction controls the regio- and E-selectivities in the (4R,5R)-DIOP-enabled synthesis of 3-alkylidene 2,3-dihydrothiophenes, while the C–H···O interaction controls the regio- and Z-selectivities in the (R)-Cy-BINAP-enabled synthesis of 2-alkylidene 2,3-dihydrothiophenes. It is suggested that the enantiocontrol originates from the steric interactions within the confined chiral environment constructed by chiral ligands.