Outcompeting hydrofunctionalization: Asymmetric remote substitution of alkynes | Science Advances

Propargylic substitution is a broadly studied basic reaction but requires a vicinal leaving group in the alkyne substrate. Here, we describe the first asymmetric remote substitution of alkynes bearing a linear alkyl-linked remote leaving group via synergistic Pd/amine catalysis. A set of modified diamine organocatalysts guarantees the high regio-, geometry- and enantioselectivity of the remote coupling between alkynes and aldehydes, during which conventionally more competitive hydrofunctionalization process is completely inhibited. Scale-up test and various derivatizations show the reliability and value of the protocol. Mechanistic studies suggest that the formation of crucial 1,3-diene intermediate from alkyne and a complex redox pathway of Pd metal are involved in the catalytic cycle.