C−S‐Selective Stille‐Coupling Enables Stereodefined Alkene Synthesis

Abstract A palladium‐catalyzed highly C−S‐selective Stille cross‐coupling between aryl thianthrenium salts and tri‐ or tetrasubstituted alkenyl stannanes is described. Herein, critical challenges including site‐ and chemoselectivity control are well addressed through C−H thianthrenation and C−S alkenylation, thereby providing an expedient access to stereodefined tri‐ and tetrasubstituted alkenes in a stereoretentive fashion. Indeed, the palladium‐catalyzed Stille‐alkenylation of poly( pseudo )halogenated arenes displays privileged capability to differentiate C−S over C−I, C−Br, C−Cl bonds, as well as oxygen‐based triflates (C−OTf), tosylates (C−OTs), carbamates and sulfamates under mild reaction conditions. Sequential and multiple cross‐couplings via selective C−X functionalization should be widely applicable for increasing functional molecular complexity. Modular installation of stereospecific alkene motifs into pharmaceuticals illustrated the synthetic application of the present protocol in drug discovery.