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

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.