Discovery and Study of New Reaction Chemistry; Applications in Complex Molecule Assembly

Abstract

The catalytic, in situ generation of metal alkynilides under conditions compatible with electrophilic reaction partners provides fresh avenues for the development of new efficient asymmetric processes leading to C–C bond-formation. We have documented that terminal acetylenes undergo stereoselective additions to aldehydes in the presence of catalytic Zn(II), amine, and (+)-or (-)-N-methyl ephedrine to give adducts in useful yields and excellent enantio-induction. The application of this method to natural products syntheses, as exemplified in the epothilone total synthesis, underscores the versatility of the process.