Copper-catalysed convergent regio- and enantioselective alkynylallylic substitution

Asymmetric allylic and propargylic substitutions have seen numerous applications in synthetic chemistry, constructing stereogenic centres vicinal to unsaturated C–C bonds. However, the merger of these two substitution processes into alkynylallylic substitution is relatively underdeveloped, probably owing to the challenge of controlling regio- and stereoselectivity. Here we report the development of enantioselective intermolecular and decarboxylative alkynylallylic aminations, alkoxylation and alkylation for the synthesis of a range of enantioenriched 1,4-enynes. Cu(I) and Cu(II) salts are both effective precatalysts for the process, which can also be readily performed on a gram scale in the presence of air and moisture with no erosion in yield or selectivity. The convergent nature of the process was shown through the synthesis of a single product from a mixture of eight regio- and enantiomeric alkynylallylic carbamates and carbonate substrates, in excellent yield and selectivity. X-ray crystallographic and mechanistic analysis reveal that the Cu(I) and Cu(II) processes probably proceed through distinct enantio-determining transition state models, involving multiple ligands.