Synthesis of β‑Difluoroalkylated Acrylonitriles in the Presence of Copper Powder

A highly regio- and
stereoselective copper-mediated cyanodifluoro­alkylation
of alkynes with ethyl difluoroiodoacetate and trimethylsilyl cyanide
(TMSCN) is described. The three-component coupling reaction provides
straightforward access to a variety of useful difluoroalkyl-substituted
acrylonitriles. The introduction of the nitrile unit is of great importance
in drug discovery for the modification of this fragment. Preliminary
mechanistic investigations indicate that a vinyl iodide intermediate
and a difluoroalkyl radical might be involved in this transformation.