Methoxycyclization of 1,5-Enynes by Coinage Metal Catalysts: Is Gold Always Superior?

Au(I) catalysts promote the intramolecular cycloisomerization of 1,n-enynes, as well as facilitate reactions with alcohols, characteristics that have led to their wide-spread in the synthesis of complex natural products. Literature reports of Cu and Ag species catalyzing the same or similar reactions are much less common. Here, we utilize molecular volcano plots to assess the activity of 45 coinage metal phosphine/phosphite catalysts possessing a variety of stereoelectronic properties for the methoxycyclization reaction of a prototypical 1,5-enyne. Our analysis reveals that the intrinsic properties of gold allow it to be coupled with a wide range of ligands, all of which exhibit high catalytic activity. On the other hand, the coupling of silver and copper with more traditional phosphines, such as triphenylphosphine, leads to catalysts with diminished catalytic ability. The activity of Ag and Cu species, however, can be enhanced by appending ligands with strong π-accepting character, which shifts these species closer to the volcano peak.