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

Au(I) catalysts promote the intramolecular cycloisomerization of 1,<em>n</em>-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.一价金（Au(I)）催化剂可催化1,n-烯炔的分子内环异构化反应，同时能够促进其与醇类的反应，这一特性使其被广泛应用于复杂天然产物的合成中。相较于金催化剂，铜（Cu）与银（Ag）物种催化同类或相似反应的文献报道则要少见得多。本文中，我们采用分子火山图（molecular volcano plots）对45种具备多样化立体电子性质的币金属（coinage metal）膦/亚磷酸酯配体催化剂在典型1,5-烯炔甲氧基环化反应中的催化活性进行了评估。分析结果表明，金的本征属性使其可与多种配体结合，且所有此类配体均展现出优异的催化活性。与之相反，银与铜结合传统膦配体（如三苯基膦（triphenylphosphine））所得到的催化剂，其催化能力会出现显著下降。不过，通过引入具有强π接受特性的配体，可以改善银、铜物种的催化活性，使这些金属物种的催化活性更趋近于火山图的峰值位点。