Selective carbon–carbon (C–C) bond formation in chemical synthesis generally requires pre-functionalized building blocks. However, the requisite pre-functionalization steps undermine the efficiency of multi-step synthetic sequences, which is particularly problematic in large-scale applications, such as in the commercial production of pharmaceuticals. Herein, we describe a selective and catalytic method for synthesizing 1,3-enynes without pre-functionalized building blocks. This method is facilitated by a tailored P,N-ligand that enables regioselective coupling and suppresses secondary E/Z-isomerization of the product. The transformation enables several classes of unactivated internal acceptor alkynes to be coupled with terminal donor alkynes to deliver 1,3-enynes in a highly regio- and stereoselective manner. The scope of compatible acceptor alkynes includes propargyl alcohols, (homo)propargyl amine derivatives, and (homo)propargyl carboxamides. The reaction is scalable and can operate effectively with 0.5 mol% catalyst loading. The products are versatile intermediates that can participate in various downstream transformations. We also present preliminary mechanistic experiments that are consistent with a redox-neutral Pd(II) catalytic cycle.

中文翻译：

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内部和末端炔烃的原子经济交叉偶联以访问1,3-Enynes

在化学合成中选择性形成碳-碳（CC）键通常需要预先功能化的构建基块。然而，必需的预功能化步骤破坏了多步合成序列的效率，这在大规模应用中，例如在药物的商业生产中，尤其成问题。在这里，我们描述了一种选择性催化方法，用于合成没有预先功能化的结构单元的1，3-烯炔。量身定制的P，N-配体可促进该方法，该配体实现区域选择性偶联并抑制产物的二次E / Z异构化。该转化使几种类型的未活化的内部受体炔与末端供体炔偶联，以高度区域和立体选择性的方式递送1，3-烯。相容的受体炔烃的范围包括炔丙醇，（均）炔丙基胺衍生物和（均）炔丙基羧酰胺。该反应是可扩展的并且可以在0.5mol％的催化剂负载下有效地进行。该产品是通用中间体，可参与各种下游转化。我们还介绍了与氧化还原中性Pd（II）催化循环一致的初步机理实验。