Transition metal–catalyzed cross-couplings have great potential to furnish complex ethers; however, challenges in the C(sp 3 )–O functionalization step have precluded general methods. Here, we describe computationally guided transition metal–ligand design that positions a hydrogen-bond acceptor anion at the reactive site to promote functionalization. A general cross-coupling of primary, secondary, and tertiary aliphatic alcohols with terminal olefins to furnish >130 ethers is achieved. The mild conditions tolerate functionality that is prone to substitution, elimination, and epimerization and achieve site selectivity in polyol settings. Mechanistic studies support the hypothesis that the ligand’s geometry and electronics direct positioning of the phosphate anion at the π-allyl-palladium terminus, facilitating the phosphate’s hydrogen-bond acceptor role toward the alcohol. Ligand-directed counteranion positioning in cationic transition metal catalysis has the potential to be a general strategy for promoting challenging bimolecular reactivity.

中文翻译：

---

钯催化醇与烯烃的交叉偶联，通过对阴离子的位置调节


过渡金属催化的交叉偶联具有提供复杂醚的巨大潜力;然而，C（sp 3 ）-O 官能团化步骤中的挑战排除了通用方法。在这里，我们描述了计算引导的过渡金属配体设计，该设计将氢键受体阴离子定位在反应位点以促进官能化。实现了伯、仲和叔脂肪醇与末端烯烃的一般交叉偶联，以提供 >130 醚。温和的条件可耐受容易取代、消除和差向异构化的功能，并在多元醇设置中实现位点选择性。机理研究支持这样一个假设，即配体的几何形状和电子学直接将磷酸盐阴离子定位在 π-烯丙基-钯末端，从而促进磷酸盐对醇的氢键受体作用。阳离子过渡金属催化中的配体定向反阴离子定位有可能成为促进具有挑战性的双分子反应性的通用策略。