Z‑Selective Dienylation Enables Stereodivergent Construction of Dienes and Unravels a Ligand-Driven Mechanistic Dichotomy

The development of stereoselective and efficient reactions for the construction of conjugated dienes and polyenes has remained at the forefront of organic chemistry, due to their key roles in medicinal chemistry, organic synthesis, and material science. The synthesis of conjugated dienes and polyenes is typically accomplished in a multistep manner by the sequential installation of individual CC bonds because it allows for control of stereoselectivity and efficiency of formation of each double bond. A conceptually distinct dienylation approach entails a stereoselective appendage of a four-carbon unit, shortcutting diene synthesis. Dienylation with sulfolene provided a direct route to E-dienes, but the synthesis of substantially more challenging Z-dienes remained elusive. Here, we report that a highly Z-selective dienylation can now be achieved by a simple adjustment of a ligand, enabling stereodivergent synthesis of E- and Z-dienes from one reagent and in one step. A detailed mechanistic investigation of the E- and Z-selective dienylation provided insight into the divergent behavior of the two catalytic systems and revealed that differences in relative stabilities of catalytically active palladium phosphine complexes have a major impact on the stereochemical outcomes of the dienylation.

共轭二烯烃（conjugated dienes）与多烯烃（polyenes）的立体选择性高效构建反应开发始终是有机化学领域的前沿研究热点，这源于其在药物化学、有机合成及材料科学中的关键作用。传统上，共轭二烯烃与多烯烃的合成通常通过多步策略逐步构建独立的碳碳双键（C=C）来实现，该方法可精准控制每一个双键的立体选择性与生成效率。
一种概念上截然不同的二烯基化（dienylation）策略，是通过向分子中引入四碳单元实现立体选择性加成，从而大幅缩短二烯烃的合成步骤。利用环丁砜（sulfolene）进行的二烯基化反应可直接得到E型二烯烃，但极具挑战性的Z型二烯烃合成始终未能取得突破。
本研究报道，仅需简单调整配体即可实现高Z选择性的二烯基化反应，从而可通过单一试剂、单一步骤完成E型与Z型二烯烃的立体发散合成。针对E型与Z型选择性二烯基化反应的详细机理研究，揭示了两类催化体系的差异化行为，并发现具有催化活性的钯膦配合物（palladium phosphine complexes）的相对稳定性差异，对二烯基化反应的立体化学结果具有决定性影响。