Acid/Base-Tuned Asymmetric Reductive Heck and Denitrogenative Heck Reactions of In Situ-Formed α,β-Unsaturated Hydrazone

Despite significant progress in the catalytic asymmetric 1,4-additions between various Michael donors and acceptors, the exploration of organohalide donors remains elusive. Herein, we report the Pd(0)-catalyzed asymmetric intramolecular 1,4-additions of vinyl/aryl iodides to α,β-unsaturated hydrazones, featuring in situ-formed hydrazone and acid/base-tuned reaction pathways. Due to its strong coordination ability, the hydrazone is capable of steering the C–C bond formation to follow the 1,4-addition mechanism instead of the conventional alkene insertion, thus enabling the generation of vinylhydrazinyl–Pd2+ species via the Zimmerman–Traxler chairlike transition state. Notably, this species preferentially undergoes protonation under acidic conditions, furnishing a reductive Heck reaction with the aid of a native hydrazine reductant, while it is susceptible to β-HN elimination under basic conditions to achieve a denitrogenative Heck reaction. The catalytic protocol affords highly enantioselective access to diverse heterocycles, with alkene and hydrazone groups poised for further chemical manipulations.尽管各类迈克尔供体与受体之间的催化不对称1,4-加成反应已取得显著进展，但有机卤化物供体的相关探索仍较为匮乏。在此，我们报道钯(0)催化的乙烯基/芳基碘化物与α,β-不饱和腙的分子内不对称1,4-加成反应，该反应以原位生成的腙为特征，且反应路径可通过酸/碱进行调控。由于腙具有较强的配位能力，其可引导碳碳键形成遵循1,4-加成机理而非传统的烯烃插入路径，进而通过齐默曼-特拉克勒（Zimmerman–Traxler）椅式过渡态生成乙烯基肼基-钯(II)物种。值得注意的是，该物种在酸性条件下优先发生质子化，在原位肼还原剂的辅助下发生还原Heck反应；而在碱性条件下则易发生β-HN消除，从而实现脱氮Heck反应。该催化方法可高对映选择性地构建各类杂环，所得产物携带的烯烃与腙基团可用于后续的化学修饰。