Ligand-Controlled Regiodivergent Double Hydroboration of Pyridines: A Catalytic Platform for the Synthesis of Diverse Functionalized Piperidines

Regiodivergent multiple hydroelementation of pyridines is a potentially powerful method to straightforwardly provide a diverse array of functionalized piperidines having C(sp3)–[E] bond(s) (E ≠ H). However, such regiodivergent consecutive additions of H[E] (E = Bpin, SiEt3, etc.) to pyridines have remained unknown to date. In this study, we report the regiodivergent triple hydroelementation of pyridines, enabled by Rh-catalyzed regiodivergent double hydroboration followed by hydroelementation (E = H or P), which selectively produces two pairs of multifunctionalized piperidine isomers. Additionally, asymmetric double hydroboration of pyridines using chiral phosphine ligands has been achieved, offering a route to multifunctionalized chiral piperidines. Experimental mechanistic investigations into the regiodivergent double hydroboration reveal the formation of two distinct Rh catalytic species, dependent on the phosphine ligands employed. Computational studies corroborate these findings, elucidating the divergent catalyst initiation pathways and the mechanism of C(sp3)–B bond formation.吡啶（pyridine）的区域发散性多步氢元素加成反应，是一种可便捷制备一系列结构多样、带有C(sp³)-[E]键（E≠H）的官能化哌啶（piperidine）的极具应用潜力的方法。然而，迄今为止，将H[E]（E=频哪醇硼酸酯基（Bpin）、三乙基硅基（SiEt₃）等）连续区域发散性加成至吡啶的反应仍未见诸报道。本研究报道了铑（Rh）催化的吡啶区域发散性三步氢元素加成反应：该反应通过铑催化的区域发散性双氢硼化反应与后续氢元素加成（E=H或P）实现，可选择性生成两组多官能化哌啶异构体。此外，本研究还利用手性膦配体（chiral phosphine ligands）实现了吡啶的不对称双氢硼化反应，为合成多官能化手性哌啶提供了可行途径。针对该区域发散性双氢硼化反应的实验机理研究表明，反应会根据所使用的膦配体生成两种不同的铑催化活性物种。计算研究验证了上述结论，阐明了差异化的催化剂引发路径以及C(sp³)-B键的形成机理。