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.

吡啶的区域发散型多氢元素化反应（regiodivergent multiple hydroelementation）是一种极具应用潜力的高效方法，可直接构建一系列带有C(sp³)-[E]键（E≠H）的官能团化哌啶。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）进行区域发散型连续加成至吡啶的反应仍未见报道。本研究报道了吡啶的区域发散型三重氢元素化反应，该反应通过铑（Rh）催化的区域发散型双硼氢化反应后接续氢元素化反应（E=H或P）实现，可选择性生成两组多官能团化哌啶异构体。此外，本研究利用手性膦配体实现了吡啶的不对称双硼氢化反应，为制备多官能团化手性哌啶提供了一条合成途径。针对区域发散型双硼氢化反应的实验机理研究表明，根据所使用的膦配体不同，会形成两种不同的铑催化活性物种。计算研究验证了上述发现，阐明了发散式催化剂引发路径以及C(sp³)-B键的形成机制。