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.