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.