Hydrogen Bonding-Mediated Regio- and Stereoselective Divergent Synthesis of C4-Substituted Pyridines via N-Boryl Pyridyl Radicals.

Herein, we leverage intramolecular hydrogen bonding to selectively regulate the radical cross-coupling reaction, enabling the precise synthesis of C4-substituted pyridines with excellent regio- and stereoselectivity. Moreover, this unexpected strategy could be strategically applied to divergently forge functionalized pyridines via two-step, one-pot protocols involving traceless C-H activation. Notably, a CFTR potentiator (UCCF-29) could be readily prepared in 67% overall yield through this chemistry, achieving a 36% increase in yield relative to those with current methods. Mechanistic studies reveal that intramolecular hydrogen bonding is the driving force for the observed regio- and stereoselectivity. These powerful tools for pyridine synthesis not only provide a new solution for modulating the selectivity of the N-boryl pyridyl radical-driven process but also hold significant potential for accelerating drug discovery.