Selective Pyridine-Directed C-H Activation Enabled Synthesis of Pyridine-pyridone α-Helix Mimics

The exploration of pyridine-directed C-H activation in 2benzyl-6-phenylpyridine revealed selective bromination at the ortho- phenyl position via Rh catalysis, rather than the ortho-benzyl position. In contrast, the corresponding alkylation was unsuccessful, suggesting a preference for the Rh(III) pathway to minimize steric congestion from pyridine disubstitution. This mechanistic insight facilitated the development of a room-temperature C-H activation-bromination method, enabling the synthesis of a pyridine-pyridone alpha-helix mimic.