Asymmetric C3-Allylation of Pyridines

Asymmetric intermolecular C-H functionalizationof pyridinesat C3 is unprecedented. Herein, we report the first examples of suchtransformations: specifically, C3-allylation of pyridines via tandemborane and iridium catalysis. First, borane-catalyzed pyridine hydroborationgenerates nucleophilic dihydropyridines; then, the dihydropyridineundergoes enantioselective iridium-catalyzed allylation; and finally,oxidative aromatization with air as the oxidant gives the C3-allylatedpyridine. This protocol provides direct access to C3-allylated pyridineswith excellent enantioselectivity (up to >99% ee) and is suitablefor late-stage functionalization of pyridine-containing drugs.

Automated summary

Asymmetric intermolecular C-H functionalization of pyridines at C3 is achieved by tandem borane and iridium catalysis. The protocol involves borane-catalyzed pyridine hydroboration to generate nucleophilic dihydropyridines, followed by enantioselective iridium-catalyzed allylation of the dihydropyridine, and then oxidative aromatization using air as the oxidant to obtain C3-allylated pyridines. This method allows for the direct synthesis of C3-allylated pyridines with excellent enantioselectivity (up to >99% ee) and is applicable for late-stage functionalization of pyridine-containing drugs.