Dual C2 Synthon Strategy for the Synthesis of Pyrimidines: Copper-Catalyzed Aerobic α,β-C(sp3)-H Bond Difunctionalization of Tertiary Alkylamines

Herein, we describe a two-component methodology developed for the synthesis of pyrimidine derivatives using tertiary alkylamines and amidines. Tertiary alkylamines serve as dual C2 synthons through copper-catalyzed aerobic difunctionalization of the alpha,beta-C(sp3)-H bonds. The process operates under mild conditions and uses atmospheric oxygen as the oxidant. Notably, by this methodology yields up to 85% yields are obtained and a broad substrate scope is shown. Mechanistic studies indicate that the annulation proceeds via a radical-mediated oxidation and C-N bond coupling process. This approach provides a pathway for synthesizing various heterocycles by employing tertiary alkylamines as dual C2 synthons.