Combining (CH<sub>2</sub>O)<sub><i>n</i></sub> and (NH<sub>4</sub>)<sub>2</sub>CO<sub>3</sub> as a Formamidine Equivalent for “Four-in-One” Synthesis of Fluoroalkylated 2-<i>H</i>-Pyrimidines
Wei Han, Yuanyuan Ren, Ming-Yao Tang, Yi‐Fan Ji, Danhua Ge, Mengtao Ma, Zhi‐Liang Shen, Xue‐Qiang Chu
Abstract
Multicomponent reactions hold the potential to maximize the synthetic efficiency in the preparation of diverse and complex molecular scaffolds. An unprecedented formal [3+1+1+1] annulation approach for the one-step synthesis of fluoroalkylated 2- H -pyrimidines commencing from perfluoroalkyl alkenes, paraformaldehyde, and ammonium carbonate is described. By harnessing readily accessible (CH 2 O) n and cheap (NH 4 ) 2 CO 3 as a formamidine surrogate, this method effectively replaces traditionally preformed amidines with a pyrimidine assembly. The multicomponent reaction proceeds in a step-economical, operationally simple, metal-free, and additive-free manner, featuring a broad substrate scope, excellent functional group compatibility, and scalability. The potential for the synthetic elaboration of the obtained 2- H -pyrimidine is further demonstrated in the alkylation and vinylation of its C2 position.