Synthesis of <i>N</i>‐Difluoromethyl Carbonyl Compounds from <i>N</i>‐Difluoromethylcarbamoyl Fluorides
Chunyang Hu, Lvqi Jiang, Zihao Guo, Yasir Mumtaz, Jie Liu, Jiarong Qin, Yixing Chen, Zhongquan Lin, Wenbin Yi
Abstract
Abstract Fluorinated small molecules are commonly used in functional small‐molecule chemistry, and N ‐difluoromethyl ( N ‐CF 2 H) compounds are particularly intriguing due to their unique and unexplored physiochemical properties. However, despite limited progress, a general methodological approach to the synthesis of N ‐CF 2 H compounds remains elusive. Here, guided by computation, we present a simple and practical protocol to access N ‐CF 2 H amides and related carbonyl derivatives. The protocol involves a one‐pot conversion of thioformamides through desulfurization‐fluorination and acylation, providing N ‐difluoromethylcarbamoyl fluoride building blocks that can be further diversified to a variety of unexplored N ‐CF 2 H carbonyl compounds with rich functionality. Additionally, preliminary studies on their properties and stability showcased their potential application in pharmaceuticals and agrochemicals.