DOI: 10.1021/acs.orglett.6c03916 ISSN: 1523-7060
In Situ Generated Difluoroketene as a C1 Synthon for the [4 + 1] Annulation to 5-Difluoromethyl-1,2,4-oxadiazoles
Jie Huang, Xiaolei Zhang, Zhi-Qiang Li, Jian Zhang, Cheng-Qiang Wang, Chao FengAbstract
Herein, we report an efficient synthesis of 5-difluoromethyl-1,2,4-oxadiazoles through a [4 + 1] annulation process, utilizing in situ generated difluoroketene from readily accessible difluorobromoacetylsilane as the one-carbon building block. This method features simple operation, mild reaction conditions, and broad substrate compatibility with respect to amidoximes. Furthermore, the practicality and robustness of this protocol are further underscored by successful gram-scale reactions and downstream synthetic transformations.