Defluorinative Carboimination of Trifluoromethyl Ketones
Xiaolong Zhang, Yongquan Ning, Zhaohong Liu, Shuang Li, Giuseppe Zanoni, Xihe Bi
Abstract
The monofunctionalized carbodefluorination of readily accessible CF3 groups is acknowledged as an attractive approach for the preparation of partially fluorinated molecules. However, their defluorinative difunctionalization remains a challenging and unmet goal. Herein, we report a defluorinative carboimination of trifluoromethyl ketones via a strategy of silver carbene-initiated rearrangement, in which both the C–F bond and carbonyl group of trifluoromethyl ketones are functionalized simultaneously, thus providing a straightforward synthetic method for medicinally relevant α,α-difluoroimines. The current approach involves a silver carbene-initiated intramolecular cascade process by integrating successive cleavage of the C–F bond and formation of C–C and C═N bonds on a single molecule entity, which differs relevantly from the stepwise mechanism of reported carbodefluorination of CF3 groups. Mechanistic studies disclose that silver catalysis plays a critical role, particularly in the stages of C–F bond cleavage and aza-Claisen rearrangement.