posted on 2022-07-08, 12:03authored byXiaolong Zhang, Yongquan Ning, Zhaohong Liu, Shuang Li, Giuseppe Zanoni, Xihe Bi
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 CN 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.