关键词: 路易斯碱-硼自由基, 碳-氟键断裂, 脱氟氘化, 自旋中心转移

Deuterated mono- and difluoroalkyl groups have attracted increasing attention in medicinal and biological studies. Controllable snipping one or two fluorine atoms from widely accessible trifluoromethyl groups followed by deuteration is an attractive method to access these molecules, whereas this has been hindered by the challenges associated with the chemoselectivity control during the defluoriantion process. Herein, a strategy for chemoselective deuterodefluorination reaction of trifluoro- and difluoroalkylacetamides via spin-center shifts is reported. The reaction starts with the attack of a deuterated 4-dimethylaminopyridine-boryl radical (DMAP-BD₂) to the amide oxygen atom, followed by a spin-center shift process to trigger the C—F bond scission. The resulting α,α-difluorocarbonyl radicals undergo deuterium atom transfer to afford the CF₂D-products in high yields and high levels of D-incorporation. Notably, increasing the amount of DMAP-BD₃ enables the selective cleavage of the two C—F bonds, leading to CFD₂-products in good yields meanwhile maintaining good levels of D-incorporation.

Key words: Lewis base-boryl radical, C—F bond cleavage, deuterodefluorination, spin-center shift