硼自由基促进的三氟乙酰胺选择性脱单氟和双氟氘代反应  

Selective Mono-and Di-deuterodefluorination of Trifluoroacetamides Promoted by Boryl Radicals

作　　者：顾秋予 彭天宇 薄明成 汪义丰 Gu Qiuyu;Peng Tianyu;Bo Mingcheng;Wang Yifeng(Department of Chemistry,University of Science and Technology of China,Hefei 230026)

机构地区：[1]中国科学技术大学化学系,合肥230026

出　　处：《有机化学》2023年第5期1832-1842,共11页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.21971226);中央高校基本科研业务费专项资金(No.WK2060000017)资助项目。

摘　　要：氘代单氟烷基和二氟烷基化合物在医学和生物学研究中受到了越来越多的关注.从可广泛获得的三氟甲基化合物出发,可控地切断一个或两个碳-氟键并氘代是制备这类分子的一种有效方法,但是脱氟过程中化学选择性地控制仍具挑战.报道了一种通过自旋中心转移实现的三氟乙酰胺选择性脱单氟和双氟氘化反应.首先,氘代4-二甲氨基吡啶-硼自由基(DMAP-BD_(2)·)加成到羰基氧上,然后发生自旋中心转移引发碳-氟键断裂,生成的二氟烷基自由基经过氘原子转移,能以良好的收率和氘代率得到氘代二氟烷基产物.增加4-二甲氨基吡啶-硼烷的用量可以选择性切断两个C—F键,从而高效地制备氘代单氟烷基化合物.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-BD_(2)·) 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 CF_(2)D-products in high yields and high levels of D-incorporation.Notably,increasing the amount of DMAP-BD_(3) enables the selective cleavage of the two C—F bonds,leading to CFD_(2)-products in good yields meanwhile maintaining good levels of D-incorporation.

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 

分 类 号：O621.25[理学—有机化学]