中国科学技术大学Yi-Feng Wang小组和加州大学洛杉矶分校的Kendall N. Houk的一项最新研究发现，三氟乙酰酰胺和乙酸酯通过自旋中心移位进行连续的C-F键功能化。 该研究于2021年3月4日发表于国际一流学术期刊《科学》。

课题组描述了三氟乙酰胺和三氟乙酸酯连续C-F键官能化的一般策略。反应开始于一个羰基氧原子被一个4-二甲氨基吡啶-硼基自由基激活，随后自旋中心的移动触发C-F键的断裂。化学选择性可控的两阶段过程能够连续生成二氟和单氟烷基自由基，这些自由基被选择性地用不同的自由基陷阱功能化，从而产生不同的氟化产物。课题组通过实验和计算方法建立了反应机理和化学选择性的来源。

据了解，易接近的三氟甲基的去氟功能化是获得部分氟化分子的经济途径。然而，在保持高化学选择性的同时，控制一个或两个氟原子的置换仍然是一个巨大的挑战。

附：英文原文

Title: Sequential C–F bond functionalizations of trifluoroacetamides and acetates via spin-center shifts

Author: You-Jie Yu, Feng-Lian Zhang, Tian-Yu Peng, Chang-Ling Wang, Jie Cheng, Chen Chen, Kendall N. Houk, Yi-Feng Wang

Issue&Volume: 2021/03/04

Abstract: Defluorinative functionalization of readily accessible trifluoromethyl groups constitutes an economical route to partially fluorinated molecules. However, controllable replacement of one or two fluorine atoms while maintaining high chemoselectivity remains a formidable challenge. Here we describe a general strategy for sequential C–F bond functionalizations of trifluoroacetamides and trifluoroacetates. The reaction begins with activation of a carbonyl oxygen atom by a 4-dimethylaminopyridine-boryl radical, followed by a spin-center shift to trigger the C–F bond scission. A chemoselectivity-controllable two-stage process enables sequential generation of difluoro- and monofluoroalkyl radicals, which are selectively functionalized with different radical traps to afford diverse fluorinated products. The reaction mechanism and the origin of chemoselectivity were established by experimental and computational approaches.

DOI: 10.1126/science.abg0781

Source: https://science.sciencemag.org/content/early/2021/03/03/science.abg0781