Sequential C–F bond functionalizations of trifluoroacetamides and acetates via spin-center shifts
Sequential C–F bond functionalizations of trifluoroacetamides and acetates via spin-center shifts
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DOI：
10.1126/science.abg0781
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发表时间：
2021-03
期刊：
影响因子：
56.9
通讯作者：
You-Jie Yu;Feng-Lian Zhang;Tian-Yu Peng;Chang-ling Wang;Jie Cheng;Cheng Chen;K. Houk;Yi‐Feng Wang
中科院分区：
文献类型：
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作者：
You-Jie Yu;Feng-Lian Zhang;Tian-Yu Peng;Chang-ling Wang;Jie Cheng;Cheng Chen;K. Houk;Yi‐Feng Wang
在制药或农业化学研究中，通过添加一个或多个氟原子来改变碳化合物的性质通常是有用的。然而，用于制备单-、二-或三氟碳中心的方法往往以不方便的方式彼此不同。Yu等人开发了一种自由基反应，该反应可以连续地从与酰胺或酯相邻的三氟甲基基团中除去一个或两个氟原子。该机制依赖于在羰基氧的硼基自由基攻击后的自旋中心移位。自由基反应可以连续地从酰胺或酯附近的三氟甲基基团中除去一个或两个氟。容易获得的三氟甲基的脱氟官能化构成了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可控地取代一个或两个氟原子仍然是一个巨大的挑战。在这里，我们描述了一个一般的战略顺序碳-氟（C-F）键官能化的三氟乙酰胺和三氟乙酸酯。反应开始于4-二甲基氨基吡啶-硼基自由基活化羰基氧原子，随后是自旋中心移动以触发C-F键断裂。一种化学选择性可控的两阶段方法能够连续生成二氟和单氟烷基自由基，其用不同的自由基捕获剂选择性地官能化以提供不同的氟化产物。通过实验和计算的方法建立了反应机理和化学选择性的起源。
Sequentially snipping off fluorines It is often useful in pharmaceutical or agrochemical research to modify the properties of carbon compounds by appending one or more fluorine atoms. However, the methods used to prepare mono-, di-, or trifluorocarbon centers tend to differ from each other in inconvenient ways. Yu et al. developed a radical reaction that can successively remove one or two fluorine atoms from trifluoromethyl groups adjacent to amides or esters. The mechanism relies on a spin-center shift after attack at the carbonyl oxygen by a boryl radical. Science, this issue p. 1232 A radical reaction can successively remove one or two fluorines from trifluoromethyl groups adjacent to amides or esters. Defluorinative functionalization of readily accessible trifluoromethyl groups constitutes an economical route to partially fluorinated molecules. However, the controllable replacement of one or two fluorine atoms while maintaining high chemoselectivity remains a formidable challenge. Here we describe a general strategy for sequential carbon-fluorine (C–F) bond functionalizations of trifluoroacetamides and trifluoroacetates. The reaction begins with the 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.