生物启迪的硼自由基介导SCS策略：实现三氟乙酰基化合物可控脱氟烷基化

生物启迪的硼自由基介导SCS策略：实现三氟乙酰基化合物可控脱氟烷基化

2021年，中国科学技术大学汪义丰教授与Houk教授合作，受生物体内C-O键断裂合成DNA的启发，开发了一种硼自由基介导的SCS策略，用于实现三氟乙酰基化合物的高度可调控脱氟烷基化反应[64]。该方法能够高选择性地制备结构新颖的二氟烷基化合物、单氟烷基化合物以及单氟代季碳中心分子。值得一提的是，该反应首次实现了三氟甲基分步可控的脱氟官能化。

反应机理

作者认为，在4-二甲氨基吡啶硼烷(DMAP·BH3)、苯硫酚(PhSH)、自由基引发剂和碱的共同作用下，三氟乙酰基化合物首先经历一次SCS过程，诱导β-C-F键断裂，生成二氟碳自由基。随后，该自由基与烯烃发生自由基加成，从而构建烷基二氟衍生物。而单氟烷基化合物的制备则需要再进行一次SCS过程。DFT计算结果也为该反应机理的合理性提供了理论支持。

英文翻译及润色:

Boron Radical-Mediated SCS Strategy Inspired by Biology: Enabling Controllable Defluoroalkylation of Trifluoroacetyl Compounds

Inspired by the C-O bond cleavage and DNA synthesis in living organisms, Professor Wang Yifeng and Professor Houk from the University of Science and Technology of China collaborated to develop a boron radical-mediated SCS (Single Carbon-Sulfur) process for highly tunable defluoroalkylation reactions of trifluoroacetyl compounds in 2021 [64]. This method enables the selective preparation of structurally novel difluoroalkylated compounds, monofluoroalkylated compounds, and monofluorinated quaternary carbon centers. Notably, this reaction represents the first example of stepwise and controllable defluorofunctionalization of trifluoromethyl groups.

Reaction Mechanism

The authors proposed that trifluoroacetyl compounds, under the combined action of 4-dimethylaminopyridine borane complex (DMAP·BH3), phenylthiol (PhSH), a radical initiator, and a base, undergo a single SCS process, leading to the cleavage of the β-C-F bond and generation of a difluorocarbon radical. This radical then undergoes radical addition to an alkene, thereby constructing alkyl difluorides. For the preparation of monofluoroalkylated compounds, a second SCS process is required. Density functional theory (DFT) calculations further support the rationality of this reaction process.