Divergent, Stereospecific Mono- and Difluoromethylation of Boronic Esters
Divergent, Stereospecific Mono- and Difluoromethylation of Boronic Esters
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DOI：
10.1002/anie.202002246
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发表时间：
2020-03-24
影响因子：
16.6
通讯作者：
Aggarwal, Varinder K.
中科院分区：
文献类型：
--
作者：
Fasano, Valerio;Winter, Nils;Aggarwal, Varinder K.
将氟掺入农用化学品和药物中以改善其生物学性质具有相当大的兴趣。虽然已经报道了许多用于安装CH 2F和CHF 2基团的方法，但它们主要限于自由基反应，其总是外消旋的。本文报道了氟碘甲基锂与硼酸酯的发散性立体定向反应，得到α-氟硼酸酯。这些独特的中间体可分别通过质子或氟脱硼化容易地转化为相应的单氟甲基化或二氟甲基化化合物。使用高度不稳定的氟碘甲基锂是允许1，2-迁移超过碳负离子竞争分解的关键。DFT计算为实验结果提供了信息和支持。
There is considerable interest in incorporating fluorine into agrochemicals and pharmaceuticals to improve their biological properties. Whilst a number of methods have been reported for installing CH2F and CHF2 groups, they are mainly limited to radical reactions, which are invariably racemic. Herein, we report the divergent, stereospecific reaction of fluoroiodomethyllithium with boronic esters to give alpha-fluoro-boronic esters. These unique intermediates can be readily transformed into the corresponding mono- or difluoromethylated compounds through proto- or fluorodeboronation, respectively. The use of the highly unstable fluoroiodomethyllithium was key to allowing rapid 1,2-migration over competing decomposition of the carbanion. DFT calculations informed and supported the experimental findings.