Li Bao-Sheng, Wang Yuhuang, Proctor Rupert S J, Zhang Yuexia, Webster Richard D, Yang Song, Song Baoan, Chi Yonggui Robin
Division of Chemistry &Biological Chemistry, Nanyang Technological University, School of Physical &Mathematical Sciences, Singapore 637371, Singapore.
Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, China.
Nat Commun. 2016 Sep 27;7:12933. doi: 10.1038/ncomms12933.
Benzyl bromides and related molecules are among the most common substrates in organic synthesis. They are typically used as electrophiles in nucleophilic substitution reactions. These molecules can also be activated via single-electron-transfer (SET) process for radical reactions. Representative recent progress includes α-carbon benzylation of ketones and aldehydes via photoredox catalysis. Here we disclose the generation of (nitro)benzyl radicals via N-heterocyclic carbene (NHC) catalysis under reductive conditions. The radical intermediates generated via NHC catalysis undergo formal 1,2-addition with ketones to eventually afford tertiary alcohol products. The overall process constitutes a formal polarity-inversion of benzyl bromide, allowing a direct coupling of two initially electrophilic carbons. Our study provides a new carbene-catalysed reaction mode that should enable unconventional transformation of (nitro)benzyl bromides under mild organocatalytic conditions.
苄基溴及相关分子是有机合成中最常见的底物之一。它们通常在亲核取代反应中用作亲电试剂。这些分子也可以通过单电子转移（SET）过程被活化以进行自由基反应。近期的代表性进展包括通过光氧化还原催化实现酮和醛的α-碳苄基化。在此，我们披露了在还原条件下通过N-杂环卡宾（NHC）催化生成（硝基）苄基自由基。通过NHC催化生成的自由基中间体与酮进行形式上的1,2-加成，最终得到叔醇产物。整个过程构成了苄基溴的形式上的极性反转，使得两个最初的亲电碳能够直接偶联。我们的研究提供了一种新的卡宾催化反应模式，该模式应能在温和的有机催化条件下实现（硝基）苄基溴的非常规转化。
