Three-Component Coupling Based on Flash Chemistry. Carbolithiation of Benzyne with Functionalized Aryllithiums Followed by Reactions with Electrophiles

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• 作者：Aiichiro Nagaki ; Daisuke Ichinari ; Jun-ichi Yoshida
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：September 3, 2014
• 年：2014
• 卷：136
• 期：35
• 页码：12245-12248
• 全文大小：319K
• ISSN：1520-5126

文摘

A flow microreactor method for three-component coupling of benzyne was developed based on flash chemistry. o-Bromophenyllithium generated from 1-bromo-2-iodobenzene and a functionalized aryllithium generated from the corresponding aryl halide were mixed at 鈭?0 掳C. In the subsequent reactor o-bromophenyllithium is decomposed to generate benzyne without affecting the functionalized aryllithium at 鈭?0 掳C, and carbolithiation of benzyne with the aryllithium took place spontaneously. The resulting functionalized biaryllithium was reacted with an electrophile in the subsequent reactor to give the corresponding three-component coupling product. The precise optimization of reaction conditions using the temperature鈥搑esidence time mapping is responsible for the success of the present transformation. The present method has been successfully applied to the synthesis of boscalid.