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

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 —70 °C. In the subsequent reactor o-bromophenyllithium is decomposed to generate benzyne without affecting the functionalized aryllithium at —30 °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-residence time mapping is responsible for the success of the present transformation. The present method has been successfully applied to the synthesis of boscalid. [ABSTRACT FROM AUTHOR]