title: Three-component coupling based on flash chemistry. Carbolithiation of benzyne with functionalized aryllithiums followed by reactions with electrophiles.
abstract: 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.
authors.affiliation: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University , Nishikyo-ku, Kyoto 615-8510, Japan.
authors.forename: Aiichiro
authors.initials: A
authors.lastname: Nagaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichinari
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Yoshida