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

• Published in: Journal of the American Chemical Society Vol. 136; no. 35; pp. 12245 - 12248
• Main Authors: Nagaki, Aiichiro, Ichinari, Daisuke, Yoshida, Jun-ichi
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 03.09.2014; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; OXIDATION; REACTORS; INSERTION; REDUCTION; SPACE INTEGRATION; GENERATION; ARYNES; EFFICIENT; FLOW-MICROREACTOR APPROACH; EXCHANGE-REACTIONS
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja5071762

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.