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. <i>o</i>-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 <i>o</i>-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

Feasibility Study on Continuous Flow Controlled/Living Anionic Polymerization Processes

A practical microchemical reaction system for keeping process flow at defined conditions, which is one of the key issues of industrial production, was developed. Controlled/living anionic polymerization was chosen as a test reaction because the molecular weight and molecular weight distribution of polymer products are quite sensitive to the relative flow rate of an initiator solution and that of a monomer solution. The polymerization of styrene in THF/hexane was carried out using a flow microreactor system consisting of two T-shaped micromixers and two microtube reactors using Smoothflow pumps at 0 °C. Poly­(styrene) with higher molecular weight such as Mn > 10000 could be synthesized using <i>s</i>-BuLi (Mn = 14 000, <i>M</i>_w/<i>M</i>_n = 1.11). <i>n</i>-BuLi could also be used as an initiator. The continuous operation was performed for 3 h without any problems to obtain ca. 1 kg of the polymer, indicating the feasibility of continuous flow processes for controlled/living anionic polymerization on a relatively large scale