Many successful applications reported in the literature speak well for the power of the flow-microreactor method in chemical synthesis. The reaction time in a flow microreactor is defined as the residence time between a reagent inlet and the quencher inlet, which can be controlled precisely and reduced to millisecond order by adjusting the length between these positions and the flow speed. Such a feature of flow microreactors enables the use of short-lived highly reactive intermediates for synthesis. Various intermediates can be rapidly generated and transferred to another location in the flow system for use in subsequent reactions before they decompose. In this presentation, we report that a flow microreactor system enables the generation of various unstable organolithium compounds.
Keywords: microreactor, organolithium, unstable intermediates
References
1 Organolithiums Bearing Aldehyde Carbonyl Groups. A Flash Chemistry Approach. Nagaki, A.; Tsuchihashi, Y.; Haraki, S.; Yoshida, J. Org. Biomol. Chem. 2015, 13 (26), 7140-7145.
2 A Flow-Microreactor Approach to Protecting-Group-Free Synthesis Using Organolithium Compounds. Kim, H.; Nagaki, A.; Yoshida, J. Nat. Commun. 2011, 2 (264), 1-6.
3 Generation and Reaction of Carbamoyl Anions in Flow: Applications in the Three-Component Synthesis of Functionalized -Ketoamides. Nagaki, A.; Takahashi, Y.; Yoshida, J. Angew. Chem., Int. Ed. 2016, 55 (17), 5327-5331.
4 Remarkable Chemoselectivity by Flash Chemistry. Reactions of Difunctional Electrophiles with Functionalized Aryllithiums. Nagaki, A.; Imai, K.; Ishiuchi, S.; Yoshida, J. Angew. Chem., Int. Ed. 2015, 54 (6), 1914-1918.
5 Three-Component Coupling Based on Flash Chemistry. Carbolithiation of Benzyne with Functionalized Aryllithiums Followed by Reactions with Electrophiles. Nagaki, A.; Ichinari, D.; Yoshida, J. J. Am. Chem. Soc. 2014, 136 (35), 12245-12248.

I received his Ph.D. in 2005 from Kyoto University under the supervision of Professor Jun-ichi Yoshida. I worked with Professor Hiroaki Suga, Tokyo University from 2005 as a postdoctoral fellow. In 2006, he became an assistant professor of Kyoto University. I became junior associate professor in 2013 and was promoted to associate professor in 2018. My current research interests are organic synthesis, polymer synthesis, and microreactor synthesis. Awards: Takeda Pharmaceutical Co., Ltd. Award in Synthetic Organic Chemistry, Japan (2012), Incentive Award in Synthetic Organic Chemistry, Japan (2012), and Young Innovator Award on Chemistry and Micro-Nano Systems (2013).