Fluoro-Substituted Methyllithium Chemistry: External Quenching Method Using Flow Microreactors

Marco Colella; Arianna Tota; Yusuke Takahashi; Ryosuke Higuma; Susumu Ishikawa; Leonardo Degennaro; Renzo Luisi; Aiichiro Nagaki

doi:10.1002/anie.202003831

Fluoro-Substituted Methyllithium Chemistry: External Quenching Method Using Flow Microreactors

Angew Chem Int Ed Engl. 2020 Jun 26;59(27):10924-10928. doi: 10.1002/anie.202003831. Epub 2020 Apr 28.

Authors

Marco Colella¹, Arianna Tota¹, Yusuke Takahashi², Ryosuke Higuma², Susumu Ishikawa², Leonardo Degennaro¹, Renzo Luisi¹, Aiichiro Nagaki²

Affiliations

¹ Department of Pharmacy-Drug Sciences, Flow Chemistry and Microreactor Technology FLAME-Lab, University of Bari "A. Moro", Via E. Orabona 4, 70125, Bari, Italy.
² Department of Synthetic and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto, 615-8510, Japan.

PMID: 32239778
DOI: 10.1002/anie.202003831

Abstract

The external quenching method based on flow microreactors allows the generation and use of short-lived fluoro-substituted methyllithium reagents, such as fluoromethyllithium, fluoroiodomethyllithium, and fluoroiodostannylmethyllithium. Highly chemoselective reactions have been developed, opening new opportunities in the synthesis of fluorinated molecules using fluorinated organometallics.

Keywords: amides; flow chemistry; lithium; microreactor; reactive intermediates.