Convergent approach for direct cross-coupling enabled by flash irreversible generation of cationic and anionic species

• Published in: Nature communications Vol. 15; no. 1; pp. 4873 - 9
• Main Authors: Soutome, Hiroki, Yamashita, Hiroki, Shimizu, Yutaka, Takumi, Masahiro, Ashikari, Yosuke, Nagaki, Aiichiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.06.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/933; 639/638/549/933; 639/638/549/976; Biosynthesis; Cations; Chemistry; Confined spaces; Cross coupling; Decomposition reactions; Efficiency; Humanities and Social Sciences; Intermediates; Methods; Microreactors; multidisciplinary; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-48723-1

In biosynthesis multiple kinds of reactive intermediates are generated, transported, and reacted across different parts of organisms, enabling highly sophisticated synthetic reactions. Herein we report a convergent synthetic approach, which utilizes dual intermediates of cationic and carbanionic species in a single step, hinted at by the ideal reaction conditions. By reactions of unsaturated precursors, such as enamines, with a superacid in a flow microreactor, cationic species, such as iminium ions, are generated rapidly and irreversibly, and before decomposition, they are transported to react with rapidly and independently generated carbanions, enabling direct C-C bond formation. Taking advantage of the reactivity of these double reactive intermediates, the reaction take place within a few seconds, enabling synthetic reactions which are not applicable in conventional reactions. Optimizing the transport, mobility and diffusion of reactants and intermediates in a confined space can accelerate reactions. Here the authors study the reaction of highly reactive intermediates such as short-lived cationic and anionic species in a flow reactor.