Integrated Synthesis Using Isothiocyanate-Substituted Aryllithiums by Flow Chemistry

Hyune-Jea Lee; Daiki Torii; Yongju Jeon; Jun-ichi Yoshida; Heejin Kim

doi:10.1055/s-0040-1707251

Synlett, Table of Contents

Synlett 2020; 31(19): 1899-1902
DOI: 10.1055/s-0040-1707251

cluster

Integrated Synthesis Using Isothiocyanate-Substituted Aryllithiums by Flow Chemistry

Hyune-Jea Lee

^aDepartment of Chemistry, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea Email: heejinkim@korea.ac.kr

,

Daiki Torii

^bDepartment of Synthetic Chemistry and Biological Chemistry, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan

,

Yongju Jeon

^aDepartment of Chemistry, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea Email: heejinkim@korea.ac.kr

,

Jun-ichi Yoshida∗

^bDepartment of Synthetic Chemistry and Biological Chemistry, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan

^cNational Institute of Technology, Suzuka College, Shiroko-cho, Suzuka, Mie 510-0294, Japan

,

Heejin Kim∗

^aDepartment of Chemistry, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea Email: heejinkim@korea.ac.kr

^bDepartment of Synthetic Chemistry and Biological Chemistry, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan

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Abstract

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Dedicated to Prof. Jun-ichi Yoshida (1952–2019) for his pioneering work on flow chemistry

Published as part of the Cluster Integrated Synthesis Using Continuous-Flow Technologies

Abstract

The isothiocyanate (NCS) group is an attractive functional group in the field of organic and pharmaceutical chemistry. It can be transformed into other heteroatomic functional groups. It usually acts as the inductive group of biological activity and has also been traditionally used as the fluorescent-labeling reagent. However, it is not compatible with strong bases. When the NCS group is at para position in halobenzenes, it generally undergoes nucleophilic additions upon reaction with strong bases. To the best of our knowledge, there is currently no general methodology for the formation and reactions of NCS-functionalized aryllithiums for meta and para substituents. Herein, we report the continuous-flow generation of NCS-substituted aryllithiums from the corresponding haloarenes via a selective halogen–lithium exchange reaction and its reaction with various electrophiles to yield NCS-containing products. We also achieved an integrated synthesis through sequential reactions of the NCS-containing compounds with additional nucleophiles using the continuous-flow reactors.

Key words

isothiocyanate - organolithium - flow chemistry - microreactor - integrated synthesis

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References

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