Synlett 2020; 31(19): 1899-1902
DOI: 10.1055/s-0040-1707251
cluster
© Georg Thieme Verlag Stuttgart · New York

Integrated Synthesis Using Isothiocyanate-Substituted Aryllithiums by Flow Chemistry

Hyune-Jea Lee
a   Department of Chemistry, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea   Email: heejinkim@korea.ac.kr
,
Daiki Torii
b   Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan
,
Yongju Jeon
a   Department of Chemistry, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea   Email: heejinkim@korea.ac.kr
,
Jun-ichi Yoshida
b   Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan
c   National Institute of Technology, Suzuka College, Shiroko-cho, Suzuka, Mie 510-0294, Japan
,
Heejin Kim
a   Department of Chemistry, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea   Email: heejinkim@korea.ac.kr
b   Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan
› Author Affiliations
We acknowledge the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIP) (No. 2019R1G1A1100681 and No. 2020R1C1C1014408).
Further Information

Publication History

Received: 23 June 2020

Accepted after revision: 21 July 2020

Publication Date:
21 August 2020 (online)


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.

Supporting Information

 
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