Regioselective Ortho-Arylation of Polyhalo-Substituted (Hetero)Aryl Tosylates Using an Integrated Continuous Flow/Batch Protocol

Yong Ju Kwon, Seungmi Lee, Inji Shin, Won Suk Kim

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The regioselective ortho arylation of polyhalo-substituted (hetero)aryl tosylates has been investigated employing an integrated continuous flow/batch protocol. The regioselective ortho metalation of (hetero)aryl tosylates using n-BuLi and ZnCl2 was effectively achieved using continuous flow chemistry in a short residence time of 10.92 s, without removal of the tosyloxy group. The Pd-catalyzed Negishi coupling reactions of various (hetero)aryl iodides with the resulting arylzinc species proceeded readily at room temperature in 31% to 98% yields. Finally, the method was applied to the synthesis of perampanel in four linear steps, with an overall yield of 43%. (Figure presented.).

Original languageEnglish
Pages (from-to)263-268
Number of pages6
JournalAdvanced Synthesis and Catalysis
Volume365
Issue number2
DOIs
StatePublished - 24 Jan 2023

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) (NRF‐2022R1F1A1074510, NRF‐2022R1H1A2011719, NRF‐2022R1I1A1A01071676, NRF‐2019M1A2A2072417, NRF‐2021R1A6A1A10039823).

Publisher Copyright:
© 2023 Wiley-VCH GmbH.

Keywords

  • (Hetero)aryl tosylates
  • Continuous flow chemistry
  • Ortho metalation
  • Perampanel
  • Regioselective Negishi coupling

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