Regioselective Ortho-Arylation of Polyhalo-Substituted (Hetero)Aryl Tosylates Using an Integrated Continuous Flow/Batch Protocol
- 주제(키워드) (Hetero)aryl tosylates , Continuous flow chemistry , Ortho metalation , Perampanel , Regioselective Negishi coupling
- 등재 SCIE, SCOPUS
- 발행기관 John Wiley and Sons Inc
- 발행년도 2023
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000204005
- 본문언어 영어
- Published As https://doi.org/10.1002/adsc.202201194
초록/요약
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.). © 2023 Wiley-VCH GmbH.
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