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Selective Synthesis of 3‐(α‐Fluorovinyl)indoles and 3‐Acylindoles via the Cascade Reactions of 1‐Phenylpyrazolidinones with α,α‐Difluoromethylene Alkynes
Author(s) -
Yang Yujie,
Li Na,
Zhao Jie,
Jiang Yuqin,
Zhang Xinying,
Fan Xuesen
Publication year - 2021
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.202100441
Subject(s) - chemistry , moiety , regioselectivity , indole test , ring (chemistry) , combinatorial chemistry , stereochemistry , selectivity , bond cleavage , organic chemistry , catalysis
Presented herein is a selective synthesis of 3‐(α‐fluorovinyl)indoles and 3‐acylindoles via the coupling of 1‐phenylpyrazolidinones with α,α‐difluoromethylene alkynes. Mechanistically, the formation of 3‐(α‐fluorovinyl)indoles is resulted from a cascade process including Rh(III)‐catalyzed ortho ‐C−H bond cleavage, regioselective triple bond insertion, pyrazolidinone ring‐opening, indole ring‐formation and HF elimination. Interestingly, when this reaction was carried out in CH 3 OH/H 2 O instead of CH 3 CN, the in situ formed 3‐(α‐fluorovinyl)indoles readily undergo a hydration process to afford 3‐acylindole derivatives. This protocol features with controllable selectivity, simultaneous formation of both the heterocyclic scaffold and the monofluoroalkenyl moiety, atom‐economy, substrate diversity, good functional group tolerance and redox‐neutral reaction conditions. Anticancer screening of selected products against two human cancer cell lines demonstrated their potential as lead compounds for drug development.