Synlett
DOI: 10.1055/a-1709-3098
synpacts

New Avenues in Copper-Mediated Trifluoromethylation Reactions Using Fluoroform as the CF3 Source

Xinkan Yang
,
This work was supported by the Research Grants Council of Hong Kong (NSFC/RGC Joint Research Scheme, N_CUHK403/20) and the Chinese University of Hong Kong (Faculty of Science, Direct Grant for Research). We also thank the Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences for funding.


Dedicated to Professor Benjamin List on winning the Nobel Prize in Chemistry 2021

Abstract

Organic molecules containing the trifluoromethyl (CF3) group play a vital role in pharmaceuticals, agrochemicals, and materials. New trifluoromethylation methods should encompass capabilities to address issues in efficiency, selectivity, and CF3 source all at once. Fluoroform (CF3H), an industrial byproduct, has emerged as an attractive CF3 source. The reaction profile of the [CuCF3] reagent derived from fluo­roform has surpassed its original applications in cross-coupling-type trifluoromethylation. We have discovered a host of unique copper-mediated trifluoromethylation reactions using [CuCF3] from fluoroform, especially under oxidative conditions, to deliver efficient and selective synthesis of trifluoromethylated compounds.

1 Introduction

2 Construction of C–CF3 Bonds for the Synthesis of Trifluoromethylated Building Blocks

2.1 C(sp)–CF3 Bond Formation

2.2 C(sp2)–CF3 Bond Formation

2.3 C(sp3)–CF3 Bond Formation

3 Domino Synthesis of Trifluoromethylated Heterocycles

3.1 3-(Trifluoromethyl)indoles

3.2 3-(Trifluoromethyl)benzofurans

3.3 2-(Trifluoromethyl)indoles

4 Trifluoromethylative Difunctionalization of Arynes

4.1 Trifluoromethylation–Allylation of Arynes

4.2 1,2-Bis(trifluoromethylation) of Arynes

5 Pentafluoroethylation of Unactivated Alkenes

6 Conclusion



Publication History

Received: 10 November 2021

Accepted after revision: 30 November 2021

Publication Date:
30 November 2021 (online)

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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