Synlett 2021; 32(11): 1060-1071
DOI: 10.1055/a-1297-6902
account

Diazocarbonyl Compounds in Organofluorine Chemistry

,
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, Svante Arrhenius väg 16c, 106 91 Stockholm, Sweden
› Author Affiliations
We thank the Knut och Alice Wallenbergs Foundation (Dnr: 2018.0066) and Swedish Research Council (VR) for financial support.


Abstract

Diazocarbonyl compounds are useful substrates in di- and trifunctionalization reactions based on F/CF3/SCF3 introduction. In the presented reactions, various electrophilic F/CF3/SCF3-transfer reagents were used. The majority of the reactions were based on rhodium catalysis and the application of various oxygen nucleophiles, such as alcohols, cyclic/acyclic ethers, and carboxylic acids. The oxyfluorination reactions were further developed to provide a new fluorine-18 labeling method. Density functional theory (DFT) modeling studies were performed to get a deeper mechanistic understanding of these reactions. These DFT modeling studies indicated that the catalytic reactions proceed through formation of rhodium carbene and oxonium ylide intermediates. The oxonium ylides undergo tautomerization to enol ether type species that subsequently react with the electrophilic F/CF3/SCF3-transfer reagents. We also present an arylation–trifluoromethylthiolation reaction for simultaneous introduction of C–SCF3 and C–C bonds into diazocarbonyl compounds. This reaction does not proceed by rhodium catalysis, but follows a Hooz-type mechanism.

1 Introduction

2 Diazocarbonyl Compounds: Versatile Substrates in Organic ­Synthesis

3 Fluorination, Trifluoromethylation, and Trifluoromethylthiolation of Diazo Substrates

3.1 Metal-Free Reactions

3.2 Metal-Catalyzed Reactions with Nucleophilic Reagents

3.3 Metal-Catalyzed Reactions with Electrophilic Reagents

4 Oxyfluorination Reactions

4.1 Fluorobenziodoxole as a Fluorine Source

4.2 [18F]Fluorobenziodoxole as a Fluorine Source for Radiolabeling

4.3 Oxyfluorination with NFSI

5 Oxytrifluoromethylation

6 Oxytrifluoromethylthiolation

7 Arylation–Trifluoromethylthiolation Reaction

8 Conclusions and Outlook



Publication History

Received: 14 September 2020

Accepted after revision: 26 October 2020

Accepted Manuscript online:
26 October 2020

Article published online:
23 November 2020

© 2020. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany