Zinc-Mediated C–H Metalations in Modern Organic Synthesis

Daria K. Wanic; Rebecca Melvin; Graeme Barker

doi:10.1055/a-2155-3423

Synthesis, Table of Contents

Synthesis 2023; 55(21): 3487-3501
DOI: 10.1055/a-2155-3423

special topic

C–H Bond Functionalization of Heterocycles

Zinc-Mediated C–H Metalations in Modern Organic Synthesis

Daria K. Wanic

^aInstitute of Chemical Sciences, Heriot-Watt University, Riccarton, Edinburgh, EH14 4AS, UK

,

Rebecca Melvin

^aInstitute of Chemical Sciences, Heriot-Watt University, Riccarton, Edinburgh, EH14 4AS, UK

,

Graeme Barker ∗

^aInstitute of Chemical Sciences, Heriot-Watt University, Riccarton, Edinburgh, EH14 4AS, UK

^bContinuum Flow Lab, Heriot-Watt University, Riccarton, Edinburgh, EH14 4AS, UK

› Author Affiliations

Abstract

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Abstract

C–H Deprotometalations have long occupied a key role in modern organic synthesis in both the research laboratory and pharmaceutical and fine chemical manufacture, thanks to readily accessible reagents and well-established procedures. Typically, organolithiums are the reagent of choice thanks to high reactivity and ease of use but these are incompatible with base- and nucleophile-sensitive functional groups. In comparison, organozinc base complexes offer a milder approach to deprotonative C–H functionalisations, and compatibility with a wide range of functionalities which would be problematic when using the alternative organolithium or organomagnesium reagents has now been demonstrated. Here, we review the current state of the art in zinc-mediated C–H metalations at substituted arenes, heteroarenes, and Csp³–H sites.

1 Introduction

2 Csp²–H Functionalisation Using Zinc Bases

2.1 Functionalised Arenes

2.2 Heterocycles

3 Csp³–H Functionalisation Using Zinc Bases

3.1 Zinc Enolate Formation: Traditional Approach

3.2 Zinc Enolate Formation via Zinc Bases

3.3 Non-Enolic Csp³–H Zincations

4 Conclusion

Key words

metalation - organozinc - C–H functionalisation - deprotonation

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References

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