Zinc-Mediated C–H Metalations in Modern Organic Synthesis

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

Publication History

Received: 10 July 2023

Accepted after revision: 16 August 2023

Accepted Manuscript online:
16 August 2023

Article published online:
15 September 2023

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