Zinc-Mediated C–H Metalations in Modern Organic Synthesis

Abstract

AbstractC–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 Introduction2 Csp2–H Functionalisation Using Zinc Bases2.1 Functionalised Arenes2.2 Heterocycles3 Csp3–H Functionalisation Using Zinc Bases3.1 Zinc Enolate Formation: Traditional Approach3.2 Zinc Enolate Formation via Zinc Bases3.3 Non-Enolic Csp3–H Zincations4 Conclusion