Synthesis and Reactivity of Organozinc Reagents Derived From γ-Bromocrotonate Ester in Continuous Flow

Rose G. Boivin; André B. Charette

doi:10.1055/a-2722-7093

Synthesis, Table of Contents

Synthesis
DOI: 10.1055/a-2722-7093

Paper

Published As Part Of The Special Topic Dedicated To Prof. Paul Knochel

Synthesis and Reactivity of Organozinc Reagents Derived From γ-Bromocrotonate Ester in Continuous Flow

Authors

Rose G. Boivin

¹FRQNT Centre in Green Chemistry and Catalysis, Centre for Continuous Flow Synthesis, Department of Chemistry, Université de Montréal, Montréal, Canada (Ringgold ID: RIN5622)
André B. Charette

¹FRQNT Centre in Green Chemistry and Catalysis, Centre for Continuous Flow Synthesis, Department of Chemistry, Université de Montréal, Montréal, Canada (Ringgold ID: RIN5622)

Abstract

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Dedication

This paper is dedicated to Professor Paul Knochel on the occasion of his 70^th birthday.

Abstract

The Reformatsky reaction is a well-established method for the synthesis of β-hydroxyesters, a structural motif commonly found in natural products. While continuous-flow adaptations of the traditional Reformatsky reaction, which offer improved safety and efficiency, have been reported, related transformations using γ-bromocrotonate esters have not yet been explored in flow chemistry. Under batch conditions, the corresponding organozinc reagent can yield both γ- and α-adducts, depending on the metal employed and the specific reaction parameters. In this study, we report the first Reformatsky-type reaction in continuous flow using ethyl γ-bromocrotonate, with conditions optimized to favor γ-selectivity and the synthesis of homoallylic alcohols. Zinc dust was utilized as the reagent, and the reaction scope was demonstrated with a variety of carbonyl compounds, including in a four-step synthesis of piperine. Furthermore, the synthesis of ethyl γ-bromocrotonate was efficiently accomplished under continuous-flow conditions on a multigram scale via a Wohl–Ziegler bromination.

Keywords

Organozinc - Zinc column - Flow chemistry - Homoallylic alcohols - Reformatsky reaction - α,β,γ,δ-Insaturated product - Piperine - Natural product

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References

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