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DOI: 10.1055/a-2722-7093
Synthesis and Reactivity of Organozinc Reagents Derived From γ-Bromocrotonate Ester in Continuous Flow
Autoren
This research was supported in part by the Natural Science and Engineering Research Council of Canada (NSERC) under a discovery grant from NSERC (Canada) (RGPIN-2019-06113, RGPIN-2025-04411), the Canada Foundation for Innovation (22007-2008,41475-2021), and the FRQNT Centre in Green Chemistry and Catalysis (CGCC) (FRQNT-2020-RS4-265155-CCVC), and the Université de Montréal.
Gefördert durch: Institute Courtois
Gefördert durch: Natural Sciences and Engineering Research Council of Canada RGPIN-2019-06113,RGPIN-2025-04411
Gefördert durch: Université de Montréal
Gefördert durch: Canada Foundation for Innovation 22007-2008,41475-2021
Dedication
This paper is dedicated to Professor Paul Knochel on the occasion of his 70th 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 productPublikationsverlauf
Eingereicht: 27. August 2025
Angenommen nach Revision: 13. Oktober 2025
Accepted Manuscript online:
13. Oktober 2025
Artikel online veröffentlicht:
14. November 2025
© 2025. Thieme. All rights reserved.
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