Elsevier

Tetrahedron

Volume 58, Issue 24, 10 June 2002, Pages 4787-4799
Tetrahedron

Preparation of α-functionalized alkenylmagnesium reagents via a halide–magnesium exchange

https://doi.org/10.1016/S0040-4020(02)00439-8Get rights and content

Abstract

A general preparation of alkenylmagnesium derivatives bearing an electron-withdrawing function in the α-position (Y=CN, CO2R, CONR2, SO2Ph) has been made possible by using a low temperature (−40 to −30°C) bromine–magnesium exchange with i-PrMgBr in THF. This reaction has also been used to prepare 5-magnesiated-1,3-dioxin-4-one derivatives bearing an alkoxy substituent in β-position to the carbon–magnesium bond.

Introduction

Functionalized arylmagnesium compounds are readily prepared by an iodine–magnesium exchange.1 The reaction proceeds at low temperature (−30°C) if the aromatic ring bears electron-withdrawing substituents. Similarly, for alkenyl iodides or bromides, a fast halogen–magnesium exchange is observed if an electron-withdrawing group is attached to the double bond.2 Recently, we report some examples of alkenylmagnesium compounds bearing an electron-withdrawing function at the sp2-carbon atom attached to magnesium.3 Herein, we wish to report our full results on this topic. The inductive effect of the functional group is important, such that in most cases, functionalized alkenyl bromides of type 1 can be used for the generation of the Grignard reagents 2 (Scheme 1).

Most exchange reactions occurred between −50°C and −40°C and were complete within 1–12 h. The resulting alkenylmagnesium compounds reacted well with a range of electrophiles E+ leading to products of type 3 (Scheme 1). The reaction sequence is quite general and electron-withdrawing groups such as Y=CN, CO2R, or SO2R facilitate the bromine–magnesium exchange considerably.

Section snippets

Results and discussion

First, we examined 2-bromonitriles 1a and 1b as precursors for the bromine–magnesium exchange. These nitriles were prepared in two or three steps from the cinnamonitrile (4) and 4-heptanone (5). Thus, the bromination of 4 in CHCl3 furnished the dibromide 64 in 76% yield. In the presence of piperidine in ethanol,5 an elimination of hydrobromic acid furnished the desired bromonitrile 1a6 as an E/Z mixture in 84% yield (Scheme 2).

The unsaturated nitrile 7 was obtained by the condensation of

Conclusion

In summary, we have shown that various alkenyl bromides of type 1 undergo a fast Br/Mg-exchange providing the corresponding magnesiated species. Electron-withdrawing groups like Y=CN, CO2t-Bu, CONR2 and SO2Ph considerably facilitated the rate of exchange and allowed an efficient preparation of polyfunctional alkenylmagnesium compounds. This mild halogen–magnesium exchange has been applied to the preparation of 5-magnesiated-1,3-dioxin-4-one derivatives bearing an alkoxy substituent at

General methods

Unless otherwise indicated, all reactions were carried out under an argon atmosphere. THF, Et2O and t-butyl methyl ether (TBME) were distilled from sodium/benzophenone, CH2Cl2 and DMF from CaH2. Reactions were monitored by gas chromatography (GC) analysis of worked up reaction aliquots. Analytical thin-layer chromatography (TLC) was performed using Merck silica gel (60 F-254) plates (0.25 mm) precoated with a fluorescent indicator. Column chromatography was carried out on silica gel 60 (70–230

Acknowledgements

We thank the DFG (Leibniz program) and the Fonds der Chemischen Industrie for financial support. We thank Chemetall GmbH (Frankfurt) and Degussa AG (Hanau) and BASF AG for the generous gift of chemicals.

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