1,4-Bis(bromomagnesio)butane1

[23708-48-7]  · C4H8Br2Mg2  · 1,4-Bis(bromomagnesio)butane  · (MW 264.53)

(constructing block agent: transformation of many functional groups into cyclopentane, spiro[4.4]nonane, and spiro[4.5]decane synthetic intermediates, and metallacycles)

Solubility: sol THF, ether, and toluene.

Form Supplied in: generally prepared in THF.

Analysis of Reagent Purity: titration.2

Preparative Methods: the following preparative method was found to be of general use for the preparation of various 1,n-bis(bromomagnesio)alkanes (n = 4-6), as well as for primary, secondary, and unsaturated di-Grignard reagents, from the corresponding dibromides.3 1,4-Dibromobutane (69 mmol) dissolved in anhydrous THF (150 mL) is added dropwise to Magnesium turnings (150 mmol) covered with a few mL of the dibromide solution. The exothermic reaction starts within a few minutes and is controlled by the rate of addition of the dibromide, avoiding excessive heating. After an additional 2 to 6 h period, the formation of the reagent is completed (yield ~90%) (eq 1). However, for 1,3-bis(bromomagnesio)propane, this procedure is not suitable, as the elimination product is mostly formed. Therefore, one should refer to the appropriate literature for that particular case.4

Handling, Storage, and Precautions: solutions are highly flammable; must be stored in the absence of proton sources, carbon acids, and oxygen. Flasks and Schlenk tubes should be flushed with dry Ar or N2. Handle with standard syringe technique to prevent contact of the solutions with oxygen and moisture. Solutions can be stored at 0 °C for months.

Synthetic Applications.

1,4-Bis(bromomagnesio)butane is a remarkable annulation reagent. It carries out annulation readily, unlike the pentane or propane analogs. 1,3-Bis(bromomagnesio)propane undergoes hydride transfer and/or addition reaction with electrophiles, furnishing reduction products, a,o-diadducts, and cyclobutane derivatives.4 With 1,6-bis(bromomagnesio)hexane, 1,6-diaddition compounds are obtained in good yield, while the annulation with carboxylic acid derivatives produces modest yields.

Cyclopentane Derivatives.

The reaction of 1,4-bis(bromomagnesio)butane with esters leads to the formation of cyclopentanols.5 The application of this annulation process is important for the synthesis of cyclopentanol derivatives substituted with functionalized alkyl groups (eq 2) that are difficult to obtain from the corresponding Grignard reagent and cyclopentanone.6

Another advantage of this methodology is the production of trans-1,2-disubstituted cyclopentanols with 1,4-bis(bromomagnesio)pentane (eq 3).3b This stereoselection is complementary to that obtained by direct addition of an alkyl Grignard to 2-methylcyclopentanone, which gives mainly cis-1,2-disubstituted cyclopentanols.7

Lactones undergo the annulation process with 1,4-bis(bromomagnesio)butane.8 Eq 4 shows annulation on dihydrocoumarin.9 Yields are higher than observed with 1,5-Bis(bromomagnesio)pentane, which also forms products of intermolecular attack and hydride transfer.

Oximes of 3-alkyl-3-(1-hydroxycyclopentyl)alkan-2-ones were prepared in high yields from 4,4-dialkylisoxazol-5-ones and 1,4-bis(bromomagnesio)butane (eq 5).3a,10 These results contrast with those obtained for primary Grignard reagents, which produce only the corresponding 5-hydroxy-2-isoxazolines (eq 6).11

Symmetrically and unsymmetrically substituted cyclic anhydrides are converted in good yield to spirolactones.12 For unsymmetrical cyclic anhydrides, preferential attack takes place on the more accessible carbonyl group, followed by a second nucleophilic addition to the intermediate ketone, leading to five-carbon annulation (eq 7).12b This methodology was successfully used for the construction of linearly fused polyquinane, a class of fused ring compounds containing only cyclopentane rings.13

Organobiscuprates.

In the presence of the Copper(I) Bromide-dimethyl sulfide complex, 1,4-bis(bromomagnesio)butane reacts with 3-halocycloalk-2-en-1-ones to afford spiro ketones.14 This annulation methodology was applied, for example, to 1,4-bis(bromomagnesio)pentane and 3-bromocyclopent-2-en-1-one to form cis-1-methylspiro[4.4]nonan-2-one (eq 8) (see also 1,5-Bis(bromomagnesio)pentane).

Metallacyclopentanes.

The synthesis of various metallacyclopentanes from metal dihalides and 1,4-bis(bromomagnesio)butane constitutes a useful application of the di-Grignard reagent.15 These metallacycles may then be used in synthetic applications (see 1,4-Dilithiobutane). The formation of chiral 2,5-dimethylborolane illustrates such an approach (eq 9).16

Related Reagents.

1,5-Bis(bromomagnesio)pentane; 1,4-Dilithiobutane; 1,5-Dilithiopentane.


1. (a) Kharasch, M. S.; Reinmuth, O. Grignard Reactions of Nonmetallic Substances; Prentice-Hall: New York, 1954; pp. 769-772; (b) Lindsell, W. E. In Comprehensive Organometallic Chemistry; Wilkinson, G., Ed.; Pergamon: Oxford, 1982; vol. 1, Chapter 4.
2. Gilman, H.; Wilkinson, P. D.; Fishel, W. P.; Meyers, C. H. JACS 1923, 45, 150.
3. (a) Canonne, P.; Thibeault, D.; Fytas, G. T 1986, 42, 4203. (b) Canonne, P.; Bernatchez, M. JOC 1987, 52, 4025.
4. Bickelhaupt, F. In Organometallics in Organic Synthesis 2; Werner, H.; Erter, G., Eds., Springer: Berlin, 1989; pp 145-160 and references therein.
5. (a) Canonne, P.; Bélanger, D.; Lemay, G. TL 1981, 22, 4995. (b) Canonne, P.; Bernatchez, M. JOC 1986, 51, 2147. (c) FF 1988, 13, 138.
6. Canonne, P.; Belley, M.; Fytas, G.; Plamondon, J. CJC 1988, 66, 168.
7. (a) Battioni, J.-P.; Capmau, M.-L.; Chodkiewicz, W. BSF(2) 1969, 976. (b) Corey, E. J.; Kuwajima, I. JACS 1970, 92, 395. (c) Battioni, J.-P.; Chodkiewicz, W. BSF(2) 1971, 1824.
8. Canonne, P.; Boulanger, R.; Bernatchez, M. TL 1987, 28, 4997.
9. Canonne, P.; Bélanger, D.; Lemay, G. S 1980, 301.
10. Canonne, P.; Fytas, G.; Thibeault, D. TL 1983, 24, 2991.
11. (a) Lo Vecchio, G.; Cum, G.; Stagno D'Alcontres, G. TL 1964, 3495. (b) Petrus, F.; Verducci, J.; Vidal, Y. BSF(2) 1973, 3079. (c) Jacquier, R.; Petrus, F.; Verducci, J.; Vidal, Y. TL 1974, 387 and references therein.
12. (a) Canonne, P.; Bélanger, D. CC 1980, 125. (b) Canonne, P.; Lemay, G.; Bélanger, D. TL 1980, 21, 4167.
13. Suryanarayana Murthy, Y. V.; Narayana Pillai, C. T 1992, 48, 5331.
14. Canonne, P.; Boulanger, R.; Angers, P. T 1991, 32, 5861.
15. Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. In Principles and Applications of Organotransition Metal Chemistry; University Science Books: Mill Valley, CA, 1987; pp 459-520.
16. (a) Masamune, S.; Kim, B. M.; Petersen, J. S.; Sato, T.; Veenstra, S. J.; Imai, T. JACS 1985, 107, 4549. (b) FF 1988, 13, 119.

Perséphone Canonne & Paul Angers

Université Laval, Québec, Canada



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