1,5-Bis(bromomagnesio)pentane1

[23708-48-7]  · C5H10Br2Mg2  · 1,5-Bis(bromomagnesio)pentane  · (MW 278.55)

(constructing block agent: transformation of many functional groups into cyclohexane, spiro[4.5]decane, and spiro[5.5]undecane synthetic intermediates, and a,o-difunctional compounds)

Physical Data: d 0.999 g cm-3.

Solubility: sol THF, ether, and toluene.

Form Supplied in: the reagent is available in THF (0.5 M).

Analysis of Reagent Purity: titration.2

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

Structure.

The observation of the existence of Schlenk's equilibrium was first confirmed in the preparation of magnesiocycloalkanes.3,4 During the preparation and use of 1,5-bis(bromomagnesio)pentane at low temperature, MgBr2 precipitates from THF solution (eq 1).5

Synthetic Applications.

Bis(bromomagnesio)pentane mainly undergoes carbon-carbon bond formation with carbon electrophiles to provide a,o-difunctional6-8 and cyclohexane derivatives.9-11 However, in the presence of hindered electrophiles, the addition is accompanied by a reduction process which leads also to the formation of monoaddition adducts.

Reaction with Esters.

The earliest uses of 1,5-bis(bromomagnesio)pentane were as an annulation reagent with carboxylic esters.9 Reactions with hindered substituted esters form some products derived from intramolecular reduction (eq 2), in contrast to 1,4-Bis(bromomagnesio)butane.12

Reaction with Lactones.

Similarly, this reagent led to a general one-pot synthesis of (hydroxyalkyl)cyclohexanols by a double nucleophilic addition to the carbonyl group of lactones. The obtained diols were converted, by appropriate transformations, into spirolactones and spiro ethers (eq 3).13

Seven-carbon annulation using 1,6-bis(bromomagnesio)hexane was achieved with various carboxylic acid derivatives and coumarins. A typical example is given with the synthesis of 3,4-dihydrospiro[2H]-1-benzopyran-2,1-cycloheptane, a spirochroman (eq 4).14

Reaction with Carboxylic Anhydrides.

The reaction of 1,5-bis(bromomagnesio)pentane with cyclic anhydrides gives spirolactones.5,15 The intermediate carboxylate diminishes the formation of reduction products so that intramolecular Grignard addition takes place almost exclusively (eq 5).

The reaction of the di-Grignard reagent with bridged bicyclic anhydrides gives good to excellent yields if a stoichiometric or excess amount of reagent is used.16 The reaction is chemoselective and, for unsymmetrical anhydrides, takes place at the less hindered carbonyl group. Thus reaction of 1,5-bis(bromomagnesio)pentane with endo- and exo-furan and cyclopentadiene adducts produces bridged bicyclic spirolactones in 80-100% yields. The furan adducts lead, by subsequent distillation, via a retro Diels-Alder reaction, to a convenient synthesis of spirobutenolides (eq 6).17 This reaction can also be used with primary Grignard reagents and 1,4-Bis(bromomagnesio)butane

The spiroannulation process also works well with heterocyclic anhydrides.18 Examples are regioselective cyclizations with pyridinecarboxylic, isatoic, and azaisatoic anhydrides (eq 7).

Reaction with 3-Halocycloalk-2-en-1-ones.

Spiro ketones are formed when the di-Grignard reagent is used, in the presence of CuBr.MeS, with 3-halocycloalk-2-en-1-ones (eq 8).19 Replacement of the di-Grignard reagent with 1,n-dilithioalkane and 2 equiv of copper(I) thiophenoxide leads to more side products.

This methodology was successfully extended to an unsaturated di-Grignard in a synthesis of the spirosesquiterpene b-vetivone (eq 9).

1,5-Bis(bromomagnesio)pentane-CuI was also used with alkylidenecyanoacetates. Quaternary-substituted hydrocarbons were obtained, but in very low yields.20

a,o-Difunctional Compounds.

1,5-Bis(bromomagnesio)pentane has been widely used for the preparation of a,o-difunctional compounds. Carbon dioxide, aldehydes, and ketones were usually selected as electrophiles. This procedure is typified by the reaction with cyclohexanone (eq 10).7b,8,21

Reaction with Trialkylboranes.

The reaction of 1,5-bis(bromomagnesio)pentane with trialkylboranes in benzene gives selective boron-magnesium transmetalation to alkylmagnesium bromides (eq 11). The transformation proceeds fast in benzene and toluene, relatively fast in ether, but extremely slowly in THF.22

Related Reagents.

1,4-Bis(bromomagnesio)butane; 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. (a) Gilman, H.; Wilkinson, P. D.; Fishel, W. P.; Meyers, C. H. JACS 1923, 45, 150. (b) Gilman, H.; Cartledge, F. K.; Sim, S.-Y. JOM 1963, 1, 8. (c) Watson, S. C.; Eastham, J. F. JOM 1967, 9, 165.
3. (a) Denise, B.; Fauvarque, J.-F.; Ducom, J. TL 1970, 335. (b) Ducom, J.; Denise, B.; JOM 1971, 26, 305.
4. (a) Emschwiller, G. CR(C) 1926, 183, 665. (b) Spek, A. L.; Schat, G.; Holtkamp, H. C.; Blomberg, C.; Bickelhaupt, F. JOM 1977, 131, 331.
5. Canonne, P.; Bélanger, D.; Lemay, G.; Foscolos, G. B. JOC 1981, 46, 3091.
6. von Braun, J. CB 1907, 40, 4065.
7. (a) Buchta, E.; Weidinger, H. LA 1953, 580, 109. (b) Colonge, J.; David, R. BSF(2) 1959, 1248.
8. Denise, B.; Ducom, J.; Fauvarque, J.-F. BSF(2) 1972, 990.
9. Grignard, V.; Vignon, G. CR(C) 1907, 144, 1358.
10. Nenitzescu, C. D.; Necsoiu, I. JACS 1950, 72, 3483.
11. Ferles, M.; Lebl, M.; Silhankova, A.; Stern, P.; Wimmer, Z. CCC 1975, 40, 1571.
12. Canonne, P.; Bélanger, D.; Lemay, G. TL 1981, 22, 4995.
13. (a) Canonne, P.; Foscolos, G.; Lemay, G. B. CC 1979, 691; (b) Canonne, P.; Foscolos, G. B.; Bélanger, D. JOC 1980, 45, 1828.
14. Canonne, P.; Bélanger, D.; Lemay, G. H 1981, 15, 455.
15. (a) Canonne, P.; Bélanger, D. CC 1980, 125. (b) Canonne, P.; Lemay, G.; Bélanger, D. TL 1980, 21, 4167. (c) FF 1982, 10, 192.
16. Canonne, P.; Bélanger, D.; Lemay, G. JOC 1982, 47, 3953.
17. (a) Canonne, P.; Akssira, M.; Lemay, G. TL 1981, 22, 2611. (b) FF 1984, 11, 249.
18. Canonne, P.; Boulanger, R.; Chantegrel, B. T 1987, 43, 663.
19. Canonne, P.; Boulanger, R.; Angers, P. TL 1991, 32, 5861.
20. Schisla, R. M.; Hammann, W. C. JOC 1970, 35, 3224.
21. Kreuchunas, A. JACS 1953, 75, 4278.
22. Kondu, K.; Murahashi, S.-I. TL 1979, 1237.

Perséphone Canonne & Paul Angers

Université Laval, Québec, Canada



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.