2-Methoxyallyl Bromide

(R = Me)

[26562-24-3]  · C4H7BrO  · 2-Methoxyallyl Bromide  · (MW 151.01) (R = Et)

[26562-26-5]  · C5H9BrO  · 2-Ethoxyallyl Bromide  · (MW 165.04)

(three-carbon electrophile in alkylations;1 three-carbon component in arene cycloadditions;2 bromoacetone equivalent;1 cyclopentenone annulation reagent;3 acetone equivalent in nucleophilic additions4)

Alternate Names: 3-bromo-2-methoxy-1-propene; 1-(bromomethyl)vinyl methyl ether.

Physical Data: a mixture of 2-methoxyallyl bromide, 1-bromo-2-methoxypropene, and 1-bromo-2,2-dimethoxypropane in a ratio of 65:21:14 has bp 134-137 °C; d 1.16 g cm-3.4 A mixture of 2-ethoxyallyl bromide and 1-bromo-2-ethoxypropene in a ratio of approx 3:1 has bp 53-55 °C/26 mmHg.5

Solubility: sol common organic solvents (i.e. diethyl ether, THF).

Analysis of Reagent Purity: gas chromatography using Carbowax 20M (or comparable) stationary phase.1,6

Preparative Methods: Greenwood and Hoffman reported that treatment of 2-Methoxypropene with N-Bromosuccinimide in CCl4 at 55-65 °C provides a CCl4 solution of 2-methoxyallyl bromide and 1-bromo-2-methoxypropene in an approx 3:1 ratio.6 Alternatively, Jacobson's modification of existing pyrolytic procedures, pyrolysis of 1-bromo-2,2-dimethoxypropane in the presence of diisopropylethylammonium tosylate, results in a 65:21:14 ratio of 2-methoxyallyl bromide, 1-bromo-2-methoxypropene, and 1-bromo-2,2-dimethoxypropane with high mass recovery (85-90%).1 In both cases the product mixtures are utilized in subsequent reactions. Polymerization limits the latter procedure to a scale of 30 g or less. 2-Ethoxyallyl bromide has been synthesized by pyrolysis of 1-bromo-2,2-diethoxypropane.5 The mixture, a 3:1 ratio of 2-ethoxyallyl bromide and 1-bromo-2-ethoxypropene, is obtained in approx. 50% overall yield.

Purification: purification is performed by distillation. Synthetic procedures provide the reagent as a mixture containing 60-70% of 2-methoxyallyl bromide.4-6 The remainder consists of 1-bromo-2-methoxypropene and/or 1-bromo-2,2-dimethoxypropane, depending on the method of synthesis.

Handling, Storage, and Precautions: neat 2-methoxyallyl bromide is unstable at rt and sensitive to moisture.6 Mixtures obtained from the thermal cracking of 1-bromo-2,2-dimethoxypropane have been stored for extended periods at -20 °C.1 Alternatively, a 50% solution in CCl4 may be stored over Na2CO3 at rt in the dark.6 Caution: this is an alkylation reagent; proper protective equipment should be worn and its use restricted to a fume hood.

Alkylations.

2-Methoxyallyl bromide (1) has been utilized as a three-carbon electrophile (bromoacetone equivalent) with carbanions derived from enamines,1,7 esters,1 nitriles,1,8 ketones,1,3 sulfones,10,11 b-keto esters,1 and substituted malonates (eq 1).1 Dianions of carboxylic acids have been alkylated at the a-position1 and, in the case of a,b-unsaturated acids, at the g-position in the presence of CuBr.SMe2 (see Copper(I) Bromide).12 Additional nucleophiles have included Grignard reagents,13 copper enolates derived from conjugate additions,14,15 alcohols (eq 2),16 and lithiated aromatics (2-aryl-5-methyl-1,3,4-oxadiazoles and 4,5-diphenyl-2-methyl-1,3 oxazole) (eq 3).17,18 The enol is more easily hydrolyzed to the ketone than other electrophilic acetone synthons (see 2,3-Dichloropropene and Propargyl Chloride).1 Alternatively, the enol functionality has been retained in the synthesis of 1,3-dienes.11,16

Cyclopentenone Annulation.

Alkylation of ketones with (1), followed by hydrolysis, results in 1,4-diketones which provide a cyclopentenone upon base-induced cyclization. This methodology has been utilized for the de novo synthesis of substituted cyclopentenones and the annulation of cyclopentenones on to existing cyclic systems (eq 4).1,3,9

[4 + 3] Cycloaddition.

In the presence of Silver(I) Trifluoroacetate and Sodium Carbonate, furan and (1) undergo a [4 + 3] cycloaddition, presumably via a 2-methoxyallyl cation, to give 8-oxabicyclo[3.2.1]oct-6-en-3-one after an acidic workup (eq 5).2,19 Other dienes also react in this manner, albeit in low yields.20,21

Nucleophilic Addition.

p-(2-Methoxyallyl)nickel bromide, prepared from (1) and Tetracarbonylnickel, reacts with aryl, alkyl, and vinyl halides, aldehydes, and ketones to give acetone addition products after mild acid hydrolysis (eq 6).4

Related Reagents.

Bromoacetone; 3-Chloro-2-trimethylsilyloxy-1-propene; 2,3-Dichloropropene; Methallyl Bromide; Propargyl Chloride.


1. Jacobson, R. M.; Raths, R. A.; McDonald, J. H., III JOC 1977, 42, 2545.
2. Hill, A. E.; Greenwood, G.; Hoffmann, H. M. R. JACS 1973, 95, 1338.
3. Rigby, J. H.; Moore, T. L.; Rege, S. JOC 1986, 51, 2398.
4. Hegedus, L. S.; Stiverson, R. K. JACS 1974, 96, 3250.
5. Horning, D. E.; Kavadias, G.; Muchowski, J. M. CJC 1970, 48, 975.
6. Hoffmann, H. M. R.; Greenwood, G. JOC 1972, 37, 611.
7. Meyers, A. I.; Williams, D. R.; Erickson, G. W.; White, S.; Druelinger, M. JACS 1981, 103, 3081.
8. Yue, C.; Royer, J.; Husson, H. P. JOC 1992, 57, 4211.
9. Mikolajczyk, M.; Zatorski, A. JOC 1991, 56, 1217.
10. Ogura, F.; Otsubo, T.; Sakamoto, T.; Yamaguchi, H. BCJ 1984, 57, 1691.
11. Radisson, X.; Kwiatkowski, P. L.; Fuchs, P. L. SC 1987, 17, 39.
12. Savu, P. M.; Katzenellenbogen, J. A. JOC 1981, 46, 239.
13. Lai, Y. H.; Chen, P. TL 1988, 29, 3483.
14. Dixon, A. J.; Taylor, R. J. K.; Newton, R. F.; Wadsworth, A. TL 1982, 23, 327.
15. Dixon, A. J.; Taylor, R. J. K.; Newton, R. F.; Wadsworth, A. H.; Klinkert, G. JCS(P1) 1982, 1923.
16. Sasaki, T.; Ohno, M.; Ito, E. JCS(P1) 1983, 3027.
17. Sasaki, T.; Ohno, M.; Ito, E.; Asai, K. T 1984, 40, 2703.
18. Kachinsky, J. L. C.; Salomon, R. G. JOC 1986, 51, 1393.
19. Wilson, S. R.; Sawicki, R. A.; Huffman, J. C. JOC 1981, 46, 3887.
20. Hoffmann, H. M. R.; Hill, A. E. AG 1974, 86, 127.
21. Hill, A. E.; Hoffmann, H. M. R. JACS 1974, 96, 4597.

Heinrich J. Schostarez

Upjohn Laboratories, Kalamazoo, MI, USA



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