Methyl (Z)-(2)-(Bromomethyl)-2-butenoate

[60941-07-3]  · C6H9BrO2  · Methyl (Z)-(2)-(Bromomethyl)-2-butenoate  · (MW 193.05)

(synthon for a-methylene-g-butyrolactones1,2 and allylic and vinylic substitution products3)

Alternate Name: methyl b-bromotiglate.

Physical Data: bp 68 °C/3 mmHg.2

Preparative Methods: allylic bromination of methyl 3-hydroxy-2-methylenebutanoate4 with N-Bromosuccinimide/Dimethyl Sulfoxide5 or Hydrogen Bromide/Sulfuric Acid.2

Synthesis of a-Methylene-g-Butyrolactones.

Dreiding was the first to demonstrate that treatment of the title reagent (1) and cyclohexanone with zinc in THF gave a 78% yield of the spirocyclohexane a-methylene-g-butyrolactone (eq 1).1 When Reformatsky conditions were applied to (1) and 2-methylpropanal, a diastereomeric mixture of the exo-methylene lactones was obtained (eq 2).6 In contrast, allylic chromium complexes of the reagent react with aliphatic and aromatic aldehydes to give a-methylene-g-butyrolactones diastereoselectively in good yields (eq 3).2 The title reagent (1) and an aluminum/tin reagent gave a 54% yield of the uncyclized product which could be cyclized to the lactone in a separate step (eq 4).2

Nucleophilic Displacements.

Both allylic and vinylic products are obtained from the nucleophilic displacement of bromide from the reagent (eq 5).3 The product distribution is dependent on the nature of the base and nucleophile and in most cases both substitution routes are observed. Attack at the allylic carbon of the reagent (to give 2) is favored by increasing the steric bulk of the nucleophile and using Sodium Ethoxide in ethanol as base. For example, when R is hydrogen (eq 5) a 4:1 ratio of normal (2) to rearranged (3) product is obtained using sodium ethoxide in ethanol. This is reversed to give a 1:4 ratio of (2) to (3) when Sodium Hydride in THF is the base-solvent system. When R is benzyl, only allylic product (2) is obtained with NaOEt/EtOH and the product distribution of (2) to (3) is 4:1 with sodium hydride as base.

Natural Product Synthesis.

Zinc-mediated coupling of methyl b-bromotiglate has been used in the synthesis of necic acid and related compounds.7 Thus addition of (1) to zinc in DMSO gave an 85% yield of the dimer (4) (eq 6). In contrast, treatment of (1) with Magnesium in THF gave a mixture of (4), (5), and (6) in a ratio of 11:7:1 (eq 6). Mikanecic acid-type structures can be obtained by treating the reagent with Potassium t-Butoxide (eq 7).5 Recently, the reagent has been used as a synthon in the synthesis of kijanolide.8

Related Reagents.

Ethyl 2-(Bromomethyl)acrylate.


1. Löffler, A.; Pratt, R. D.; Pucknat, J.; Gelbard, G.; Dreiding, A. S. C 1969, 23, 413.
2. Drewes, S. E.; Hoole, R. F. A. SC 1985, 15, 1067.
3. Ameer, F.; Drewes, S. E.; Emslie, N. D.; Kaye, P. T.; Mann, R. L. JCS(P1) 1983, 2293.
4. Hoffmann, H. M. R.; Rabe, J. JOC 1985, 50, 3849.
5. Goldberg, O.; Dreiding, A. S. HCA 1976, 59, 1904.
6. Birtwistle, D. H.; Brown, J. M.; Herbert, R. H.; James, A. P.; Lee, K.-F.; Taylor, R. J. CC 1989, 194.
7. Ameer, F.; Drewes, S. E.; Hoole, R.; Kaye, P. T.; Pitchford, A. T. JCS(P1) 1985, 2713.
8. Roush, W. R.; Brown, B. B. JOC 1993, 58, 2151.

Paul D. Johnson & Paul A. Aristoff

The Upjohn Company, Kalamazoo, MI, USA



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