4-Ethylenedioxybutylmagnesium Bromide

[91083-05-5]  · C6H11BrMgO2  · 4-Ethylenedioxybutylmagnesium Bromide  · (MW 219.36)

(nucleophilic Grignard reagent used as a synthetic equivalent of the 4-oxobutyl anion)

Solubility: sol THF.

Handling, Storage, and Precautions: Grignard reagent sensitive to moisture; normally prepared in THF solution and used immediately.

Nucleophilic Additions.

This Grignard reagent and its magnesium chloride counterpart, like the analogous organolithium reagent, are employed in synthetic chemistry as synthons for the 4-oxobutyl anion; the Grignard reagents appear, however, to have been subject to much less widespread use than the organolithium reagent. They are normally used in THF as solvent. Both reagents are unstable under some circumstances, but the bromide may be readily prepared by stirring the bromoacetal precursor (ca. 2-3 M in THF) with crushed Magnesium turnings (1.5 equiv) at rt under a dry nitrogen atmosphere, with periodical external cooling.1 For efficient formation, the chloride reagent is best prepared from a ca. 5 M solution of the chloroacetal in THF at below 30 °C.2 Less concentrated solutions require higher temperatures, inevitably resulting in partial decomposition to the alkoxide of 2-cyclobutyloxyethanol.2,3 The solutions of Grignard reagent are normally diluted with diethyl ether or THF before use.

Both reagents are effective nucleophiles. The bromide has been added to carbonyl groups, including those of a,b-unsaturated aldehydes,4 and to cyanides without disruption of an adjacent aziridine unit (eq 1).1 Copper-catalyzed conjugate addition to carboxymethyl alkynes also takes place; in this application the intermediate underwent Dieckmann-type cyclization, providing access to functionalized cyclopentenones (eq 2).5 The more common chloride reagent undergoes acylation with anhydrides6 and acid chlorides,9 addition to carbonyl groups,2 including those of a-chloro ketones,7 and conjugate addition-elimination to b-alkoxy-a,b-unsaturated ketones.8 Copper-catalyzed conjugate addition to a,b-unsaturated ketones is also reported,9,10 hydrolysis and cyclization of the products leading to cyclohexenyl ketones (eq 3). The reagent is also reported to undergo addition to oxazolidines with concomitant ring cleavage (eq 4).11

Related Reagents.

The functionally related organometallic reagents (1),12 (2),13 and (3)14 have been prepared. See also 2-(2-Bromoethyl)-1,3-dioxane, 3-Butenyl-1-magnesium Bromide, and 4-Ethylenedioxybutyllithium.

1. Wenkert, D.; Ferguson, S. B.; Porter, B.; Qvarnstrom, A.; McPhail, A. T. JOC 1985, 50, 4114.
2. Forbes, C. P.; Wenteler, G. L.; Wiechers, A. JCS(P1) 1977, 2353.
3. (a) Feugeas, C.; Normant, H. BSF(2) 1963, 1441. (b) Feugeas, C. BSF(2) 1963, 2568; 2579.
4. Danishefsky, S.; Funk, R. L.; Kerwin, J. F., Jr. JACS 1980, 102, 6889.
5. Crimmins, M. T.; Mascarella, S. W.; DeLoach, J. A. JOC 1984, 49, 3033.
6. van der Gen, A.; Wiedhaup, K.; Swoboda, J. J.; Dunathan, H. C.; Johnson, W. S. JACS 1973, 95, 2656.
7. Johnson, W. S.; Wiedhaup, K.; Brady, S. F.; Olson, G. L. JACS 1974, 96, 3979.
8. Overman, L. E. TL 1975, 1149.
9. Bal, S. A.; Marfat, A.; Helquist, P. JOC 1982, 47, 5045.
10. Abbott, R. E.; Spencer, T. A. JOC 1980, 45, 5398.
11. Higashiyama, K.; Nakahata, K.; Takahashi, H. H 1992, 33, 17.
12. Ryckman, D. M.; Stevens, R. V. JOC 1987, 52, 4274.
13. (a) Corey, E. J.; Balanson, R. D. JACS 1974, 96, 6516. (b) Ramón, D. J.; Yus, M. JOC 1991, 56, 3825.
14. Rigby, J. H.; McGuire, T. W. TL 1993, 34, 3017.

Philip C. Bulman Page & Andrew Lund

University of Liverpool, UK

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