3-Butenyl-1-magnesium Bromide

[7103-09-5]  · C4H7BrMg  · 3-Butenyl-1-magnesium Bromide  · (MW 159.31)

(nucleophilic Grignard reagent used as a synthetic equivalent of the 3-butenyl anion)

Solubility: normally prepared in THF and used in situ.

Handling, Storage, and Precautions: Grignard reagent sensitive to moisture. Normally prepared and used immediately.

Nucleophilic Additions.

This reagent, like the analogous organolithium reagent, is employed in synthetic chemistry as a synthetic equivalent of the 3-butenyl anion and also as a synthon for the 3-oxopropyl anion. The reagent is normally used in ether solvents, typically diethyl ether or THF, and is readily prepared under standard conditions for Grignard reagent formation by dropwise addition to Magnesium turnings, with external cooling following reaction initiation. Four principal types of addition reaction are seen: addition to carbonyl groups and their various derivatives, conjugate addition to a,b-unsaturated ketones, displacements of halides and other leaving groups from alkyl or even aryl substrates, and addition to epoxides with ring cleavage. Metal-metal exchange is also observed.

Addition to prochiral carbonyl groups of aldehydes and ketones is common, as in the representative examples shown in eqs 1-4,1-4 and often takes place with high stereoselectivity. Interestingly, addition to g-Butyrolactone takes place successfully to give the hemiacetal (eq 5).5 In contrast, simple esters have been shown to undergo double addition leading to carbinols; this property has been utilized in a clever synthesis of functionalized dienes by use of a-silyl-b,g-unsaturated esters as substrates; an in situ Peterson elimination then takes place upon alkoxide formation to give the conjugated dienes (eq 6).6 N,O-Dimethylhydroxamates have been used to limit nucleophilic addition to 1 equiv of reagent, giving the ketonic product.7

Imines are also successful substrates for the copper-catalyzed addition of 3-butenylmagnesium bromide in the presence of Lewis acids (eq 7). The d,ε-unsaturated amine products may be cyclized by intramolecular aminoselenation to produce pyrrolidine derivatives.8

Copper-catalyzed conjugate addition is an equally general and successful procedure, and was employed by Ley in his synthesis of ajugarin I in a highly stereoselective reaction (eq 8).9 In this case it was essential to add the enone, in ethereal solution, dropwise to a solution of the organometallic. Corresponding reactions with similar oxoacetals are much less stereoselective.10 Other representative examples are given in eqs 9-11.11-14

There are relatively few examples of nucleophilic substitution reactions involving this reagent. Whiting has reported the efficient displacement of a secondary pivaloyloxy group (eq 12),15 and an interesting displacement of chloride from an a-chlorinated glycine derivative is shown in eq 13.16 The reagent has also been used at -20 °C for selective aromatic nucleophilic substitution of one cyanide group from tetrafluoroterephthalonitrile in 60% yield.17

The corresponding addition to epoxides can be very efficient. For example, addition to (R)-(-)-1-nonene oxide in the presence of Copper(I) Bromide occurs at -10 °C to give the enantiomerically pure secondary alcohol in 90% yield (eq 14),18 and the THP ether of glycidol undergoes addition under similar conditions, again in 90% yield (eq 15).19

3-Butenyl-1-magnesium bromide has also been used to generate the corresponding organozinc species by metal exchange using Zinc Chloride. The organozinc species was used in enantioselective addition to aldehydes catalyzed by a spirotitanate derived from (R,R)-tartaric acid.20

Although 3-butenylmagnesium bromide is known to be in equilibrium with small amounts of cyclopropylmethylmagnesium bromide,21 cyclopropyl products are not observed.

Related Reagents.

2-(2-Bromoethyl)-1,3-dioxane; 3-(1-Ethoxyethoxy)propylmagnesium Bromide.

1. Bolis, G.; Fung, A. K. L.; Greer, J.; Kleinert, H. D.; Marcotte, P. A.; Perun, T. J.; Plattner, J. J.; Stein, H. H. JMC 1987, 30, 1729.
2. Williams, D. R.; Klingler, F. D.; Dabral, V. TL 1988, 29, 3415.
3. O'Shea, M. G.; Kitching, W. T 1989, 45, 1177.
4. Ireland, R. E.; Maienfisch, P. JOC 1988, 53, 640.
5. Kraus, G. A.; Thurston, J. TL 1987, 28, 4011.
6. Prieto, J. A.; Larson, G. L.; Berrios, R.; Santiago, A. SC 1988, 18, 1385.
7. DiMaio, J.; Gibbs, B.; Lefebvre, J.; Konishi, Y.; Munn, D.; Yue, S. Y.; Horberger, W. JMC 1992, 35, 3331.
8. Wada, M.; Aiura, H.; Akiba, K.-y. H 1987, 26, 929.
9. Ley, S. V.; Neuhaus, D.; Simpkins, N. S.; Whittle, A. J. JCS(P1) 1982, 2157; Jones, P. S.; Ley, S. V.; Simpkins, N. S.; Whittle, A. J. T 1986, 42, 6519.
10. Zoretic, P. A.; Dickerson, S. H.; Yu, B.-C.; Biggers, M. S.; Chambers, R. J.; Biggers, C. K.; Caspar, M. L. SC 1989, 19, 2869.
11. Mehta, G.; Rao, K. S. CC 1987, 1578.
12. Brown, D. S.; Marples, B. A.; Spilling, C. D. JCS(P1) 1988, 2033.
13. Zhao, S.-K.; Knors, C.; Helquist, P. JACS 1989, 111, 8527.
14. Nagumo, S.; Suemune, H.; Sakai, K. CC 1990, 1778.
15. Hobbs-Mallyon, D.; Whiting, D. A. CC 1991, 899.
16. Castelhano, A. L.; Horne, S.; Billedeau, R.; Krantz, A. TL 1986, 27, 2435.
17. Milner, D. J. JOM 1986, 302, 147.
18. Matsumoto, K.; Tsutsumi, S.; Ihori, T.; Ohta, H. JACS 1990, 112, 9614.
19. Matsumoto, K.; Suzuki, N.; Ohta, H. TL 1990, 49, 7163.
20. Seebach, D.; Behrendt, L.; Felix, D. AG(E) 1991, 30, 1008.
21. Patel, D. J.; Hamilton, C. L.; Roberts, J. D. JACS 1965, 87, 5144.

Philip C. Bulman Page & Andrew Lund

The University of Liverpool, UK

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