Crotylmagnesium Bromide

(X = Br)

[6088-87-5]  · C4H7BrMg  · Crotylmagnesium Bromide  · (MW 159.32) (X = Cl)

[6088-88-6]  · C4H7ClMg  · Crotylmagnesium Chloride  · (MW 114.86)

(agent capable of regioselective addition to carbonyl compounds1,23-27 and derivatives,28,34 unactivated C-C double bonds,43 nitro compounds,30-32 nitriles,34 imines,34 and aza aromatics,35-39 and of displacement of halogens from halo compounds.1,29,40,41)

Alternate Name: 2-butenylmagnesium bromide.

Solubility: bromide: sol diethyl ether, dibutyl ether;3 chloride: sol diethyl ether, THF.

Form Supplied in: the precursor crotyl bromide and chloride (the latter 95% predominantly (E)) are commercially available.

Analysis of Reagent Purity: titration of crotylmagnesium bromide can be carried out with s-BuOH in xylene using 1,10-phenanthroline12 or N-phenyl-1-naphthylamine14 as indicators or with a double titration method using dibromoethane.13 Other procedures are available.10,15-17

Preparative Methods: crotylmagnesium bromide and chloride can be prepared from commercial crotyl halides and Magnesium in diethyl or dibutyl ether.2,18,19 The undesired homocoupling reaction3 can be minimized by increasing the time of addition of the halide, the solvent/halide ratio, and by using 20-30 mesh magnesium turnings prepared just prior to use.1 CrotylMgBr can be prepared from commercial crotyl bromide which usually contains 13% of a-methylallyl bromide as an impurity owing to an equilibration between the two isomers (eq 1). These two isomers can be separated by low-temperature distillation,4 although this is not needed since both the bromo isomers produce the same Grignard reagent. Similarly, crotylMgCl is prepared from commercial Crotyl Chloride which is frequently5,6 a mixture of a-methylallyl chloride and cis- and trans-crotyl chlorides separable from the former by simple fractional distillation. cis-Crotyl chloride can be prepared from cis-crotyl alcohol.11

Handling, Storage, and Precautions: the precursor isomeric butenyl chlorides are much more stable than the bromides and can be stored without rearrangement for long periods of time in sealed Teflon bottles over anydrous MgSO4.18 Crotylmagnesium halides are moisture sensitive reagents, inflammable, reacting violently with water.

Structure.

Crotylmagnesium halides exist as a rapidly equilibrating mixture of two forms, the less branched being the more abundant (eq 2).7

The isotopic perturbation technique8 has been used to distinguish between the s- and p-bond structures of allyl- and crotylmagnesium reagents.9 The 13C NMR spectra of the deuterated crotyl reagents have demonstrated that crotylmagnesium halides are s-structures in which the metal is attached to the primary carbon. Alkyl-substituted allylic Grignard reagents in diethyl ether solution exist as a rapidly equilibrating mixture of (Z) and (E) primary isomers.18 Protonation and coupling constant studies have shown that the percentage of (Z) isomer decreases as the size of the alkyl substituent (R) on the carbon of the Grignard reagent increases (eq 3).

Reactions.

With few exceptions, crotylmagnesium halides react with electrophiles at the internal C atom. Treatment of crotylmagnesium halides with a wide variety of protonating agents20-22 gives rise to a mixture of 1- and 2-butene with the former usually predominating.

The reaction of unhindered carbonyl compounds with crotyl Grignards gives the g-adduct (eq 4).23 This regioselectivity can be reversed by addition of Aluminum Chloride, which results in a predominant formation of the a-adduct.24 With a hindered ketone,2 such as di-t-butyl ketone, the a-adduct is sometimes obtained because of the reversible addition of the allylic organometallic reagent.25,26 CrotylMgCl gives 1,2-addition to a,b-ethylenic ketones; the relevant stereochemistry has been studied.27

Other typical reactions with epoxides, acid chlorides, amides, and many other classes of compounds have been extensively treated;1,28d the formation of tetrahydropyridines from aryl nitriles has also been reported.34

Alkylation of crotyl Grignard reagents in the presence of Copper(I) Iodide results in almost exclusive substitution at the a-position; the reaction is very slow in the absence of CuI.29

Butenylmagnesium chloride adds to nitro compounds, leading to allylic nitrones (eq 5).30 The chemo-, regio- and stereoselectivity of this reaction,31 as well as a possible enantioselective synthesis of nitrogen derivatives (hydroxylamines and amines) by allyl Grignard addition to optically active nitroalkanes, have been reported.32

In the presence of Dichlorobis(cyclopentadienyl)titanium, Cp2TiCl2, isoprene undergoes a regioselective insertion into the allyl-magnesium bond (eq 6). This insertion has been applied to the synthesis of various natural terpenoids and related products.33

Crotylmagnesium halides add promptly to the C=N moiety of 2-alkylthiazolines, leading to 2-alkyl-2-a-methylallylthiazolidines,35 and to 2-alkylbenzothiazoles, leading to 2-alkyl-2-a-methylallylbenzothiazolines or N-alkyl-bis(a-methylallyl)methyl-o-aminobenzenethiol depending upon the experimental conditions.36 2-Heterosubstituted benzothiazoles react with crotylmagnesium halides, regioselectively producing 2-a-methylallylbenzothiazole, 2,2-bis(a-methylallyl)benzothiazoline, or N-tris(a-methylallyl)methyl-o-aminobenzenethiol depending upon the experimental conditions.37 Comparable results were obtained in the reaction of benzoxazole derivatives.38,39 Cross-coupling of crotylmagnesium halides with halogenoquinoxalines,40 -pyrimidines,41 and -pyridines42 provides a regioselective synthesis of the corresponding a-methylallyl derivatives.

CrotylMgCl adds regioselectively to the unactivated C-C double bond of some aza aromatics.43

Related Reagents.

Prenylmagnesium chloride (1),44 cyclohexenylmethylmagnesium bromide (2),44b cinnamylmagnesium bromide (3),45 and 2-pentenylmagnesium bromide (4)46 have been prepared by reacting the appropriate halide with magnesium and their reactivity is comparable with that of crotylmagnesium halides.

See also Allyllithium, Allylmagnesium Bromide, B-Crotyldiisopinocampheylborane, Crotyllithium, Crotyltrimethylsilane, Methallyllithium, and Methallylmagnesium Chloride.


1. Benkeser, R. A. S 1971, 347.
2. Benkeser, R. A.; Young, W. G.; Broxterman, W. E.; Jones, D. A., Jr.; Piaseczynski, S. J. JACS 1969, 91, 132.
3. Young, W. G.; Prater, A. N.; Winstein, S. JACS 1933, 55, 4908.
4. Winstein, S.; Young, W. G. JACS 1936, 58, 104.
5. Brubacher, L. J.; Treindl, L.; Robertson, R. E. JACS 1968, 90, 4611.
6. Magid, R. M.; Gandour, R. D. JOC 1970, 35, 269.
7. Nutzel, K. MOC 1973, 13/2a, 491.
8. Saunders, M.; Telkowski, L.; Kates, M. R. JACS 1977, 99, 8070. Saunders, M.; Kates, M. R. JACS 1977, 99, 8071. Saunders, M.; Kates, M. R.; Wiberg, K. B.; Pratt, W. JACS 1977, 99, 8072.
9. Schlosser, M.; Stahle, M. AG(E) 1980, 19, 487.
10. Gilman, H.; Wilkinson, P. D., Fishel, W. P.; Meyers, C. H. JACS 1923, 45, 150.
11. (a) Young, W. G.; Sharman, S. H.; Winstein, S. JACS 1960, 82, 1376. (b) Hatch, L. F.; Nesbitt, S. S. JACS 1950, 72, 727. (c) Sharman, S. H.; Caserio, F. F.; Nystrom, R. F.; Leak, J. C.; Young, W. G. JACS 1958, 80, 5965.
12. Watson, S. C.; Eastham, J. F. JOM 1967, 9, 165.
13. Gilman, H.; Cartledge, F. K. JOM 1964, 2, 447.
14. Bergbreiter, D. E.; Pendergrass, E. JOC 1981, 46, 219.
15. Duhamel, L.; Plaquevent, J.-C. JOC 1979, 44, 3404.
16. Winkle, M. R.; Lansinger, J. M.; Ronald, R. C. CC 1980, 87.
17. Kofron, W. G.; Baclawski, L. M. JOC 1976, 41, 1879.
18. Hutchison, D. A.; Beck, K. R.; Benkeser, R. A.; Grutzner, J. B. JACS, 1973, 95, 7075.
19. Gaudemar, M. BSF 1958, 1475.
20. Young, W. G.; Pokras, H. H. JOC 1942, 7, 233.
21. Wilson, K. W.; Roberts, J. D.; Young, W. G. JACS 1950, 72, 215.
22. Agami, C.; Andrac-Taussig, M.; Prévost, C. BSF 1966, 1915, 2596.
23. Yamamoto, Y.; Yatagai, H.; Naruta, Y.; Maruyama, K. JACS 1980, 102, 7107. Hoffmann, R. W. AG(E) 1982, 21, 555. Sjöholm, R. E. ACS 1990, 44, 82.
24. Yamamoto, Y.; Maruyama, K. JOC 1983, 48, 1564.
25. Benkeser, R. A.; Broxterman, W. E. JACS 1969, 91, 5162.
26. Benkeser, R. A.; Siklosi, M. P.; Mozdzen, E. C. JACS 1978, 100, 2134. Cram, D. J. Fundamentals of Carbanion Chemistry; Academic: New York, 1965; p. 138.
27. Zair, T.; Santelli-Rouvier, C.; Santelli, M. JOC 1993, 58, 2686.
28. (a) Yamamoto, Y. ACR 1987, 20, 243. (b) Hoffmann, R. W. AG(E) 1982, 21, 555. (c) Yamamoto, Y.; Maruyama, K. H 1982, 18, 357. (d) Courtois, G.; Miginiac, L. JOM 1974, 69, 1.
29. Derguini-Boumechal, F.; Lorne, R.; Linstrumelle, G. TL 1977, 1181.
30. Bartoli, G.; Marcantoni, E.; Petrini, M. JOC 1990, 55, 4456.
31. Bartoli, G.; Marcantoni, E.; Petrini, M. JOC 1992, 57, 5834.
32. Bartoli, G.; Marcantoni, E.; Petrini, M. CC 1991, 793.
33. Akutagawa, S.; Otsuka, S. JACS 1975, 97, 6870.
34. Grassberger, M. A.; Horvath, A.; Schulz, G. TL 1991, 32, 7393.
35. Laduranty, J.; Barbot, F.; Miginiac, L. BSF(2) 1987, 837.
36. Babudri, F.; Bartoli, G.; Ciminale, F.; Florio, S.; Ingrosso, G. TL 1984, 25, 2047.
37. Florio, S.; Epifani, E.; Ingrosso, G. T 1984, 40, 4527.
38. Florio, S.; Epifani, E.; Ingrosso, G.; Sgarra, R. T 1984, 40, 5089.
39. Babudri, F.; Florio, S.; Ronzini, L. T 1986, 14, 3905.
40. Epifani, E.; Florio, S.; Ingrosso, G.; Sgarra, R.; Stasi, F. T 1987, 43, 2769.
41. Epifani, E.; Florio, S.; Ingrosso, G.; Babudri, F. T 1989, 45, 2075.
42. Pini, D.; Lazzaroni, R.; Bertozzi, S.; Salvadori, P. G 1983, 113, 227.
43. Lazzaroni, R.; Pini, D.; Bertozzi, S.; Fatti, G. JOC 1986, 51, 505.
44. (a) Akutagawa, S.; Otsuka, S. JACS 1975, 97, 6870. (b) Linstrumelle, G.; Lorne, R.; Dang, H. P. TL 1978, 42, 4069.
45. Ebel, H. F.; Wagner, B. O. CB 1971, 104, 307.
46. Grassberger, M. A.; Horvath, A.; Schulz, G. TL 1991, 32, 7393.

Saverio Florio & Vito Capriati

University of Bari, Italy



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