Zinc Bromide1

ZnBr2

[7699-45-8]  · Br2Zn  · Zinc Bromide  · (MW 225.19)

(used in the preparation of organozinc reagents via transmetalation;1 a mild Lewis acid useful for promoting addition2 and substitution reactions3)

Physical Data: mp 394 °C; bp 697 °C (dec); d 4.201 g cm-3.

Solubility: sol Et2O, H2O (1 g/25 mL), 90% EtOH (1 g/0.5 mL).

Form Supplied in: granular white powder; principal impurity is H2O.

Analysis of Reagent Purity: melting point.

Purification: heat to 300 °C under vacuum (2 × 10-2 mmHg) for 1 h, then sublime.

Handling, Storage, and Precautions: very hygroscopic; store under anhydrous conditions. Irritant.

Organozinc Reagents.

The transmetalation of organomagnesium, organolithium, and organocopper reagents by anhydrous ZnBr2 in ethereal solvents offers a convenient method of preparing organozinc bromides and diorganozinc reagents.1a Alternatively, anhydrous ZnBr2 may be reduced by potassium metal to result in highly activated Zn0, which is useful for the preparation of zinc reagents through oxidative addition to organic halides.4 Alkyl, allylic, and propargylic zinc reagents derived by these methods have shown considerable value in their stereoselective and regioselective addition reactions with aldehydes, ketones, imines, and iminium salts.1a,5 Zinc enolates used in the Reformatsky reaction may also be prepared through transmetalation using ZnBr2.1b Organozinc species are especially useful in palladium- and nickel-catalyzed coupling reactions of sp2 carbon centers. In this fashion, sp2-sp3 (eq 1)6 and sp2-sp2 (eqs 2 and 3)7,8 carbon-carbon bonds are formed selectively in high yields. The enantioselective cross coupling of secondary Grignard reagents with vinyl bromide is strongly affected by the presence of ZnBr2, which accelerates the reaction and inverts its enantioselectivity (eq 4).9

Organozinc intermediates formed via transmetalation using ZnBr2 have been used to effect carbozincation of alkenes and alkynes through metallo-ene and metallo-Claisen reactions. Both intermolecular and intramolecular variants of these reactions have been described, often proceeding with high levels of stereoselectivity and affording organometallic products that may be used in subsequent transformations (eqs 5 and 6),10 including alkenation (eq 6).10b,c Bimetallic zinc-zirconium reagents have also been developed that offer a method for the alkenation of carbonyl compounds (eq 7).11

Concerted Ring-Forming Reactions.

The mild Lewis acid character of ZnBr2 sometime imparts a catalytic effect on thermally allowed pericyclic reactions. The rate and stereoselectivity of cycloaddition reactions (eq 8),12 including dipolar cycloadditions (eq 9),13 are significantly improved by the presence of this zinc salt.

Some intramolecular ene reactions benefit from ZnBr2 catalysis to afford the cyclic products under milder conditions, in higher yields and selectivities (eqs 10 and 11).14,15 Generally, the use of ZnBr2 is preferred over Zinc Chloride or Zinc Iodide in this type of reaction.15

Activation of C=X Bonds.

Lewis acid activation of carbonyl compounds by ZnBr2 promotes the addition of allylsilanes and silyl ketene acetals.16 Addition to imines has also been reported.17 In general, other Lewis acids have been found to be more useful, though in some instances ZnBr2 has proven to be advantageous (eq 12).2

Activation of C-X Bonds.

Even more important than carbonyl activation, ZnBr2 promotes substitution reactions with suitably active organic halides with a variety of nucleophiles. Alkylation of silyl enol ethers and silyl ketene acetals using benzyl and allyl halides proceeds smoothly (eq 13).3 Especially useful electrophiles are a-thio halides which afford products that may be desulfurized or oxidatively eliminated to result in a,b-unsaturated ketones, esters, and lactones (eq 14).18 Other electrophiles that have been used with these alkenic nucleophiles include Chloromethyl Methyl Ether, HC(OMe)3, and Acetyl Chloride.3,19

Enol ethers and allylic silanes and stannanes will engage cyclic a-seleno sulfoxides,20 o-acetoxy lactams,21 and acyl glycosides (eq 15)22 in the presence of ZnBr2 catalysis. Along these lines, it has been found that ZnBr2 is superior to Boron Trifluoride Etherate in promoting glycoside bond formation using trichloroimidate-activated glycosides (eq 16).23 Imidazole carbamates are also effective activating groups for ZnBr2-mediated glycosylation (eq 17).24

Cyclic acetals also undergo highly selective, Lewis acid-dependent ring opening substitution with Cyanotrimethylsilane (eq 18).25

Reduction.

Complexation with ZnBr2 has been shown to markedly improve stereoselectivity in the reduction of certain heteroatom-substituted ketones (eqs 19 and 20).26,27 Furthermore, the anti selectivity observed in BF3.OEt2-mediated intramolecular hydrosilylation of ketones is reversed when ZnBr2 is used instead (eq 21).28

Deprotection.

ZnBr2 is a very mild reagent for several deprotection protocols, including the detritylation of nucleotides29 and deoxynucleotides,30 N-deacylation of N,O-peracylated nucleotides,31 and the selective removal of Boc groups from secondary amines in the presence of Boc-protected primary amines.32 Perhaps the most widespread use of ZnBr2 for deprotection is in the mild removal of MEM ethers to afford free alcohols (eq 22).33

Miscellaneous.

An important method for the synthesis of stereodefined trisubstituted double bonds involves the treatment of cyclopropyl bromides with ZnBr2. The (E) isomer is obtained almost exclusively by this method (eq 23).34

The rearrangement of a variety of terpene oxides has been examined (eq 24).35 While ZnBr2 is generally a satisfactory catalyst for this purpose, other Lewis acids, including ZnCl236 and Magnesium Bromide,37 are advantageous in some instances.

In the presence of ZnBr2/48% Hydrobromic Acid, suitably functionalized cyclopropanes undergo ring expansion to afford cyclobutane (eq 25)38 and a-methylene butyrolactone products (eq 26).39 One-carbon ring expansion has been reported when certain trimethylsilyl dimethyl acetals are exposed to ZnBr2 with warming (eq 27).40


1. (a) Knochel, P. COS 1991, 1, Chapter 1.7. (b) Rathke, M. W.; Weipert, P. COS 1991, 2, Chapter 1.8.
2. For an example: Bellassoued, M.; Ennigrou, R.; Gaudemar, M. JOM 1988, 338, 149.
3. For examples: (a) Reetz, M. T.; Maier, W. F. AG(E) 1978, 17, 48. (b) Reetz, M. T.; Chatziiosifidis, I.; Löwe, W. F.; Maier, W. F. TL 1979, 1427. (c) Paterson, I. TL 1979, 1519.
4. Riecke, R. D.; Uhm, S. J.; Hudnall, P. M. CC 1973, 269.
5. For representative examples of allylic and propargylic zinc reagents: (a) Yamamoto, Y.; Nishii, S.; Maruyama, K.; Komatsu, T.; Ito, W. JACS 1986, 108, 7778. (b) Yamamoto, Y.; Ito, W. T 1988, 44, 5414. (c) Yamamoto, Y.; Ito, W.; Maruyama, K. CC 1985, 1131. (d) Yamanoto, Y.; Komatsu, T.; Maruyama, K. CC 1985, 814. (e) Fronza, G.; Fuganti, C.; Grasselli, P.; Pedrocchi-Fantoni, G.; Zirotti, C. TL 1982, 23, 4143. (f) Fujisawa, T.; Kojima, E.; Itoh, T.; Sato, T. TL 1985, 26, 6089. (g) Pornet, J.; Miginiac, L. BSF 1975, 841. (h) Yamamoto, Y.; Komatsu, T.; Maruyama, K. JOM 1985, 285, 31. (i) Bouchoule, C.; Miginiac, P. CR(C) 1968, 266, 1614. (j) Miginiac, L.; Mauzé, B. BSF 1968, 3832. (k) Arous-Chtara, R.; Gaudemar, M.; Moreau, J.-L. CR(C) 1976, 282, 687. (l) Moreau, J.-L.; Gaudemar, M. BSF 1971, 3071. (m) Miginiac, L.; Mauzé, B. BSF 1968, 2544.
6. Negishi, E.; King, A. O.; Okudado, N. JOC 1977, 42, 1821.
7. Sengupta, S.; Snieckus, V. JOC 1990, 55, 5680. See also: Gilchrist, T. L.; Summersell, R. J. TL 1987, 28, 1469.
8. (a) Jabri, N.; Alexakis, A.; Normant, J. F. BSF(2) 1983, 321. (b) Jabri, N.; Alexakis, A.; Normant, J. F. TL 1982, 23, 1589. (c) Jabri, N.; Alexakis, A.; Normant, J. F. TL 1981, 22, 959. (d) Jabri, N.; Alexakis, A.; Normant, J. F. TL 1981, 22, 3851.
9. Cross, G.; Vriesema, B. K.; Boven, G.; Kellogg, R. M.; van Bolhuis, F. JOM 1989, 370, 357.
10. (a) Courtemanche, G.; Normant, J.-F. TL 1991, 32, 5317. (b) Marek, I.; Normant, J.-F. TL 1991, 32, 5973. (c) Marek, I.; Lefrançois, J.-M.; Normant, J.-F. SL 1992, 633.
11. Tucker, C. E.; Knochel, P. JACS 1991, 113, 9888.
12. Narayana Murthy, Y. V. S.; Pillai, C. N. SC 1991, 21, 783. See also: López, R.; Carretero, J. C. TA 1991, 2, 93.
13. Kanemasa, S.; Tsuruoka, T.; Wada, E. TL 1993, 34, 87.
14. Tietze, L. F.; Biefuss, U.; Ruther, M. JOC 1989, 54, 3120. See also: (a) Tietze, L. F.; Ruther, M. CB 1990, 123, 1387. (b) Nakatani, Y.; Kawashima, K. S 1978, 147.
15. Hiroi, K.; Umemura, M. TL 1992, 33, 3343.
16. (a) Mikami, K.; Kawamoto, K.; Loh, T.-P.; Nakai, T. CC 1990, 1161. (b) Bellassoued, M.; Gaudemar, M. TL 1988, 29, 4551.
17. Gaudemar, M.; Bellassoued, M. TL 1990, 31, 349.
18. Khan, H. A.; Paterson, I. TL 1982, 23, 5083. See also: (a) Paterson, I. T 1988, 44, 4207. (b) Khan, H. A.; Paterson, I. TL 1982, 23, 4811. (c) Paterson, I.; Fleming, I. TL 1979, 20, 993, 995, 2179.
19. Fleming, I.; Goldhill, J.; Paterson, I. TL 1979, 3209.
20. Ren, P.; Ribezzo, M. JACS 1991, 113, 7803.
21. Ohta, T.; Shiokawa, S.; Iwashita, E.; Nozoe, S. H 1992, 34, 895.
22. Kozikowski, A. P.; Sorgi, K. L. TL 1982, 23, 2281.
23. Urban, F. J.; Moore, B. S.; Breitenbach, R. TL 1990, 31, 4421.
24. Ford, M. J.; Ley, S. V. SL 1990, 255.
25. Corcoran, R. C. TL 1990, 31, 2101.
26. Bartnik, R.; Lesniak, S.; Laurent, A. TL 1981, 22, 4811.
27. Barros, D.; Carreño, M. C.; Ruano, J. L. G.; Maestro, M. C. TL 1992, 33, 2733.
28. Anwar, S.; Davis, A. P. T 1988, 44, 3761.
29. Waldemeier, F.; De Bernardini, S.; Leach, C. A.; Tamm, C. HCA 1982, 65, 2472.
30. (a) Kohli, V.; Blöcker, H.; Köster, H. TL 1980, 21, 2683. (b) Matteuci, M. D.; Caruthers, M. H. TL 1980, 21, 3243.
31. Kierzek, R.; Ito, H.; Bhatt, R.; Itakura, K. TL 1981, 22, 3761.
32. Nigam, S. C.; Mann, A.; Taddei, M.; Wermuth, C.-G. SC 1989, 19, 3139.
33. Corey, E. J.; Gras, J.-L.; Ulrich, P. TL 1976, 809.
34. Johnson, W. S.; Li, T.; Faulkner, D. J.; Campbell, S. F. JACS 1968, 90, 6225. See also: (a) Brady, S. F.; Ilton, M. A.; Johnson, W. S. JACS 1968, 90, 2882. (b) Nakamura, H.; Yamamoto, H.; Nozaki, H. TL 1973, 111.
35. Lewis, J. B.; Hendrick, G. W. JOC 1965, 30, 4271. See also: (a) Settine, R. L.; Parks, G. L.; Hunter, G. L. K. JOC 1964, 29, 616. (b) Bessière-Chréieu, Y.; Bras, J. P. CR(C) 1970, 271, 200. (c) Clark, Jr., B. C.; Chafin, T. C.; Lee, P. L.; Hunter, G. L. K. JOC 1978, 43, 519. (d) Watanabe, H.; Katsuhara, J.; Yamamoto, N. BCJ 1971, 44, 1328.
36. Kaminski, J.; Schwegler, M. A.; Hoefnagel, A. J.; van Bekkum, H. RTC 1992, 111, 432.
37. Serramedan, D.; Marc, F.; Pereyre, M.; Filliatre, C.; Chabardès, P.; Delmond, B. TL 1992, 33, 4457.
38. Kwan, T. W.; Smith, M. B. SC 1992, 22, 2273.
39. Hudrlik, P. F.; Rudnick, L. R.; Korzeniowski, S. H. JACS 1973, 95, 6848.
40. (a) Tanino, K.; Katoh, T.; Kuwajima, I. TL 1988, 29, 1815. (b) Tanino, K.; Katoh, T.; Kuwajima, I. TL 1988, 29, 1819. See also: Tanino, K.; Sato, K.; Kuwajima, I. TL 1989, 30, 6551.

Glenn J. McGarvey

University of Virginia, Charlottesville, VA, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.