Allyl Bromide

[106-95-6]  · C3H5Br  · Allyl Bromide  · (MW 120.99)

(electrophilic allylating agent attacking C, N, O, S, Se, and Te nucleophiles; homoallylic alcohols obtained selectively from aldehydes by various organometallic intermediates; addition reactions provide further reagents of wide applicability)

Physical Data: mp -119.4 °C; bp 71.3 °C; d 1.398 g cm-3.

Solubility: miscible with organic solvents; sparingly sol H2O.

Form Supplied in: yellow to brown liquid.

Purification: wash with water and with aqueous NaHCO3. Dry (MgSO4 or Na2SO4) and fractionally distill.

Handling, Storage, and Precautions: highly toxic; cancer suspect agent. Protect from light in brown glass.

Allylating Agent.

Carbon alkylation generally requires nucleophilic carbanions; thus the allylation of PhC&tbond;CH is promoted with powdered Potassium Hydroxide alone or with Tetra-n-butylammonium Bromide in dioxane.1 Dimeric side products (allyl ether, Ph2C4) and rearrangement enynes (PhC&tbond;CCH=CHMe; E/Z, 3:1) accompany PhC&tbond;CCH2CH=CH2. Carbanions from acetoacetic esters,2a,2b ketones,2c malonates (K2CO3-Me2CO or PhH),3 acetonitrile,4a and cyanoacetates4b readily undergo allylation (eq 1); the necessary base may be generated electrochemically, as in the use of pyrrolidone anion to bring about allylation of dimethyl 2-(trifluoromethyl)malonate.5 Perfluoro-2-methyl-2-pentyl carbanion is generated by the addition of F- (KF or CsF) to (CF3)2CFCF=CFCF3; upon allylation (RX; X = Cl, Br, I) the rearranged product (CF3)2C(R)CF2CF2CF3 results.6 Mn enolates of dialkyl ketones may be allylated (RBr; THF-sulfolane); thus Pr2CO gives PrCOCH(R)Et in 98% yield.7

The homoallylic alcohols RCH(OH)CH2CH=CH2 are formed from the reaction of RCHO and allyl bromide through organometallic intermediates, especially those involving allyl magnesium bromide. Ketones react similarly, but more slowly. The conventional Barbier-Grignard processes have been replaced by a reductive allylation. Thus Al brings about the reaction (i) in the presence of catalytic amounts of PbBr2 in DMF, aq THF, and/or aq MeOH8a or (ii) in the presence of BiCl3 in aq THF.8b The process may be specific to aldehydes; Pb-Me3SiCl-Bu4NBr in DMF promotes allylation of aldehydes without significantly attacking ketones or a-hydroxycarboxylic esters, while esters, lactones, acid anhydrides, and acid chlorides are effectively inert.9 Correspondingly, homoallylic alcohols are formed from aldehydes and allyl chloride, bromide, or iodide using Zn-BiCl3 or Fe-BiCl3, but ketones, esters, and benzoic acid are unaffected and do not interfere.10 Fe or Al with SbCl3 in aq DMF behaves similarly.11 Electrochemical variants are reported in which Bi acts as the reductant towards the aldehyde.12 Aldehydes and ketones react in the presence of Ph3Bi to give homoallylic alcohols or their allylic ethers.13 Zn alone in DMF gives 86% yields with allyl bromide and MeCH=CHCHO;14a Cd in DMF similarly shows only 1,2-addition with RCHO or RCOR´ (eq 2).14b A complex involving Ph2CO and Yb provides Ph2RCOH (R = allyl) with allyl bromide.15

Asymmetric allylation occurs in a number of appropriately substituted systems. The Schiff base between (+)-camphor and H2NCHR´P(O)(OEt)2 is metalated (n-Butyllithium) and then reacts with allyl bromide to give the (1S,4S) analog (R = allyl) with >95% diastereomeric excess (eq 3). Sequential hydrolysis provides the (S)-ester and the (S)-phosphonic acid without appreciable racemization;16a (1R,2R,5R)-(+)- and (1S,2S,5S)-(-)-2-hydroxy-3-pinanone behave analogously.16b The bis(cyclohexylidene) acetal of D-galactodialdehyde similarly gives Schiff bases with a-alkylated glycine esters; these may be metalated (BuLi) and the anion quenched with allyl bromide with 76% diastereomeric excess.17 Lithium Diisopropylamide metalation of a chiral lactam enolate and allylation s imilarly provides a considerable diastereomeric enhancement.18 Formation of the enol from tetralone with (R)-RCH2CHPhN(CH2CH2OCH2-CH2OMe)Li (R = piperidino) and allylation provides (R)-2-allyl-1-tetralone in 92% enantiomeric excess and 89% overall yield; Lithium Bromide is a necessary co-reagent (eq 4).19

Similarly, allylation of the lactam by allyl bromide-LDA20 proceeds stereospecifically to give (1).

Allylation of Ni complexes of some Schiff bases with glycine are reported21 to yield S-a-allylglycine. A three-step synthesis of a-amino acid HCl salts relies upon diastereoselective allylation of a glycine enolate synthon with >97.6% de and in 73-90% yield.22 N,N-Dimethylhydrazones of a,b-unsaturated aldehydes23a and RCH2CH=CHCH=CHCHO23b metalate (BuLi) and allylate with rearrangement, giving RCH(R´)(CH=CH)nCHO analogs (R´ = allyl; n = 1 or 2). Ph2C=NCH2CO2-t-Bu undergoes allylation (RBr, 50% aq NaOH, CH2Cl2, rt) in the presence of chiral PTC based upon cinchonine; the products show considerable ee (50-60%).24

Carbonyl insertion occurs when Me3P-coordinated p-allyl Pd complexes are treated with CO in CH2Cl2 at rt, giving 3-butenoyl derivatives,25 and allylation of a vinyl rhenium CO complex provides an allyl vinyl ketone complex.26 Organotin species couple with allyl bromide (catalyzed by Pd complexes); while b-elimination may supervene, CHO, CO2H, and OH groups do not interfere.27a Similar coupling occurs with RSiMe3 or RSiMe2F and allyl bromide,27b but alkenylboranes in the presence of Tetrakis(triphenylphosphine)palladium(0) give alkenes by allyldeboronation.27c Tetracarbonylnickel with allyl bromide (RBr) gives p-allyl nickel bromide complexes. These can act as intermediates in the coupling of allylic systems either symmetrically28a or to give substituted alkenes by unsymmetrical coupling (eq 5).28b

p-Allyl nickel bromide complexes allylate C-2 of benzoquinones.28c Oxygen-centered attack occurs readily; the K salt of L-ascorbic acid (2) gives (allyl bromide-Me2CO) a lactone (3) which with Palladium(II) Chloride in aq DMF provides (40%) a bicyclic ketone in which the allylic side chain has become the acetonyl (MeCOCH2) residue (eq 6).29

Stannylation of monoalkylated oxiranes by Trimethylstannyllithium gives lithium alkoxides XOCH(R)CH2SnMe3 (X = Li) which react conventionally with allyl bromide to give the corresponding allyl ether (X = allyl).30 Attack at oxygen may also be achieved using other displaced groups. Stannylene acetals of acyclic diols are monoallylated using F- in a mild, selective, and high yield process.31

N-Allylation takes place easily; phthalimide reacts readily with allyl bromide (K2CO3-PEG 400; 90 °C).32 Indoles33a and pyrazoles33b may be allylated on nitrogen using PTC such as Bu4NBr (eq 7).

Salts such as Na phenylsulfinate form allyl esters; Al2O3, ultrasound, and microwaves all influence the yield.34 Correspondingly, sulfur,35,36 selenium,36 or tellurium37 attack is preparatively useful (eq 8).

Alkyl coupling reactions, mediated by Cu, are exemplified by the synthesis of CF3CH2CH=CH2 using (CF3)2CuIII(N,N-diethyldithiocarbamato),38a or using FO2SCF2I in DMF.38b

The allyl system is susceptible to further chemistry, notably epoxidation and other addition processes; the intermediates in such processes may show their own idiosyncratic chemistry39 as in the cyclization of the thioallyl substituent (4) (eq 9), itself obtained by allylation of the thiophenoxide.

Related Reagents.

Allyl Chloride; Allyl Iodide.

1. Paravyan, S. L.; Torosyan, G. O.; Babayan, A. T. ZOR 1986, 22, 706.
2. (a) Tsuji, J.; Yamada, T.; Minami, I.; Yuhara, M.; Nisar, M.; Shimizu, J. JOC 1987, 52, 2988. (b) Hughes, P.; De Virgilio, J.; Humber, L. G.; Chau Thuy; Weichman, B.; Neuman, G. JMC 1989, 32, 2134. (c) Vanderwerf, C. A.; Lemmerman, L. V. OSC 1955, 3, 44.
3. Liu, H.; Cheng, G. Huaxue Shiji 1991, 13, 248, 202 (CA 1991, 115, 255 598m).
4. (a) Tamaru, Y. JACS 1988, 110, 3994. (b) Abd el Samii, Z. K. M.; Al Ashmawy, M. I.; Mellor, J. M. JCS(P1) 1988, 2523.
5. Fuchigami, T.; Nakagawa, Y. JOC 1987, 52, 5276.
6. Dmowski, W.; Wozniacki, R. JFC 1987, 36, 385.
7. Cahiez, G.; Figadere, B.; Tozzolino, P.; Clery, P. Eur. Patent 373 993, 1990 (CA 1991, 114, 61 550y).
8. (a) Tanaka, H.; Yamashita, S.; Hamatani, T.; Ikemoto, Y.; Torii, S. SC 1987, 17, 789. (b) Wada, M.; Ohki, H.; Akiba, K. CC 1987, 708.
9. Tanaka, H.; Yamashita, S.; Hamatani, T.; Ikemoto, Y.; Torii, S. CL 1986, 1611.
10. Wada, M.; Ohki, H.; Akiba, K. TL 1986, 27, 4771.
11. Wang, W.; Shi, L.; Huang, Y. T 1990, 46, 3315.
12. (a) Minato, M.; Tsuji, J. CL 1988, 2049. (b) Tanaka, H.; Nakahara, T.; Dhimane, H.; Torii, S. TL 1989, 30, 4161.
13. Huang, Y.; Liao, Y. HC 1991, 2, 297 (CA 1991, 115, 91 330q).
14. (a) Shono, T.; Ishifune, M.; Kashimura, S. CL 1990, 449. (b) Araki, S.; Ito, H.; Butsugan, Y. JOM 1988, 347, 5.
15. Takaki, K.; Tsubaki, Y.; Beppu, F.; Fujiwara, Y. Chem. Express 1991, 6, 57 (CA 1991, 114, 163 659h).
16. (a) Schöllkopf, U.; Schuetze, R. LA 1987, 45. (b) Jacquier, R.; Ouazzani, F.; Roumestant, M. L.; Viallefont, P. PS 1988, 36, 73.
17. Schoellkopf, U.; Toelle, R.; Egert, E.; Nieger, M. LA 1987, 399.
18. Wuensch, T.; Meyers, A. I. JOC 1990, 55, 4233.
19. Murakata, M.; Nakajima, M.; Koga, K. CC 1990, 1657.
20. Baldwin, J. E.; Adlington, R. M.; Gollins, D. W.; Schofield, C. J. T 1990, 46, 4733.
21. (a) Belokon, Yu. N.; Chernoglazova, N. I.; Ivanova, E. V.; Popkov, A. N.; Saporovskaya, M. B.; Suvorov, N. N.; Belikov, V. M. IZV 1988, 2818. (b) Belokon, Yu. N.; Maleev, V. I.; Saporovskaya, M. B.; Bakhmutov, V. I.; Timofeeva, T. V.; Batsanov, A. S.; Struchkov, Yu. T.; Belikov, V. M. Koord. Khim. 1988, 14, 1565 (CA 1989, 111, 16 646).
22. Dellaria, J. F.; Santarsiero, B. D. JOC 1989, 54, 3916.
23. (a) Yamashita, M.; Matsumiya, K.; Nakano, K.; Suemitsu, R. CL 1988, 1215. (b) Matsumiya, K.; Nakano, K.; Suemitsu, R.; Yamashita, M. CL 1988, 1837.
24. (a) O'Donnell, M. J.; Bennett, W. D.; Bruder, W. A.; Jacobsen, W. N.; Knuth, K.; Leclef, B.; Polt, R. L.; Bordwell, F. G.; Mrozack, S. R.; Cripe, T. A. JACS 1988, 110, 8520. (b) O'Donnell, M. J.; Bennett, W. D.; Wu, S. JACS 1989, 111, 2353. (c) O'Donnell, M. J.; Wu, S. TA 1992, 3, 591.
25. Ozawa, F.; Son, T.; Osakada, K.; Yamamoto, A. CC 1989, 1067.
26. Casey, C. P.; Vosejpka, P. C.; Gavney, J. A. JACS 1990, 112, 4083.
27. (a) Stille, J. K. AG(E) 1986, 25, 508. (b) Hatanaka, Y.; Hiyama, T. JOC 1988, 53, 918. (c) Hatanaka, Y.; Hiyama, T. JOC 1989, 54, 268. (d) Matteson, D. S. T 1989, 45, 1859.
28. (a) Tamao, K.; Kumada, M. In Chemistry of the Metal-Carbon Bond; Hartley, F. R., Ed.; Wiley: New York, 1987; Vol. 4, pp 819-887. (b) Semmelhack, M. F. OR 1972, 19, 115. (c) Hegedus, L. S.; Waterman, E. L.; Catlin, J. E. JACS 1972, 94, 7155.
29. Poss, A. J.; Belter, R. K. SC 1988, 18, 417.
30. Mordini, A.; Taddei, M.; Seconi, G. G 1986, 116, 239.
31. (a) Nagashima, N.; Ohno, M. CL 1987, 141. (b) Nagashima, N.; Ohno, M. CPB 1991, 39, 1972.
32. Vlassa, M.; Kezdi, M.; Fenesan, M. Rev. Roum. Chim. 1989, 34, 1607 (CA 1990, 113, 6079).
33. (a) Hlasta, D. J.; Luttinger, D.; Perrone, M. H.; Silbernagel, M. J.; Ward, S. J.; Haubrich, D. R. JMC 1987, 30, 1555. (b) Diez-Barra, E.; de la Hoz, A.; Sanchez-Migallon, A.; Tejeda, J. SC 1990, 20, 2849.
34. Villemin, D.; Ben Alloum, A. SC 1990, 20, 925.
35. Nishimura, H.; Ariga, T. Jpn. Patent 02 204 487, 1990 (CA 1990, 114, 6523s).
36. Barton, D. H. R.; Crich, D. JCS(P1), 1986, 1613.
37. (a) Higa, K. T.; Harris, D. C. OM 1989, 8, 1674. (b) Higa, K. T.; Harris, D. C. US Patent Appl. 66442, 1988 (CA 1988, 109, 190 579k).
38. (a) Willert-Porada, M. A.; Burton, D. J.; Baenziger, N. C. CC 1989, 1633. (b) Chen, Q.; Wu, S. JCS(P1) 1989, 2385.
39. Shestopalov, A. M.; Rodinovskaya, L. A.; Sharanin, Yu. A.; Litvinov, V. P. Khim. Geterotsikl. Soedin. 1990, 256 (CA 1990, 113, 39 658x).

Roger Bolton

University of Surrey, Guildford, UK

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