ALLYL BROMIDE 1
Allyl Bromide 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
Br
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
[106-95-6] C3H5Br (MW 120.99)
react in the presence of Ph3Bi to give homoallylic alcohols or
InChI = 1/C3H5Br/c1-2-3-4/h2H,1,3H2
their allylic ethers.13 Zn alone in DMF gives 86% yields with
InChIKey = BHELZAPQIKSEDF-UHFFFAOYAI
allyl bromide and MeCH=CHCHO;14a Cd in DMF similarly
shows only 1,2-addition with RCHO or RCOR (eq 2).14b A
(electrophilic allylating agent attacking C, N, O, S, Se, and Te
complex involving Ph2CO and Yb provides Ph2RCOH (R = allyl)
nucleophiles; homoallylic alcohols obtained selectively from
with allyl bromide.15
aldehydes by various organometallic intermediates; addition
reactions provide further reagents of wide applicability)
R2
OH
M
Br
+ RCOR2 (2)
ć% ć%
R
Physical Data: mp -119.4 C; bp 71.3 C; d 1.398 g cm-3.
R = H, alkyl; M = Zn, Cd, Al etc.
Solubility: miscible with organic solvents; sparingly sol H2O.
Form Supplied in: yellow to brown liquid.
Asymmetric allylation occurs in a number of appropriately
Purification: wash with water and with aqueous NaHCO3. Dry
substituted systems. The Schiff base between (+)-camphor and
(MgSO4 or Na2SO4) and fractionally distill.
H2NCHR P(O)(OEt)2 is metalated (Butyllithium) and then re-
Handling, Storage, and Precautions: highly toxic; cancer suspect
acts with allyl bromide to give the (1S,4S) analog (R = allyl)
agent. Protect from light in brown glass.
with >95% diastereomeric excess (eq 3). Sequential hydroly-
sis 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
Allylating Agent. Carbon alkylation generally requires nu-
(cyclohexylidene) acetal of D-galactodialdehyde similarly gives
cleophilic carbanions; thus the allylation of PhCa"CH is pro-
Schiff bases with Ä…-alkylated glycine esters; these may be met-
moted with powdered Potassium Hydroxide alone or with
alated (BuLi) and the anion quenched with allyl bromide with
Tetrabutylammonium Bromide in dioxane.1 Dimeric side
76% diastereomeric excess.17 Lithium Diisopropylamide met-
products (allyl ether, Ph2C4) and rearrangement enynes
alation of a chiral lactam enolate and allylation similarly pro-
a"
(PhC a"CCH= CHMe; E/Z, 3:1) accompany PhC CCH2CH=
CH2. Carbanions from acetoacetic esters,2a,2b ketones,2c vides a considerable diastereomeric enhancement.18 Formation of
the enol from tetralone with (R)-RCH2CHPhN(CH2CH2OCH2-
malonates (K2CO3 Me2CO or PhH),3 acetonitrile,4a and
CH2OMe)Li (R = piperidino) and allylation provides (R)-2-allyl-
cyanoacetates4b readily undergo allylation (eq 1); the neces-
1-tetralone in 92% enantiomeric excess and 89% overall yield;
sary base may be generated electrochemically, as in the use
Lithium Bromide is a necessary co-reagent (eq 4).19
of pyrrolidone anion to bring about allylation of dimethyl 2-
(trifluoromethyl)-malonate.5 Perfluoro-2-methyl-2-pentyl carba-
nion is generated by the addition of F- (KF or CsF) to
BuLi
(CF3)2CFCF=CFCF3; upon allylation (RX; X = Cl, Br, I) the re-
(3)
R2 R2
CH2=CHCH2Br
arranged product (CF3)2C(R)CF2CF2CF3 results.6 Mn enolates
of dialkyl ketones may be allylated (RBr; THF sulfolane); thus P(O)(OEt)2 P(O)(OEt)2
H R
Pr2CO gives PrCOCH(R)Et in 98% yield.7
OO
Ph
Li
N O
N OMe
(4)
X CH2 Y + [X CH Y] RBr X CHR Y (1)
CH2=CHCH2Br
X, Y = R2 CO, CO2R2 , CN, H
Similarly, allylation of the lactam by allyl bromide LDA20
proceeds stereospecifically to give (1).
The homoallylic alcohols RCH(OH)CH2CH=CH2 are formed
from the reaction of RCHO and allyl bromide through organo-
CO2H
metallic intermediates, especially those involving allyl magne-
sium bromide. Ketones react similarly, but more slowly. The
N
O TBDMS
conventional Barbier Grignard processes have been replaced by
(1)
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 Allylation of Ni complexes of some Schiff bases with glycine
The process may be specific to aldehydes; Pb Me3SiCl Bu4NBr are reported21 to yield S-Ä…-allylglycine. A three-step synthesis of
in DMF promotes allylation of aldehydes without significantly Ä…-amino acid HCl salts relies upon diastereoselective allylation of
attacking ketones or Ä…-hydroxycarboxylic esters, while esters, a glycine enolate synthon with >97.6% de and in 73 90% yield.22
lactones, acid anhydrides, and acid chlorides are effectively N,N-Dimethylhydrazones of Ä…,²-unsaturated aldehydes23a and
Avoid Skin Contact with All Reagents
2 ALLYL BROMIDE
RCH2CH=CHCH=CHCHO23b metalate (BuLi) and allylate Alkyl coupling reactions, mediated by Cu, are exempli-
with rearrangement, giving RCH(R )(CH=CH)nCHO analogs fied by the synthesis of CF3CH2CH=CH2 using (CF3)2CuIII
(R = allyl; n = 1 or 2). Ph2C=NCH2CO2-t-Bu undergoes (N,N-diethyldithiocarbamato),38a or using FO2SCF2I in DMF.38b
allylation (RBr, 50% aq NaOH, CH2Cl2, rt) in the presence of The allyl system is susceptible to further chemistry, notably
chiral PTC based upon cinchonine; the products show consider- epoxidation and other addition processes; the intermediates in
able ee (50 60%).24 such processes may show their own idiosyncratic chemistry39
Carbonyl insertion occurs when Me3P-coordinated Ä„-allyl Pd as in the cyclization of the thioallyl substituent (4) (eq 9), itself
complexes are treated with CO in CH2Cl2 at rt, giving 3-butenoyl obtained by allylation of the thiophenoxide.
derivatives,25 and allylation of a vinyl rhenium CO complex
provides an allyl vinyl ketone complex.26 Organotin species
CO2H
couple with allyl bromide (catalyzed by Pd complexes); while
CO2H
X2
X3
²-elimination may supervene, CHO, CO2H, and OH groups do not (9)
+
N
S
interfere.27a Similar coupling occurs with RSiMe3 or RSiMe2F
N S
X
and allyl bromide,27b but alkenylboranes in the presence of
(4)
Tetrakis(triphenylphosphine)palladium(0) give alkenes by allyl-
deboronation.27c Tetracarbonylnickel with allyl bromide (RBr)
gives Ä„-allyl nickel bromide complexes. These can act as interme- Related Reagents. Allyl Chloride; Allyl Iodide.
diates in the coupling of allylic systems either symmetrically28a or
to give substituted alkenes by unsymmetrical coupling (eq 5).28b
R H R H H R
1. Paravyan, S. L.; Torosyan, G. O.; Babayan, A. T., Zh. Org. Khim. 1986,
2
(5)
22, 706.
H Br H H
2. (a) Tsuji, J.; Yamada, T.; Minami, I.; Yuhara, M.; Nisar, M.; Shimizu, J.,
J. Org. Chem. 1987, 52, 2988. (b) Hughes, P.; De Virgilio, J.; Humber,
Ä„-Allyl nickel bromide complexes allylate C-2 of
L. G.; Chau, Thuy; Weichman, B.; Neuman, G., J. Med. Chem. 1989,
benzoquinones.28c Oxygen-centered attack occurs readily;
32, 2134. (c) Vanderwerf, C. A.; Lemmerman, L. V., Org. Synth., Coll.
the K salt of L-ascorbic acid (2) gives (allyl bromide Me2CO)
Vol. 1955, 3, 44.
a lactone (3) which with Palladium(II) Chloride in aq DMF
3. Liu, H.; Cheng, G., Huaxue Shiji 1991, 13, 248, 202 (Chem. Abstr. 1991,
provides (40%) a bicyclic ketone in which the allylic side chain
115, 255 598m).
has become the acetonyl (MeCOCH2) residue (eq 6).29
4. (a) Tamaru, Y., J. Am. Chem. Soc. 1988, 110, 3994. (b) Abd el Samii, Z.
K. M.; Al Ashmawy, M. I.; Mellor, J. M., J. Chem. Soc., Perkin Trans. 1
R
HO OK
HO
1988, 2523.
O
(6) 5. Fuchigami, T.; Nakagawa, Y., J. Org. Chem. 1987, 52, 5276.
O
O
OH
O
6. Dmowski, W.; Wozniacki, R., J. Fluorine Chem. 1987, 36, 385.
H
H
OH
OH
7. Cahiez, G.; Figadere, B.; Tozzolino, P.; Clery, P., Eur. Patent 373 993,
(2) (3)
1990 (Chem. Abstr. 1991, 114, 61 550y).
8. (a) Tanaka, H.; Yamashita, S.; Hamatani, T.; Ikemoto, Y.; Torii, S., Synth.
Stannylation of monoalkylated oxiranes by Trimethylstannyl-
Commun. 1987, 17, 789. (b) Wada, M.; Ohki, H.; Akiba, K., J. Chem.
lithium gives lithium alkoxides XOCH(R)CH2SnMe3 (X = Li) Soc., Chem. Commun. 1987, 708.
which react conventionally with allyl bromide to give the
9. Tanaka, H.; Yamashita, S.; Hamatani, T.; Ikemoto, Y.; Torii, S., Chem.
Lett. 1986, 1611.
corresponding allyl ether (X = allyl).30 Attack at oxygen may
also be achieved using other displaced groups. Stannylene acetals 10. Wada, M.; Ohki, H.; Akiba, K., Tetrahedron Lett. 1986, 27, 4771.
of acyclic diols are monoallylated using F- in a mild, selective, 11. Wang, W.; Shi, L.; Huang, Y., Tetrahedron 1990, 46, 3315.
and high yield process.31
12. (a) Minato, M.; Tsuji, J., Chem. Lett. 1988, 2049. (b) Tanaka, H.;
Nakahara, T.; Dhimane, H.; Torii, S., Tetrahedron Lett. 1989, 30, 4161.
N-Allylation takes place easily; phthalimide reacts readily
ć%
with allyl bromide (K2CO3 PEG 400; 90 C).32 Indoles33a and 13. Huang, Y.; Liao, Y., Heteroatom Chem. 1991, 2, 297 (Chem. Abstr. 1991,
115 91 330q).
pyrazoles33b may be allylated on nitrogen using PTC such as
14. (a) Shono, T.; Ishifune, M.; Kashimura, S., Chem. Lett. 1990, 449.
Bu4NBr (eq 7).
(b) Araki, S.; Ito, H.; Butsugan, Y., J. Organomet. Chem. 1988, 347,
5.
RBr
15. Takaki, K.; Tsubaki, Y.; Beppu, F.; Fujiwara, Y., Chem. Express 1991,
(X = N, CH) (7)
X X
6, 57(Chem. Abstr. 1991, 114, 163 659h).
N N
16. (a) Schöllkopf, U.; Schuetze, R., Liebigs Ann. Chem. 1987, 45.
R
(b) Jacquier, R.; Ouazzani, F.; Roumestant, M. L.; Viallefont, P.,
Phosphorus Sulfur Silicon 1988, 36, 73.
Salts such as Na phenylsulfinate form allyl esters; Al2O3, ultra- 17. Schoellkopf, U.; Toelle, R.; Egert, E.; Nieger, M., Liebigs Ann. Chem.
1987, 399.
sound, and microwaves all influence the yield.34 Correspondingly,
18. Wuensch, T.; Meyers, A. I., J. Org. Chem. 1990, 55, 4233.
sulfur,35,36 selenium,36 or tellurium37 attack is preparatively use-
19. Murakata, M.; Nakajima, M.; Koga, K., J. Chem. Soc., Chem. Commun.
ful (eq 8).
1990, 1657.
20. Baldwin, J. E.; Adlington, R. M.; Gollins, D. W.; Schofield, C. J.,
RBr + R2 X R2 XR + Br (X = O, S, Se, Te) (8)
Tetrahedron 1990, 46, 4733.
A list of General Abbreviations appears on the front Endpapers
ALLYL BROMIDE 3
21. (a) Belokon, Yu. N.; Chernoglazova, N. I.; Ivanova, E. V.; Popkov, 29. Poss, A. J.; Belter, R. K., Synth. Commun. 1988, 18, 417.
A. N.; Saporovskaya, M. B.; Suvorov, N. N.; Belikov, V. M., Izv. Askad.
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Nauk SSSR, Ser. Khim. 1988, 2818. (b) Belokon, Yu. N.; Maleev, V. I.;
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N.; Ohno, M., Chem. Pharm. Bull. 1991, 39, 1972.
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(Chem. Abstr. 1989, 111 646).
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University of Surrey, Guildford, UK
Avoid Skin Contact with All Reagents