ZINC BROMIDE 1
developed that offer a method for the alkenation of carbonyl com-
Zinc Bromide1
pounds (eq 7).11
OCONEt2 1. ZnBr2, THF
ZnBr2 OCONEt2
(2)
2. Br
Li
Ph
Ph
[7699-45-8] Br2Zn (MW 225.19)
Pd(PPh3)4
InChI = 1/2BrH.Zn/h2*1H;/q;;+2/p-2/f2Br.Zn/h2*1h;/q2*-1;m
80%
InChIKey = VNDYJBBGRKZCSX-JCMKJQRZCM
ZnBr2
(used in the preparation of organozinc reagents via trans-
Pd(PPh3)4
Et
metalation;1 a mild Lewis acid useful for promoting addition2
THF Et2O
and substitution reactions3)
I
C5H11
C5H11
ć% ć%
Physical Data: mp 394 C; bp 697 C (dec); d 4.201 g cm-3.
96%
Solubility: sol Et2O, H2O (1 g/25 mL), 90% EtOH (1 g/0.5 mL).
Et
Form Supplied in: granular white powder; principal impurity is
(3)
CuLi
H2O.
2
Analysis of Reagent Purity: melting point.
ZnBr2, THF
CO2Me
ć%
Purification: heat to 300 C under vacuum (2 � 10-2 mmHg) for
Et
Pd(PPh3)4
1 h, then sublime.
CO2Me
Handling, Storage, and Precautions: very hygroscopic; store un-
I
der anhydrous conditions. Irritant.
81%
MgCl
R1 R2
Organozinc Reagents. The transmetalation of organomag-
Br
nesium, organolithium, and organocopper reagents by anhydrous
NiCl2, Et2O, 0 �C
(4)
ZnBr2 in ethereal solvents offers a convenient method of preparing
NMe2
organozinc bromides and diorganozinc reagents.1a Alternatively,
MeS PPh2
anhydrous ZnBr2 may be reduced by potassium metal to result in
highly activated Zn0, which is useful for the preparation of zinc without ZnBr2 R1 = Me, R2 = H; >95% (52% ee)
R1 = H, R2 = Me; >95% (49% ee)
with ZnBr2
reagents through oxidative addition to organic halides.4 Alkyl,
allylic, and propargylic zinc reagents derived by these methods
X
have shown considerable value in their stereoselective and regios-
TMS
1. BuLi, THF
elective addition reactions with aldehydes, ketones, imines, and
(5)
2. ZnBr2
iminium salts.1a,5 Zinc enolates used in the Reformatsky reac-
80%
OMe
tion may also be prepared through transmetalation using ZnBr2.1b
OMe
TMS
Organozinc species are especially useful in palladium-and nickel-
X = ZnBr
catalyzed coupling reactions of sp2 carbon centers. In this fashion, H2O
sp2 sp3 (eq 1)6 and sp2 sp2 (eqs 2 and 3)7,8 carbon carbon bonds X = H
are formed selectively in high yields. The enantioselective cross
t-Bu
coupling of secondary Grignard reagents with vinyl bromide is
O
t-BuO I
strongly affected by the presence of ZnBr2, which accelerates the Pr
1. t-BuLi
Zn
reaction and inverts its enantioselectivity (eq 4).9
Pr
2.
MgBr
3. ZnBr2
CO2Me
1. ZnBr2, THF
PhCH2Li (1)
CO2Me Ph
2.
Ph
M1 M2
I
1. PhCHO
Ni(PPh3)4
(6)
Pr
THF Et2O, 25 �C Pr
2. H3O+
88%
O-t-Bu 68%
O-t-Bu
95% de
M1, M2 = metal
Organozinc intermediates formed via transmetalation using
H3O+
ZnBr2 have been used to effect carbozincation of alkenes and
M1, M2 = H
alkynes through metallo-ene and metallo-Claisen reactions. Both
75%, 95% de
intermolecular and intramolecular variants of these reactions have
been described, often proceeding with high levels of stereoselec-
tivity and affording organometallic products that may be used in Concerted Ring-forming Reactions. The mild Lewis acid
subsequent transformations (eqs 5 and 6),10 including alkenation character of ZnBr2 sometime imparts a catalytic effect on ther-
(eq 6).10b,c Bimetallic zinc zirconium reagents have also been mally allowed pericyclic reactions. The rate and stereoselectivity
Avoid Skin Contact with All Reagents
2 ZINC BROMIDE
OTMS
of cycloaddition reactions (eq 8),12 including dipolar cycloaddi- 1. catalyst
+ PhCHO
tions (eq 9),13 are significantly improved by the presence of this
OTMS 2. H3O+
zinc salt.
OH CO2H
C6H13 1. ZnBr2 CHO
CO2H + (12)
C7H15
Ph
ZnBr
MgBr +
Ph OH
2. H(Cl)ZrCp2
Cp2Zr Cl
ZnBr2, THF, 20 �C, 6 h 100:0
(7)
CsF, CH2Cl2. 20 �C, 14 h 5:95
C7H15
Activation of C X Bonds. Even more important than car-
bonyl activation, ZnBr2 promotes substitution reactions with suit-
83%, 100% (E)
ably active organic halides with a variety of nucleophiles. Alky-
lation of silyl enol ethers and silyl ketene acetals using benzyl
and allyl halides proceeds smoothly (eq 13).3 Especially use-
ful electrophiles are ą-thio halides which afford products that
may be desulfurized or oxidatively eliminated to result in ą,�-
CH2Cl2 unsaturated ketones, esters, and lactones (eq 14).18 Other elec-
CO2Me
+ (8)
trophiles that have been used with these alkenic nucleophiles
0 �C
CO2Me
include Chloromethyl Methyl Ether, HC(OMe)3, and Acetyl
no catalyst, 5 h 70%, 78% endo
Chloride.3,19
with ZnBr2, 3 h 80%, 95% endo
O
Br
Ph
ZnBr2
CH2Cl2, rt
OH
OTMS
68%
(13)
H
Ph
O O
Ph
ZnBr2
+ Br
OH
N + (9)
O
Ph Ph CH2Cl2
O N
H Ph
O
65%
Ph
ZnBr2
Ph Ph
single isomer CH2Cl2, rt
83%
SPh
Some intramolecular ene reactions benefit from ZnBr2 catalysis
OTMS
1. ZnBr2
to afford the cyclic products under milder conditions, in higher + Cl
OTMS
2. H3O+
yields and selectivities (eqs 10 and 11).14,15 Generally, the use of
OTMS 92%
ZnBr2 is preferred over Zinc Chloride or Zinc Iodide in this type
of reaction.15
SPh
H H
=
Activation of C= Bonds. Lewis acid activation of carbonyl
=X
1. m-CPBA
(14)
compounds by ZnBr2 promotes the addition of allylsilanes and
2. DBU
O O O O
silyl ketene acetals.16 Addition to imines has also been reported.17
90%
H H
In general, other Lewis acids have been found to be more useful,
Enol ethers and allylic silanes and stannanes will engage
though in some instances ZnBr2 has proven to be advantageous
cyclic ą-seleno sulfoxides,20 �-acetoxy lactams,21 and acyl
(eq 12).2
glycosides (eq 15)22 in the presence of ZnBr2 catalysis. Along
these lines, it has been found that ZnBr2 is superior to Boron Tri-
fluoride Etherate in promoting glycoside bond formation using
reagent
(10)
trichloroimidate-activated glycosides (eq 16).23 Imidazole car-
MeO2CMeO2C
bamates are also effective activating groups for ZnBr2-mediated
MeO2CMeO2C
glycosylation (eq 17).24
Cyclic acetals also undergo highly selective, Lewis acid-
180 �C, o-dichlorobenzene 66% (83% de)
ZnBr2, CH2Cl2, 25 �C 79% (95% de)
dependent ring opening substitution with Cyanotrimethylsilane
(eq 18).25
O
Reduction. Complexation with ZnBr2 has been shown to
S-p-Tol
ZnBr2
O
markedly improve stereoselectivity in the reduction of certain
(11)
CN CH2Cl2 S-p-Tol
heteroatom-substituted ketones (eqs 19 and 20).26,27 Furthermore,
82%
H
the anti selectivity observed in BF3�OEt2-mediated intramolecular
R1 R2
hydrosilylation of ketones is reversed when ZnBr2 is used instead
(R1 = CN, R2 = H):(R1 = H, R2 = CN) = 88:12
(eq 21).28
A list of General Abbreviations appears on the front Endpapers
ZINC BROMIDE 3
OBz OBz Me2 Me2
Si Si
O OSiMe2H
BzO OBz BzO OBz
O O O O
ZnBr2
TMS
+ (21)
+ (15)
i-Pr i-Pr
110 �C, 3 h
i-Pr i-Pr i-Pr i-Pr
BzO O O
100%
H
BF3 � OEt2, CH2Cl2,  80 �C, 2 h 23:1
ą:� = 1:1
1:6
ZnBr2, CH2Cl2,  80 �C, 8 h
O
AcO
H
Deprotection. ZnBr2 is a very mild reagent for sev-
AcO
OAc
O
eral deprotection protocols, including the detritylation of
H
H
O
nucleotides29 and deoxynucleotides,30 N-deacylation of N,O-
+
AcO OAc H
H H H H
peracylated nucleotides,31 and the selective removal of Boc groups
O OAc
HO
from secondary amines in the presence of Boc-protected primary
H
AcO
amines.32 Perhaps the most widespread use of ZnBr2 for deprotec-
O OC(NH)CCl3
H
tion is in the mild removal of MEM ethers to afford free alcohols
(eq 22).33
ZnBr2, CH2Cl2
(16)
60%
3 � mol sieves, "
H H
ZnBr2
AcO
H
CH2Cl2
AcO
(22)
O O OMe OH
O
OAc
25 �C, 10 h
O 93%
AcO OAc
O
H H H
H
O OAc
H
H H
AcO
O O
Miscellaneous. An important method for the synthesis of
H H
stereodefined trisubstituted double bonds involves the treatment
of cyclopropyl bromides with ZnBr2. The (E) isomer is obtained
OBn
almost exclusively by this method (eq 23).34
BnO OBn
OH
Ph CO2Me
OBn 1. PBr3, LiBr
CO2Me
O O
collidine, Et2O
H
ZnBr2
THF, Et2O, "
N O
2. ZnBr2, Et2O
N 88%
>95%
OH
OBn
BnO OBn
CO2Me
(23)
(17)
OBn
O O
Br
H
(E)
MeO2C Ph
10:1 de
The rearrangement of a variety of terpene oxides has been
Ph
examined (eq 24).35 While ZnBr2 is generally a satisfactory cat-
alyst for this purpose, other Lewis acids, including ZnCl236 and
O O
TMSCN
Magnesium Bromide,37 are advantageous in some instances.
MeO
H
ZnBr2
Ph Ph
H
( )-ą-Pinene (24)
CHO
PhH, 80 �C
OH O CN NC O OH
O
+ (18)
88%
MeO MeO
ZnBr2, CH2Cl2, 25 �C, 20 h 1:250
In the presence of ZnBr2/48% Hydrobromic Acid, suitably
TiCl4, CH2Cl2, 25 �C, 20 h 250:1
functionalized cyclopropanes undergo ring expansion to afford
cyclobutane (eq 25)38 and ą-methylene butyrolactone products
H O H OH
1. ZnBr2, MeOH
N N (eq 26).39 One-carbon ring expansion has been reported when
(19)
Ph Ph Ph Ph certain trimethylsilyl dimethyl acetals are exposed to ZnBr2 with
2. NaBH4
100%
warming (eq 27).40
OH SPh
OOH O OH O
O
1. Cu(OTf)2
SPh SPh
(20)
DIBAL
i-Pr2NEt
48% HBr
S S S
+
(25)
Et
p-Tol p-Tol p-Tol
ZnBr2, THF ZnBr2, PhSH 2. 450 �C
SPh Et Et
91% 95%
81%
66:34
Avoid Skin Contact with All Reagents
4 ZINC BROMIDE
H H
123, 1387. (b) Nakatani, Y.; Kawashima, K., Synthesis 1978,
O
48% HBr, ZnBr2
147.
OH
(26)
O
EtOH, 100 �C, 6 h
CO2Et 15. Hiroi, K.; Umemura, M., Tetrahedron Lett. 1992, 33, 3343.
50%
H H
16. (a) Mikami, K.; Kawamoto, K.; Loh, T.-P.; Nakai, T., J. Chem. Soc.,
Chem. Commun. 1990, 1161. (b) Bellassoued, M.; Gaudemar, M.,
Tetrahedron Lett. 1988, 29, 4551.
TMS 17. Gaudemar, M.; Bellassoued, M., Tetrahedron Lett. 1990, 31,
OMe
349.
ZnBr2, CH2Cl2
OMe (27)
18. Khan, H. A.; Paterson, I., Tetrahedron Lett. 1982, 23, 5083. See also: (a)
40 �C, 30 min
100%
Paterson, I., Tetrahedron 1988, 44, 4207. (b) Khan, H. A.; Paterson,
OMe
I., Tetrahedron Lett. 1982, 23, 4811. (c) Paterson, I.; Fleming, I.,
Tetrahedron Lett. 1979, 20, 993, 995, 2179.
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20. Ren, P.; Ribezzo, M., J. Am. Chem. Soc. 1991, 113, 7803.
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2, Chapter 1.8.
895.
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A list of General Abbreviations appears on the front Endpapers