COPPER(II) BROMIDE 1
Copper(II) Bromide 3,7-Dibromo-2H,6H-benzodithiophene-2,6-diones (eq 4)8 and 5-
bromo-4-oxo-4,5,6,7-tetrahydroindoles (eq 5)9 are prepared by
the selective Ä…-bromination of their respective ketone starting
CuBr2
materials without bromination of the aromatic or heterocyclic
rings. 4-Carboxyoxazolines are converted to the corresponding
[7789-45-9] Br2Cu (MW 223.36) oxazoles using a mixture of CuBr2 and 1,8-Diazabicyclo[5.4.0]
undec-7-ene (eq 6).10
InChI = 1/2BrH.Cu/h2*1H;/q;;+2/p-2/f2Br.Cu/h2*1h;/q2*-1;m/
rBr2Cu/c1-3-2
O O
InChIKey = QTMDXZNDVAMKGV-NZVHWWHRCV
CuBr2, "
(3)
CO2Me CO2Me
EtOAc-CHCl3
66
(brominating agent; oxidizing agent; Lewis acid)
66%
Alternate Name: cupric bromide.
ć%
Br
Physical Data: mp 498 C; d 4.770 g cm-3.
S S
Solubility: very sol water; sol acetone, ammonia, alcohol; CuBr2
(4)
O O O O
practically insol benzene, Et2O, conc H2SO4.
MeOH
S S
83%
Form Supplied in: almost black solid crystals or crystalline
Br
powder; also supplied as reagent adsorbed on alumina (approx.
30 wt % CuBr2 on alumina).
O O
CuBr2
Purification: recryst from H2O and dried in vacuo.35
Br
EtOAc, "
Handling, Storage, and Precautions: anhydrous reagent is (5)
R = Ts, 98%
hygroscopic and should therefore be stored in the absence of R = Bz, 74%
N N
moisture.
R R
O O
CuBr2, DBU
Original Commentary N N
X X
(6)
R R
EtOAc-CHCl3
Nicholas D. P. Cosford O O
SIBIA, La Jolla, CA, USA
X = OR, NR2
Ä…
Ä…
Ä…-Bromination of Carbonyls. Copper(II) bromide is an effi-
Bromination of Alkenes and Alkynes. Heating copper(II)
cient reagent for the selective bromination of methylenes adjacent
bromide in methanol with compounds containing nonaromatic
to carbonyl functional groups.1 Thus 2 -hydroxyacetophenone
carbon carbon multiple bonds leads to di- or tribromination.11
treated with a heterogeneous mixture of CuBr2 in CHCl3 EtOAc
For example, under these conditions allyl alcohol is converted
gives complete conversion to 2-bromo-2 -hydroxyacetophenone
to 1,2-dibromo-3-hydroxypropane in 99% yield (eq 7), while
with no aromatic ring bromination (eq 1).2
propargyl alcohol produces a mixture of trans di- and tribromo-
OH O OH O
allyl alcohols (eq 8). 2 -Hydroxy-5 -methyl-4-methoxychalcone
CuBr2, "
Br
(1)
undergoes a bromination ring-closure reaction, affording 3-
EtOAc-CHCl3
bromo-6-methyl-5 -methoxyflavanone when heated with CuBr2
100%
in refluxing dioxane (eq 9).12 The mechanism of the bromination
of cyclohexene to 1,2-dibromocyclohexane with CuBr2 has been
Similar selectivity is obtained with a homogeneous solu-
studied.13
tion of the reagent in dioxane.3 A limitation of the reaction is
observed with 2 -hydroxy-4 ,6 -dimethoxyacetophenone, which Br
CuBr2
OH
undergoes aromatic nuclear bromination with CuBr2.4 Steroidal
Br OH
(7)
MeOH
ketones have been selectively Ä…-brominated with CuBr2 in the
99%
presence of a double bond without bromination of the alkene
(eq 2),5 while Å‚-bromination occurs in other steroidal enones.1
Br
Br
O
CuBr2
OH
+ Br OH
O
(8)
MeOH
OH
99% Br
Br
CuBr2
(2)
30% 18%
THF
AcO
OH O O
AcO
Br
CuBr2
(9)
Copper(II) bromide has been used to Ä…-brominate diketotetra-
dioxane
Ar O Ar
quinanes6 and to introduce a double bond into a prostanoid
"
nucleus in a one-pot bromination elimination procedure (eq 3).7
Avoid Skin Contact with All Reagents
2 COPPER(II) BROMIDE
Bromination of Aromatics. Aromatic systems are bromi- Butyl Hydroperoxide in acetic acid or anhydride (eq 14).21b While
nated by copper(II) bromide. For example, 9-bromoanthracene the yields (43 95%) are not quite as high as those obtained using
is prepared in high yield by heating anthracene and the reagent N-Bromosuccinimide, the copper(II) bromide procedure allows
in carbon tetrachloride (eq 10).14 When the 9-position is blocked the benzylic bromination of compounds which are insoluble in
by a halogen, alkyl, or aryl group, the corresponding 10- nonpolar solvents.
bromoanthracene is formed.15 Under similar conditions, 9-
acylanthracenes give 9-acyl-10-bromoanthracenes as the
Br
predominant products.16 The aromatic nuclear bromination of
CuBr2
monoalkylbenzenes has been shown to proceed cleanly under
t-BuOOH
strictly anhydrous conditions (eq 11).17a Polymethylbenzenes are (14)
X X
AcOH, D
efficiently and selectively converted to the nuclear brominated
43 95%
derivatives by CuBr2/Alumina.17b In the absence of alumina,
X = H, hal, CO2H
a mixture of products resulting from benzylic halogenation is
isolated. 3-Acetylpyrroles are nuclear monobrominated at the
4-position in high yield by CuBr2 in acetonitrile at ambient
temperature (eq 12).18 The reaction also proceeds with ethyl
3-pyrrolecarboxylates to give 4-bromopyrrole derivatives,19 Esterification Catalyst. Highly sterically hindered esters are
prepared by the reaction of S-2-pyridyl thioates and alcohols in
ć%
while an excess of brominating agent at 60 C affords 4,5-
acetonitrile with copper(II) bromide as the catalyst.22 The reac-
dibromopyrroles.20
tion proceeds at ambient temperature under mild conditions and
H Br
affords high yields of a range of sterically crowded esters such as
t-butyl 1-adamantanecarboxylate (eq 15).
CuBr2
(10)
"
R R
N
O O-t-Bu
t-BuOOH
R = H, Me, Ph, Ac
CuBr2
O S
(15)
MeCN
25 °C
89%
Br
CuBr2
(11)
+
D
1:2 Br
Conjugate Addition Catalyst. The 1,4-addition of Grig-
O O nard reagents to Ä…,²-unsaturated esters is promoted by catalytic
CuBr2 (1 5 mol %) with Chlorotrimethylsilane/HMPA (eq 16).23
X Br X
Under these conditions the copper(II) species is not reduced by
CuBr2
(12)
the Grignard reagent, resulting in high yields of the conjugate
R2 MeCN Ph N R2
Ph
N
25 °C
addition products.
R1 R1
CuBr2
CO2Me
CO2Me
TMSCl
(16)
Bromination of Allylic Alcohols. Silica gel-supported HMPA
n-BuMgBr
n-Bu
copper(II) bromide has been used for the regioselective bromi-
99%
nation of methyl 3-hydroxy-2-methylenepropanoates and 3-
hydroxy-2-methylenepropanenitriles (eq 13).21a In the absence
of silica gel, no reaction occurs between CuBr2 and these sub-
strates, while adsorption onto Al2O3, MgO, or TiO2 leads to Oxidation of Stannanes and Alcohols. Allylstannanes have
side reactions rather than the clean allylic bromination observed been oxidized with copper(II) bromide in the presence of vari-
with CuBr2/SiO2. The reaction is stereoselective with respect to ous nucleophilic reagents (H2O, ROH, AcONa, RNH2) to afford
formation of the (Z) isomer. the corresponding allylic alcohols, ethers, acetates, and amines.24
This chemistry has been extended to trimethylsilyl enol ethers,
Ar Ar Br
CuBr2
which undergo a CuBr2-induced carbon carbon bond forming
(13)
SiO2
HO X X process with allylstannanes (eq 17).25 Alkoxytributylstannanes
may be converted to the corresponding aldehyde or ketone with
X = CO2Me, CN
two equivalents of CuBr2/Lithium Bromide in THF at ambi-
ent temperature (path a, eq 18).26 A combination of copper(II)
Benzylic Bromination. Toluene and substituted methyl- bromide/Lithium tert-Butoxide oxidizes alcohols to carbonyl
benzenes undergo benzylic bromination using CuBr2 and tert- compounds quite rapidly and in high yield (path b, eq 18).27
A list of General Abbreviations appears on the front Endpapers
COPPER(II) BROMIDE 3
OTMS O
CuBr2 First Update
CHCl3
R SnBu3 +
R
(17)
Liming Zhang & Guotao Li
25 °C
University of Nevada, Reno, NV, USA
R = Ph(Ch2)2, 57%
Ä…
Ä…
Ä…-Bromination of Carbonyl Groups and One-pot
Elimination. CuBr2 Ä…-brominates a variety of carbonyl com-
R1 R1
(a) or (b)
OX
(18)
pounds. Recent examples include regioselective Ä…-bromination
O
R2 H R2 of enone esters with carefully controlled reaction temperature
(eq 23),36 Ä…,Ä… -dibromination of ketones (eq 24),37 and Ä…-
(a) X = SnBu3 (a) = CuBr2, LiBr, Bu3SnO-t-Bu
bromination of 2-acetyl-5-methylthiothiophene.38 Subsequent
(b) X = h (b) = CuBr2, LiO-t-Bu
one-pot elimination of HBr to yield alkenes is viable when an
aromatic ring is formed39 and/or the ²-hydrogen is acidic.40
Interestingly, for ²-dimethylphenylsilylketones, bromination
Desilylbromination. ²-Silyl ketones are desilylbrominated
is followed by debromosilation during the reaction, affording
to Ä…,²-unsaturated ketones with CuBr2 in DMF.28 This occurs
enones directly (eq 25).41,42
spontaneously in cyclic ketones, while with open-chain ketones
sodium bicarbonate is required to eliminate HBr from the
OO
CuBr2, CHCl3
²-bromo ketone thus formed. The carbon silicon bond in organo-
EtOAc, 55 °C, 2 h
pentafluorosilicates prepared from alkenes and alkynes is cleaved
EtO Ph
72%
with copper(II) bromide to give the corresponding alkyl and
OO
alkenyl bromides (eq 19).29 The reaction is stereoselective; thus
(E)-alkenyl bromides are obtained from (E)-alkenylsilicates.
(23)
EtO Ph
R
Br
1. HSiCl3
R R
H2PtCl6 CuBr2
K2
(19)
Br
2. KF
O
R1 SiF5 R1 Br
O
CuBr2, MeCN
R1 H
50 °C, 72 h
H
76%
Br
Reagent in the Sandmeyer and Meerwein Reactions.
H
Diazonium salts of arylamines are converted to aryl halides
H
(Sandmeyer reaction)30 in the presence of copper(II) halides.
OH
Recent procedures have utilized t-butyl nitrite/CuBr231 or t-butyl
thionitrite/CuBr232 combinations to afford aryl bromides from
(24)
the corresponding arylamines in high yields (eq 20). The copper
salt-catalyzed haloarylation of alkenes with arenediazonium salts
H
(Meerwein reaction) also proceeds with copper(II) halides. For
example, treatment of p-aminoacetophenone with t-butyl nitrite/
(+)-totarol
CuBr2 in the presence of excess acrylic acid gives p-acetyl-
Ä…-bromohydrocinnamic acid (59% yield, eq 21).33 The intra- O
O
CuBr2, CHCl3
molecular version of this reaction, which affords halogenated
AcOEt, 1 h, reflux
dihydrobenzofurans, has been accomplished by reacting arene- (25)
55%
Ph
diazonium tetrafluoroborates with CuBr2 in DMSO (eq 22).34
Me Si
Me
Me
Me
Br
NH2
CuBr2
t-BuONO
X
X
(20)
Ä„
Bromination and Bromocyclization of C C Ä„ Bonds.
Ä„
MeCN, D
Dibromination of alkenyl glycosides is realized in excellent yields
X = H, hal, CO2R, NO2, OMe, etc.
with the combination of CuBr2/LiBr (1:2). This reagent combi-
nation performs much better than Br2/Et4NBr and NBS/Et4NBr
NH2
with phthaloyl-protected glucosamines and tolerates a range of
CO2H
CuBr2
carbohydrate protecting groups (eq 26).43 In the presence of
CO2H
t-BuONO
(21) an appropriate internal nucleophile, bromocyclization of C C
+ OBr
MeCN, 25 °C
Ä„ bonds takes place. For example, ²-bromobutenolides are ob-
59%
tained in excellent yields from 2,3-allenoic acids in the presence
O
of 4 equiv of CuBr2 (eq 27),44 Moreover, CuBr2-mediated bro-
CuBr2 mocyclization of 2-alkynylthioanisoles and 2-alkynylbenzoates
Br
N2 BF4
DMSO
(assisted by 0.1 equiv of Cy2NH · HBr) affords 2-substituted
(22)
25 °C
3-bromobenzo[b]thiophenes45 and 5-bromoisocoumarins,46
82%
O
O
respectively, in generally good yields. Bromolactonization with
Avoid Skin Contact with All Reagents
4 COPPER(II) BROMIDE
CuBr2, 85 °C, 30 h O
CuBr2/Al2O347 has been used as key step in the synthesis of
MeCN/H2O (4:1)
O
(-)-stemoamide (eq 28).48,49
R = Me
81%
Br Me
OBn
CuBr2 (5 equiv)/LiBr2 (10 equiv)
O R
MeCN:THF(3:1), rt, 16 h
(30)
BnO
O
99%
COOEt
NPhth
Br
OBn
O
O
CuBr2, 85 °C, 10 h
OBn
MeCN/H2O (4:1)
Br
O
(26)
BnO R = H
Br
O
79%
NPhth
OBn
Bromination of Aromatics. Various azaindoles and diaza-
indoles have been selectively brominated at the 3-position in good
Me
efficiency with CuBr2, even in the presence of electron-rich aryl
CuBr2 (4 equiv)
substituents (eq 31).52,53 Similarly, CuBr2 selectively brominates
Acetone:H2O (2:1)
"
65 70 °C, 2 h
the pyrrole ring of 2-(2 -hydroxybenzoyl)pyrrole, yielding the 4,5-
CO2H
98%
dibrominated product in 95% yield.54
Me
Br
Br
CuBr2 (3 equiv)
(27)
MeCN, rt
O
O (31)
90%
N N
O N O N
H H
1. NaOH
MeO2C
2. CuBr2/Al2O3
CHCl3
O
Me
N
Conversion of Hydrazones into gem-Dibromides. Treat-
H
ment of hydrazones derived from either aliphatic aldehydes or
ketones with CuBr2/LiOtBu gives gem-dibromides in fair to good
Me
Me
yields (eq 32 ).55 Moreover, LiOtBu can be conveniently replaced
Br
O
O
with Et3N without affecting yield.56 The hydrazone prepared from
O
N
O (28)
+
N
H
Ä…-tetralone leads to the vinyl bromide instead,57 but an aromatic
H
O
O
aldehyde has been converted into an Ä…,Ä…-dibromotoluene deriva-
Et3N
tive via the hydrazone intermediate.58
25%
31%
1. NH2NH2, MeOH, 4 Å MS, rt
2. LiOtBu-CuBr2, rt
Bromination of Alkylidenecyclopropanes. Depending on
81%
the amount of CuBr2, di- or tetrabromination of benzylidene-
cyclopropane can be realized (eq 29). Using 2 equiv of CuBr2,
O
Br Br
synthetically useful Z-2,4-dibromobutenes are formed in excel-
lent yields.50 Cyclopropylideneacetic acids and/or esters, upon
E:Z = 3:2 E:Z = 3:2
ć%
reacting with CuBr2 at 85 C, undergo rearrangement, yielding
1. NH2NH2, MeOH, 4 Å MS, rt
2. CuBr2, Et3N, 0 °C
either furanones or dihydropyranones depending on the Ä…-
(32)
82%
substitution (eq 30).51
Br
CuBr2 (2 equiv)
65 °C, 14 h, MeCN
Oxidation of Amines. Secondary amines are oxidized to
82%
imines by premixed CuBr2/LiOtBu in good yields in less than
Br Ph
30 mins.59 For unsymmetrical cases such as benzyl alkyl amines,
benzylic oxidation is preferred (eq 33). Primary amines can be
(29)
oxidized to nitriles with slightly more than 4 equiv of the reagent.
Ph
Br Nitriles are also prepared in good yields from Ä…-monosubstituted
Br glycines using the same reagent (eq 34), while ketones are
CuBr2 (4 equiv)
85 °C, 4 h, MeCN
obtained from Ä…,Ä…-disubstituted glycines after hydrolysis, and
Br
82%
Br Ph
from Ä…,Ä…-disubstituted Ä…-hydroxy acids.60
A list of General Abbreviations appears on the front Endpapers
COPPER(II) BROMIDE 5
LiOtBu-CuBr2 (2.2 equiv) Me
N Ph
O LiOtBu-CuBr2 (4.2 equiv)
THF, rt, 22 min
H
THF, 50 °C, 5 min
95%
MeO
N NH2
85%
H
Me
O
(37)
N Ph N Ph
N OtBu
H
MeO MeO
3 : 2 (33)
O O
NH3
N
LiOtBu-CuBr2 (4.4 equiv)
THF, rt, 2.5 h
N N N N
(34)
COO
H H
72%
p-O2NPhOLi-CuBr2
LiOtBu-CuBr2
(4 equiv) 86% 97%
(6 equiv)
Bn2NH, THF, 50 °C,
THF, rt, 20 min
20 min
Oxidation of 1,2-Diols. CuBr2/LiOtBu oxidatively cleaves
tert-1,2-diols at ambient temperature, yielding ketones. This
method is particularly useful for oxidizing trans-cyclic diols,
O O
where NaIO4 is ineffective and toxic Pb(OAc)4 performs the
reaction only slowly.61
N NBn2 N OtBu
(38)
H H
Oxidation of N -Phenylhydrazides. CuBr2/LiOtBu also
oxidizes N -phenylhydrazides efficiently, converting them into
t-butyl esters in fair to good yields (eq 35).62 The parent
Oxidant in Pd-catalyzed Reactions. In Pd(II)-catalyzed
hydrazides do react but less efficiently.
functionalization of alkenes, excess CuBr2 is used to oxidize
Pd C bonds to Br C bonds or to regenerate Pd(II) from Pd(0).
For example, highly enantioselective dibromination of terminal
O O
LiOtBu-CuBr2 (4 equiv)
H H
alkenes is realized using PdBr2[(S)-BINAP] and CuBr2/LiBr
THF, rt, 2 h
N NHPh N
(eq 39),66 and Pd(O2CCF3)2 catalyzes intramolecular bromo-
Cbz N Cbz OtBu
78%
Me Me H
Me Me
amination of alkenes in the presence of CuBr2 (eq 40).67 In
(35)
the PdBr2-catalyzed cyclization of 2-alkynylphenols, 0.2 equiv
Et3NHI is found to be essential for selective alkoxybromination
to form 3-bromobenzofurans in the presence of CuBr2 (3 equiv).68
A combination of Pd(OAc)2 (cat), Cu(OAc)2, and CuBr2 has been
Oxidation of Primary Carboxamides and N-Substituted
used to realize a selective ortho-bromination of acetanilide.69
Ureas. CuBr2/LiOtBu oxidizes primary carboxamides to
N-(t-butoxycarbonyl)amines in good yields (eq 36).63 Sim-
i
Pr
PdBr2[(S)-BINAP] (2.5 mol %)
ilar to Hoffmann reaction, a nitrene intermediate is pro-
LiBr (0.2 M), CuBr2 (2.2 M)
O
posed. Hindered amides are also substrates, but oxidation of
H2O/THF (1:6), rt, O2, 4d
3-phenylpropionamide gives poor results. Similarly, the car-
95%
i
Pr
bamoyl group in N-substituted ureas can be oxidized to a
i
nitrene-type intermediate, which upon dimerization and fur- Pr Br
ther oxidation, yields Boc-protected amines.64 CuBr2 works O * Br
(39)
well with N-arylureas (eq 37), but CuCl2 is preferred with
N-alkylureas. N,N-Disubstituted ureas do not afford the car- i
Pr
bamates. The proposed intermediates, N,N -dialkyldiazenedi-
94% ee
carboxamides, can be easily prepared and indeed are oxidized
readily by CuBr2/LiOtBu to render Boc-protected amines (eq 38).
To avoid the strong basicity of lithium tert-butoxide, lithium
Pd(O2CCF3)2 (0.1 equiv)
4-nitrophenoxide is a viable alternative. Moreover, this improved
CuBr2 (3 equiv), K2CO3
oxidizing system allows one-pot synthesis of trisubstituted ureas
THF, rt, 24 h
via in situ trapping of the isocyanate intermediate.65
99%
NHTs
Br Br
O
LiOtBu-CuBr2 (4.2 equiv)
+ (40)
H
THF, rt, 3 h
N
N
(36) N
NH2 93%
CO2tBu Ts
Ts
Me
3
Me : 1
Avoid Skin Contact with All Reagents
6 COPPER(II) BROMIDE
Synthesis of Bromosilanes from Hydrosilanes. In the pres- 7. Miller, D. D.; Moorthy, K. B.; Hamada, A., Tetrahedron Lett. 1983,
24, 555.
ence of a catalytic amount of CuI, CuBr2 (2 equiv) converts hy-
8. Nakatsuka, M.; Nakasuji, K.; Murata, I.; Watanabe, I.; Saito, G.; Enoki,
drosilanes into monobromosilanes at room temperature in good
T.; Inokuchi, H., Chem. Lett. 1983, 905.
yield.70 Substrates include monohydrosilanes, dihydrosilanes, tri-
9. Matsumoto, M.; Ishida, Y.; Watanabe, N., Heterocycles 1985, 23, 165.
hydrosilanes, and 1,2-dihydrodisilane. However, with di- and
10. Barrish, J. C.; Singh, J.; Spergel, S. H.; Han, W.-C.; Kissick, T. P.;
trihydrosilanes the second bromination employing 4 equiv of
Kronenthal, D. R.; Mueller, R. H., J. Org. Chem. 1993, 58, 4494.
CuBr2 is much slower.
11. Castro, C. E.; Gaughan, E. J.; Owsley, D. C., J. Org. Chem. 1965,
30, 587.
Lewis Acids. A substoichiometric amount of CuBr2 promotes
12. Doifode, K. B., J. Org. Chem. 1962, 27, 2665.
the one-pot imino Diels Alder reaction between in situ gener-
13. Koyano, T., Bull. Chem. Soc. Jpn. 1971, 44, 1158.
ated N-benzylideneanilines and electron-rich alkenes, affording
14. (a) See Ref. 1a, p 162. (b) Mosnaim, D.; Nonhebel, D. C., Tetrahedron
tetrahydroquinolines in good yield (eq 41).71 Water formed dur-
1969, 25, 1591.
ing the reaction and aniline substrates seemingly do not deac-
15. Mosnaim, D.; Nonhebel, D. C.; Russell, J. A., Tetrahedron 1969, 25,
tivate CuBr2. Bis(indol-3-yl)methanes are prepared efficiently
3485.
from various aldehydes and indole in the presence of 5 mol % of
16. Nonhebel, D. C.; Russell, J. A., Tetrahedron 1970, 26, 2781.
CuBr2 (eq 42). The reaction is slow and incomplete with ketone
17. (a) Kovacic, P.; Davis, K. E., J. Am. Chem. Soc. 1964, 86, 427.
substrates.72 CuBr2 also catalyzes the desilylation of TBS ethers,
(b) Kodomari, M.; Satoh, H.; Yoshitomi, S., Bull. Chem. Soc. Jpn. 1988,
tolerating functional groups such as ketals, alkenes, and allyl and
61, 4149.
benzyl groups. However, TBDPS and THP groups are cleaved,
18. Petruso, S.; Caronna, S.; Sprio, V., J. Heterocycl. Chem. 1990, 27, 1209.
albeit in a lesser extent.73 A combination of CuBr2/Bu4NBr
19. Petruso, S.; Caronna, S.; Sferlazzo, M.; Sprio, V., J. Heterocycl. Chem.
has been used to activate thioglycoside donors although the
1990, 27, 1277.
selectivity for Ä…-glycosidic linkages varies.74 76 Using the same
20. Petruso, S.; Caronna, S., J. Heterocycl. Chem. 1992, 29, 355.
reagent combination, the alkylthio group in alkoxy-/siloxymethyl
21. (a) Gruiec, A.; Foucaud, A.; Moinet, C., Nouv. J. Chim. 1991, 15, 943.
alkyl sulfide can be similarly replaced with alkoxy, phenoxy, and
(b) Chaintreau, A.; Adrian, G.; Couturier, D., Synth. Commun. 1981, 11,
carboxy groups, offering a mild and neutral method for hydroxyl
669.
group protection.77 CuBr2 and especially CuCl2 can activate sugar
22. Kim, S.; Lee, J. I., J. Org. Chem. 1984, 49, 1712.
oxazolines, leading to efficient formation of ²-glycosides.78
23. Sakata, H.; Aoki, Y.; Kuwajima, I., Tetrahedron Lett. 1990, 31, 1161.
CuBr2 (50%) 24. Takeda, T.; Inoue, T.; Fujiwara, T., Chem. Lett. 1988, 985.
O
MeCN, rt, 2 h
25. Takeda, T.; Ogawa, S.; Koyama, M.; Kato, T.; Fujiwara, T., Chem. Lett.
PhNH2 + PhCHO
+
76%
1989, 1257.
26. Yamaguchi, J.; Takeda, T., Chem. Lett. 1992, 423.
H
N Ph
27. Yamaguchi, J.; Yamamoto, S.; Takeda, T., Chem. Lett. 1992, 1185.
28. (a) Fieser & Fieser 1989, 14, 100. (b) Fieser & Fieser 1980, 8, 196.
(41)
29. Yoshida, J.; Tamao, K.; Kakui, T.; Kurita, A.; Murata, M.; Yamada, K.;
Kumada, M., Organometallics 1982, 1, 369.
O
30. Dickerman, S. C.; DeSouza, D. J.; Jacobson, N., J. Org. Chem. 1969, 34,
cis/trans = 21/79
710.
31. Doyle, M. P.; Siegfried, B.; Dellaria, J. F., J. Org. Chem. 1977, 42, 2426.
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