COPPER(I) BROMIDE 1
a higher order alkynyl cuprate,9 prepared from CuBr·DMS. The
Copper(I) Bromide1
chemistry of organocopper reagents in DMS has now become a
flourishing subfield of organometallic chemistry.5 9
CuBr
For the first decade of the modern era of organocopper
reagents, CuI was used almost exclusively as the precursor to
[7787-70-4] BrCu (MW 143.45)
organocopper(I) and organocuprate reagents.1f In 1975, House
introduced the DMS complex of CuBr, symbolized CuBr·SMe2
InChI = 1/BrH.Cu/h1H;/q;+1/p-1/fBr.Cu/h1h;/q-1;m
or CuBr·DMS, as  a convenient precursor for the generation of
InChIKey = NKNDPYCGAZPOFS-ZFYMQJCYCJ
lithium organocuprates .10 Unlike the commercial CuBr, which
CuBr·SMe2 is invariably contaminated with traces of colored CuII impurities,
[54678-23-8] C2H6BrCuS (MW 205.59) CuBr·DMS is a microcrystalline white solid. This material should
be stored under a dry, inert atmosphere in a refrigerator in order to
InChI = 1/C2H6S.BrH.Cu/c1-3-2;;/h1-2H3;1H;/q;;+1/p-1/fC2H
ć%
minimize the loss of DMS, which is quite volatile (bp 38 C). It is
6S.Br.Cu/h;1h;/q;-1;m
not surprising that Lipshutz found that low quality material gave
InChIKey = PMHQVHHXPFUNSP-GUDWEBAYCB
poor results.11 This author has found that for ultraprecision work,
(precursor for organocopper(I) reagents and organocuprates;1a f where stoichiometry is of paramount importance, the ultrapure
catalyst for diazo chemistry) (99.999%) grade of CuBr is preferable.5
Nevertheless, in a side-by-side comparison of seven CuI salts
Alternate Name: cuprous bromide.
ć% (CuCN, CuI, CuBr, CuBr·DMS, CuCl, CuOTf, and CuSCN) as
Physical Data: mp 504 C; the complex with dimethyl sulfide
ć% precursors of a typical alkyl and a typical aryl cuprate (Lithium
(DMS) decomposes at ca. 130 C; d 4.720 g cm-3.
Dibutylcuprate and Lithium Diphenylcuprate, respectively),
Solubility: insoluble in H2O and most organic solvents; partially
CuBr·DMS and Copper(I) Cyanide were found to give the
soluble in dimethyl sulfide.
best results.12 The comparison between ultrapure CuBr and
Form Supplied in: light green or blue-tinged white solid. 99.999%
CuBr·DMS is especially interesting, as it demonstrates a dra-
grade available. The DMS complex is a white solid.
matic effect for just 1 equiv of DMS in THF and especially in
Preparative Methods: commercial copper bromide is often con-
ether. Another example of a significant difference between CuBr
taminated; the use of freshly prepared or purified copper bro-
and CuBr·DMS is provided by Davis s study of 1,6 vs. 1,4 and
mide is strongly advised. Copper bromide can be prepared by
1,2-addition (eq 1).13
reduction of CuBr238 or CuSO4 NaBr.39
Purity: the colored impurities in the title reagent can be removed
from the commercial samples by dissolving an appropriate
R R
OO O
RMgCl
quantity of CuBr in a saturated aqueous solution of KBr over HO
++ (1)
30 min. Subsequent cooling, treating with charcoal, filtering,
CuBr" DMS
and diluting with water allows for the formation of the CuBr
R
precipitate.40 Traces of iron salts can be removed via the sul-
No Cu 4 1 3
fide complex.41 Alternatively, copper bromide can be purified CuBr 4 1 15
CuBr" DMS 3 1 30
by precipitation from 48% HBr. The precipitate is filtered and
washed sequentially with water, ethanol, and ether, then finally
dried under vacuum.42
Some of the most fundamental studies in organocopper chem-
Handling, Storage, and Precautions: maintenance of a dry N2 or
istry have been carried out using CuBr or CuBr·DMS as starting
Ar atmosphere is recommended. The DMS complex must be
materials. House showed that the chemoselectivity of Lithium
tightly sealed to prevent loss of DMS. Storage of this complex
Dimethylcuprate Lithium Bromide could be completely con-
in a cold place is recommended.
trolled by the choice of solvent.14 Thus a molecule with remote
bromoalkane and Ä…-enone functional groups gave only conjugate
addition in ether DMS and only displacement of the Br when
Original Commentary
HMPA (Hexamethylphosphoric Triamide) was present (eq 2). In
Steven H. Bertz & Edward H. Fairchild
LONZA, Annandale, NJ, USA
O
Me2CuLi·LiBr
t-Bu
Precursor for Organocopper(I) Reagents and Organocup-
ether DMS
rates. Although Phenylcopper was prepared from Copper(I)
O
Iodide by Reich in 19232 and Gilman in 1936,3 the material
(CH2)3Br
used for the modern characterization of this archetypal arylcop-
t-Bu
(2)
per(I) is prepared from CuBr,4 which continues to be a favored
precursor for new organocopper(I) compounds.5 9 For example,
O
(CH2)3Br
Bertz discovered that halide-free organocopper compounds can
Me2CuLi·LiBr
t-Bu
be prepared from CuBr in Dimethyl Sulfide (DMS), owing to the
ether DMS HMPA
precipitation of LiBr from this solvent.5 Thus it was possible to
prepare and structurally characterize the first bona fide  higher
(CH2)3Me
order cuprate.5a,6 Weiss recently reported the second example,
Avoid Skin Contact with All Reagents
2 COPPER(I) BROMIDE
13
a recent C NMR study it was shown that phenylcuprates are interesting example involves the use of organocopper reagents
dimeric in nonpolar solvents and monomeric in polar solvents.15 bearing protected Ä…-hydroxy or Ä…-thio functions.28a The prepara-
It was further conjectured that the dimer is responsible for the tion of Å‚-silylvinylcopper reagents via the addition of Ä…-silylated
conjugate addition reaction, and the monomer is responsible for organocopper reagents to alkynes has also been described.28b
the (much slower) SN2-like displacement reaction. The carbocupration of alkynes is the key step in the synthesis
The preparation of the first higher order cuprate, Ph5Cu2Li3 = of Å‚,Å‚-disubstituted allylboronates.29 The stannylalumination of
[Ph3CuLi3][Ph2Cu] or Ph3CuLi2 +Ph2CuLi, from CuBr/DMS 1-alkynes is catalyzed by CuI and involves stannylcupration by an
was mentioned above.5 House first proposed higher order intermediate stannylcopper(I) reagent.30
Ph3CuLi2 in solutions prepared from 3 equiv of PhLi and CuBr in The use of Grignard reagents in conjunction with CuI salts has
ether to account for the higher reactivity observed for this mixture been thoroughly reviewed.1a,d A very edifying example of the
13 6
in certain coupling reactions.16 However, C NMR and Li NMR difference between organocopper reagents prepared from lithium
studies did not detect any higher order phenylcuprate in ether or reagents vs. Grignard reagents has been provided by Curran
THF, only in DMS.5 While the presence of a small amount of (eq 4).31
higher order cuprate acting as a catalytic intermediate cannot be
ruled out, a more plausible explanation involves the attack of PhLi
H
R R
O
on a cuprate-complexed intermediate.
RLi + CuBr·DMS
+ (4)
O
or
The first thermally stable phosphido- and amidocuprates were
H H
R2 MgBr + CuBr·DMS
CO2H CO2H
prepared from CuBr·SMe2.17 (It was also shown that LiBr has a
H
beneficial effect on the reactions of organocuprates with typical
substrates.17c) Chiral amidocuprates have been extensively stud-
Me2CuLi·LiBr, THF 62 38
ied because of their potential for asymmetric induction.18 20 The
Me2CuLi·LiBr, ether 54 46
MeCu·MgBr2 98 2
chiral auxiliary has also been put on the substrate, e.g. cuprates
MeCu·LiBr 86 14
have been added to chiral unsaturated imides.21 A good recent
MeCu·LiI 76 24
review provides many more examples.1b
MeCu(CN)Li 75 25
Whereas Grignard reagents and lithium reagents generally give
Yields were 90 97%, except for the cuprate from CuCN: 60%
thiophilic addition to dithioesters, the corresponding organocop-
per reagents give carbophilic addition.22 The best yields were
In chemistry that is clearly related to that of organocop-
obtained with CuBr·DMS and Copper(I) Trifluoromethanesul-
per reagents, aryl bromides and aryl iodides undergo a Gabriel
fonate; good results were also obtained with CuCN and CuI.
reaction with potassium phthalimide in the presence of CuBr (or
This carbophilic addition has been applied to 1,3-thiazole-5(4H)-
CuI).32 They also undergo coupling reactions with the sodium
thiones.23 It is interesting to note that CuBr has also been used in
salts of active methylene compounds catalyzed by CuBr.33
the preparation of the dithioesters (eq 3).24
Copper-assisted nucleophilic substitution of aryl halogen has been
reviewed.1g In a potentially far-reaching development, thermally
stable, yet reactive formulations of organocuprates suitable for
S SH
CS2 MeI R2CuLi·LiBr
commercialization have been patented.34
R2 MgX (3)
CuBr (5 10%) R2 SMe R R2
R
Catalysts for Diazo Chemistry. CuBr has been used in other
reactions besides those involving organocuprates. It is a popular
catalyst for the activation of Diazomethane, e.g. tropylium per-
Nakamura and Kuwajima have reported the CuBr·DMS
chlorate is isolated in 85% yield starting from benzene.35 CuBr
catalyzed acylation and conjugate addition reactions of the Zn
has been used for the activation of diazoacetic esters,1j but not as
homoenolate from 1-alkoxy-1-siloxycyclopropanes and Zinc
often as CuCN, and especially CuCl. CuBr is the preferred cata-
Chloride.25a They have also reported the Chlorotrimethylsilane/
lyst for the Sandmeyer reaction of arenediazonium salts to afford
HMPA accelerated conjugate addition of stoichiometric
bromoarenes,36 and for the Meerwein reaction, the arylation of
organocopper reagents prepared from CuBr·DMS,25b and of
alkenes by diazonium salts.37
catalytic copper reagents,25c to Ä…,²-unsaturated ketones and alde-
hydes. This procedure appears to be more general than that based
Related Reagents. Copper(I) Bromide Lithium Trimethoxy-
on putative cuprates of intermediate stoichiometry (see Copper(I)
aluminum Hydride; Copper(I) Bromide Sodium Bis(2-methoxy-
Iodide). In a very significant observation, they report that
ethoxy)aluminum Hydride; Copper(I) Chloride; Copper(I)
 reagents derived from cuprous iodide consistently gave lower
Chloride Oxygen; Copper(I) Chloride-tetrabutylammonium
yields .25b
Chloride Copper(I) Chloride Sulfur Dioxide; Copper(I) Cyanide;
Wipf has used CuBr·DMS to catalyze the addition of alkyl and
Copper(I) Iodide; Copper(I) Trifluoromethanesulfonate.
alkenylzirconocenes to acid chlorides to yield ketones,26a and
also the 1,4-addition of alkylzirconocenes to Ä…-enones.26b The
hydrozirconation of alkynes followed by transmetalation to CuI
was devised by Schwartz et al.,27 who used CuI and Copper(I)
Chloride. Transmetalation from Al, B, Pb, Mn, Hg, Sm, Sn, Te,
First Update
Ti, Zn, and Zr to Cu has been reviewed recently.1h
Carbocupration of alkynes by organocopper reagents is a very Irina Denissova & Louis Barriault
important area, as judged by the number of citations.1a,i An University of Ottawa, Ottawa, Ontario, Canada
A list of General Abbreviations appears on the front Endpapers
COPPER(I) BROMIDE 3
Allylic Substitution and Cross-coupling Reactions. Copper There are only a few examples of copper-mediated catalytic
bromide and its DMS complex are still widely used to prepare asymmetric allylic substitution reactions employing a chiral lig-
organocopper reagents and organocuprates.43,44 Reference 44 and on copper. Knochel and Dubner reported the substitution of
describes the preparative methods and the most common use of various unsymmetrical allyl chlorides with hindered diorganoz-
organocopper reagents such as application in conjugated additions inc reagents in the presence of 1 mol % of CuBr·DMS and 10
and substitution reactions, including asymmetric versions. It pro- mol % of chiral ferrocenyl amines.47,48 The reaction was highly
vides updated information on the organocopper reactions reported regioselective (Å‚-selectivity) and resulted in products with enan-
in the original chapter of Encyclopedia of Reagents. tiomeric excess of up to 98%,48 but the method was limited
In the past decade the allylic substitution reaction has received to highly hindered dialkylzinc reagents. Later, Feringa and co-
increasing attention, especially its asymmetric catalytic version workers used 1 mol % of CuBr·DMS and phosphoramidite ligand
allowing for the formation of branched chiral products. Several to catalyze allyl alkylation with diethyl and dibutyl zinc and cin-
methods employing copper(I) salts were developed. The copper- namyl bromide.49
mediated allylic substitution reaction can follow two routes, either The use of bimetallic catalyst systems in order to improve
SN2 displacement of the leaving group (Å‚-substitution) or SN2 existing and to explore new transformations is popular in mod-
displacement (Ä…-substitution) (eq 5). ern transition-metal-catalyzed organic synthesis. Copper(I) salts
are known to accelerate reactions catalyzed by PdL4. Their use as
co-catalysts in combination with a palladium catalyst in the Stille
reaction has been widely reported, particularly for cross-coupling
RY
of sterically hindered reactants. For example, Saa showed that
either CuBr or CuI can be employed in 2 4 fold excess rela-
tive to the palladium catalyst for synthesis of highly hindered
2,2 ,6-trisubstituted and even 2,2 ,6,6 -tetrasubstituted biaryls as
CuX CuX
SN22 pathway SN2 pathway
R1M R1M well as terphenyls.50 The groups of Farina,51 Liebeskind,51 53 and
Espinet54 studied the nature of the  copper effect. They demon-
strated that copper(I) participates in the scavenging of a free lig-
R RR1
(5)
and L, released during the oxidation of PdL4 in the catalytic cycle,
thus promoting formation of the species responsible for the trans-
R1
metalation step. Also, Liebeskind suggested that in some cases
Cu(I) can transmetalate Sn, resulting in a more reactive organocop-
R1 = alkyl, aryl, vinyl, allyl per species.52 The majority of the articles related to the copper-
Y = Br, Cl, SO2Ph, OR2, O(P)(OR2)2, OC(O)R2 assisted Stille coupling employed copper iodide.51,52,54 57 How-
M = Li, MgX, ZnX, etc. ever, in some cases copper bromide,50,58,59 copper chloride,60,61
copper cyanide,62 and copper oxide63,57 were superior to CuI.
Clearly, the choice of a copper salt is strongly dependent on
the reaction substrate. Guillaumet and co-workers have recently
Interestingly, it is possible to control the regioselectivity of the
described a Stille type reaction between various aryl and vinyl
reaction by changing the stoichiometry of the copper reagent.
stannanes and electron-poor heteroaromatic derivatives bearing a
Calo and co-workers have studied the allylic substitution reaction
thiomethyl ether function as a leaving group.64 The authors re-
with allylic electrophiles containing heterocyclic leaving groups
port that a stoichiometric amount of copper(I) salt and palladium
and Grignard reagents in the presence of stoichiometric amounts
[Pd(PPh3)4] catalyst were essential for the reaction to proceed.
of CuBr.45 The authors have found that the substitution with
The performances of copper bromide, copper bromide·DMS, cop-
RCuMgBr2 cuprates, formed with an excess of CuBr, was en-
per iodide, and copper(I) methylsalicylate in the cross-coupling
tirely SN2 selective, whereas R2CuMgBr cuprates gave SN2 prod-
between 3-methylthiotriazine with 2-tributylstannylfuran were
ucts. The regioselectivity was also affected by the reaction solvent.
compared (eq 3). CuBr·DMS complex resulted in the highest yield
Thus, diethyl ether favored the SN2 route, while THF facilitated
(90%), whereas CuI, CuBr, and copper(I) methylsalicylate gave
the SN2 pathway. Breit and Demel reported the first catalytic
only 50% and 60% yields.
example of syn-selective allylic substitution using CuBr·DMS as a
Another example of the accelerating effect of copper salts is
catalyst and employing ortho-diphenylphosphanylbenzoyl group
the cross-coupling reaction of (Z)-1,2-difluoroethenylzinc iodide
as a reagent directed leaving group (eq 6).46
and various aryl iodides in the presence of tetra-kispalladium and
copper(I) bromide reported by Burton.65 In the absence of copper
bromide, the reaction would not go to completion.
Ph
Me
Copper bromide can also be successfully applied as a
O
20 mol % CuBr Ph co-catalyst with various palladium species in Sonogashira
O
Me
1.1 equiv MeMgI, Et2O, rt
coupling,66,67 though copper iodide is most commonly used.68
PPh2 85% Me
Copper bromide is commonly used as a catalyst in cross-coup-
ling reactions of vinyl zinc compounds. For instance, Shibuya
regioselectivity 96:4
described the cross-coupling reaction of [(diethoxyphospho-
E:Z = 95:5
(6)
ee > 99% ryl)difluoromethyl]zinc bromide with ²-iodo alkenoates catalyzed
E:Z >99:1
by copper bromide.69 Burton utilized copper bromide for a
ee > 99%
Avoid Skin Contact with All Reagents
4 COPPER(I) BROMIDE
self-coupling of Ä…-halovinyl zinc compounds in order to gener- materials with controlled molecular weight and well-defined
ate fluorinated cumulated butatrienes in high yields (eq 7).70 chain architectures. Although many transition metal complexes
catalyze ATRP, according to a comprehensive review by
Matyjaszewski and Xia:  copper catalysts are superior in ATRP
R1 Br R1 R1
cat CuBr
in terms of versatility and cost. 76 Among copper catalysts,
(7)
" "
DMF
copper bromide and copper chloride are most commonly used.
R2 Zn R2 R2
65-72%
Matyjaszewski first reported in 1995 that copper bromide and
copper chloride complexed by three molecules of bipyridine in
R1 = Ph, C6F5
the presence of commercially available alkyl halides served as
R2 = CF3, C2F5, C3F7
efficient initiators for the controlled polymerization of styrene,
MA, and MMA.74,77 Polymers with molecular weights up to
100 000 and quite narrow polydispersities were synthesized with
good control. Ligands can considerably increase the rate of poly-
Copper Bromide as a Lewis Acid. Recently, Knochel has re-
merization either by making the catalyst more soluble or by
ported an enantioselective synthesis of propargylamines by copper
changing the redox potential of the catalyst system. Polydentate
bromide/Quinap-catalyzed addition of alkynes to enamines with
ligands such as phenatroline, its derivatives, substituted 2,2 :6 ,2 -
enantioselectivities ranging from 50 to 90% (eq 8).71
terpyridine, pyridineimines, and multidentate branched and linear
aliphatic amines are often used in ATRP.
R2
5 mol % CuBr, 5.5 mol % Quinap
R1 + R4 N
ATRC Atom Transfer Radical Cyclization. Another area
R3 toluene, rt, 24-96 h
where reductive properties of copper(I) bromide are exploited is
in the atom transfer radical cyclization of a C X bond across
N
a carbon-carbon multiple bond. Organostannane reagents are
known to catalyze this type of reaction;78 however their toxicity,
PPh2
high cost, and difficulties related to purification impose a
certain limitation on their use. Like ATRP, a number of transition-
Quinap
metal catalysts can be employed. For example, RuCl2(PPh3)3,
FeCl2[P(OEt)3]3,79 and Ni80 metal have been reported to
R1
catalyze atom transfer with 2,2,2-trichlorinated carbonyl com-
pounds. However, copper(I) halide complexes (mostly copper
R4
(8)
chloride and copper bromide) are by far the most applicable
N
because of their low cost, simple work-up procedure (many
R2 R3
times only flashing through a silica column is required), and the
50-99% yields
catalytic nature of the process. Clark has investigated 5-exo81,82
55-90% ee s
and 5-endo83 cyclizations of various substituted bromo
acetamides catalyzed by copper bromide (eq 9).
This is a first example of metal-catalyzed enantioselective ad-
dition of alkynes to enamines. A number of alkynes bearing
different functionalities were successfully used. Among the vari-
C5H11
ous metal salts tested, including Sc(OTf)3, Zn(OTf)2, Yb(OTf)3, N
30 mol %
I II
N
and Cu and Cu salts, copper(I) and copper(II) demonstrated
Me
Br
Me
the best results. Dax has previously reported that copper chloride Br
30 mol % CuBr
(not catalytic) promoted a reaction of resin-bound propargylamine
CH2Cl2, rt, 48 h
O
O
N N
and various imines formed in situ from the corresponding sec- 97%
ondary amine and paraformaldehyde.72 Carreira has shown that Ts Ts
the [IrCl(COD)2] complex can catalyze the addition reaction of
trimethylsilylacetylene to imines as well.73
30 mol % CuBr
Br
30 mol % ligand
CH2Cl2, rt, 20 min
Reductive Properties of Copper Bromide.
O
O
N
N
99%
Bn
Bn
ATRP Atom Transfer Radical Polymerization. ATRP was
developed independently by the groups of Matyjaszewski74 and
Sawamoto75 in 1995, and it became one of the most success-
Me2N NMe2
ful methods for controlled/living radical polymerization systems. N
In this type of polymerization, a reversible metal-catalyzed atom
ligand =
transfer is used to generate the propagating radicals as opposed
NMe2
to thermally or photochemically promoted homolytic cleavage.
(9)
ATRP allows for the preparation of a vast range of polymeric
A list of General Abbreviations appears on the front Endpapers
COPPER(I) BROMIDE 5
He has also studied 4-exo cyclization of terminally substituted In the presence of 1 equiv of copper bromide in TEA/DMA at
ć%
enamides, which allowed for the synthesis of ²-lactams in very 150 C, bis-propynylpyrimidines were converted into the desired
high yields (eq 10).84 bis-pyrrolopyrimidines in 48 52% yield.
Cohen discovered that copper bromide dimethyl sulfide
complex can be an alternative to copper(I) triflate or
Br
tetrakis(acetonitrile) copper(I) in removing the thiophenoxide
30 mol % CuBr, 30 mol % ligand
Br group.90 CuBr·DMS showed comparable results with little or no
CH2Cl2, rt, 20 min
yield loss, though more vigorous conditions were required. How-
N
O
N
97% Bn
O
ever, the much lower cost compared to that of copper(I) triflate or
Bn
N
tetrakis(acetonitrile) copper(I) as well as its easy and safe handling
N N
make CuBr·DMS an attractive substitute.
ligand =
N
A combination of CuBr Ag2CO3 or CuBr H2O was used to
catalyze the addition of various Grignard reagents to vinyltri-
phenylphosphonium bromide followed by an addition of alkyl
or aryl aldehyde to yield alkenes.91 In the absence of either sil-
ver carbonate or water, the desired product was obtained in only
30 mol % CuBr
25% yield. Copper chloride could also be employed in the re-
30 mol % ligand
(10)
Br
action, giving similar results. The reaction of lithium cuprates
toluene, reflux
82%
O with vinyltriphenylphosphonium bromide followed by the reac-
N
N
Bn
O tion with an aldehyde has been previously demonstrated.92 The
Bn
addition of phenyllithium cuprate to vinyltriphenylphosphonium
2.8:1 mixture of diastereomers
bromide and consequent reaction of the resulting phosphorane
with para-N,N-dimethylaminobenzaldehyde gave a 45:55 mixture
of E- and Z-isomers. Alternatively, the reaction of phenylmagne-
sium bromide in the presence of CuBr Ag2CO3 resulted in higher
Interestingly, no product resulting from the 5-endo attack was
yields and gave 100% E-selectivity.
ć%
detected even at 110 C in toluene. The 5-exo atom transfer radi-
CuBr is also used to catalyze the Crabbe reaction, in which
cal cyclization of 1-halo-N-propargylacetamides catalyzed by the
various alk-1-ynes react with an excess of formaldehyde and
tripyridylamine copper bromide complex has been reported.85 A
di-isopropylamine in the presence of catalytic copper bromide
recent review summarizes the majority of the examples related to
in refluxing dioxane to give the corresponding allene homologs
copper-mediated ATRC.86
(eq 12).93
Reductive Homocoupling. Ghelfi used copper(I) bromide to
promote a reductive homocoupling of Ä…-bromo-Ä…-chlorocarboxy-
CH2O, iPr2NH, CuBr R
(12)
"
lates to dimethyl Ä…,Ä… -dichloro-succinate derivatives in the pres- R
1.5-30 h
H
ence of CuBr/LiOCH3 in methanol.87 Lithium methoxide was
40-62 %
necessary for the reaction to occur. It was speculated that the
reductive power of copper(I) increases in the presence of the
methoxy ligands. The same coupling can be also performed using
The reaction does not proceed in the absence of copper bromide,
a CuBr/Fe0 couple.88 In this case, the authors proposed that orig-
though its role is not precisely known. Copper in oxidation states
inally Fe0 was oxidized to FeII by copper(I) bromide, thus giving
(0), (I), and (II) has been detected in the course of the reaction.
rise to FeBr2 which would then initiate a homocoupling. When
copper bromide was replaced by copper chloride, less satisfactory
results were obtained.
1. (a) Lipshutz, B. H.; Sengupta, S., Org. React. 1992, 41, 135. (b) Rossiter,
B. E.; Swingle, N. M., Chem. Rev. 1992, 92, 771. (c) Chapdelaine,
Miscellaneous. Gevorgyan has recently reported a
M. J.; Hulce, M., Org. React. 1990, 38, 225. (d) Erdik, E., Tetrahedron
copper-assisted double pyrrolization of pyrimidine derivatives
1984, 40, 641. (e) Posner, G. H., An Introduction to Synthesis Using
into the bis-pyrrolopyrimidines allowing for construction of a
Organocopper Reagents; Wiley: New York, 1980. (f) Posner, G. H., Org.
5-6-5 tricyclic heteroaromatic skeleton (eq 11).89
React. 1975, 22, 253; also see: Posner, G. H., Org. React. 1972, 19, 1.
(g) Lindley, J., Tetrahedron 1984, 40, 1433. (h) Wipf, P., Synthesis 1993,
537. (i) Normant, J. F.; Alexakis, A., Synthesis 1981, 841. (j) Dave, V.;
R2
R2
Warnhoff, E. W., Org. React. 1970, 18, 217.
R1
R1 CuBr, Et3N-DMA
2. Reich, M. R., C. R. Hebd. Seances Acad. Sci., Ser. C 1923, 177, 322.
(11)
3. Gilman, H.; Straley, J. M., Recl. Trav. Chim. Pays-Bas 1936, 55, 821.
150 °C, 10 h N N
N N
4. Costa, G.; Camus, A.; Gatti, L.; Marsich, N., J. Organomet. Chem. 1966,
48-52%
5, 568.
5. (a) Bertz, S. H.; Dabbagh, G., J. Am. Chem. Soc. 1988, 110, 3668.
(b) Bertz, S. H.; Dabbagh, G., Tetrahedron 1989, 45, 425.
R1 = H, R2 = Me
6. Olmstead, M. M.; Power, P. P., J. Am. Chem. Soc. 1990, 112, 8008.
R1 = Me, R2 = H
7. Lenders, B.; Grove, D. M.; Smeets, W. J. J.; van der Sluis, P.; Spek,
R1 = C2H5, R2 = H
A. L.; van Koten, G., J. Organomet. Chem. 1991, 10, 786.
Avoid Skin Contact with All Reagents
6 COPPER(I) BROMIDE
8. Kapteijn, G. M.; Wehman-Ooyevaar, I. C. M.; Grove, D. M.; Smeets, W. 42. Dieter, R. K.; Silks, L. A., III; Fishpaugh, J. R.; Kastner, M. E., J. Am.
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