[Pd(Cl)2(P(NC5H10)(C6H 11)2)2] - A highly effective and extremely versatile palladium-based negishi catalyst that efficiently and reliably operates at low catalyst loadings

Article abstract of DOI:10.1002/chem.201001201

[Pd(Cl)₂(P(NC₅H₁₀)-(C₆H ₁₁)₂]₂] (1) has been prepared in quantitative yield by reacting commercially available [Pd(cod)(Cl)₂] (cod = cyclooctadiene) with readily prepared 1-(dicyclohexylphosphanyl)piperidine in toluene under N₂ within a few minutes at room temperature. Complex 1 has proved to be an excellent Negishi catalyst, capable of quantitatively coupling a wide variety of electronically activated, non-activated, deactivated, sterically hindered, heterocyclic, and functionalized aryl bromides with various (also heterocyclic) arylzinc reagents, typically within a few minutes at 100°C in the presence of just 0.01 mol% of catalyst. Aryl bromides containing nitro, nitrile, ether, ester, hydroxy, carbonyl, and carboxyl groups, as well as acetais, lactones, amides, anilines, alkenes, carboxylic acids, acetic acids, and pyridines and pyrimidines, have been successfully used as coupling partners. Furthermore, electronic and steric variations are tolerated in both reaction partners. Experimental observations strongly indicate that a molecular mechanism is operative.

Full text of DOI:10.1002/chem.201001201

DOI: 10.1002/chem.201001201
[Pd(Cl)2{PACHTUNGTRENNUNG(NC5H10)ACHUTNTGERN(NUGN C6H11)2}2]—A Highly Effective and Extremely Versatile
Palladium-Based Negishi Catalyst that Efficiently and Reliably Operates at
Low Catalyst Loadings
Jeanne L. Bolliger and Christian M. Frech*[a]
Abstract:
(C6H11)2}2] (1) has been prepared in
quantitative yield by reacting commer-
cially available [Pd(cod)(Cl)2] (cod=
cyclooctadiene) with readily prepared
1-(dicyclohexylphosphanyl)piperidine
in toluene under N2 within a few mi-
nutes at room temperature. Complex 1
has proved to be an excellent Negishi
catalyst, capable of quantitatively cou-
pling a wide variety of electronically
activated, non-activated, deactivated,
[Pd(Cl)2{P
(NC5H10)-
sterically hindered, heterocyclic, and
functionalized aryl bromides with vari-
ous (also heterocyclic) arylzinc re-
agents, typically within a few minutes
at 1008C in the presence of just
0.01 mol% of catalyst. Aryl bromides
containing nitro, nitrile, ether, ester,
hydroxy, carbonyl, and carboxyl
groups, as well as acetals, lactones,
amides, anilines, alkenes, carboxylic
acids, acetic acids, and pyridines and
pyrimidines, have been successfully
used as coupling partners. Further-
more, electronic and steric variations
are tolerated in both reaction partners.
Experimental observations strongly in-
dicate that a molecular mechanism is
operative.
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
Keywords:
arylzinc reagents
·
À
biaryls
· C C coupling · cross-
coupling · Negishi cross-coupling ·
palladium
Introduction
tions of aryl- as well as alkylzinc reagents from highly func-
tionalized precursors have been described) have significantly
broadened the scope and applicability of the Negishi reac-
tion in organic synthesis.[3] Nowadays, the Negishi reaction
belongs to an indispensable set of palladium-catalyzed
cross-coupling reactions and finds application in all areas of
organic chemistry. Together with the Suzuki reaction, it is
among the most important methods for the catalytic forma-
tion of symmetric and nonsymmetric biaryls,[4–6] which are
found, for example, in polymers,[7] biologically active com-
pounds,[8] ligands,[9] and various materials.[10]
The Negishi reaction (cross-coupling of an aryl halide with
an organozinc reagent) is an extremely versatile and mild
synthetic method for the formation of carbon–carbon bonds,
which (in contrast to the Kumada reaction) tolerates a wide
variety of functional groups (Scheme 1).[1,2] Recent improve-
ments in the preparation of organozinc reagents (prepara-
Even though recent developments have led to a consider-
able increase in the activity of Negishi catalysts, some of
which are very effective and allow the coupling of sterically
hindered substrates and even aryl chlorides at low catalyst
loadings and occasionally at room temperature,[11] a typical
protocol for this reaction still requires prolonged reaction
times and relatively high catalyst loadings (typically 0.5–
5 mol%), highlighting the need for more efficient systems.[12]
Moreover, their (multistep) syntheses are often time-con-
suming, difficult, and/or require the use of expensive starting
materials. Furthermore, many of these catalysts suffer from
poor thermal stability, low functional group tolerance, and/
or sensitivity towards air, and hence require inconvenient
inert-atmosphere techniques for their successful use. In ad-
dition, modified reaction conditions are often reported for
Scheme 1. Negishi cross-coupling reaction between aryl bromides and
bisACHTUNGTRENNUNG(aryl)zinc reagents.
[a] J. L. Bolliger, C. M. Frech
Department of Inorganic Chemistry, University of Zꢀrich
Winterthurerstrasse 190, 8057 Zꢀrich (Switzerland)
Fax : (+41)44-635-6802
E-mail: chfrech@aci.uzh.ch
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201001201.
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FULL PAPER
different substrates, which may strongly limit their applica-
tion in industrial processes.
We report herein the catalytic performance of the simple,
inexpensive, and readily prepared palladium complex
the presence of just 0.01 mol% of catalyst.[14] Moreover,
electronic and steric variations are tolerated in both reaction
partners. Exemplary reactions were performed with diphe-
nylzinc, bis(4-methoxyphenyl)zinc, bis[4-(dimethylamino)-
phenyl]zinc, sterically hindered dinaphthalen-1-ylzinc, bis(2-
methoxyphenyl)zinc, bis(2,5-dimethoxyphenyl)zinc, bis(2-
methylphenyl)zinc, and bis(2,4,6-trimethylphenyl)zinc, as
well as with 4-ethoxycarbonylphenylzinc iodide, bis[2-(dieth-
oxymethyl)phenyl]zinc, bis[3-(diethoxymethyl)phenyl]zinc,
and dithiophen-2-ylzinc, both aryl groups of which were in-
corporated into the generated biaryls. Performing the Ne-
gishi reactions in N-methylpyrrolidone (NMP) afforded the
highest conversion rates and yields.
[Pd(Cl)2{PACHTUNGTRENNUNG(NC5H10)ACHTUNGTRENNUNG(C6H11)2}2] (1) in the Negishi cross-cou-
pling reaction with aryl bromides (aryl chlorides have not
been tested) and demonstrate that 1 is an extremely effi-
cient, reliable, and versatile Negishi catalyst with excellent
functional group tolerance, which allows electronic and
steric variations in both reaction partners. Furthermore, the
reaction protocol presented is highly convenient, simple,
and, most importantly, universally applicable. Moreover, the
biaryls are cleanly and quantitatively formed, typically
within a few minutes at 1008C in the presence of just
For example, coupling reactions between diphenylzinc
and electronically activated aryl bromides, such as 1-bromo-
4-nitrobenzene, 4-bromobenzonitrile, methyl 3-bromoben-
zoate, and 5-bromo-2-benzofuran-1(3H)-one, or with non-
activated phenyl bromide, 1-bromo-4-ethenylbenzene, and
2,7-dibromofluorene, afforded the coupling products in
>90% yield within only 5 min (Scheme 3). The same level
of activity was observed when electronically deactivated 1-
bromo-4-methoxybenzene, 4’-bromo-2’-methylacetanilide, 4-
bromoaniline, and 4-bromo-N,N-dimethylaniline or sterically
hindered substrates, such as 1-bromo-2-methylbenzene, 2-
bromo-1,3,5-trimethoxybenzene, and 2’-bromo-2,6-dime-
thoxybiphenyl, were used as coupling partners, with which
>93% conversion was obtained in almost all of the reac-
tions examined after 5 min. Even 2’-bromo-2,6-bis(1-methyl-
ethoxy)biphenyl, a highly sterically hindered substrate, was
smoothly coupled with diphenylzinc: 89% conversion into
2,6-bis(1-methylethoxy)-1,1’:2’,1’’-terphenyl was achieved
after 2 h. Excellent performance of the catalyst was also
noted for various (also sterically hindered) bromophenols,
4-bromobenzoic acid, as well as (4-bromophenyl)acetic acid,
which generally afforded the coupling products in >90%
yield within 15 min. Similar conversion rates and yields were
also observed for 3-bromopyridines, such as 3-bromopyri-
dine, 3-bromoquinoline, 5-bromo-2-methoxypyridine, 5-bro-
mopyridin-3-amine, N-(5-bromopyridin-2-yl)acetamide, 5-
bromo-6-methylpyridin-2-amine, as well as 5-bromopyrimi-
dine and 2,6-dibromopyridine. On the other hand, although
very high yields were obtained, prolonged reaction times
were required when 2-bromopyridines, such as 2-bromo-3-
methylpyridine and 2-bromo-3-methoxypyridine, were used
as coupling partners.
0.01 mol% of catalyst. The dichloro
phanyl)piperidine]} complex [Pd(Cl)2{P
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
(1), an extremely effective Suzuki catalyst, was chosen be-
cause it promotes the formation of palladium nanoparticles
(palladium nanoparticles have been shown to be the catalyt-
ically active form of 1 in the Suzuki reaction)[13] and also be-
cause it can operate through homogeneous mechanisms.
Indeed, mechanistic investigations performed here have in-
dicated that 1 operates through a molecular mechanism in
the Negishi reaction.
Results and Discussion
The palladium complex [Pd(Cl)2{PACHTUNRGTNNEGU(NC5H10)CAHTUGNTRENN(GUN C6H11)2}2] (1)
was prepared in quantitative yield within a few minutes at
room temperature by reaction of commercially available
[PdACHTUNGTRENNUNG(cod)(Cl)2] (cod=cyclooctadiene) with two equivalents
of readily prepared 1-(dicyclohexylphosphanyl)piperidine in
toluene under N2 (Scheme 2).[13]
Scheme 2. Synthesis of 1; Cy=cyclohexyl.
Excellent performance was also observed when using di-
AHCTUNGTREGaNNUN rylzinc reagents with increased electron density on the aryl
À
Complex 1 is an extremely active, reliable, and versatile
Negishi catalyst with excellent functional group tolerance,
which successfully couples a wide variety of substrates.
These may contain nitro, nitrile, acetal, ketone, ether, ester,
lactone, amide, aniline, alkene, phenol, carboxylic acid,
acetic acid, pyridine, or pyrimidine moieties. The aryl bro-
mides may be electronically activated, non-activated, deacti-
vated, and/or sterically hindered or heterocyclic, and are
coupled with various (also heterocyclic) arylzinc reagents in
excellent yields, generally within a few minutes at 1008C in
unit. For example, complete C C bond formation within
only 15 min was generally achieved in coupling reactions be-
tween bis(4-methoxyphenyl)zinc and various electronically
activated, non-activated, or deactivated aryl bromides, such
as 4-bromobenzonitrile, 1,4-dibromobenzene, 1-bromo-4-
ethenylbenzene, 1-bromo-2-(diethoxymethyl)benzene, and
4-bromo-N,N-dimethylaniline (Scheme 4). Essentially the
same yields were obtained, but slightly lower conversion
rates were sometimes noted, when sterically hindered 1-
bromo-2-methylbenzene and 2-bromo-1,3,5-trimethylben-
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C. M. Frech and J. L. Bolliger
ic acid into 4’-methoxybiphenyl-
4-carboxylic acid. Similar con-
version rates and yields were
observed when using 3-bromo-
pyridines, 5-bromopyrimidine,
and 2,6-dibromopyridine as
coupling partners. Exemplary
reactions were performed with
3-bromopyridine, 3-bromoqui-
noline, 5-bromo-2-methoxypyri-
dine,
5-bromo-6-methylpyri-
dine-2-amine, and 5-bromopyri-
dine-3-carboxamide. Quantita-
tive conversions were achieved,
although prolonged reaction
times were required for 2-bro-
mopyridines. Essentially the
same performance was noted
with bis[4-(dimethylamino)phe-
nyl]zinc as the coupling partner.
Whereas similar conversion
rates and yields were achieved
when sterically hindered diaryl-
AHCTUNGTERGzNNUN inc reagents, such as bis(2-
methylphenyl)zinc and dinaph-
thalen-1-ylzinc, were used as
coupling partners, reduced cata-
lytic activity was noted with
bis(2,4,6-trimethylphenyl)zinc
(Scheme 5). For example, cou-
pling reactions of electronically
activated aryl bromides such as
1-bromo-4-nitrobenzene and 4-
bromobenzonitrile, non-activat-
ed aryl bromides such as 5-
bromo-2-benzofuran-1ACTHNUTRGNE(NUG 3H)-
one, phenyl bromide, 1-bromo-
4-ethenylbenzene, 4’-bromo-2’-
methylacetanilide, and 1,3,5-tri-
bromobenzene, or deactivated
aryl bromides such as 4-bromo-
N,N-dimethylaniline with bis(2-
Scheme 3. Negishi cross-coupling reactions of aryl bromides with diphenylzinc catalyzed by 1. Reaction condi-
tions: 2.0 mmol aryl bromide, 1.1 mmol diphenylzinc (relative to bromide), 4 mL NMP, catalyst (0.01 mol%)
added in solution (THF), reaction performed at 1008C. The conversions were determined by GC-MS, based
on aryl bromide; yields of the isolated products are given in brackets. [a] 2.1 mmol of diphenylzinc was used.
[b] Isolated as the aldehyde.
methylphenyl)zinc
generally
yielded the respective biaryls
within a few minutes. 2’-Bromo-
2,6-dimethoxybiphenyl and 2’-
zene were used as coupling partners. Impressively, even 2’-
bromo-2,6-dimethoxybiphenyl and 2’-bromo-2,6-bis(1-meth-
ylethoxy)biphenyl were smoothly coupled with bis(4-me-
thoxyphenyl)zinc to give 2,4’’,6-trimethoxy-1,1’:2’,1’’-ter-
phenyl and 4’’-methoxy-2,6-bis(1-methylethoxy)-1,1’:2’,1’’-
terphenyl in yields of 96% and 83%, respectively, in reac-
tion times of just 2 h. Slightly improved conversions were
noted when bromophenols were used as coupling partners,
which quantitatively yielded the respective coupling prod-
ucts within 2 h. On the other hand, a reaction time of 5 min
was sufficient for the complete conversion of 4-bromobenzo-
bromo-2,6-bis(1-methylethoxy)biphenyl were also success-
fully converted into 2,6-dimethoxy-2’’-methyl-1,1’:2’,1’’-ter-
phenyl (95%) and 2’’-methyl-2,6-bis(1-methylethoxy)-
1,1’:2’,1’’-terphenyl (89%) within 30 min and 3 h, respective-
À
ly. Similarly, whereas complete C C bond formation was
achieved within 15 min with 4-bromophenol, 4-bromo-3-
methylphenol, and 4-bromobenzoic acid as coupling part-
ners, prolonged reaction times were required to fully con-
vert 4-bromo-3,5-dimethylphenol and 2-bromophenol into
the respective biaryls. Similar conversion rates and yields
were noted for 3-bromopyridines, 5-bromopyrimidine, and
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[Pd(Cl)2{PACHTUNGTRENNUNG(NC5H10)ACHTUNGTRENNUNG(C6H11)2}2] as a Versatile Catalyst for Negishi Couplings
FULL PAPER
Scheme 4. Negishi cross-coupling reactions of aryl bromides with bis(4-methoxyphenyl)zinc and bis[4-(dimethylamino)phenyl]zinc catalyzed by 1. Reac-
tion conditions: 2.0 mmol aryl bromide, 1.1 mmol diarylzinc (relative to bromide), 4 mL NMP, catalyst (0.01 mol%) added in solution (THF), reaction
performed at 1008C. The conversions were determined by GC-MS, based on aryl bromide; yields of the isolated products are given in brackets. [a] Isolat-
ed as the aldehyde. [b] 2.1 mmol of diarylzinc was used.
2,6-dibromopyridine. On the other hand, prolonged reaction
times were required to fully convert 2-bromopyridine and 2-
bromo-3-methylpyridine into 2-(2-methylphenyl)pyridine
Whereas the same level of activity was observed for dinaph-
thalen-1-ylzinc, comparable yields but a decreased catalytic
activity were observed for bis(2,4,6-trimethylphenyl)zinc as
coupling partner. For example, although full conversions of
and
3-methyl-2-(2-methylphenyl)pyridine,
respectively.
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C. M. Frech and J. L. Bolliger
Scheme 5. Negishi cross-coupling reactions of aryl bromides with bis(2-methylphenyl)zinc, dinaphthalen-1-ylzinc, and bis(2,4,6-trimethylphenyl)zinc cata-
lyzed by 1. Reaction conditions: 2.0 mmol aryl bromide, 1.1 mmol diarylzinc (relative to bromide), 4 mL NMP, catalyst (0.01 mol%) added in solution
(THF), reaction performed at 1008C. The conversions were determined by GC-MS, based on aryl bromide; yields of the isolated products are given in
brackets. [a] 2.1 mmol of diarylzinc was used. [b] Isolated as the aldehyde.
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[Pd(Cl)2{PACHTUNGTRENNUNG(NC5H10)ACHTUNGTRENNUNG(C6H11)2}2] as a Versatile Catalyst for Negishi Couplings
FULL PAPER
1-bromo-3-(diethoxymethyl)benzene, 4-bromo-N,N-dimethy-
laniline, 1-bromo-2-methylbenzene, and 4-bromobenzoic
acid into 1-[3-(diethoxymethyl)phenyl]naphthalene, N,N-di-
tained for phenols and pyridines, albeit only after extended
reaction times.
À
Excellent performance was found in C C bond-forming
methyl-4-naphthalen-1-ylaniline,
1-(2-methylphenyl)naph-
reactions with electron-deficient [4-(ethoxycarbonyl)phenyl]-
thalene, and 4-naphthalen-1-ylbenzoic acid, respectively,
were achieved within 5 min, reaction times of 2 h or more
were required for the formation of 3’-(diethoxymethyl)-
2,4,6-trimethylbiphenyl, N,N,2’,4’,6’-pentamethylbiphenyl-4-
amine, 2,2’,4,6-tetramethylbiphenyl, and 2’,4’,6’-trimethylbi-
phenyl-4-carboxylic acid, respectively.
ACHTUNGTREN(NUGN iodo)zinc as a coupling partner, with which a >90% yield
of the respective biaryl was obtained within 30 min in
almost all of the reactions examined. Examples include reac-
tions with electronically activated 1-bromo-4-nitrobenzene
and methyl 4-bromobenzoate, non-activated phenyl bromide
and 1-bromo-4-ethenylbenzene, and deactivated 1-bromo-4-
methoxybenzene, 1-bromo-3-(diethoxymethyl)benzene, and
4-bromo-N,N-dimethylaniline, as well as with sterically hin-
dered 1-bromo-2-(diethoxymethyl)benzene, 1-bromo-2-
methylbenzene, 1-bromo-2-methoxybenzene, 2-bromo-1,3,5-
trimethylbenzene, and even 2’-bromo-2,6-dimethoxybiphe-
Further reactions were performed with bis(2,4,6-trime-
thylphenyl)zinc and sterically hindered aryl bromides, such
as 1-bromo-2-methoxybenzene, 9-bromoanthracene, and 2-
bromo-1,3,5-trimethylbenzene. While full conversions into
2’-methoxy-2,4,6-trimethylbiphenyl and 9-(2,4,6-trimethyl-
phenyl)anthracene were achieved within 24 h, almost no ac-
tivity was observed with 2-bromo-1,3,5-trimethylbenzene.
A slightly reduced level of activity was generally noted
for sterically hindered diarylzinc reagents with increased
electron density on the aryl unit, such as bis(2-methoxyphe-
nyl)zinc and bis(2,5-dimethoxyphenyl)zinc (Scheme 6), for
which reaction times of 1 h were required to achieve >90%
conversion to the respective biaryls. Exemplary reactions
were performed with aryl bromides such as 4-bromobenzo-
nitrile, methyl 3-bromobenzoate, phenyl bromide, 1-bromo-
4-ethenylbenzene, 1-bromo-2-methylbenzene, 1-bromo-3-
(diethoxymethyl)benzene, 1-bromo-4-methoxybenzene, and
4-bromo-N,N-dimethylaniline. Excellent yields were ob-
AHCTUNGTREGnNNUN yl (Scheme 7). Whereas very high conversion rates and
yields were observed with 3-bromopyridines and 2,6-dibro-
mopyridine, prolonged reaction times were required for the
complete conversion of 2-bromopyridines into the corre-
sponding biaryls. Essentially the same level of performance
was noted in coupling reactions carried out with bis[2-(di-
ethoxymethyl)phenyl]zinc and bis[3-(diethoxymethyl)phe-
nyl]zinc, with which >90% conversion to the respective (di-
ethoxymethyl)biphenyls (which were isolated as biphenyl
carbaldehydes) was obtained in almost all of the reactions
examined.
High yields were obtained, but only after reaction times
of between 2 and 24 h, with dithiophen-2-ylzinc as a cou-
pling partner. The results obtained are summarized in
Scheme 8.
Overall, complex 1 is one of
the most convenient, versatile,
and active Negishi catalysts re-
ported to date,[15] and enables a
wide variety of aryl bromides to
be coupled with diarylzinc re-
agents in very high yields. The
couplings are performed using
just 0.01 mol% of catalyst, are
generally complete within a few
minutes, and, most importantly,
the same reaction protocol
could be used in all of the reac-
tions examined. In contrast to
1, which reliably operates at
very low catalyst loadings, most
of the hitherto reported palladi-
um-based Negishi catalysts
have had to be deployed at 1–
5 mol% to efficiently couple
aryl bromides with arylzinc hal-
ides or diarylzinc reagents.[16–18]
Exceptions
AHCTUNGTREGUN(NN C3H5)(Cl)]2/tedicyp(tedicyp=
cis,cis,cis-1,2,3,4-tetrakis(diphe-
nylphosphinomethyl)cyclopen-
tane), which has been reported
include
[Pd-
Scheme 6. Negishi cross-coupling reactions of aryl bromides with bis(2-methoxyphenyl)zinc and bis(2,5-dime-
thoxyphenyl)zinc catalyzed by 1. Reaction conditions: 2.0 mmol aryl halide, 1.1 mmol diarylzinc (relative to
bromide), 4 mL NMP, catalyst (0.01 mol%) added in solution (THF), reaction performed at 1008C. The con-
versions were determined by GC-MS, based on aryl bromide; yields of the isolated products are given in
brackets. [a] Isolated as the aldehyde. [b] 2.1 mmol of diarylzinc was used.
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C. M. Frech and J. L. Bolliger
Scheme 7. Negishi cross-coupling reactions of aryl bromides with [4-(ethoxycarbonyl)phenyl]
ethoxymethyl)phenyl]zinc catalyzed by 1. Reaction conditions: 2.0 mmol aryl bromide, 1.1 mmol diarylzinc or 2.2 mmol [4-(ethoxycarbonyl)phenyl]-
ACHTUNGTRENNUNG(iodo)zinc (relative to bromide), 4 mL NMP, catalyst (0.01 mol%) added in solution (THF), reaction performed at 1008C. The conversions were deter-
ACHTUNGERTN(NUNG iodo)zinc, bis[2-(diethoxymethyl)phenyl]zinc, and bis[3-(di-
mined by GC-MS, based on aryl bromide; yields of the isolated products are given in brackets. [a] Isolated as the aldehyde. [b] 4.2 mmol of diarylzinc
was used.
to efficiently catalyze Negishi reactions of various aryl bro-
mides with phenylzinc bromide at 708C at a level of 0.1–
0.001 mol% of palladium.[19] Also, the NHC-containing
active palladium catalysts reported to date, which are capa-
ble of coupling aryl chlorides with arylzinc halides, have
been those of Buchwald and Fu.[2f,11b]
[Pd(Cl)
(NC5H4Cl)] (NHC=N-heterocyclic carbene) com-
However, apart from the excellent catalytic activity and
functional group tolerance of 1 in the Negishi reaction, a
further advantage of 1 when compared with (water-insolu-
ble) phosphine-based systems is its reactivity towards water.
It has recently been demonstrated that dichloroACHTNUTRGNE{NUG bis[1-(dicy-
clohexylphosphanyl)piperidine]}palladium degrades in the
presence of water in air at elevated temperatures to form di-
plex (PEPPSI catalyst) effectively promotes the coupling of
aryl bromides with various arylzinc iodides at 25–508C at a
level of 0.5 mol% of palladium.[20] A few examples of the
coupling of sterically demanding aryl bromides with sterical-
ly hindered arylzinc chlorides at 70–1008C in the presence
of 1 mol% of catalyst have been reported.[2f] The most
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[Pd(Cl)2{PACHTUNGTRENNUNG(NC5H10)ACHTUNGTRENNUNG(C6H11)2}2] as a Versatile Catalyst for Negishi Couplings
FULL PAPER
cally hindered and functional-
ized aryl bromides with various
diarylzinc reagents in NMP,
generally within less than
15 min at 1008C in the presence
of just 0.01 mol% of catalyst.
Apart from aldehyde-contain-
ing substrates, which lead to the
generation
of
significant
amounts of unidentified by-
products, nitro, nitrile, acetal,
ketone, ether, ester, lactone,
amide, aniline, alkene, phenol,
carboxylic acid, acetic acid, pyr-
idine, and pyrimidine moieties
are all compatible with the re-
action conditions. Moreover,
electronic and steric variations
are tolerated in both reaction
partners. The catalyst is readily
prepared from very inexpensive
staring materials. Moreover, the
Scheme 8. Negishi cross-coupling reactions of aryl bromides with dithiophen-2-ylzinc catalyzed by 1. Reaction
conditions: 2.0 mmol aryl bromide, 1.1 mmol dithiophen-2-ylzinc (relative to bromide), 4 mL NMP, catalyst
(0.01 mol%) added in solution (THF), reaction performed at 1008C. The conversions were determined by
GC-MS, based on aryl bromide; yields of the isolated products are given in brackets. [a] Isolated as the alde-
hyde. [b] 2.1 mmol of dithiophen-2-ylzinc was used.
cyclohexyl phosphinate.[13] In a similar way, treatment of 1
with aqueous hydrochloric acid in air (and thus, under work-
up conditions) leads to rapid degradation of the catalyst and
ligand to form decomposition products, which are easily sep-
arated from the coupling products.[21]
presented reaction protocol is very simple and, most impor-
tantly, is the same for all the reactions examined, which
makes our catalyst very attractive for organic laboratories.
Even though the formation of palladium nanoparticles
cannot be completely excluded (a mercury drop test was
positive), the experimental results obtained indicate that 1
operates through a homogeneous (classical) mechanism,
which impressively demonstrates that 1 not only promotes
the formation of palladium nanoparticles, but can also oper-
ate through a homogeneous mechanism.
Although detailed mechanistic investigations have not
been performed, the following experimental observations
strongly indicate that 1 catalyzes the Negishi reaction
through the generally accepted (classical) reaction mecha-
nism.[22] 1) The catalytic activities of 1, dichloro
ACHTUNGTRENNUNG
CTHUNGTRENNUNG
Experimental Section
N
CHTUNGTRENNUNG
sigmoidal-shaped kinetics with an induction period been ob-
served. 3) The catalytic activity of bis[1-(dicyclohexylphos-
phanyl)piperidine]palladium (2) is the same as that of 1.[26]
4) Treatment of 1 with a slight excess (ꢀ1.2 equiv) of diphe-
nylzinc at 258C exclusively yielded complex 2 and the corre-
sponding amount of biphenyl. 5) Treatment of 2 with an
excess (ꢀ10 equiv) of phenyl bromide cleanly yielded the
General procedures: All synthetic operations for the catalyst preparation
were carried out in oven-dried glassware using a combination of glove-
box (M. Braun 150B-G-II) and Schlenk techniques under a N2 atmos-
phere. Solvents were reagent grade or better, and were freshly distilled
under a N2 atmosphere by standard procedures. Deuterated solvents
were purchased from Armar, dried by standard procedures, and degassed
by freeze-pump-thaw cycles before use. All chemicals were purchased
from Aldrich Chemical Co. or Acros Organics and were used as re-
ceived.
phenyl
bromide
complex
[Pd(Br)ACHTGNUTRENU(NG C6H5){PACTHUGNTREN(NNUG C6H11)2-
Analysis: 1H, 13C{1H}, and 31P{1H} NMR spectroscopic data were record-
ed at 500.13, 125.76, and 202.46 MHz, respectively, on a Bruker DRX-
500 spectrometer or at 300.1, 121.5, and 75.4 MHz, respectively, on a
Varian Gemini spectrometer. Chemical shifts (d) are expressed in parts
per million (ppm), and coupling constants (J) are in Hz. The 1H and
13C NMR chemical shifts are reported relative to tetramethylsilane; the
resonance of the residual protons of the solvent was used as an internal
ACHTUNGTRENNUNG
plex 3 showed the same catalytic activity as that of 1 or 2.
7) Treatment of 3 with approximately 0.55 equiv of bis(4-
methoxyphenyl)zinc exclusively yielded complex 2 and the
corresponding amount of 4-methoxybiphenyl.[27]
1
standard for H (d=7.15 for benzene; d=3.58, 1.73 for tetrahydrofuran)
and all deuterium solvent peaks were used for 13C (d=128.0 for benzene;
d=67.4, 25.2 for tetrahydrofuran). All measurements were carried out at
298 K. Abbreviations used in the description of NMR spectroscopic data
are as follows: s=singlet; d=doublet; t=triplet; m=multiplet; br=
broad. Elemental analyses were performed on a Leco CHNS-932 ana-
lyzer at the University of Zurich, Switzerland.
Conclusion
Complex 1 is an extremely efficient, versatile, and reliable
Negishi catalyst with excellent functional group tolerance,
capable of quantitatively coupling a wide variety of elec-
tronically activated, non-activated, deactivated, and/or steri-
Preparation of [Pd(Cl)2{P
(100 mg, 0.35 mmol) was suspended in toluene (10 mL). After the addi-
ACHTUGNRTNE(UNGN NC5H10)ACHUTNRTGENNUNG 2ACHTUNGTRENNUNG(cod)]
(C6H11)2}2] (1):[13] [Pd(Cl)
Chem. Eur. J. 2010, 16, 11072 – 11081
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11079

C. M. Frech and J. L. Bolliger
tion of a solution of two equivalents of P
(NC5H10)
E
tion Metal Reagents and Catalysts: Innovations in Organic Synthesis,
Wiley, New York, 2000; d) N. Miyaura (Ed.), Cross-Coupling Reac-
tions: A Practical Guide, Springer, Berlin, 2002; e) K. Tamao, N.
Miyaura, Top. Curr. Chem. 2002, 219, 1; f) J. Hassan, M. Sevignon,
C. Gozzi, E. Schulz, M. Lemaire, Chem. Rev. 2002, 102, 1359, and
references therein; g) E.-i. Negishi, Q. Hu, Z. Huang, G. Wang, N.
Yin, Palladium- or Nickel-Catalyzed Cross-Coupling Reactions with
Organozincs and Related Organometals in The Chemistry of Orga-
nozinc Compounds (Eds.: Z. Rappoport, I. Marek), Wiley, New
York, 2006, Chapter 11.
(10 mL), the reaction mixture was stirred for 10 min. Removal of the vol-
atiles under reduced pressure, addition of pentane, followed by filtration
afforded the yellow, analytically pure palladium complex 1 in almost
quantitative yield. 31P{1H} NMR (C6D6): d=80.0 ppm (s;
ACHTUNGTRENNUNG
(C6H11)2); 1H NMR (C6D6): d=3.21 (brs, 8H), 3.62 (brs, 4H), 3.32–2.28
(m, 4H), 1.95–1.16 ppm (m, 48H); 13C{1H} NMR (C6D6): d=51.8 (t, J=
49.5 Hz), 35.9 (t, J=50.3 Hz), 30.4, 28.6, 27.5–27.2 (overlapping signals),
25.0 ppm.
Preparation of [Pd{P
(C6H11)2}2] (1) (50 mg, 0.07 mmol) was dissolved in THF (10 mL) and the
ACHTUNGTRENNUNG(NC5H10)AHCTNURTGENNUNG ACHTUNGTREN(NUGN NC5H10)-
(C6H11)2}2] (2):[26] [Pd(Cl)2{P
[2] a) E.-i. Negishi, F. T. Luo, R. Frisbee, H. Matsushita, Heterocycles
1982, 18, 117; b) C. E. Tucker, T. N. Majid, P. Knochel, J. Am. Chem.
Soc. 1992, 114, 3983; c) J. A. Miller, R. P. Farrell, Tetrahedron Lett.
1998, 39, 7275; d) T. Sakamoto, Y. Kondo, N. Murata, H. Yamanaka,
Tetrahedron Lett. 1992, 33, 5373; e) T. Sakamoto, Y. Kondo, N.
Murata, H. Yamanaka, Tetrahedron 1993, 49, 9713; f) S. P. Stanforth,
Tetrahedron 1998, 54, 263, and references therein.
[3] a) P. Knochel, R. D. Singer, Chem. Rev. 1993, 93, 2117; b) A. Boudi-
er, L. O. Bromm, M. Lotz, P. Knochel, Angew. Chem. 2000, 112,
4584; Angew. Chem. Int. Ed. 2000, 39, 4414; c) S. Q. Huo, Org. Lett.
2003, 5, 423; d) C. Jubert, P. Knochel, J. Org. Chem. 1992, 57, 5425;
e) R. Giovannini, P. Knochel, J. Am. Chem. Soc. 1998, 120, 11186;
f) A. Krasovskiy, V. Malakhov, A. Gavryushin, P. Knochel, Angew.
Chem. 2006, 118, 6186; Angew. Chem. Int. Ed. 2006, 45, 6040; g) S.
C¸ alimsiz, M. Sayah, D. Mallik, M. G. Organ, Angew. Chem. 2010,
122, 2014; Angew. Chem. Int. Ed. 2010, 49, 2058.
[4] N. Miyaura, K. Yamada, A. Suzuki, Tetrahedron Lett. 1979, 20, 3437.
[5] a) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457; b) A. Suzuki in
Metal-Catalyzed Cross-Coupling Reactions (Eds.: F. Diederich, P. J.
Stang), Wiley-VCH, Weinheim, 1998, Chapter 2; c) A. Suzuki, J. Or-
ganomet. Chem. 1999, 576, 147; d) S. R. Chemler, D. Trauner, S. J.
Danishefsky, Angew. Chem. 2001, 113, 4676; Angew. Chem. Int. Ed.
2001, 40, 4544; e) A. F. Littke, G. C. Fu, Angew. Chem. 2002, 114,
4350; Angew. Chem. Int. Ed. 2002, 41, 4176; f) N. Miyaura, Top.
Curr. Chem. 2002, 219, 11; g) S. Kotha, K. Lahiri, D. Kashinath, Tet-
rahedron 2002, 58, 9633; h) F. Bellina, A. Carpita, R. Rossi, Synthe-
sis 2004, 2419; i) T. E. Barder, S. D. Walker, J. R. Martinelli, S. L.
Buchwald, J. Am. Chem. Soc. 2005, 127, 4685; j) K. C. Nicolaou,
P. G. Bulger, D. Sarlah, Angew. Chem. 2005, 117, 4516; Angew.
Chem. Int. Ed. 2005, 44, 4442; k) N. T. S. Phan, M. V. D. Sluys, C. W.
Jones, Adv. Synth. Catal. 2006, 348, 609; l) S. Nara, J. Martinez, C.-
G. Wermuth, I. Parrot, Synlett 2006, 3185.
[6] a) S. Y. Cho, M. Shibasaki, Tetrahedron: Asymmetry 1998, 9, 3751;
b) A. N. Cammidge, K. V. L. Crꢃpy, Chem. Commun. 2000, 1723;
c) J. Yin, S. L. Buchwald, J. Am. Chem. Soc. 2000, 122, 12051;
d) A. S. Castanet, F. Colobert, P. E. Broutin, M. Obringer, Tetrahe-
dron: Asymmetry 2002, 13, 659; e) A. Herrbach, A. Marinetti, O.
Baudoin, D. Guenard, F. Gueritte, J. Org. Chem. 2003, 68, 4897;
f) A. N. Cammidge, K. V. L. Crꢃpy, Tetrahedron 2004, 60, 4377; g) K.
Mikami, T. Miyamoto, M. Hatano, Chem. Commun. 2004, 2082.
[7] M. Kertesz, C. H. Choi, S. Yang, Chem. Rev. 2005, 105, 3448.
[8] a) A. Markham, K. L. Goa, Drugs 1997, 54, 299; b) R. Capdeville,
E. Buchdunger, J. Zimmermann, A. Matter, Nat. Rev. Drug Discov-
ery 2002, 1, 493; c) J. Boren, M. Cascante, S. Marin, B. Comin-
Anduix, J. J. Centelles, S. Lim, S. Bassilian, S. Ahmed, W. N. Lee,
L. G. Boros, J. Biol. Chem. 2001, 276, 37747.
ACHTUNGTRENNUNG
solution was stirred for about 10 h at room temperature in the presence
of an excess (ꢀ50 equiv) of metallic sodium. Removal of the volatiles
under reduced pressure and extraction of the reduced 1 with pentane, fol-
lowed by filtration and evaporation of the solvent under reduced pres-
sure, afforded the brownish, analytically pure palladium complex 2 in
96% yield. 31P{1H} NMR ([D8]THF): d=97.9 ppm (s;
ACHTUNGTRENNUNG
(C6H11)2); 1H NMR ([D8]THF): d=3.26 (brs, 4H), 1.91–1.19 ppm (m,
60H); 13C{1H} NMR ([D8]THF): d=53.7, 39.0, 30.7, 28.4, 28.1, 27.8,
26.1 ppm; elemental analysis calcd (%) for C34H64N2P2Pd: C 61.02, H
9.64, N 4.19; found: C 61.25, H 9.80, N 4.22.
Preparation of [Pd(Br)
ACHTUNGTRENNUNG(C6H5){PCAHTUTNGRNE(NGU C6H11)2AHCTNUGRETGNN(UN NC5H10)}2] (3): [Pd{PCATHNUGTRENUN(GN NC5H10)-
ACHTUNGTRENNUNG
solution was stirred for approximately 3 h at room temperature in the
presence of an excess (ꢀ10 equiv) of phenyl bromide. Removal of the
volatiles under reduced pressure and extraction of 3 with pentane, fol-
lowed by filtration and evaporation of the solvent under reduced pres-
sure, afforded the off-white, analytically pure palladium complex 3 in
93% yield. 31P{1H} NMR ([D8]THF): d=74.4 ppm (s;
1
N
8H), 1.72–0.91 ppm (m, 56H); 13C{1H} NMR ([D8]THF): d=156.6 (t, J=
22.8 Hz), 139.2, 127.5, 122.7, 52.7, 38.8 (t, J=46.5 Hz), 30.27, 29.8, 28.4 (t,
J=16.8 Hz), 27.9 (t, J=28.8 Hz), 27.7 (unresolved triplet), 27.6,
25.6 ppm; elemental analysis calcd (%) for C40H69BrN2P2Pd: C 58.15, H
8.42, N 3.39; found: C 57.99, H 8.37, N 3.36.
General procedure for Negishi cross-coupling reactions: All catalytic re-
actions were carried out in air. A round-bottomed flask was charged with
the aryl bromide (2.0 mmol), a slight excess (1.1 equiv of aryl component
relative to bromide) of freshly prepared arylzinc reagent (ꢀ1.0m; THF/
NMP, 1:2), and N-methylpyrrolidone (NMP) (2.5 mL). The mixture was
vigorously stirred and heated at 1008C. Then, the requisite amount of
catalyst was added by means of a syringe as a solution in THF. Samples
were withdrawn from the reaction mixture at timed intervals, quenched
with approximately 1m aqueous HCl, extracted with ethyl acetate, and
analyzed by GC-MS (for reactions performed with substrates containing
basic groups, samples were quenched with approximately 1m NaOH and
extracted with diethyl ether/THF mixtures). At the end of the catalysis,
the reaction mixtures were allowed to cool to room temperature,
quenched with 1m aqueous HCl, and extracted with ethyl acetate (3ꢂ
40 mL). When biaryls containing basic groups, such as pyridine, pyrimi-
dine, and anilines, were used as coupling partners, the reaction mixtures
were diluted with diethyl ether and filtered through silica prior to extrac-
tion. The combined extracts were dried (MgSO4) and concentrated to
dryness. If necessary, the crude material was purified by flash chromatog-
raphy on silica gel.
[9] H. Tomori, J. M. Fox, S. L. Buchwald, J. Org. Chem. 2000, 65, 5334.
[10] S. Lightowler, M. Hird, Chem. Mater. 2005, 17, 5538.
[11] a) J. E. Milne, S. L. Buchwald, J. Am. Chem. Soc. 2004, 126, 13028;
b) C. Dai, G. C. Fu, J. Am. Chem. Soc. 2001, 123, 2719; c) C. Han,
S. L. Buchwald, J. Am. Chem. Soc. 2009, 131, 7532; d) L. Wang, Z.-
X. Wang, Org. Lett. 2007, 9, 4335; e) N. Yoshikai, H. Mashima, E.
Nakamura, J. Am. Chem. Soc. 2005, 127, 17978; f) N. Yoshikai, H.
Matsuda, E. Nakamura, J. Am. Chem. Soc. 2009, 131, 9590; g) G. Y.
Li, Angew. Chem. 2001, 113, 1561; Angew. Chem. Int. Ed. 2001, 40,
1513; h) J. Zhou, G. C. Fu, J. Am. Chem. Soc. 2003, 125, 12527.
[12] It should be noted that even though highly active Negishi catalysts,
capable of efficiently coupling aryl chlorides with aryl/alkylzinc re-
agents (by molecular mechanisms) have been reported, this does not
Acknowledgements
Financial support from the University of Zurich and the Swiss National
Science Foundation (SNSF) is acknowledged.
[1] See, for example: a) F. Diederich, P. J. Stang (Eds.), Metal-Catalyzed
Cross-Coupling Reactions, Wiley-VCH, Weinheim, 1998; b) A. de
Meijere, F. Diederich (Eds.), Metal-Catalyzed Cross-Coupling Reac-
tions, 2nd ed., Wiley-VCH, Weinheim, 2004; c) J. Tsuji (Ed.), Transi-
11080
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ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 11072 – 11081

[Pd(Cl)2{PACHTUNGTRENNUNG(NC5H10)ACHTUNGTRENNUNG(C6H11)2}2] as a Versatile Catalyst for Negishi Couplings
FULL PAPER
imply that they will exhibit a significantly increased activity when
aryl bromides are used as coupling partners.
[23] For a mechanistic study of the Negishi cross-coupling involving an
aryl chloro-bis(triphenylphosphine) complex of palladium, see: J. A.
Casares, P. Espinet, B. Fuentes, G. Salas, J. Am. Chem. Soc. 2007,
129, 3508.
[13] J. L. Bolliger, C. M. Frech, Chem. Eur. J. 2010, 16, 4075.
[14] Apart from reactions performed with 3-bromopyridines as coupling
partners, in which significant debromination (up to 15%) was ob-
tained, side-product formation (debromination or homocoupling)
has only very rarely been observed, and if so, below the 5% level.
[15] It should be mentioned that even though the dichloro-bis(tricyclo-
[24] The steric bulk and s-donor strength of 1,1’,1’’-(phosphanetriyl)tripi-
peridine, 1-(dicyclohexylphosphanyl)piperidine, and tricyclohexyl-
phosphine are almost identical (as indicated by the CO stretching
frequencies in complexes of the type trans-[Rh(CO)(Cl)ACHTUNGTRENNUNG
(PR3)2]).[25]
hexylphosphine)complex [Pd(Cl)
G
Thus, similar catalytic activities would be expected were a molecular
mechanism to be operative. On the other hand, different catalytic
activities would be expected if palladium nanoparticles were the cat-
same catalytic activity in the Negishi cross-coupling reaction as 1,
the latter represents a significant improvement compared with the
phosphine-based system, since catalyst 1 (in contrast to [Pd(Cl)2-
alytically active form of 1, [Pd(Cl)2{P
(PCy3)2].
ACHTGNUERTN(UNNG NC5H10)3}2], and/or [Pd(Cl)2-
(PCy3)2]) promotes the formation of palladium nanoparticles as well
ACHTUNGTRENNUNG
as operating through a homogeneous mechanism, depending on the
reaction conditions applied. For example, whereas 1 also effectively
catalyzes the Suzuki reaction,[13] only a very poor catalytic activity
was found for dichloro-bis(tricyclohexylphosphine)palladium.
[16] a) C. Amatore, A. Jutand, S. Negri, J.-C. Fauvarque, J. Organomet.
Chem. 1990, 390, 389; b) R. C. Borner, R. F. W. Jackson, J. Chem.
Soc. Chem. Commun. 1994, 845; c) M. Kuroboshi, K. Mizuno, K.
Kanie, T. Hiyama, Tetrahedron Lett. 1995, 36, 563; d) T. R. Hoye, M.
Chen, J. Org. Chem. 1996, 61, 7940; e) L. Oehberg, J. Westman, Syn-
lett 2001, 1893.
[17] a) S. Marquais, M. Arlt, Tetrahedron Lett. 1996, 37, 5491; b) M. Arlt,
H. Boettcher, A. Riethmueller, G. Schneider, G. D. Bartoszyk, H.
Greiner, C. A. Seyfried, Bioorg. Med. Chem. Lett. 1998, 8, 2033;
c) E. G. Corley, K. Conrad, J. A. Murry, C. Savarin, J. Holko, G.
Boice, J. Org. Chem. 2004, 69, 5120.
[25] M. L. Clarke, D. J. Cole-Hamilton, M. Z. Slawin, J. D. Woolins,
Chem. Commun. 2000, 2065.
[26] Complex 2 was synthesized in analogy to related literature exam-
ples: a) C. M. Frech, L. J. W. Shimon, D. Milstein, Angew. Chem.
2005, 117, 1737; Angew. Chem. Int. Ed. 2005, 44, 1709; b) J. L. Bol-
liger, O. Blacque, C. M. Frech, Chem. Eur. J. 2008, 14, 7969.
[27] It is important to note that even though all of these results indicate
the operation of a molecular reaction mechanism, the involvement
of palladium nanoparticles in the catalytic cycle cannot be complete-
ly excluded (under the chosen reaction conditions),[28] as the mercu-
ry test was positive (with 1 as well as with [Pd(Cl)2ACTHNGUTERNNUG
(PCy3)2]).[29] For
example, the cross-coupling of 2-bromo-1,3,5-trimethylbenzene with
bis(4-methoxyphenyl)zinc (Scheme 4) diminished from >98% con-
version within 5 min to less than 63% in the presence of metallic
mercury. Similarly, when a few drops of metallic mercury were
added to the catalytic reaction mixtures after 2 min, the catalysis
[18] a) M. G. Organ, S. Avola, I. Dubovyk, N. Hadei, E. A. B. Kantchev,
C. J. OꢄBrien, C. Valente, Cent. Eur. J. Chem. 2006, 12, 4749; b) M.
Rottlꢅnder, P. Knochel, Synlett 1997, 1084.
was efficiently stopped,[30] suggesting that both
AHCTUNTGREG(NUNN PCy3)2] are pre-catalysts that are transformed into palladium nano-
1 and [Pd(Cl)2-
[19] I. Kondolff, H. Doucet, M. Santelli, Organometallics 2006, 25, 5219.
[20] S. Sase, M. Jaric, A. Metzger, V. Malakhov, P. Knochel, J. Org.
Chem. 2008, 73, 7380.
particles. However, degradation of 2 in the presence of metallic mer-
cury might provide an explanation for the result obtained from the
mercury drop test.
[21] The use of catalysts containing water-soluble phosphanes offers sim-
ilar advantages. See, for example: a) C. J. Li, Chem. Rev. 2005, 105,
3095; b) N. Pinault, D. W. Bruce, Coord. Chem. Rev. 2003, 241; c) F.
Alonso, I. P. M. Yus, Tetrahedron 2005, 61, 11711.
[22] The catalytically active species derived from dichloro-bis(phosphine)
complexes of palladium in the Negishi reaction are generally accept-
ed to be coordinatively unsaturated 14eÀ Pd0 complexes of the type
[28] Nanoparticles have been assumed to be catalytically active in the
Negishi reaction. See, for example: a) D. Astruc, F. Lu, J. R. Ara-
nzaes, Angew. Chem. 2005, 117, 8062; Angew. Chem. Int. Ed. 2005,
44, 7852; b) D. Astruc, Inorg. Chem. 2007, 46, 1884; c) J. Liu, Y.
Deng, H. Wang, G. Yu, B. Wu, H. Zeng, Q. Li, T. B. Marder, Z.
Yang, A. Lei, Org. Lett. 2008, 10, 2661.
[29] For a comprehensive review article about the problem of distin-
guishing true homogeneous catalysis from soluble or other metal-
particle heterogeneous catalysis under reducing conditions, see: J. A.
Widegren, R. G. Finke, J. Mol. Catal. A 2003, 198, 317 and referen-
ces therein.
[PdACHTUNGTRENNUNG(PR3)2] (arylation of [Pd(Cl)2ACHUTGNTREN(NNGU PR3)2] and subsequent reductive
elimination of the respective homocoupling product generates the
catalytically active species), which undergo oxidative addition of
aryl halides to yield the tetracoordinated PdII intermediates of the
general formula of [Pd(Ar)(X)
G
[30] For the kinetics, see Graph S1 in the Supporting Information.
gives the corresponding diaryl-bis(phosphine) complexes. Finally,
cis/trans isomerization (or phosphine dissociation) followed by re-
ductive elimination of the coupling product (and phosphine re-coor-
dination) regenerates the catalyst.[23]
Received: May 5, 2010
Published online: August 16, 2010
Chem. Eur. J. 2010, 16, 11072 – 11081
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11081