Palladium-catalyzed intermolecular ene-yne coupling: Development of an atom-efficient Mizoroki-Heck-type reaction

Article abstract of DOI:10.1002/anie.200705558

(Chemical Equation Presented) Direct and to the point: A palladium(II) catalytic system based on a palladium hydride species provides access to highly substituted 1,3-dienes through a direct coupling of alkynes with alkenes in a base-free Mizoroki-Heck-type reaction with full atom economy (see scheme; R=amide, borate, C(OH)Me₂, O-alkyl).

Full text of DOI:10.1002/anie.200705558

Communications
DOI: 10.1002/anie.200705558
Heck Coupling
Palladium-Catalyzed Intermolecular Ene–Yne Coupling:
Development of an Atom-Efficient Mizoroki–Heck-Type Reaction**
Anders T. Lindhardt (neØ Hansen), Mette Louise H. Mantel, and Troels Skrydstrup*
Palladium-catalyzed reactions have become widely accepted
in organic synthesis for carbon–carbon bond assembly, and
are frequently invoked by the pharmaceutical, agrochemical,
and fine-chemicals industry for the production of important
organic-based molecules.[1] The vast majority of such reac-
tions (e.g. the Suzuki–Miyaura, Migita–Kosugi–Stille, Sono-
gashira, Hiyama, and Negishi reactions) involve the coupling
of an aryl or vinyl halide with an organometallic fragment.
The disadvantage of these reactions is that two functionalized
We demonstrated previously the ability of alkenyl tosy-
lates and phosphates, such as 1, with a bulky substituent at C1
to undergo Pd0-catalyzed Mizoroki–Heck coupling with 1,2-
migration (Scheme 1).[9,10] An alkyne-coordinated PdII hy-
dride species I was proposed to be the intermediate for this
reaction.
À
starting materials are required for the C C bond-forming
step, whereby this functionality is lost in the product. Hence,
atom economy is compromised in favor of reactivity. The
Mizoroki–Heck reaction displays greater atom efficiency, as
the functionalization of only one of the coupling partners is
required for the synthesis of aryl alkenes or butadiene
systems.[2] More rewarding, but highly challenging, is the
development of reaction conditions for similar transforma-
tions with nonfunctionalized coupling partners[3] to improve
the overall atom economy of these processes.[4] One such
reaction, a powerful synthetic tool for the synthesis of cyclic
dienes, is the palladium-catalyzed enyne cycloisomerization
developed by Trost and co-workers.[5,6] This intramolecular
isomerization of an enyne has been well developed, in
contrast to the corresponding intermolecular coupling of
alkynes with olefins for the preparation of 1,3-dienes.[7,8]
Herein, we report an effective catalyst system composed
of a palladium complex with a basic, hindered alkyl phosphine
for the Mizoroki–Heck-type coupling of disubstituted alkynes
with electron-deficient alkenes to give 1,3-butadienes. We
also reveal that these coupling reactions do not appear to
proceed through a cycloaddition mechanism, but that a
palladium hydride species is probably the active catalyst.
Scheme 1. Crossover experiment with diphenylacetylene. cod=1,5-
cyclooctadiene,Cy =cyclohexyl,DMF =N,N-dimethylformamide.
To confirm the existence of this palladium hydride
intermediate,[11] we conducted a crossover experiment to
determine whether an alkyne added to the reaction mixture
could be incorporated into the final coupling product(s). The
coupling of the 1-tert-butylvinyl phosphate 1 with N-tert-
butylacrylamide[9] in the presence of diphenylacetylene
(3 equiv) gave the diene 2 in 90% yield (Scheme 1).[12]
However, further examination of this reaction (Table 1)
revealed that the omission of the vinyl phosphate, lithium
chloride, and the amine base (despite the use of the
protonated ligand PtBu3HBF4), led to the same coupling
product in high yield.
The structure of the phosphine ligand was found to be
crucial to the effectiveness of the reaction. Of the ligands
tested, only PtBu3 and diadamantylbutylphosphane (cata-
CXium A), examples of monodentate bulky alkyl phos-
phines,[13] displayed good reactivity (Table 1, entries 1 and
7). None of the other ligands tested, including bidentate
ligands and biphenyl phosphine ligands, showed any reactivity
for this transformation (Table 1, entries 2–6). Furthermore,
the conditions reported by Trost and co-workers for the
cycloisomerization of enynes to cyclic dienes ([Pd2(dba)3],
P(o-Tol)3, AcOH)[5] were ineffective in promoting this trans-
formation. DMF was found to be the best solvent for the
[*] Dr. A. T. Lindhardt (neØ Hansen),M. L. H. Mantel,
Prof. Dr. T. Skrydstrup
The Center for Insoluble Protein Structures (inSPIN)
Department of Chemistry and Interdisciplinary Nanoscience Center
University of Aarhus
Langelandsgade 140,8000 Aarhus (Denmark)
Fax: (+45)8619-6199
E-mail: ts@chem.au.dk
[**] We thank the Danish National Research Foundation,the Lundbeck
Foundation,the Carlsberg Foundation,the OChem and INano
Graduate Schools,and the University of Aarhus for generous
financial support of this research. We thank Dr. Jacob Overgaard for
X-ray crystallographic analysis,and we are grateful for a donation of
ligands and catalysts from Degussa and Solvias. We thank Karin
Dooleweerdt for synthesizing the ynamide.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Chemie
Table 1: Optimization of the intermolecular ene–yne coupling.
Table 2: Palladium-catalyzed intermolecular coupling of alkynes with
alkenes.
Entry
Ligand
Solvent
T [8C]
Yield [%][a]
Z/E
Entry
R
R’
Y
Yield [%][a,b]
1
2
3
4
5
6
7
8
9
PtBu3HBF4
S-Phos
X-Phos
DMF
DMF
DMF
DMF
DMF
DMF
DMF
toluene
dioxane
MeCN
100
100
100
100
100
100
100
100
100
80
86
NR
NR
NR
NR
1:0
–
–
–
–
1
2
Ph
Ph
Ph
Ph
C(O)NHtBu
C(O)OnBu
88
84 (2:1)
PPh3
3
4
Ph
Ph
Ph
Ph
67
76
PCy3HBF4
dppf[b]
NR
–
cataCXium A
PtBu3HBF4
PtBu3HBF4
PtBu3HBF4
(80)[c]
64
1:0
2:1
4:1
1:0
77
5
6
7
8
9
10
11
12
Ph
p-CNC6H4
Ph
p-CNC6H4
C(O)NH2
C(O)NHtBu
80 (3:1)
77 (2:1)
72
63 (2:1)
24
10
(45)[c]
[a] Yield of the isolated product after chromatographic purification.
[b] Only 5 mol% of the ligand was added. [c] Conversion determined
from the H NMR spectrum of the crude reaction mixture. dppf=1,1’-
bis(diphenylphosphanyl)ferrocene,NR =no reaction,S-Phos =2-dicy-
clohexylphosphanyl-2’,6’-dimethoxybiphenyl,X-Phos
phosphanyl-2’,4’,6’-triisopropylbiphenyl.
p-MeOC6H4 p-MeOC6H4 C(O)NHtBu
EtOC(O)
Ph
Ph
Ph
Ph
EtOC(O)
H
Ph
Ph
Ph
C(O)NHtBu
C(O)NHtBu
p-(CONHtBu)C6H4
p-OMeC6H4
1
76
=2-dicyclohexyl-
71 (4:1)
CH2NHTs
98[c]
[a] Yield of the isolated product after chromatographic purification.
[b] Isomer ratios (Z/E) are given in parentheses. [c] A mixture of a
minimum of five stereoisomers was obtained. However,after hydro-
genation,a single compound, N-tosyl-4,5-diphenylpentanamine, was
isolated. Boc=tert-butoxycarbonyl,Ts =p-toluenesulfonyl.
coupling; the use of other solvents led to lower yields and
mixtures of the cis and trans products (Table 1, entries 8–10).
The lowering of the reaction temperature had a detrimental
effect on the coupling yield (results not shown).
The palladium source did not appear to have a substantial
impact on the outcome of the reaction. Both palladium(II)
and palladium(0) complexes (e.g. [PdCl2(cod)], Pd(OAc)2,
[PdCl2(PhCN)2], [Pd(PtBu3)2], [Pd2(dba)3]) proved effective
in terms of the coupling yield. Nevertheless, in certain cases
(with Pd(OAc)2, [Pd(PtBu3)2]), mixtures of cis and trans
stereoisomers were obtained. Furthermore, we could
decrease the number of equivalents of the alkene: The two
coupling reagents could be used in an almost equimolar ratio
without a substantial influence on the coupling yield. In the
absence of either the palladium metal or the phosphine
ligand, no coupling was observed.
The scope of the reaction was examined with a variety of
symmetrical disubstituted alkynes (Table 2). Diphenylacetyl-
ene underwent efficient coupling with acrylamides and
acrylates to give 1,3-dienes in 67–88% yield (Table 2,
entries 1–5). The same alkyne displayed good reactivity
towards two styrene derivatives (Table 2, entries 10 and
11).[14] The coupling of diphenylacetylene with N-tosylallyl-
amine also proved possible but afforded a series of isomeric
alkenes, which were difficult to separate. However, hydro-
genation of the product mixture afforded a single compound,
N-tosyl-4,5-diphenylpentanamine, which was isolated in 98%
yield (Table 2, entry 12). Other symmetrical alkynes were also
compatible with the reaction conditions in the coupling with
N-tert-butylacrylamide (Table 2, entries 6–8). However, the
addition to phenyl acetylene was less effective (Table 2,
entry 9), possibly as a result of the instability of this acetylene
at the temperature required for the reaction.
Scheme 2. Intermolecular ene–yne coupling with disubstituted non-
symmetrical acetylenes.
on the alkyne and observed no significant influence of
electronic factors on the regioselectivity of the reaction
(Scheme 2a,b). Steric effects were more important, as illus-
trated by the coupling of tert-butyl phenyl acetylene with N-
tert-butylacrylamide to provide a 10:1 mixture of regioisom-
Nonsymmetrical disubstituted acetylenes were also inves-
tigated as substrates (Scheme 2). We examined substrates in
which para-substituted phenyl groups with either electron-
withdrawing or electron-donating substituents were present
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ers in favor of the product with a terminal tert-butyl group
(Scheme 2c).
the desired 1,3-diene in nearly quantitative yield (Scheme 4).
Even more interestingly, the coupling product was obtained in
87% yield when the reaction was performed at 208C.
A potential mechanism for these catalytic transformations
is depicted in Scheme 3. The heating of PdII or Pd0 complexes
in the presence of PtBu3 in DMF could generate a PdII hydride
species, which would undergo hydropalladation with the
Scheme 4. Intermolecular ene–yne coupling catalyzed by [Pd(H)Cl-
(PtBu3)2].
Although these results do not rule out the involvement of
the cycloaddition mechanism in the reactions performed with
a palladium salt and trialkyl phosphine ligand at 1008C, they
do provide evidence that palladium hydride species can
indeed catalyze the intermolecular ene–yne coupling reac-
tion.
Unfortunately, the use of this palladium hydride complex
was impractical. The complex is generated from expensive
[Pd(PtBu3)2]in a glove box and when isolated shows signs of
decomposition after several hours under argon. Hence, we
had to synthesize this complex prior to each set of coupling
experiments performed. We therefore investigated the possi-
bility of generating this hydride species in situ under the ene–
yne coupling conditions. To this end, a series of additives were
tested in substoichiometric quantities in the coupling of
diphenylacetylene with N-tert-butylacrylamide in the pres-
ence of [Pd2(dba)3]and P tBu3 (Table 3), from which the Pd
hydride species could in principle be generated under the
reaction conditions employed. Of the wide range of additives
examined, only the acid chlorides (Table 3, entries 7 and 8)
catalyzed the reaction in an efficient manner at 508C to give
the coupling product in high yield.[18] When the reaction
temperature was decreased, the coupling product was
obtained in lower yield after 24 h. The coupling reaction
Scheme 3. Proposed mechanism of the intermolecular ene–yne cou-
pling. dba=dibenzylideneacetone.
alkyne to generate an alkenyl PdII intermediate similar in
structure to the complex obtained from the oxidative addition
of Pd0 into a vinyl halide bond. Subsequent reaction with the
alkene then occurs through a classical Heck mechanism to
finally regenerate the PdII hydride for the next cycle. Bulky
trialkyl phosphine ligands were found to catalyze these
reactions effectively. This observation may be explained by
the nature of the Pd complexes formed when such phosphine
ligands are used. PdII complexes containing the ligand PtBu3
have been reported previously to form a T-shaped metal
species rather than the more commonly observed tetracoor-
dinate square-planar-type complexes.[15] As alkynes are also
known to coordinate strongly to PdII and Pd0 complexes as
Table 3: Optimization of the intermolecular ene–yne coupling through
the in situ generation of a Pd hydride species.
[16]
both p-acceptor and p-donor ligands,
it is possible that a
strong complex is formed between the alkyne and the Pd
hydride species produced after the b-hydride-elimination
step. Hence, the hydropalladation step may be sufficiently fast
that base-promoted reduction of the Pd hydride species can
not compete, as observed in our initial experiments
(Scheme 1).
Alternatively, a [2+2+1]cycloaddition mechanism via a
palladacyclopentene intermediate is possible, as proposed
previously by Watanabe and co-workers for a ruthenium-
catalyzed codimerization of acetylenes with olefins.[7a,14] In
this reaction, which is similar to our Pd-catalyzed intermo-
lecular ene–yne coupling, high reaction temperatures are
required. To probe which of the two mechanisms operates in
these reactions, we prepared the palladium(II) hydride
complex [HPdCl(PtBu3)2]from commercially available [Pd-
(PtBu3)2]and HCl according to the procedure of Hills and
Fu.[17] This complex catalyzed the coupling of diphenylacety-
lene with N-tert-butylacrylamide at both 100 and 508C to give
Entry
Additive
Conv. [%][a]
NR
Yield [%][b]
1
2
3
4
5
6
7
8
9
AcOH
PhI
–
–
–
–
–
[c]
–
NR
8
p-AcC6H4Cl
HCl in Et2O
BnCl
butyl chloride
isobutyryl chloride
adipoyl chloride[d]
–
15
NR
100
100
NR
–
97
96
–
1
[a] The conversion was determined from the H NMR spectrum of the
crude reaction mixture. [b] Yield of the isolated product after chromato-
graphic purification. [c] N-tert-Butyl cinnamide was detected in the crude
product by 1H NMR spectroscopic analysis. [c] Adipoyl chloride:
0.15 equivalents. Bn=benzyl.
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was carried out in THF. The use of other solvents, such as
toluene, dioxane, dimethoxyethane, and EtOAc, also led to
the formation of the coupling product in at least 95% yield.
These new coupling conditions were then tested with a
variety of disubstituted alkyne substrates, many of which did
not undergo effective coupling under the previous conditions
in DMF at 1008C (Table 4). Di(p-acetylphenyl)acetylene was
coupled with N-tert-butylacrylamide in near quantitative yield
(Table 4, entry 1). The treatment of the same coupling
partners under similar conditions to those in Table 2 led to
a multitude of products according to NMR analysis. Similarly,
higher coupling yields were observed with di(p-cyanophenyl)-
acetylene (Table 2, entry 2)[12] and the ynamide in entry 3 of
with dihydrofuran provided exclusively the a-coupling prod-
uct, a result that indicates a Heck-type mechanism. Again,
modified reaction conditions were required to obtain the
coupling products in good yields.
In conclusion, we have demonstrated the potential for
carrying out intermolecular ene–yne coupling reactions
between disubstituted acetylenes and olefins. These reactions
appear to be catalyzed by a palladium hydride species.
Further studies are in progress to increase the scope of these
reactions, for example, to the use of monosubstituted
acetylene substrates, by modifying the reaction conditions.
Table 4, a heteroatom-substituted alkyne.[12] In the latter case, Experimental Section
(2E,4Z)-2: Diphenylacetylene (104.3 mg, 0.59 mmol), tert-butylacryl-
the best results in terms of yield and regioselectivity were
obtained at 808C with a higher catalyst loading. The alkynyl
phosphonate in entry 4 of Table 4 was also a suitable
substrate, the reaction of which proceeded with good
regioselectivity. Diaryl acetylenes were also coupled success-
fully with a vinyl boronic ester and an allylic alcohol (Table 4,
entries 5, 6, and 8). Finally, the reaction of diphenylacetylene
amide (49.6 mg, 0.39 mmol), PtBu3HBF4 (11.3 mg, 0.04 mmol), and
[PdCl2(cod)](5.6 mg, 0.02 mmol) were dissolved in DMF (3 mL) in a
glove box under an argon atmosphere. The sample vial was fitted with
a Teflon-sealed screw cap and removed from the glove box. The
reaction mixture was heated at 1008C for 24 h. The crude product was
purified by flash chromatography on silica gel (EtOAc/pentane 1:9)
to afford (2E,4Z)-2 (105 mg, 88%) as a single isomer. 1H NMR
Table 4: Palladium-catalyzed intermolecular ene–yne coupling with in situ generation of a Pd hydride species.[a]
Entry
1[b]
Alkyne
Alkene
Product
Yield [%][a]
95
2[b] [12]
92
59
3[c]
(Z/E 15:1)[12]
(Z/E 7:1)
4[d]
78
5[e]
61
88
6[c,f]
(Z/E 7:1)
(Z/E 4:1)
7[g]
63
92
8[e,h]
[a] Yield of the isolated product after chromatographic purification. [b] The reaction was carried out in EtOAc/toluene (1:1). [c] The reaction was
carried out in toluene at 808C with [Pd2(dba)3] (5 mol%),P tBu3 (20 mol%),isobutyryl chloride (20 mol%),and acrylamide (3 equiv). [d] The reaction
was carried out in EtOAc for 42 h. Ratio of product regioisomers: 19:1. [e] The reaction was carried out in EtOAc. [f] The reaction was carried out in
toluene at 808C with 2 equivalents of the alkene. [g] The reaction was carried out in dioxane. [h] Alkene: 4 equivalents.
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Communications
(400 MHz, C6D6): d = 8.40 (d, J = 14.8 Hz, 1H), 7.60–7.51 (m, 6H),
2002, 102, 813; c) V. Balraju, R. V. Dev, S. S. Reddy, J. Iqbal,
Tetrahedron Lett. 2006, 47, 3569.
7.32–7.29 (m, 4H), 7.08 (s, 1H), 5.92 (d, J = 14.8 Hz, 1H), 5.06 (br s,
1H), 1.62 ppm (s, 9H); 13C NMR (100 MHz, C6D6): d = 164.9, 145.6,
140.2, 138.7, 137.2, 136.6, 130.3, 129.8, 129.4, 128.3, 128.0, 127.8, 125.2,
50.9, 28.8 ppm; HRMS: m/z calcd for C21H23NO: 328.1677 [M+Na]+;
found: 328.1680.
[7]For a Ru-catalyzed version of this reaction to give 1,3-dienes,
see: a) T. Mitsudo, S.-W. Zhang, M. Nagao, Y. Watanabe, J.
Chem. Soc. Chem. Commun. 1991, 598; b) C. S. Yi, D. W. Lee, Y.
Chen, Organometallics 1999, 18, 2043. In reference [7b]only
coupling with ethylene was described.
Table 4, entry 2: 4,4’-Ethynediyldibenzonitrile (133.5 mg,
0.293 mmol), tert-butylacrylamide (49.6 mg, 0.39 mmol), PtBu3
(7.8 mg, 0.04 mmol), and [Pd2(dba)3](8.9 mg, 0.01 mmol) were
dissolved in EtOAc/toluene (1:1, 4 mL) in a glove box under an
argon atmosphere. Isobutyryl chloride was then added from a stock
solution (0.05 mgmLÀ1, 83.1 mL) in EtOAc. The sample vial was fitted
with a Teflon-sealed screw cap and removed from the glove box. The
reaction mixture was heated at 508C for 17 h. The crude product was
purified by flash chromatography on silica gel (EtOAc/CH2Cl2/
pentane 1:1:3) to afford (2E,4Z)-N-tert-butyl-4,5-bis(4-cyanophenyl)-
[8]The Ru-catalyzed coupling of alkynes with alkenes for the
synthesis of 1,4-dienes and related compounds is well known; for
representative examples, see: a) B. M. Trost, A. F. Indolese,
T. J. J. Müller, B. Treptow, J. Am. Chem. Soc. 1995, 117, 615;
b) B. M. Trost, T. J. J. Müller, J. Martinez, J. Am. Chem. Soc.
1995, 117, 1888; c) B. M. Trost, T. J. J. Müller, J. Am. Chem. Soc.
1994, 116, 4985; d) B. M. Trost, J. A. Martinez, R. J. Kulawiec,
A. F. Indolese, J. Am. Chem. Soc. 1993, 115, 10402; e) B. M.
Trost, J.-P. Surivet, F. D. Toste, J. Am. Chem. Soc. 2001, 123, 2897;
f) B. M. Trost, H. C. Shen, A. B. Pinkerton, Chem. Eur. J. 2002, 8,
2341; g) B. M. Trost, F. D. Toste, Tetrahedron Lett. 1999, 40, 7739;
h) S. DØrien, P. H. Dixneuf, J. Chem. Soc. Chem. Commun. 1994,
2551; i) S. DØrien, L. Ropartz, J. Le Paih, P. H. Dixneuf, J. Org.
Chem. 1999, 64, 3524.
1
penta-2,4-dienamide (127.2 mg, 92%) as a colorless solid. H NMR
(400 MHz, CDCl3): d = 7.71 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 14.8 Hz,
1H), 7.40 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 6.95 (d, J =
8.4 Hz, 2H), 6.90 (s, 1H), 5.43 (br s, 1H), 5.37 (d, J = 14.8 Hz, 1H),
1.34 ppm (s, 9H); 13C NMR (100 MHz, CDCl3): d = 164.4, 143.1,
142.1, 140.9, 139.8, 135.3, 133.1, 132.1, 130.4, 130.1, 126.8, 118.5, 118.3,
112.3, 111.5, 51.7, 28.8 ppm; HRMS: m/z calculated for C23H21N3O:
378.1582 [M+Na]+; found: 378.1576.
[9]a) A. L. Hansen, J.-P. Ebran, M. Ahlquist, P.-O. Norrby, T.
Skrydstrup, Angew. Chem. 2006, 118, 3427; Angew. Chem. Int.
Ed. 2006, 45, 3349; b) J. P. Ebran, A. L. Hansen, T. Gøgsig, T.
Skrydstrup, J. Am. Chem. Soc. 2007, 129, 6931.
[10]For examples of 1,2-migration in the Kumada and Negishi cross-
coupling reactions, see: a) M. E. Limmert, A. H. Roy, J. F.
Hartwig, J. Org. Chem. 2005, 70, 9364; b) A. L. Hansen, J.-P.
Ebran, T. Gøgsig, T. Skrydstrup, J. Org. Chem. 2007, 72, 6464.
[11]For a review on palladium hydride complexes, see: V. V.
Grushin, Chem. Rev. 1996, 96, 2011.
[12]The structure of the product (major isomer, where applicable)
was determined by X-ray structural analysis. CCDC-669443 (2),
-669444 (diene from Table 4, entry 2), and -632284 (diene from
Table 4, entry 3) contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data_request/cif. As the alkene functionality
originating from the alkyne was found to have the Z configura-
tion in these three products, the products (major isomer, where
applicable) of all other reactions reported were tentatively
assigned this configuration.
[13]For references on the development of bulky electron-rich
phosphines and their application in coupling reactions, notably
by the research groups of Fu, Buchwald, Hartwig, and Beller,
see: A. Zapf, M. Beller, Chem. Commun. 2005, 431.
[14]Interestingly, styrene derivatives were not compatible with the
Ru-mediated ene–yne coupling reported by Watanabe and co-
workers (see reference [7a]). A [2+2+1]cycloaddition step with
a five-membered cyclic ruthenium intermediate was proposed
for these reactions.
Received: December 5, 2007
Published online: February 26, 2008
Keywords: alkenes · alkynes · Mizoroki–Heck reaction ·
.
palladium · phosphane ligands
[1]a) J.-P. Corbet, G. Mignani, Chem. Rev. 2006, 106, 2651; b) Metal-
Catalyzed Cross-Coupling Reactions, 2nd ed. (Eds.: A. de Mei-
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[2]For some recent reviews on the Heck reaction, see: a) R. F.
Heck, Synlett 2006, 2855; b) N. T. S. Phan, M. Van Der Sluys,
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Beletskaya, M. Yus, Tetrahedron 2005, 61, 11771.
[3]For two recent examples of the Pd-catalyzed coupling of
À
nonfunctionalized arenes by C H activation, see: a) D. R.
Stuart, K. Fagnou, Science 2007, 316, 1172; b) D. R. Stuart, E.
Villemure, K. Fagnou, J. Am. Chem. Soc. 2007, 129, 12072, and
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addition of Pd0 into the carbon–halide bond, followed by
decarbonylation and subsequent b-hydride elimination.
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