Efficient heck reactions catalyzed by palladium(0) and -(II) complexes bearing n-heterocyclic carbene and amide functionalities

Article abstract of DOI:10.1021/om1006402

A palladium(0) NHC complex Pd⁰(LH¹)₂(MA) (MA = maleic anhydride) was prepared from the amide-imidazolium salt [LH ¹H²]Cl (H¹ = NH proton; H² NCHN proton). The X-ray diffraction studies confirmed that a η²-MA ligand and two monodentate NHC ligands with the H¹ protons remaining intact are coordinated. These NH protons are involved in intra- or intermolecular hydrogen bonds stabilizing the solid-state structure. Degradation of Pd(LH¹)₂(MA) in air leads to the formation of the chelate complex trans-Pd^IIL₂ and other unidentified products. Negative-ion electrospray mass spectrometry revealed some intriguing Pd(0) species, including a 14-electron [Pd⁰L]^- species that bears only a bidentate NHC/amido ligand. The anionic amido group imparts a high electron density on a palladium center, as shown by X-ray photoelectron study. The palladium(0) precatalyst is highly efficient in catalyzing Heck reactions with activated aryl chlorides in ionic liquid. For deactivating aryl chlorides and bulky aryl bromides, cis-Pd^IIL₂ is more effective. A range of Heck-coupled products can be prepared by Pd ⁰(LH¹)₂(MA) and cis-Pd^IIL ₂. The latter complex also successfully mediates one-pot sequential Heck/Heck and Suzuki/Heck coupling reactions with 4-bromochlorobenzene as substrate.

Full text of DOI:10.1021/om1006402

Organometallics 2010, 29, 3901–3911 3901
DOI: 10.1021/om1006402
Efficient Heck Reactions Catalyzed by Palladium(0) and -(II) Complexes
Bearing N-Heterocyclic Carbene and Amide Functionalities
Jhen-Yi Lee, Pi-Yun Cheng, Yi-Hua Tsai, Guan-Ru Lin, Shih-Pu Liu,
Ming-Han Sie, and Hon Man Lee*
Department of Chemistry, National Changhua University of Education, Changhua 50058,
Taiwan, Republic of China
Received July 2, 2010
A palladium(0) NHC complex Pd0(LH1)2(MA) (MA = maleic anhydride) was prepared from the
amide-imidazolium salt [LH1H2]Cl (H1 = NH proton; H2 NCHN proton). The X-ray diffraction
studies confirmed that a η2-MA ligand and two monodentate NHC ligands with the H1 protons
remaining intact are coordinated. These NH protons are involved in intra- or intermolecular
hydrogen bonds stabilizing the solid-state structure. Degradation of Pd(LH1)2(MA) in air leads to
the formation of the chelate complex trans-PdIIL2 and other unidentified products. Negative-ion
electrospray mass spectrometry revealed some intriguing Pd(0) species, including a 14-electron
[Pd0L]- species that bears only a bidentate NHC/amido ligand. The anionic amido group imparts a
high electron density on a palladium center, as shown by X-ray photoelectron study. The palladium-
(0) precatalyst is highly efficient in catalyzing Heck reactions with activated aryl chlorides in ionic
liquid. For deactivating aryl chlorides and bulky aryl bromides, cis-PdIIL2 is more effective. A range
of Heck-coupled products can be prepared by Pd0(LH1)2(MA) and cis-PdIIL2. The latter complex
also successfully mediates one-pot sequential Heck/Heck and Suzuki/Heck coupling reactions with
4-bromochlorobenzene as substrate.
Introduction
for new effective ligands9-14 and ligand-free catalyst systems.15,16
Trialkylphosphines furnish by far most reactive catalyst
systems for the activation of deactivated aryl chlorides and
hindered/electronically deactivated coupling partners.17
However, the preparation of these ligands and their deriva-
tives typically involves substances of poor air-stability and
are, in general, expensive. Hence, the development of low-
cost phosphine-free catalyst systems for the challenging
substrates is more desirable for industrial applications, and
such molecular catalyst systems are still relatively few.14,18
Lately, N-heterocyclic carbenes (NHCs) are attracting atten-
tion because of their versatility in various C-C coupling
reactions.19-26 Although many reports have already shown
The palladium-catalyzed Heck reaction is a powerful tool
to prepare arylated alkenes in fine chemical synthesis.1-4
There are many catalyst systems that can be used to catalyze
the cross-coupling reactions, but typically reactive aryl ha-
lides (bromides and iodides) and activated alkenes are re-
quired as coupling reactants.1-4 Aryl chlorides are more
attractive substrates for industrial applications because of
their low cost and availability.5-7 However, these substrates,
especially deactivated aryl chlorides, are reluctant to undergo
catalytic reactions due to their strong C-Cl bonds.5-8 Efforts
have been made to meet the challenge, including the search
(13) Morales-Morales, D.; Redon, R.; Yung, C.; Jensen, C. M. Chem.
Commun. 2000, 1619.
(14) Srinivas, P.; Likhar, P.; Maheswaran, H.; Sridhar, B.; Ravikumar,
*Corresponding author. Tel: þ886 4 7232105, ext. 3523. Fax: þ886 4
7211190. E-mail: leehm@cc.ncue.edu.tw.
(1) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009.
(2) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2.
(3) Alonso, F.; Beletskaya, I. P.; Yus, M. Tetrahedron 2005, 61,
11771.
(4) Corbet, J.-P.; Mignani, G. Chem. Rev. 2006, 106, 2651.
(5) Zapf, A.; Beller, M. Top. Catal. 2002, 19, 101.
(6) Whitcombe, N. J.; Hii, K. K.; Gibson, S. E. Tetrahedron 2001, 57,
7449.
K.; Kantam, M. L. Chem.—Eur. J. 2009, 15, 1578.
(15) Calo, V.; Nacci, A.; Monopoli, A.; Cotugno, P. Angew. Chem.,
ꢀ
Int. Ed. 2009, 48, 6101.
(16) Kleist, W.; Prockl, S.; Kohler, K. Catal. Lett. 2008, 125, 197.
(17) Fu, G. C. Acc. Chem. Res. 2008, 41, 1555.
€
€
(18) Selvakumar, K.; Zapf, A.; Beller, M. Org. Lett. 2002, 4, 3031.
(19) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290.
(20) Hillier, A. C.; Grasa, G. A.; Viciu, M. S.; Lee, H. M.; Yang, C.;
Nolan, S. P. J. Organomet. Chem. 2002, 653, 69.
(7) Bedford, R. B.; Cazin, C. S. J.; Holder, D. Coord. Chem. Rev.
€
2004, 248, 2283.
(8) Herrmann, W. A.; Bohm, V. P. W.; Reisinger, C.-P. J. Organomet.
(21) Herrmann, W. A.; Ofele, K.; von Preysing, D.; Schneider, S. K.
€
J. Organomet. Chem. 2003, 687, 229.
Chem. 1999, 576, 23.
(9) Herrmann, W. A.; Brossmer, C.; Reisinger, C.-P.; Riermeier,
T. H.; Ofele, K.; Beller, M. Chem.—Eur. J. 1997, 3, 1357.
(22) Christmann, U.; Vilar, R. Angew. Chem., Int. Ed. 2005, 44, 366.
(23) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew. Chem.,
Int. Ed. 2007, 46, 2768.
€
€
(10) Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 6989.
(11) Yi, C.; Hua, R. Tetrahedron Lett. 2006, 47, 2573.
(12) Schnyder, A.; Indolese, A. F.; Studer, M.; Blaser, H.-U. Angew.
Chem., Int. Ed. 2002, 41, 3668.
(24) Wurtz, S.; Glorius, F. Acc. Chem. Res. 2008, 41, 1523.
(25) Marion, N.; Nolan, S. P. Acc. Chem. Res. 2008, 41, 1440.
(26) Organ, M. G.; C-alimsiz, S.; Sayah, M.; Hoi, K. H.; Lough, A. J.
Angew. Chem., Int. Ed. 2009, 48, 2383.
r
2010 American Chemical Society
Published on Web 08/09/2010
pubs.acs.org/Organometallics

3902 Organometallics, Vol. 29, No. 17, 2010
Lee et al.
Scheme 1. Synthesis of Palladium(0) NHC Complexes
Chart 1. NHC Ligands and Their Precursor
While the applications of palladium(II) NHC precatalysts in
various C-C coupling reactions are ubiquitous in the litera-
ture, the use of preformed palladium(0) NHC complexes is
relatively rare.18,29,46-58 On the basis of all these thoughts,
we hope to develop new palladium(0) complexes derived
from [LH1H2]Cl for the Heck reactions. Our results illustrate
that palladium(0) precatalysts bearing the combination of
NHC and amido functionalities indeed deliver highly pro-
mising catalytic performances in Heck reactions of activated
aryl chlorides with alkenes. However, for challenging sub-
strates of deactivated aryl chlorides and hindered/electro-
nically deactivated coupling partners, palladium(II) precata-
lysts of L are more efficient. Since deprotonation of H1
protons leads to anionic Pd(0)L species, negative-ion electro-
spray mass spectrometry was carried out to give insight into
active species derived from the palladium(0) precursors.
that palladium complexes with NHC ligands performed well
in Heck reactions with a variety of aryl bromides and acti-
vated aryl chlorides, their reactivity with deactivated aryl chlori-
des is somewhat limited.27-37 Beller et al. demonstrated that
palladium(0) complexes with IMes were effective catalyst
systems for the Heck reactions of activated and nonactivated
aryl chlorides.18 However, their uses for deactivated aryl
chlorides were not mentioned.
Nickel(II)38 and palladium(II)39,40 complexes derived from
[LH1H2]Cl have been reported by us (Chart 1). Palladium(II)
complexes with similar ligand frameworks have also been
published by others.41-44 This NHC ligand system, derived
from cheap starting materials,39 contains a NH (H1) proton
that upon deprotonation forms an anionic bidentate carbene/
amide ligand, L. Such anionic amide functionality can im-
part higher electron density on a palladium center and thus
can enhance the oxidative addition of a C-Cl bond.14 On the
other hand, defined palladium(0) precatalysts are desirable
for more active and productive catalysts compared to the
commonly applied in situ generated, undefined catalyst systems.45
Results and Discussion
Preparation of Palladium(0) Carbene Complexes. The new
palladium complexes 3a,b were synthesized by treatment of
the ligand precursors 1a,b with the known palladium pre-
cursor 259 in the presence of K2CO3 at ambient temperature
(Scheme 1). After thorough washing with methanol, yellow
solids of 3a and 3b were obtained with decent yields of 50%
and 57%, receptively. These compounds are air-stable in
solid forms. However, they are air-sensitive in solution with
€
(27) Herrmann, W. A.; Elison, M.; Fischer, J.; Kocher, C.; Artus,
G. R. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 2371.
(28) McGuinness, D. S.; Green, M. J.; Cavell, K. J.; Skelton, B. W.;
White, A. H. J. Organomet. Chem. 1998, 565, 165.
(29) McGuinness, D. S.; Cavell, K. J.; Skelton, B. W.; White, A. H.
Organometallics 1999, 18, 1596.
€
(30) Schwarz, J.; Bohm, V. P. W.; Gardiner, M. G.; Grosche, M.;
€
€
Herrmann, W. A.; Hieringer, W.; Raudaschl-Sieber, G. Chem.—Eur. J.
2000, 6, 1773.
(31) Grundemann, S.; Albrecht, M.; Loch, J. A.; Faller, J. W.;
Crabtree, R. H. Organometallics 2001, 20, 5485.
(32) Yang, C.; Lee, H. M.; Nolan, S. P. Org. Lett. 2001, 3, 1511.
(33) Loch, J. A.; Albrecht, M.; Peris, E.; Mata, J.; Faller, J. W.;
Crabtree, R. H. Organometallics 2002, 21, 700.
(46) Gstottmayr, C. W. K.; Bohm, V. P. W.; Herdtweck, E.; Grosche,
M.; Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1363.
(47) Fantasia, S.; Nolan, S. P. Chem.—Eur. J. 2008, 14, 6987.
(48) Selvakumar, K.; Zapf, A.; Spannenberg, A.; Beller, M. Chem.—
Eur. J. 2002, 8, 3901.
(49) Clement, N. D.; Cavell, K. J.; Ooi, L.-l. Organometallics 2006,
25, 4155.
(50) Jackstell, R.; Harkal, S.; Jiao, H.; Spannenberg, A.; Borgmann,
(34) Lee, H. M.; Zeng, J. Y.; Hu, C.-H.; Lee, M.-T. Inorg. Chem.
€
2004, 43, 6822.
C.; Rottger, D.; Nierlich, F.; Elliot, M.; Niven, S.; Cavell, K.; Navarro,
(35) Hahn, F. E.; Jahnke, M. C.; Pape, T. Organometallics 2006, 25,
5927.
(36) Kantchev, E. A. B.; Peh, G.-R.; Zhang, C.; Ying, J. Y. Org. Lett.
O.; Viciu, M. S.; Nolan, S. P.; Beller, M. Chem.—Eur. J. 2004, 10, 3891.
(51) Jackstell, R.; Andreu, M. G.; Frisch, A.; Selvakumar, K.; Zapf,
€
A.; Klein, H.; Spannenberg, A.; Rottger, D.; Briel, O.; Karch, R.; Beller,
2008, 10, 3949.
M. Angew. Chem., Int. Ed. 2002, 41, 986.
(52) Konnick, M. M.; Guzei, I. A.; Stahl, S. S. J. Am. Chem. Soc.
2004, 126, 10212.
(37) Peh, G.-R.; Kantchev, E. A. B.; Zhang, C.; Ying, J. Y. Org.
Biomol. Chem 2009, 7, 2110.
(38) Liao, C.-Y.; Chan, K.-T.; Chang, Y.-C.; Chen, C.-Y.; Tu, C.-Y.;
Hu, C.-H.; Lee, H. M. Organometallics 2007, 26, 5826.
(39) Liao, C.-Y.; Chan, K.-T.; Zeng, J.-Y.; Hu, C.-H.; Tu, C.-Y.; Lee,
H. M. Organometallics 2007, 26, 1692.
(40) Liao, C.-Y.; Chan, K.-T.; Tu, C.-Y.; Chang, Y.-W.; Hu, C.-H.;
Lee, H. M. Chem.—Eur. J. 2009, 15, 405.
(41) Sakaguchi, S.; Yoo, Kyung S.; O’Neill, J.; Lee, Joo H.; Stewart,
T.; Jung, K. W. Angew. Chem., Int. Ed. 2008, 47, 9326.
(42) Yoo, K. S.; O’Neill, J.; Sakaguchi, S.; Giles, R.; Lee, J. H.; Jung,
K. W. J. Org. Chem. 2009, 75, 95.
(43) Sakaguchi, S.; Kawakami, M.; O’Neill, J.; Yoo, K. S.; Jung,
K. W. J. Organomet. Chem. 2010, 695, 195.
(53) Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F.
Angew. Chem., Int. Ed. 2003, 42, 3690.
(54) Arentsen, K.; Caddick, S.; Cloke, F. G. N.; Herring, A. P.;
Hitchcock, P. B. Tetrahedron Lett. 2004, 45, 3511.
(55) Caddick, S.; Cloke, F. G. N.; Clentsmith, G. K. B.; Hitchcock,
P. B.; McKerrecher, D.; Titcomb, L. R.; Williams, M. R. V. J.
Organomet. Chem. 2001, 617-618, 635.
(56) Sprengers, J. W.; Wassenaar, J.; Clement, N. D.; Cavell, K. J.;
Elsevier, C. J. Angew. Chem., Int. Ed. 2005, 44, 2026.
€
€
(57) Bohm, V. P. W.; Gstottmayr, C. W. K.; Weskamp, T.; Herr-
mann, W. A. J. Organomet. Chem. 2000, 595, 186.
(58) Hauwert, P.; Maestri, G.; Sprengers, J. W.; Catellani, M.; Elsevier,
C. Angew. Chem., Int. Ed. 2008, 47, 3223.
(44) Kumar, S.; Shaikh, M. M.; Ghosh, P. J. Organomet. Chem. 2009,
694, 4162.
(45) Andreu, M. G.; Zapf, A.; Beller, M. Chem. Commun. 2000, 2475.
(59) Cavell, K. J.; Stufkens, D. J.; Vrieze, K. Inorg. Chim. Acta 1981,
47, 67.

Article
Organometallics, Vol. 29, No. 17, 2010 3903
Scheme 2. Proposed Decomposition Pathway of 3a
the need of protection under nitrogen atmosphere. The two
new compounds are Pd(LH1)2(MA) (MA = maleic an-
hydride), which are characterized by 1H and 13C{1H}
NMR spectroscopy, elemental analyses, and X-ray structural
studies. Pd(tmiy)2(MA)29 (tmiy = 1,3,4,5-tetramethylimi-
dazol-2-ylidene) and Pd(IMes)(MA)2 (IMes = 1,3-bis(2,4,6-
trimethylphenyl)imidazol-2-ylidene) are relevant compounds
published in the literature.56 A comparison of Pd(LH1)2-
(MA) with Pd(IMes)(MA)2 clearly indicates the small steric
bulk of the LH1 ligand such that in the former complex two
of the NHC ligands can coordinate to the palladium center.
The successful formation of palladium carbene complexes is
indicated by the absence of proton signals at ca. 9.4 ppm due
to the NCHN protons on their ligand precursors. The
ligands on 3a and 3b are coordinated in a monodentate
rather than chelating fashion, as the NH protons are still
observed at ca. 10.2 ppm. The large coordination-induced
shifts (CIS) for the protons of maleic anhydride, Δδ(H) =
-3.42 and -3.51 ppm for 3a and 3b, respectively, are very
similar to those in Pd(tmiy)2(MA) (tmiy = 1,3,4,5-tetra-
methylimidazol-2-ylidene)29 and Pd(py)2(MA),60 reflecting a
similar electron-rich palladium center in 3a,b. Three down-
field 13C peaks in the range 165-188 ppm were observed in their
respective spectra, corresponding to the carbene and the two
different carbonyl carbons. The assignments of these signals were
assisted by acquiring the HMBC spectra (see Figure 1S for the
HMBC spectrum of 3a in the Supporting Information). In each
case, the presence of correlation peaks from the two methylene
groups of protons to the most downfield signal unambiguously
established that the carbene signals for 3a and 3b are at 187.9 and
186.9 ppm, respectively. The chemical shift of these signals is
comparable to that of 185.5 ppm in Pd(tmiy)2(MA).29
3a in air were, nevertheless, unsuccessful, as complex decom-
position occurred, as evidenced by the formation of palladium
black and the messy 1H NMR spectrum of the reaction mixture.
Electrospray Ionization Mass Spectrometry (ESI-MS). In
order to understand the behavior of 3a,b and hopefully
observe short-lived reactive intermediates in solution, we
performed ESI-MS studies (Table 1). The soft ionization
technique allows few fragmentation products, and the ions
are transferred from solution to the gas phase in a smooth
manner that is ideal for observation of short-lived molecular
ions.61 The positive-ion mass spectra of 3a,b show the
absence of molecular peaks, but major positive ions corre-
sponding to a chelate Pd(II) complex, [PdL2 þ H]þ, were
detected. Thus species A, which are [4a þ H]þ and [4b þ H]þ,
are observed at m/z = 787.1 and 687.2, respectively. Inter-
estingly, species B, due to the decarbonylation from species A,
were also observed. The negative-ion ESI-MS studies, contrast-
ingly, exhibit only Pd(0) species. The [M - H]- peaks were
observed at m/z = 884.9 and 784.9 for 3a and 3b, respectively.
In each case, the base peak is due to species D, which is a Pd(0)
species bearing one chelating carbene ligand and maleic anhy-
dride. Consistent with the observation from the positive-ion mode,
decarbonylation products E were also indentified. Importantly,
small amounts of intriguing species F, which are Pd(0) species
bearing only one chelating carbene ligand, were observed in both
spectra. Deprotonation of the amido NH and decoordination of
maleic anhydride lead to this anionic, 14-electron [Pd0L]- species,
which is probably an active species in C-C coupling reactions
conducted under basic conditions. The experimental isotopic
patterns of all m/zpeaks match well with their theoretical patterns.
Crystallographic Studies. All the new palladium complexes
described in this paper have been successfully structurally char-
acterized. Figures 2 and 3 display their thermal ellipsoid plots.
Crystallographic data and selected bond distance and angles are
listed in Tables 2 and 3, respectively. The Pd atoms in 3a and 3b
adopt distorted square-planar coordination geometry. In each
case, the sum of the four bond angles about the Pd atom equals
360°. However, the C-Pd-C angles from carbenes are wider
than the ideal 90° (3a: 95.28(14)°; 3b: 97.5(2)°). Intriguingly, the
two Pd-carbene distances in each complex are unequal in length.
Complexes 3a,b are unstable in solution, especially under
air. Thus an attempted recrystallization of 3a in dichloro-
methane without N2 protection resulted in the isolation of
colorless crystals after ca. 4-5 days, the structure of which
was revealed by X-ray crystallography as trans Pd(II) chelate
complex 4a (Scheme 2). The kinetic product, cis-4a, had
already been prepared and structurally characterized by us
elsewhere.39 Noteworthy, palladium peroxo complexes have
been isolated when monodentate NHC palladium(0) com-
plexes were exposed to air.47,52 The formation of 4a can be
postulated via a similar transient peroxo intermediate, and
subsequent proton exchange between the amido groups and
peroxo ligand furnishes the formation of a chelate ring. In
˚
For example in 3a, one is 2.043(4) A, whereas the other one is
˚
longer, at 2.070(3) A. ThePd-carbene distances in 3a and 3b are
within the normal range of relevant Pd(0)-carbene structures.46-54
In each case, the maleic anhydride is close to perpendicular to
the square coordination plane. The corresponding interplanar
angles in 3a and 3b are 77.32(12)° and 81.99(16)°, respectively.
A key feature in the molecular structures of 3a and 3b is the
1
fact, during the preparation of 3a,b in Scheme 1, the H
NMR spectroscopy of the reaction mixture always indicated
the presence of a minute amount of cis-4a,b, which was easily
removed by washing withmethanol. Attempts to isolatetrans-
4a in large quantity by stirring a dichloromethane solution of
presence of classical NH OdC hydrogen bonds. In the
3 3 3
molecular structure of 3a, there are two intramolecular NH
OdC hydrogen bonds (Table 1S in Supporting Information).
3 3 3
€
(60) Kluwer, A. M.; Elsevier, C. J.; Buhl, M.; Lutz, M.; Spek, A. L.
Angew. Chem., Int. Ed. 2003, 42, 3501.
(61) Santos, L. S.; Knaack, L.; Metzger, J. O. Int. J. Mass Spectrom.
2005, 246, 84.

3904 Organometallics, Vol. 29, No. 17, 2010
Lee et al.
Table 1. ESI-MS Data of 3a and 3ba
a Relative abundance in parentheses. The site for the proton in species C is ambiguous.
˚
of 2.902(4) A but a similar contact angle of 160.3°. In
contrast to 3a, due to the difference in the relative orientation
of the two unsymmetrical carbene ligands (see also Figure 2S
in Supporting Information), only one intramolecular NH
OdC hydrogen bond exists in 3b. It links the two carbene
3 3 3
˚
ligands with a N O contact distance of 2.916(6) A and a
3 3 3
NH O contact angle of 164.0°. The other NH hydrogen
3 3 3
bond donor links with the CdO on the maleic anhydride in
an intermolecular fashion, forming a dimeric structure (see
Table 2S and Figure 3S in Supporting Information). The
overall stability of 3a and 3b in the solid state can be attri-
buted to the presence of such intramolecular forces.
Complex 4a is situated in a special position with inversion
site symmetry in the monoclinic unit cell P21/c. The Pd atom
adopts a distorted square-planar environment with trans
ligand coordination. The bite angle of the ligand is 85.7°,
which is similar to those in cis-4a (see Table 3).39 The Pd-C
˚
distance of 2.006(7) A is, however, longer than that in the cis
˚
isomer (1.972(2) A), indicating the stronger trans influence of
the carbene than the amido group. Consistently, the Pd-N
distances in the cis form are long (2.0851(19) and 2.0818(17) A),
Figure 1. Experimental isotopic pattern at m/z 446.4 in the mass
spectrum of 3a (white). The theoretical isotopic pattern is shown
in black.
˚
˚
whereas that in the trans form is shorter (2.040(6) A).
The arylated alkene products from the Heck reactions,
(E)-1,2,3-trimethoxy-5-styrylbenzene (8) and (E)-1,3,5-trii-
sopropyl-2-styrylbenzene (9), were also successfully structu-
rally characterized by X-ray diffraction studies. Figure 4
displays their molecular structures. The interplanar angle
between the two aromatic rings in the trimethoxy compound
One of them is between an amido NH on the carbene ligand
and a CdO on the maleic anhydride with N O contact
3 3 3
˚
distance of 2.963(4) A and NH O contact angle of 160.0°.
3 3 3
The other hydrogen bond between the two carbene ligands is
slightly stronger, reflecting a shorter N O contact distance
3 3 3

Article
Organometallics, Vol. 29, No. 17, 2010 3905
Figure 2. Molecular structures of 3a (left) and 3b (right) with 50% probability ellipsoids for non-H atoms. Hydrogen atoms except
those involved in intramolecular hydrogen bonding have been omitted for clarity. Hydrogen bonds are shown with broken lines.
Table 2. Crystallographic Data of 3a, 3b, trans-4, 8, and 9
3a
3b 0.5C4H8O
trans-4
8
9
3
empirical formula
fw
cryst syst
C
48H40N6O5Pd
C40H36N6O5Pd C4H8O
C44H36N6O2Pd
787.19
monoclinic
P21/c
11.4007(19)
16.954(3)
9.7297(15)
90
109.090(4)
90
1777.3(5)
150(2)
2
3531
241
0.0641
0.2373
C17H18O3
270.31
monoclinic
P21/c
9.2272(4)
12.3242(5)
13.7756(7)
90
113.227(4)
90
1439.56(11)
110(2)
4
3089
184
0.0358
0.0533
C23H30
306.47
monoclinic
P21/c
9.9567(3)
11.2769(3)
17.4701(5)
90
100.638(3)
90
1929.84(10)
110(2)
4
3
887.26
monoclinic
P21/c
13.6550(10)
18.4052(13)
16.0293(12)
90
99.876(2)
90
3968.8(5)
150(2)
4
10 127
541
0.0508
0.1592
859.25
monoclinic
C2/c
30.870(4)
9.9302(12)
27.134(3)
90
94.039(6)
90
8297.2(17)
150(2)
8
space group
˚
a, A
˚
b, A
˚
c, A
R, deg
β, deg
γ, deg
3
˚
V, A
T, K
Z
no. of unique data
no. of params refined
R1a [I > 2σI]
wR2b (all data)
P
8696
542
4150
317
0.0390
0.0894
0.0646
0.1405
P
P
P
aR1 = ( Fo| - |Fc )/ |Fo|. b wR2 = [ (|Fo|2 - |Fc|2)2/ (Fo2)]1/2
.
is 14.7(1)°, which is comparable to that of 16.92(3)° in (E)-
1,2,3-trimethoxy-4-styrylbenzene.62 In sharp contrast, due to
the presence of steric bulkiness of the two o-isopropyl
groups, the two aromatic rings in 9 are close to orthogonal
to each other with an interplanar angle of 82.6(1)°.
X-ray Photoelectron Spectroscopy (XPS). The electronic
property of the palladium(0) complex 3b and the palladium-
(II) complex cis-4b was probed by XPS. The binding energies
of Pd electrons in the core 3d3/2 and the 3d5/2 orbitals in 3b
are 340.7 and 335.4 eV, which compare favorably with those
of 340.5 and 335.1 eV in Pd(0). Intriguingly, the correspond-
ing binding energies in cis-4b are 341.7 and 336.6 eV, which
are close to those in elemental Pd(0)63 and thus very low for a
Pd(II) atom,64 reflecting the strong electron-donating effect
of the anionic amido groups. These low binding energies in
ꢁ
(62) Sopkova-de Oliveira Santos, J.; Bazin, M.-A.; Lohier, J.-F.; El
Kihel, L.; Rault, S. Acta Crystallogr. 2009, C65, o311.
(63) Moulder, J. F.; Stickle, W. F.; Sobol, P. E.; Bomben, K. D.
Handbook of X-ray Photoelectron Spectroscopy; Perkin-Elmer Corpora-
tion: Eden Prairie, MN, 1992.
(64) Boekman, F.; Gogoll, A.; Pettersson, L. G. M.; Bohman, O.;
Siegbahn, H. O. G. Organometallics 1992, 11, 1784.
Figure 3. Molecular structures of trans-4a with 50% probability
ellipsoids for non-H atoms. Hydrogen atoms have been omitted
for clarity.

3906 Organometallics, Vol. 29, No. 17, 2010
Table 3. Selected Bond Distances (A) and Angles (deg) of 3a, 3b, trans-4a, and cis-4a
Lee et al.
a
˚
3a
3b
trans-4a
cis-4a39
Pd1—C1, 2.043(4)
Pd1—C23, 2.070(3)
Pd1—C1, 2.049(5)
Pd1—C19, 2.066(5)
Pd1—C1, 2.006(7)
Pd1—N3, 2.040(6)
Pd1—C1, 1.972(2)
Pd1—C23, 1.972(2)
Pd1—C45, 2.114(4)
Pd1—C46, 2.115(3)
Pd1—C39, 2.102(5)
Pd1—C40, 2.110(5)
Pd1—N3, 2.0851(19)
Pd1—N6, 2.0818(17)
C1—Pd1—N3, 86.45(8)
C23—Pd1—N6, 84.50(8)
C1—Pd1—C23, 95.50(9)
N3—Pd1—N6, 93.46(7)
C1—Pd1—N6, 177.70(8)
C23—Pd1—N3, 177.01(9)
C1—Pd1—C23, 95.28(14)
C1—Pd1—C46, 110.33(14)
C23—Pd1—C45, 114.03(14)
C45—Pd1—C46, 40.08(14)
C1—Pd1—C45, 150.41(14)
C23—Pd1—C46, 153.11(14)
C1—Pd1—C19, 97.5(2)
C1—Pd1—C39, 110.3(2)
C19—Pd1—C40, 112.7(2)
C39—Pd1—C40, 39.68(19)
C1—Pd1—C40, 149.8(2)
C19—Pd1—C39, 151.9(2)
C1—Pd1—N3, 85.7(2)
a Symmetry code =1-x, 2-y, 2-z.
Figure 4. Left: molecular structure of 8 with 50% probability ellipsoids for non-H atoms. Right: molecular structure of 9 with 50%
probability ellipsoids for non-H atoms.
Table 4. Heck Reaction of 4-Chloroacetophenone and Styrenea
entry
cat.
3a
temp, °C
solvent
yield, % (5:50)
1
2
3
4
5
6
7
8
120
120
120
110
120
120
140
120
120
140
140
organic
organic
organic
IL
IL
IL
IL
IL
IL
IL
36 (92:8)
40 (92:8)
13 (100:0)
94 (94:6)
>99 (93:7)
92 (96:4)b
98 (94:6)
0
3b
cis-4b
3b
3b
3b
3b
cis-4b
trans-4b
cis-4b
trans-4b
9
10
11
0
96 (93:7)
>99 (93:7)
IL
a 1.0 mmol of 4-chloroacetophenone, 1.4 mmol of styrene, 1.1 mmol of NaOAc, 5 mL of DMA or 2 g of TBAB, 0.5 mol % [Pd] cat., 110-140 °C, 2 h.
Yields and regioselectivity determined by NMR using 1,3,5-trimethoxybenzene as internal standard. b Isolated yield with regioselectivity determined by
NMR.
cis-PdIIL2 are, in fact, similar to those of 342.0 and 336.7 eV
in cis-PdII(LH1)(PCy3)Cl2, possessing a strong electron-
donating PCy3 ligand.40 For comparison, the binding energies
in Pd(II) complexes with a bidentate carbene of abnormal
binding are much higher, at ca. 348.0 and 342.6 eV.65
Catalytic Studies. The catalytic performances of com-
plexes 3a,b in Heck reactions of aryl halides with alkenes
were studied. The reaction between 4-chloroacetophenone
and styrene was chosen as the benchmark for initial investi-
gation (Table 4). We screened the reactions in the commonly
used highly polar organic solvent N,N-dimethylacetamide
(DMA) and the ionic liquid tetra-n-butylammonium bro-
mide (TBAB), which is a solid at ambient temperature but a
liquid at high temperature. The green solvent not only offers
the advantages of low vapor pressure, high boiling point,
cheap price, availability, and recyclability but also shortens
the workup time, as the procedure to remove high-boiling
solvent is replaced by a simple extraction procedure. Reports
have demonstrated that palladium-catalyzed coupling reac-
tions can be performed effectively in ionic liquids.18,66,67 It is
worthy to mention that ionic liquids were also employed as
(66) Albrecht, M.; Stoeckli-Evans, H. Chem. Commun. 2005, 4705.
(67) Wang, R.; Zeng, Z.; Twamley, B.; Piekarski, M. M.; Shreeve,
J. n. M. Eur. J. Org. Chem. 2007, 2007, 655.
(65) Heckenroth, M.; Kluser, E.; Neels, A.; Albrecht, M. Angew.
Chem., Int. Ed. 2007, 46, 6293.

Article
Organometallics, Vol. 29, No. 17, 2010 3907
Scheme 3. One-Pot Sequential Palladium-Catalyzed Cross-Coupling Reactions
into an active Pd0 species, such as [Pd0L]- (species F), is facile
at a higher temperature, leading to the resulting activity. The
time-yield curves for 3b and cis-4b over a period of 2 h were
obtained in order to shed light on their behavior in catalyst
activation. Figure 5 clearly shows that the catalyst activation
of the palladium(0) complex is much faster than the palladium(II)
complex. For palladium(0) complex 3b, catalytic activity starts
instantaneously, giving a ca. 85% yield in the initial 20 min,
whereas there is a long activation period of 1 h for the bis-
chelate Pd(II) complex cis-4b to form active catalytic species.
As demonstrated above, a low loading of 3b as precatalyst
(0.5 mol %) was sufficient to obtain 4-acetylstilbene almost
quantitatively in 2 h with the activated substrate 4-chloroace-
tophenone. However, these conditions were not suitable with
challenging substrates including hindered aryl bromides and
nonactivated and deactivated aryl chlorides. Instead, we found
that robust palladium(II) complex cis-4b outperforms palla-
dium(0) complex 3b in utilizing these substrates. The substrate
scope of cis-4b with hindered aryl bromides was explored in
Table 5. A general condition was established involving 3 mol %
of cis-4b at 140 °C in 12 h, and the catalyst system is capable of
delivering good trans product yields with a range of challenging
aryl bromide substrates. For example, the catalyst system can
utilize the deactivating substrate 5-bromo-1,2,3-trimethoxyben-
zene to synthesize 8 in 72% yield (entry 3). Hindered aryl
bromides with two o-substitutents can also be coupled effec-
tively (entries 4/5 and 10/11). In particular, a decent 52% yield
of 9 can be achieved from the very bulky 1-bromo-2,4,6-
triisopropylbenzene (entry 4). Both of the coupled products 8
and 9 were successfully characterized by X-ray diffraction
studies (vide supra). Complex 3b is not suitable for bulky aryl
bromides, as illustrated in entry 5, showing that (E)-2,4,6-
trimethylstilbene (10) was obtained from 2-bromomesitylene
in only 22% yield, whereas cis-4b delivered a high 81% yield.
(E)-3,4,5,40-Tetramethoxystilbene (11), designated as DMU-
212, is attracting interest recently because it has emerged as a
strong candidate for antitumor applications.69 Entry 6 shows
Figure 5. Time-yield curves of 3b and cis-4b in the Heck reaction
between 4-chloroacetophenone and styrene.
solvent in Heck reactions catalyzed by palladium nanoparti-
cles.15,68 Entries 1 and 2 show that 36-40% yields of 4-acetyl-
stilbene canbe achieved in 2 h using 0.5 mol% of palladium(0)
precatalysts at 120 °C with DMA as solvent. Complex 3b
is slightly more efficient than 3a. Bis(bidentate) palladium(II)
complex cis-4b reported by us earlier39 affords a poor 13%
yield at 120 °C (entry 3). Its ineffectiveness can be attributed
to the insufficient formation of active Pd(0) species from cis-
4b at such low temperature. Replacing the organic solvent
with TBAB leads to a substantial increase in product yields.
For example, complex 3b gives a yield of only 40% in DMA
(entry 2), but a quantitative yield was obtained in 2 h using
the ionic liquid as solvent (entry 5). As shown by entries 4, 5,
and 7, the optimal temperature for the catalytic reaction is
120 °C. Entries 8 and 9 confirmed that both cis- and trans-4b
were ineffective even in ionic liquid at this temperature. To
our surprise, excellent yields of 96% and 99% were obtained
by raising the reaction temperature to 140 °C(entries10and11).
This reflects that the conversion of the precatalyst PdIIL2
(68) Ye, C.; Xiao, J.-C.; Twamley, B.; LaLonde, A. D.; Norton,
M. G.; Shreeve, J. n. M. Eur. J. Org. Chem. 2007, 2007, 5095.
(69) Cross, G. G.; Eisnor, C. R.; Gossage, R. A.; Jenkins, H. A.
Tetrahedron Lett. 2006, 47, 2245.

3908 Organometallics, Vol. 29, No. 17, 2010
Table 5. Heck Reactions of Bulky Aryl Bromidesa
Lee et al.
a 1.0 mmol of aryl bromide, 1.4 mmol of alkene, 1.1 mmol of NaOAc, 2 g of TBAB, 0.5 or 3 mol % cis-4b unless otherwise stated, 140 °C, 12 h, isolated
yields. b 3 mol % 3b as precatalyst.
that it can be prepared in 56% yield with a mere 3 mol % Pd
precatalyst loading, which is much more cost-effective than the
reported procedure, which requires a 40 mol % of Pd loading.69
The catalyst system of cis-4b is also effective for a range
of aryl chlorides (Table 6). A comparison between entry 1
and 2 clear reflects the higher effectiveness of cis-4b than 3b.
Entries 2 and 3 indicate that the trans and cis isomers of cis-
4b give the same product yield. For activating aryl chlorides,
a 0.5 mol % of 3b or cis-4b loading is sufficient to afford high
isolated yields of coupled products (90-98%) in 2 or 12 h
(entries 9, 10, 14-16). For nonactivated chlorobenzene
as substrate, a 0.5 mol % of cis-4b affords stilbene (20) and
(E)-3-phenylacrylic acid n-butyl ester (25) in 71% and 55%,
respectively (entries 8 and 13). For deactivated substrates, a
higher loading of 1.5-3 mol % of cis-4b is needed to deliver
decent yields of coupled products (42-72%) (entries 4, 6, 7,
11, 12). For example, 4-methoxystilbene (17) can be obtained
in 72% yield from 4-chloroanisole in 12 h with a 1.5 mol % of
Pd loading (entry 4).
The higher activity of cis-4b compared with 3b with challen-
ging substrates can be explained by the continuous supply of
active Pd(0) species from the robust Pd(II) cis-4b. In contrast,
the instantaneously high concentration of Pd(0) active species
from Pd(0) 3b may lead to fast coupling activity with activated
aryl chlorides, but such high concentration is favorable to
catalyst deactivation when prolong heating is needed for

Article
Organometallics, Vol. 29, No. 17, 2010 3909
Table 6. Heck Reactions of Aryl Chloridesa
a 1.0 mmol of aryl chloride, 1.4 mmol of alkene, 1.1 mmol of NaOAc, 2 g of TBAB, 0.5-3 mol % [Pd] cat., 140 °C, 2 or 12 h, isolated yields with
regioselectivity determined by NMR.
challenging substrates, which eventually leads to poorer pro-
duct yields. The catalyst system derived from L is capable of
utilizing deactivated aryl chlorides, reflecting its higher efficient
than the palladium(0) IMes system reported in the literature.18
One-pot sequential cross-coupling reactions of aryl dihalides
are attracting interests because of the possibilities of obtaining
difunctionalized arenes in a single step with less waste
genaration.70 So far only a few examples using a single pre-
catalyst in the sequential C-C coupling have been reported and
the aryl dihalides were limited to those containing Br and I.70,71
(70) Zhang, X.; Liu, A.; Chen, W. Org. Lett. 2008, 10, 3849.
(71) Flaherty, D. P.; Dong, Y.; Vennerstrom, J. L. Tetrahedron Lett.
2009, 50, 6228.

3910 Organometallics, Vol. 29, No. 17, 2010
Lee et al.
The use of cheaper 4-bromochlorobenzene has been demon-
strated in a recent report for sequential Heck/Heck but not
Suzuki/Heck coupling reactions.15 We found that cis-4b
performs well in both the sequential Heck/Heck coupling
reactions and Suzuki/Heck coupling reactions to generate
the desired products using 4-bromochlorobenzene as substrate
(Scheme 3). Thus (E)-butyl 3-(4-styrylphenyl)acrylate (29) and
1-methoxy-4-(4-styrylstyryl)benzene (30) can be obtained
in 64 and 51% yields, respectively, from the Heck/Heck
coupling reactions. We reported that cis-4b is a precatalyst
for Suzuki coupling reactions capable of utilizing aryl
bromides but not chlorides. Thus cis-4b can generate
4-chlorobiphenyl via Suzuki coupling chemoselectively
and the subsequent coupling with styrene generates the
desirable product, (E)-4-styrylbiphenyl (31), in 58% yield.
Consistently, the reverse of the coupling sequence leads
to the isolation of (E)-1-chloro-4-styrylbenzene only. Thus
our system is markedly more effective than that reported by
Chen et al. in which the more reactive 4-bromoiodobenzene
had to be used in the sequential Heck/Suzuki coupling
sequence.70
PHI 1600 system using Mg KR radiation (hv = 1253.6 eV) at
National Tsing Hua University (Taiwan).
Synthesis of 3a. To a 50 mL Schlenk flask containing
complex 2 (0.10 g, 0.268 mmol), 1a (0.20 g, 0.537 mmol),
and potassium carbonate (0.074 g, 0.537 mmol) was added dry
DMF (8 mL). The mixture was allowed to stir for 5 h at
ambient temperature. The solvent was completely removed
under vacuum. The residue was dissolved in dichloro-
methane. The organic layer was then washed twice with water.
After drying with anhydrous magnesium sulfate, the solvent was
completely removed under vacuum. The residue was washed
with diethyl ether and subsequently with methanol. The air-
stable yellow solid was then filtered on a frit and dried under
vacuum. Yield: 0.12 g (50%); mp 195.2-196.4 °C (dec); 1H
NMR (300 MHz, DMSO-d6, 25 °C, TMS): δ 3.58 (s, 2H,
CCHdCHC), 5.09 (s, 4H, CH2CdO), 5.48 (AB quartet, 2J(H,
H) = 7.5 Hz, Δν = 24.0 Hz, 4H, NpCHaHb), 6.82 (s, 2H, imi-
H), 6.99 (t, 3J(H,H) = 7.2 Hz, 2H, p-Ph-H), 7.11-7.19 (m, 6H,
Ph-H and Np-H), 7.23 (s, 2H, imi-H), 7.31 (t, 3J(H,H) = 7.5 Hz,
2H, Np-H), 7.37-7.48 (m, 8H, Ph-H and Np-H), 7.78 (d, 3J(H,
H) = 4.2 Hz, 2H, Np-H), 7.86 (d, 3J(H,H) = 3.8 Hz, 2H, Np-
H), 7.95 (d, 3J(H,H) = 4.1 Hz, 2H, Np-H), 10.20 (s, 2H, NH);
13C{1H} NMR (75 MHz, DMSO-d6, 25 °C, TMS): δ 38.6
(CCH=CHC), 51.9 (NpCH2), 53.7 (CH2CdO), 119.6 (CH),
121.2 (CH), 123.7 (CH), 125.6 (CH), 126.2 (CH), 126.8 (CH),
126.9 (CH), 128.6 (CH), 128.7 (CH), 128.9 (CH), 130.9 (CH),
132.6 (CH), 133.5 (CH), 138.8 (O=CNHC), 166.1 (CH2-
CdO), 173.9 (CHCO=O), 187.9 (NCN); elemental analysis
calcd (%) for C48H40N6O5Pd: C, 64.97; H, 4.54; N, 9.47;
found: C, 64.68; H, 4.55; N, 9.03%; Crystals suitable for
X-ray crystallography were obtained by vapor diffusion of dried
diethyl ether into a dried THF solution of the solid mixture
under nitrogen.
Conclusions
We prepared palladium(0) complexes 3a,b based on the
amido-functionalized NHC ligands. As revealed by the ESI-
MS study, facile deprotonation of the NH proton and
decoordination of one carbene ligand allow the formation
of an anionic electron-rich species F, which is postulated as
an active species in coupling reactions. The anionic amide
functionality imparts a higher electron density on the palladium
center as indicated by the XPS study. Hence, palladium(0)
complex 3b is highly effective in catalyzing Heck coupling
reactions with activated aryl chlorides in TBAB ionic liquid.
However, for electron-deactivating aryl chlorides and bulky
aryl bromides, palladium(II) complex cis-4b becomes more
efficient. The prolong heating required for demanding sub-
strates is not favorable for the palladium(0) precatalyst. The
robustness of the palladium(II) precatalyst may allow a
constant supply of Pd(0) active species over a long period
of time. Favorably, the combination of 3b and cis-4b
enables the access of a wide range of coupled products from
challenging substrates. Complex cis-4b is also promising in
one-pot sequential Heck/Heck and Suzuki/Heck coupling
reactions to generate unsymmetrical substituted arenes
from cheap 4-bromochlorobenzene. In view of the general-
ity and simple, practical, and green operating procedure,
the catalyst systems of 3b and cis-4b are expected to find
wide interests.
Synthesis of 3b. The preparation was similar to that of 1.
Complex 2 (0.20 g, 0.537 mmol), 1b (0.35 g, 1.07 mmol), and
potassium carbonate (0.15 g, 1.07 mmol) were used. A pale
yellow crystal was obtained. Yield: 0.24 g (57%); mp 163.8-
167.8 °C (dec); 1H NMR (300 MHz, DMSO-d6, 25 °C, TMS):
δ 3.49 (s, 2H, CCH=CHC), 4.96-5.07 (m, 8H, CH2CdO
and PhCH2), 7.03-7.28 (m, 20H, imi-H and Ph-H), 7.47 (d,
3J(H,H) = 3.9 Hz, 4H, o-Ph-H), 10.17 (s, 2H, NH); 13C{1H}
NMR 75 MHz, DMSO-d6, 25 °C, TMS): δ 38.1 (CCH=
CHC), 53.2 (PhCH2), 53.4 (CH2CdO), 119.3 (CH), 121.21
(CH), 123.4 (CH), 123.5 (CH), 127.3 (CH), 128.2 (CH), 128.6
(CH), 137.2 (CH), 138.5 (O=CNHC), 165.8 (CH2CdO),
173.5 (CHCO=O), 186.9 (NCN). analysis calcd (%) for C40
-
H36N6O5Pd: C, 61.05; H, 4.61; N, 10.69; found: C, 61.28; H,
5.08; N, 10.21%; Crystals suitable for X-ray crystallography
were obtained by vapor diffusion of dried diethyl ether into a
dried dichloromethane solution of the solid mixture under
nitrogen.
Synthesis of trans-4a. Crystals suitable for X-ray crystallo-
graphy were grown in ca. 4-5 days by slow evaporation of a
dichloromethane solution of 3a in air.
Catalytic Heck Reaction. In a typical run, a Schlenk tube was
charged with aryl halide (1.0 mmol), alkene (1.4 mmol), anhy-
drous sodium acetate (1.1 mmol), and an appropriate amount of
palladium precatalyst (0.5-3 mol %). The flask was thoroughly
degassed, added with DMA (5 mL) via a syringe or TBAB (2 g
for conventional heating; 1 g for microwave irradiation), and
then placed in a preheated oil bath at the appropriate tempera-
ture listed in Table 4-6. After the mixture was cooled, in case of
using DMA, the solvent was removed completely under high
vacuum. The residue was then dissolved in diethyl ether (10 mL).
The organic portion was then washed with water (3 ꢀ 10 mL)
and dried over anhydrous MgSO4. In the case of using TBAB,
after the mixture was cooled, the mixture was diluted with water
(10 mL) and extracted with ether (3 ꢀ 10 mL). The combined
organic portions were dried over anhydrous MgSO4. After
filtration, the solvent was removed completely under vacuum.
Experimental Section
General Information. All manipulations were performed un-
der a dry nitrogen atmosphere using standard Schlenk techni-
ques. Solvents were dried with standard procedures. Starting
chemicals were purchased from commercial source and used as
received. Compounds 1,38 2,59 and cis-4b39 were prepared accor-
ding to literature procedures. 1H, and 13C{1H} NMR spectra were
recorded at 300.13 and 75.48 MHz, respectively, on a Bruker
AV-300 spectrometer. Elemental analyses were performed on a
Thermo Flash 2000 CHN-O elemental analyzer. ESI-MS was
carried out on a Finnigan/Thermo Quest MAT 95XL mass
spectrometer at National Chung Hsing University (Taiwan).
X-ray photoelectron spectroscopy was performed on a ESCA

Article
Organometallics, Vol. 29, No. 17, 2010 3911
Products5,72 6-8,73 9,74 10,75 11,69 12,76 13,77 15,78 16,76 17-22,72
23-26,79 and 27-2880 were indentified by comparison of NMR
data with those in the literature; yields and regioselectivity were
determined by integration ratio using 1,3,5-trimethoxylbenzene
as internal standard or after purification with column chroma-
tography on silica gel.
(E)-Butyl 3-(3,4,5-trimethoxyphenyl)acrylate (14). A white
solid. 1H NMR (300 MHz, CDCl3, 25 °C, TMS): δ 0.92 (t,
3J(H,H) = 7.5 Hz, 3H, CH3CH2), 1.40 (m, 2H, CH2CH3), 1.65
(m, 2H, CH2CH2CH2), 3.84 (s, 3H, p-OCH3), 3.85 (s, 6H, m-
OCH3), 4.17(t, 3J(H,H) = 6.6 Hz, 2H, OCH2), 6.31(d, 3J(H,H) =
8.1 Hz, 1H, CdCHCO), 6.71 (s, 2H, Ar-H), 7.56 (d, 3J(H,H) =
8.1 Hz, 1H, CCHdCH). 13C{1H} NMR (75 MHz, CDCl3, 25 °C,
TMS): δ 13.7 (CH2CH3), 19.1 (CH2CH3), 30.7 (CH2CH2CH2),
55.9 (m-OCH3), 60.8 (p-OCH3), 64.3 (OCH2), 105.0 (Ar-CH),
117.4 (CdCHCO), 129.8 (Ar-C), 139.9 (p-COCH3), 144.4 (CCHd
CH), 153.3 (m-COCH3), 166.9 (CdO). HRMS (EI): calcd
C16H22O5 294.1467; found 294.1458.
Sequential Heck/Heck Coupling. A Schlenk tube was charged
with 4-bromochlorobenzene (1.0 mmol), n-butyl acrylate or
4-methyoxylstyrene (1.4 mmol), anhydrous sodium acetate
(1.1 mmol), cis-4b (20.6 mg, 3.0 mmol %), and TBAB (2 g).
The mixture was heated at 140 °C for 6 h. It was then allowed to
cool to room temperature, styrene (160.9 μL, 1.4 mmol) was
added, and the mixture was heated to 140 °C for another 12 h.
The workup procedure was similar to that for the Heck reaction.
The residue was then purified by column chromatography on
silica gel to give the desired product. Products 2970 and 3071 were
characterized by comparison of NMR data with those in the
literature.
to 140 °C for another 12 h. The workup procedure was similar to
that for the Heck reaction. The residue was then purified by
column chromatography on silica gel to give the desired pro-
duct. Product 31 was characterized by comparison of NMR
data with those in the literature.81
X-ray Diffraction Studies. For compounds 3a, 3b, and trans-4,
data were collected at 150(2) K on a Bruker APEX II equipped
with a CCD area detector and a graphite monochromator
˚
utilizing Mo KR radiation (λ = 0.71073 A). The unit cell para-
meters were obtained by least-squares refinement. Data collec-
tion and reduction were performed using the Bruker APEX2
and SAINT software.82 Absorption corrections were performed
using the SADABS program.83 Compounds 8 and 9 were
collected at 110(2) K on an Xcalibur Oxford Diffraction dif-
fractometer equipped with a Sapphire-3 CCD area detector at
National Chung Hsing University (Taiwan). Graphite-mono-
˚
chromatized Mo KR radiation was used (λ = 0.71073 A). Data
collection and reduction were performed using the Oxford
Diffraction CrysAlisPro software.84 All the structures were
solved by direct methods and refined by full-matrix least-
squares methods against F2 with the SHELXTL software
package.85 All non-H atoms were refined anisotropically. All
H-atoms in 3a, 3b 0.5C4H8O, trans-4a, and 8 and those on C22
3
in 9 were fixed at calculated positions and refined with the use of
a riding model. H atoms in 9, except those on C22, were located
in the electron density map and freely refined. Crystallographic
data are listed in Table 1. CCDC-755879 (3a), -755880
(3b 0.5C4H8O), -755881 (trans-4a), -764706 (8), and -764707
3
(9) 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.
Sequential Suzuki/Heck Coupling. A Schlenk tube was charged
with phenylboronic acid (1.3 mmol), K3PO4 H2O (2.0 mmol),
3
and TBAB (2 g) and then placed in a preheated oil bath at
100 °C. 4-Bromochlorobenzene (1 mmol) was then added. The
mixture was heated at 100 °C for 6 h. It was then allowed to cool
to room temperature. 4-Methyoxylstyrene (1.4 mmol) and
NaOAc (1.1 mmol) were added, and the mixture was heated
Acknowledgment. We are grateful to the National
Science Council of Taiwan for financial support of this
work. We also thank the National Center for High-
performance Computing of Taiwan for computing time
and financial support of the Conquest software.
(72) Wang, L.; Li, H.; Li, P. Tetrahedron 2009, 65, 364.
(73) Yasuda, M.; Isami, T.; Kubo, J.; Mizutani, M.; Yamashita, T.;
Shima, K. J. Org. Chem. 1992, 57, 1351.
(74) Martin, V.; Blakey, S. Tetrahedron Lett. 2008, 49, 6800.
(75) Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S. L. J.
Am. Chem. Soc. 2005, 127, 4685.
Supporting Information Available: Full crystallographic data
for all the structures are provided as a CIF file. HMBC spectrum
of 3a and additional crystallographic data and graphics of 3a
and 3b. This material is available free of charge via the Internet
at http://pubs.acs.org.
(76) Andappan, M. M. S.; Nilsson, P.; Larhed, M. Mol. Diversity
2003, 7, 97.
(77) Martinez, R.; Voica, F.; Genet, J.-P.; Darses, S. Org. Lett. 2007,
9, 3213.
(78) Feuerstein, M.; Doucet, H.; Santelli, M. Synlett 2001, 2001,
1980.
(79) Mino, T.; Shirae, Y.; Sasai, Y.; Sakamoto, M.; Fujita, T. J. Org.
(81) Thimmaiah, M.; Zhang, X.; Fang, S. Tetrahedron Lett. 2008, 49,
5605.
(82) APEX2 and SAINT; Bruker AXS Inc.:Madison, WI, 2007.
€
(83) Sheldrick, G. M. SADABS; University of Gottingen, Germany,
1996.
Chem. 2006, 71, 6834.
(80) Feuerstein, M.; Doucet, H.; Santelli, M. J. Org. Chem. 2001, 66,
5923.
(84) CrysAlisPro; Oxford Diffraction Ltd.: Abingdon, England, 2009.
(85) Sheldrick, G. Acta Crystallogr. 2008, A64, 112.