Modular chelated palladium diaminocarbene complexes: Synthesis, characterization, and optimization of catalytic Suzuki-Miyaura cross-coupling activity by ligand modification

Article abstract of DOI:10.1021/om050786f

A general, two-step procedure is reported for the modular synthesis of a series of palladium complexes of chelating Chugaev-type diaminocarbene ligands via metal-templated addition of hydrazines to alkylisocyanides. This method afforded high yields of (dicarbene)palladium dihalide complexes with methyl, isopropyl, cyclohexyl, and tert-butyl substituents by addition of hydrazine to the corresponding alkylisocyanide, and analogous backbone-substituted complexes were prepared by palladium-templated addition of methylhydrazine to methylisocyanide. The complexes were fully characterized by IR, ¹H NMR, and ¹³C NMR spectroscopies. X-ray crystallographic analyses of four (dicarbene)palladium dibromide complexes revealed structural similarities with complexes of imidizole-based N-heterocyclic carbenes (NHCs), characterizing these chelating ligands as strongly donating, resonance-stabilized diaminocarbenes. To examine whether these ligands are amenable to cross-coupling catalyst optimization via systematic ligand modification, a set of 10 (dicarbene)palladium dihalide complexes was tested as precatalysts in the Suzuki-Miyaura coupling of bromobenzene with phenylboronic acid. Substantial variations in catalytic activity were observed, and a backbone-substituted palladium dicarbene complex derived from methylhydrazine was identified as the most active precatalyst. Catalyst activities did not correlate with ligand sterics, and subtle electronic perturbation of carbene donor ability by the alkyl groups is proposed to be the origin of the differences in activity. The optimized catalyst was found to give high yields in Suzuki-Miyaura cross-couplings of electron-poor aryl chlorides and a range of aryl bromides, although elevated temperatures (120°C) were necessary. Coupling reactions conducted open to air showed little formation of homocoupling byproduct and minimal loss of yield in most cases, identifying the optimized system as a rare example of an air-tolerant Suzuki-Miyaura catalyst. This study highlights the importance of a modular ligand design in fine-tuning the activity of a homogeneous catalyst.

Full text of DOI:10.1021/om050786f

Organometallics 2006, 25, 491-505
491
Modular Chelated Palladium Diaminocarbene Complexes:
Synthesis, Characterization, and Optimization of Catalytic
Suzuki-Miyaura Cross-Coupling Activity by Ligand Modification
†
†
‡
,†
Adriana I. Moncada, Sudhakar Manne, Joseph M. Tanski, and LeGrande M. Slaughter*
Departments of Chemistry, Oklahoma State UniVersity, Stillwater, Oklahoma 74078, and
Vassar College, Poughkeepsie, New York 12604
ReceiVed September 11, 2005
A general, two-step procedure is reported for the modular synthesis of a series of palladium complexes
of chelating Chugaev-type diaminocarbene ligands via metal-templated addition of hydrazines to
alkylisocyanides. This method afforded high yields of (dicarbene)palladium dihalide complexes with
methyl, isopropyl, cyclohexyl, and tert-butyl substituents by addition of hydrazine to the corresponding
alkylisocyanide, and analogous backbone-substituted complexes were prepared by palladium-templated
1
addition of methylhydrazine to methylisocyanide. The complexes were fully characterized by IR, H
NMR, and 13C NMR spectroscopies. X-ray crystallographic analyses of four (dicarbene)palladium
dibromide complexes revealed structural similarities with complexes of imidizole-based N-heterocyclic
carbenes (NHCs), characterizing these chelating ligands as strongly donating, resonance-stabilized
diaminocarbenes. To examine whether these ligands are amenable to cross-coupling catalyst optimization
via systematic ligand modification, a set of 10 (dicarbene)palladium dihalide complexes was tested as
precatalysts in the Suzuki-Miyaura coupling of bromobenzene with phenylboronic acid. Substantial
variations in catalytic activity were observed, and a backbone-substituted palladium dicarbene complex
derived from methylhydrazine was identified as the most active precatalyst. Catalyst activities did not
correlate with ligand sterics, and subtle electronic perturbation of carbene donor ability by the alkyl
groups is proposed to be the origin of the differences in activity. The optimized catalyst was found to
give high yields in Suzuki-Miyaura cross-couplings of electron-poor aryl chlorides and a range of aryl
bromides, although elevated temperatures (120 °C) were necessary. Coupling reactions conducted open
to air showed little formation of homocoupling byproduct and minimal loss of yield in most cases,
identifying the optimized system as a rare example of an air-tolerant Suzuki-Miyaura catalyst. This
study highlights the importance of a modular ligand design in fine-tuning the activity of a homogeneous
catalyst.
6
Introduction
catalytic application of diaminocarbene ligands, primarily “N-
heterocyclic carbenes” (NHCs) derived from imidazolium
Access to new ligand types is a critical component of the
design of novel homogeneous transition metal catalysts. Because
drastic changes in catalytic activity can result from apparently
7
cations. Diaminocarbenes function as exceptionally strong
σ-donors to late transition metals, with binding energies
exceeding those of the most basic phosphines by as much as
0 kcal/mol, and they lack the electrophilic reactivity of
Fischer-type carbenes. The high catalytic activities achieved
by a number of NHC-based catalysts have been attributed in
part to this strong donor ability, in combination with the unique
steric demands and enhanced thermal stability of these
ligands compared with phosphines. Catalyst advances with
particular promise for synthetic applications have been achieved
using NHC ligands in ruthenium-catalyzed ring-closing olefin
1
minor modifications of ligand structure, ligand designs that
8
1
allow systematic variation of steric and electronic properties
are particularly valuable. Notable examples of such modular
ligand designs include salens, which have been structurally
modified to optimize a range of synthetically useful catalytic
6
8
,9
10
2
3
asymmetric reactions, and R-diimines, which have been shown
to engender substantial changes in the activity of late-metal
olefin polymerization catalysts upon modular variation of ligand
electronic properties.4
Since Arduengo’s discovery of stable imidazol-2-ylidenes in
991,5 substantial efforts have focused on the design and
(4) Popeney, C.; Guan, Z. Organometallics 2005, 24, 1145-1155.
1
(
5) Arduengo, A. J.; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991,
*
To whom correspondence should be addressed. E-mail:
113, 361-363.
lms@chem.okstate.edu.
(6) Bourissou, D.; Guerret, O.; Gabba ¨ı , F.; Bertrand, G. Chem. ReV. 2000,
100, 39-91.
†
Oklahoma State University.
Vassar College.
‡
(7) (a) Herrmann, W. A.; K o¨ cher, C. Angew. Chem., Int. Ed. Engl. 1997,
36, 2162-2187. (b) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41,
1290-1309.
(8) Huang, J.; Schanz, H.-J.; Stevens, E. D.; Nolan, S. P. Organometallics
1999, 18, 2370-2375.
(9) Dorta, R.; Stevens, E. D.; Scott, N. M.; Costabile, C.; Cavallo, L.;
Hoff, C. D.; Nolan, S. P. J. Am. Chem. Soc. 2005, 127, 2485-2495.
(10) Huang, J.; Stevens, E. D.; Nolan, S. P.; Peterson, J. L. J. Am. Chem.
Soc. 1999, 121, 2674-2678.
(1) For an example involving carbene ligands, see: Trnka, T. M.;
Morgan, J. P.; Sanford, M. S.; Wilhelm, T. E.; Scholl, M.; Choi, T.-L.;
Ding, S.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 2546-
558.
2
(
2) (a) Katsuki, T. Synlett 2003, 281-297. (b) Yoon, T. P.; Jacobsen, E.
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169-1203.
(
1
1
0.1021/om050786f CCC: $33.50 © 2006 American Chemical Society
Publication on Web 12/15/2005

492 Organometallics, Vol. 25, No. 2, 2006
Moncada et al.
to metals. Metalation via the free dicarbene can be accomplished
2
6,27
in some cases,
but problems can result from reaction of the
strong base required to deprotonate the imidazolium precursor
2
8
with acidic protons on linking groups. The free carbenes are
also very air-sensitive and are usually formed in moderate yields
2
6,29
at best.
Chelating bis(NHC) ligands have been prepared by
metal-mediated cleavage of tethered enetetramines in a few
3
0
31
cases, including an early report by Lappert and co-workers,
but this approach is limited by the need for a previously
Figure 1. Chelating NHC (A) and Chugaev carbene (B) ligands,
and a monodentate “open” diaminocarbene ligand (C).
32
synthesized enetetramine precursor. In situ treatment of a bis-
imidazolium salt with a base in the presence of a metal precursor
has also been employed, but yields are variable, and in some
metathesis,1
0,11
palladium-catalyzed Suzuki-Miyaura cross-
3
3
coupling,1
2-17
nickel-catalyzed cycloaddition, palladium-
18
2
instances the bis(NHC) coordination mode (i.e., bridging vs κ -
19
catalyzed aerobic alcohol oxidation, and platinum-catalyzed
hydrosilylation.20 All of these examples employ monodentate
NHC ligands, which can be readily modified at the nitrogen
substituent but have otherwise limited potential for systematic
variation.
3
4
coordination) has been difficult to control. Direct reaction of
metal acetates with imidazolium salts is an attractively simple
metalation route, but it appears to be generally applicable only
for palladium and often requires harsh temperatures for bidentate
NHCs (130-170 °C).
effective at milder temperatures (refluxing THF) for benzan-
2
1,35
This method has been reported to be
Chelating dicarbene ligands offer greater modularity in
principle, because the chelate backbone can be modified to vary
36
nulated bidentate bis(NHC) ligands. The silver-carbene trans-
metalation strategy introduced by Wang and Lin37 has been
successfully extended to chelating carbene ligands in a few
21,22
bite angle or introduce chirality.
In practice, however,
chelating carbenes (e.g., A, Figure 1) have not been as widely
investigated in catalysis as monodentate NHCs,2
3-25
perhaps
2
2,28,38
cases,
but this method depends on the formation of a
due to a lack of general synthetic procedures for their attachment
suitable silver carbene precursor and sometimes results in bis-
2
8
(NHC)-bridged bimetallic complexes. To realize the catalytic
(11) (a) Weskamp, T.; Schattenmann, W. C.; Spiegler, M.; Herrmann,
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39
modular variation would be advantageous.
(
12) Zhang, C.; Huang, J.; Trudell, M. L.; Nolan, S. P. J. Org. Chem.
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we found an intriguing starting point in “Chugaev-type”
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(
coupling reactions, see: Herrmann, W. A.; Elison, M.; Fischer, J.; Kocher,
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(
25) Chelating NHC ligands have been successfully employed in the
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2
47. Rh-catalyzed transfer hydrogenation: (e) Albrecht, M.; Crabtree, R.
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6
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Modular Palladium Diaminocarbene Complexes
Organometallics, Vol. 25, No. 2, 2006 493
carbenes (B, Figure 1),40,41 a relatively unexplored class of
chelate ligands prepared by metal-templated addition of hydra-
zines or other bifunctional nucleophiles to cis-coordinated
isocyanides. These ligands are historically interesting because
Chugaev’s original platinum complexes predate Fischer’s
seminal report of metal carbenes42 by 49 years.43 However, they
As an entry into modular dicarbene-ligated catalysts with
potential catalytic utility, we have explored the synthesis of a
series of palladium Chugaev carbene complexes derived from
bulky alkylisocyanides. Reported examples of Chugaev-type
carbene ligands have been prepared almost exclusively from
methylisocyanide, with the exception of a platinum-bound
41
5
1,52
example formed from tert-butylisocyanide
and two gold
were not recognized as carbene complexes until 1970, when
spectroscopic studies by Rouschias and Shaw44 and crystal-
complexes derived from phenyl- and p-tolylisocyanides.56
Palladium-NHC catalysts for the Suzuki-Miyaura cross-
lographic studies by Burke, Balch, and Enemark45 established
their chelating structures. These ligands contain nitrogen-
stabilized carbene moieties analogous to those in imidazole-
based NHCs, suggesting that they might possess comparably
strong donor properties that could be favorable for catalyst
development. Indeed, the structurally similar “open” diami-
nocarbenes first prepared by Alder and co-workers (C, Figure
1
2-17
coupling reaction
have shown high activity and broad
substrate scope comparable to those achieved by the best
6
0-64
phosphine-based systems,
and therefore we viewed this
reaction as ideal for testing our objective of optimizing catalytic
activity through variation of the ligand structure. We have
published a preliminary communication demonstrating that a
palladium Chugaev carbene complex readily prepared from
cyclohexylisocyanide is an effective precatalyst for Suzuki-
Miyaura coupling of a range of aryl bromides, with the
advantage of operating under air without significant loss of yield
4
6
1
)
have been shown to be even stronger donor ligands than
47
NHCs. The large variety of available metal-isocyanide com-
4
8
plexes suggests that this synthetic route could potentially be
generalized to a range of catalytically important metals, and
this is supported by reports of chelating Chugaev-type carbenes
prepared from isocyanide complexes of Pt(II),
Fe(II),54 Ru(II), and Au(III). In addition, similar chelating
6
5
in many cases. We now report a general, two-step procedure
for the synthesis of a series of palladium complexes of Chugaev-
type carbene ligands from alkylisocyanides. Preparation of a
series of these chelating ligands from different isocyanides and
hydrazines has not been previously reported for any metal. The
reported method provides rapid access to a small catalyst
41,49-52
45,53
Pd(II),
55
56
carbene ligands have been synthesized from diamines such as
,6-diaminopyridine57 and 1,2-ethylenediamine, indicating that
58
2
“
library” without the need for air-sensitive techniques. We find
the metal-templated synthetic strategy could possibly be ex-
tended to a range of structurally diverse bis-carbene ligands,
including chiral examples. Assembly of chelating carbene
ligands directly at the metal center could substantially reduce
the number of synthetic steps needed to introduce desired
structural elements.59
that ligand modification results in substantial changes in the
activity of these complexes as Suzuki-Miyaura catalysts, and
we have identified backbone-substituted Chugaev carbenes
derived from methylhydrazine as the most promising for the
formation of highly active, air-tolerant Suzuki-Miyaura cata-
lysts. The convenient synthesis of this series of catalysts provides
a promising starting point for the design of tunable catalysts
containing modular, structurally diverse chelating carbene
ligands.
(40) The English transliteration “Chugaev” is cited in Chemical Abstracts
and most English language journals, whereas “Tschugajeff” is employed
in the German literature.
(
41) (a) Tschugajeff, L.; Skanawy-Grigorjewa, M. J. Russ. Chem. Soc.
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80-581.
43) Numerous examples of monodentate aminocarbenes prepared from
1
Results
(
Syntheses. The two-step procedure we reported for the
synthesis of a palladium Chugaev carbene complex from
cyclohexylisocyanide proved readily adaptable to commer-
cially available isopropylisocyanide and tert-butylisocyanide.
For comparison, we also used this method to prepare the
previously reported methylisocyanide-derived complexes.4
5
(
6
5
isocyanides are known. For a review, see: Michelin, R. A.; Pombeiro, A.
J. L.; Guedes da Silva, M. F. C. Coord. Chem. ReV. 2001, 218, 75-112.
(
44) Rouschias, G.; Shaw, B. L. Chem. Commun. 1970, 183.
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5,49
9
2, 2555-2557.
(
46) (a) Alder, R. W.; Allen, P. R.; Murray, M.; Orpen, A. G. Angew.
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F. E.; Langenhahn, V.; Meier, N.; L u¨ gger, T.; Fehlhammer, W. P. Chem.
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of these NH-containing carbenes into a tetradentate chelating carbene at Pt
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T.; Le Van, D. Angew. Chem., Int. Ed. 2005, 44, 3759-3763. For a review
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E. Chem. Commun. 1997, 1513-1514.
(
47) Denk, K.; Sirsch, P.; Herrmann, W. A. J. Organomet. Chem. 2002,
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49, 219-224.
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1
1
2, 193-233. (e) Singleton, E.; Oosthuizen, H. E. AdV. Organomet. Chem.
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(
49) Rouschias, G.; Shaw, B. L. J. Chem. Soc. A 1971, 2097-2104.
(
50) Butler, W. M.; Enemark, J. H.; Parks, J.; Balch, A. L. Inorg. Chem.
(60) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1998, 37, 3387-
1
973, 12, 451-457.
51) Lai, S.-W.; Cheung, K.-K.; Chan, M. C.-W.; Che, C.-M. Angew.
Chem., Int. Ed. 1998, 37, 182-184.
52) Lai, S.-W.; Chan, M. C. W.; Wang, Y.; Lam, H.-W.; Peng, S.-M.;
Che, C.-M. J. Organomet. Chem. 2001, 617-618, 133-140.
3388.
(
(61) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020-
4028.
(62) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998,
120, 9722-9723.
(63) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L. J. Am.
Chem. Soc. 1999, 121, 9550-9561.
(64) (a) Walker, S. D.; Barder, T. E.; Martinelli, J. R.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2004, 43, 1871-1876. (b) Barder, T. E.; Walker,
S. D.; Martinelli, J. R.; Buchwald, S. L. J. Am. Chem. Soc. 2005, 127,
4685-4696.
(65) Moncada, A. I.; Khan, M. A.; Slaughter, L. M. Tetrahedron Lett.
2005, 46, 1399-1403.
(
(53) Butler, W. M.; Enemark, J. H. Inorg. Chem. 1971, 10, 2416-2419.
(54) Balch, A. L.; Miller, J. J. Am. Chem. Soc. 1972, 94, 417-420.
(55) Doonan, D. J.; Balch, A. L. Inorg. Chem. 1974, 13, 921-927.
(56) Us o´ n, R.; Laguna, A.; Villacampa, M. D.; Jones, P. G.; Sheldrick,
G. M. Dalton 1984, 2035-2038.
(
(
57) Balch, A. L.; Parks, J. E. J. Am. Chem. Soc. 1974, 96, 4114-4121.
58) Fehlhammer, W. P.; Bliss, T.; Sperber, W.; Fuchs, J. Z. Naturforsch.
B 1994, 49, 494-500.

4
94 Organometallics, Vol. 25, No. 2, 2006
Scheme 1. Synthesis of Chelating Palladium Diaminocarbene Complexes from Hydrazine
Moncada et al.
Scheme 2. Synthesis of Palladium Diaminocarbene Complexes from Methylhydrazine
Aqueous solutions of [Pd(CNR)4]Cl2, prepared in situ by
reaction of PdCl2 with 4 equiv of alkylisocyanide in the presence
of excess KCl, were treated with excess hydrazine hydrate to
give yellow solutions of cationic complexes 1a-d (Scheme 1).
Complexes of this type, bearing two isocyanide ligands and a
deprotonated form of the dicarbene ligand that is formally a
carbene-imidoyl chelate, have been previously reported as the
in these solvents and somewhat soluble in CH3CN. The
dibromide complexes are generally more soluble than the
corresponding dichloride complexes.
A similar procedure using methylhydrazine and methyliso-
cyanide led to palladium complexes 1e, 2e, and 3e (Scheme 2),
containing Chugaev carbene ligands with methyl-substituted
backbones. The platinum analogues of 1e and 2e were previ-
first species isolated in syntheses of platinum4
9,50,52
and gold
56
49,50
ously reported by Balch and co-workers.
Attempts to prepare
Chugaev-type carbene complexes as well as the known pal-
ladium complex 1a.45,49 Precipitation of 1a-d as yellow or
orange solids was achieved by addition of excess LiClO4. The
only parameter that required significant adjustment in order to
optimize yields was the amount of LiClO4, which varied from
analogous complexes from methylhydrazine and bulkier alkyl-
isocyanides failed, as the cationic complex 1 either did not form
or could not be precipitated from solution. Efforts to prepare
dicarbene complexes from 2,6-dimethylphenylisocyanide and
hydrazine were also unsuccessful, leading to no apparent
reaction in water or uncharacterizable solids in alcoholic
solvents. Possible reasons for the failure to form carbene
complexes in this case are the insolublity of the arylisocyanide
8
equiv for 1b to 4 equiv for 1d. The procedure for 1c (R )
Cy) differed slightly, as the chloride salt precipitated im-
mediately upon addition of hydrazine. In this case the anion
exchange was accomplished by washing the solid with aqueous
LiClO4. To obtain reproducibly pure products in subsequent
transformations, it was necessary to recrystallize 1a, 1b, and
in H O and the known preference for formation of the
2
bis(isocyanide) palladium dihalide complexes over the tetrakis-
(isocyanide) palladium complexes when the less nucleophilic
4
8a,59c
1
d from Et2O/CH3CN or Et2O/CH3Cl, and the reported yields
arylisocyanides are employed.
in trans isocyanide ligands that are incapable of undergoing
chelative hydrazine addition.
The latter effect could result
(Scheme 1) are for recrystallized product for all complexes
6
6
except 1c. Attempts to use solutions of 1a-d in subsequent
reactions without isolation of the complex led to products with
significant impurities.
Spectroscopic Characterization. The conversion of precur-
sor complexes 1a-e into dihalide complexes 2a-e and 3a-e
is conveniently monitored by observing the disappearance of
(Dicarbene)palladium dihalide complexes were sought as
potential Suzuki cross-coupling precatalysts. Both dichloride
the two characteristic isocyanide CtN stretching bands in the
(
2a-d) and dibromide complexes (3a-d) were readily prepared
-1
2
210-2260 cm region of the IR spectra (Table 1). In addition,
by addition of 3 M HCl or HBr, either directly to the solid
all of the dicarbene complexes exhibit two to four N-H
compound (1a) or to an acetonitrile solution (1b-d) (Scheme
-1
stretches in the 3000-3500 cm range and two or three bands
1
). Reduction of solvent volume, followed by addition of Et2O
-1
corresponding to CdN stretching in the 1520-1600 cm range.
in all cases except 2a and 3a, allowed precipitation of analyti-
cally pure 2 and 3, which were isolated in good to excellent
yields. This procedure appears superior to the original syntheses
of 2a, for which solubility problems were cited and yields were
These assignments are consistent with IR spectral data reported
for the original methylisocyanide-derived platinum Chugaev
49
carbene complexes.
1
The most distinctive features of the H NMR spectra of the
45,49
not reported.
The use of larger alkyl isocyanides significantly
palladium dicarbene complexes are the ligand N-H resonances,
improved the solubilities of these complexes. The parent
Chugaev carbene complexes 2a and 3a dissolve with difficulty
and only in polar aprotic solvents such as DMSO, DMF, and
DMA, whereas the bulkier dihalide complexes are very soluble
(
66) (a) Hahn, F. E.; L u¨ gger, T. J. Organomet. Chem. 1994, 481, 189-
93. (b) Hahn, F. E.; L u¨ gger, T.; Beinhoff, M. Z. Naturforsch. B 2004, 59,
196-201.
1

Modular Palladium Diaminocarbene Complexes
Organometallics, Vol. 25, No. 2, 2006 495
Table 1. Selected IR Spectral Data for Palladium Diaminocarbene Complexesa,b
compound
ν(NH)
ν(CtN)
ν(CdN)
precursors (1)
1
1
1
1
1
a
b
c
d
e
3452, 3439, 3340
3458, 3412, 3300
3381, 3157
3464, 3436, 3426
3465, 3355
2251, 2241
2230, 2218
2220, 2210
2225, 2210
2255, 2243
1582, 1531
1570, 1536
1572, 1539
1570, 1523
1582, 1522
dihalides (2, 3)
2
3
2
3
2
3
2
3
2
3
a
a
b
b
c
3362, 3205, 3142, 3085
3338, 3186, 3135, 3066
3327, 3194, 3119, 3089
3327, 3192, 3121, 3092
3320, 3177, 3115, 3074
3282, 3181, 3124, 3086
3323, 3309, 3274
3324, 3288, 3265, 3194
3317, 3293, 3256
3295, 3262, 3186
1601, 1529
1597, 1530
1603, 1504
1598, 1516
1592, 1501
1586, 1510
1572, 1512
1571, 1513
c
d
d
e
1591, 1540, 1506
1593, 1544, 1508
e
a
Collected from Nujol mulls, frequencies in cm-1. b Full IR spectral data are compiled in the Supporting Information.
which appear in the δ 4.5-11.2 range (Table 2). For cationic
NMR spectrum of backbone-substituted analogue 1e, which
1
complexes 1a-d, room-temperature H NMR spectra in CD3CN
shows coupling between the two more upfield methyl peaks
1
or CD2Cl2 exhibit two broad N-H signals in a 2:1 ratio (e.g.,
and the terminal N-H groups. However, a H COSY experiment
1b, 1d, Table 2), suggesting a fluxional structure with averaged
with isopropyl-substituted complex 1b revealed cross-peaks
signals for the “terminal” N-Hb and N-Hc groups. For 1b,
cooling to -70 °C in CD2Cl2 revealed three broad but distinct
N-H peaks, indicating that the Hb/Hc exchange is slowed at
low temperature. Similar observations were reported for the
platinum analogue of 1a.50 Given that the conjugate acid forms
of Chugaev-type carbene ligands (e.g., 2, 3) are known to be
subject to deprotonation at the “internal”, hydrazine-derived
i
between the more downfield Pr C-H signal and the terminal
N-H peak, establishing that the R1/R2 chemical shift assign-
ments of 1b are reversed relative to the methyl-substituted
1
complexes. H NMR assignments for the alkyl resonances of
1
c and 1d are made assuming that the pattern observed for 1b
applies for alkyl groups larger than methyl. For the dihalide
complexes 2a-e and 3a-e, the R1 chemical shifts are between
those observed for the dicarbene and isocyanide alkyl groups
of the corresponding cation 1a-e in most cases. For methyl-
hydrazine-derived complexes 2e and 3e, the methyl resonance
that does not show coupling to an N-H group is assigned to
the backbone methyl group (R3).
5
7
N-Ha positions, reversible protonation/deprotonation of the
internal nitrogens is a likely mechanism for the observed N-H
exhange (Scheme 3). This exchange occurs even in carefully
dried CD3CN or CD2Cl2, suggesting that it is catalyzed by
1
minute traces of H2O or acid. However, H NMR spectra of
a-d acquired in undried DMSO-d6 display three distinct N-H
1
signals that are much less broad than those observed in other
solvents, indicating slow N-H exchange. We postulate that the
propensity of DMSO to form hydrogen bonds with the internal
N-H groups of these ligands (vide infra) inhibits the exchange
process. Methylhydrazine-derived complex 1e cannot undergo
the proposed exchange process, and it displays two N-H peaks
in both CD3CN and DMSO-d6. No N-H exchange is evident
for the palladium dihalide complexes 2a-e and 3a-e, which
contain the protonated form of the dicarbene ligand. Two sharp
N-H resonances are observed for all dihalide complexes except
backbone-substituted complexes 2e and 3e, which show three
signals. The upfield N-H signals appearing in the δ 7.6-8.1
The fluxionality of cationic complexes 1a-d is also apparent
in their C NMR spectra (Table 3). No signals for the carbene
13
or imidoyl carbons are apparent in room-temperature spectra,
and again only two sets of alkyl resonances are observed.
1
3
However, a C NMR spectrum of complex 1d taken at -50
C in CD2Cl2 exhibits sharp signals for the carbene and imidoyl
°
carbons at δ 190.1 and 174.6 as well as two isocyanide
resonances at δ 132.9 and 131.9. In addition, four sets of tert-
butyl resonances can be discerned, indicating a static structure
1
3
on the time scale of the C NMR experiment. The solubilities
of the other cationic complexes in CD2Cl2 are insufficient to
i
13
range exhibit coupling to the R1 R-protons for R1 ) Me, Pr,
obtain low-temperature C NMR spectra. Backbone-substituted
13
and Cy, and therefore the downfield N-H signals (δ 9.9-11.2)
are assigned as the internal N-H groups for all of the palladium
carbene complexes.
complex 1e displays a static room-temperature C NMR
13
spectrum analogous to the low-temperature C NMR spectrum
of 1d. The carbene and imidoyl resonances of 1d and 1e could
not be definitively assigned, but comparison with the carbene
shifts of complexes 2a-e and 3a-e makes it likely that the
more upfield resonances (at δ 174.6 and 172.9, respectively)
1
Two sets of alkyl H NMR signals are observed for cationic
complexes 1a-d, corresponding to the dicarbene terminal alkyl
groups (R1) and the isocyanide alkyl groups (R2). These signals
do not split into four inequivalent sets even under conditions
in which the N-H exchange is slowed (i.e., DMSO, other
13
belong to the carbenes. The carbene C chemical shifts of the
dihalide complexes 2a-e and 3a-e (δ 176-183) are similar
to the value of δ 186 reported by Herrmann and co-workers
1
solvents at low temperature), suggesting that the H chemical
shift differences between R1 or R2 groups on opposite sides of
complexes 1a-d would be very small if the static structure
depicted above Table 2 were attained. Consistent with this, the
static complex 1e displays only one peak for the isocyanide R2
groups. For 1a, the more upfield methyl resonance at δ 2.64 is
ascribed to the dicarbene ligand by analogy with the reported
platinum analogue.50 This assignment is supported by the H
23
for an analogous chelating (bis-NHC)PdI2 complex, supporting
the depiction of the Chugaev-type dicarbene ligands as pos-
sessing similar electronic properties and σ-donor abilities to
6
7
imidazole-based chelating dicarbene ligands.
Structural Characterization. An X-ray crystallographic
analysis of cationic “precursor” complex 1b (Figure 2) supports
1

4
96 Organometallics, Vol. 25, No. 2, 2006
Table 2. 1H NMR Data for Palladium Diaminocarbene Complexesa
Moncada et al.
compound
precursors
solvent
NH
R1
R2, R3
1a
DMSO-d6
10.05 (br s, 1H, Ha), 7.55 (br s,
2.64 (br s, 6H)
3.52 (s, 6H)
1
H, Hb), 5.56 (br s, 1H, Hc)
8.49 (br s, 1H, Ha), 5.10 (br s,
H, Hb,c)
bb
CD3CN
4.19 (sept, 2H, JHH)6.4 Hz, CH),
3
3.70 (sept, 2H, JHH)6.6 Hz,
3
1
3
3
2
1.45 (d, 12H, JHH)6.4 Hz, CH3)
CH), 1.17 (d, 12H, JHH)6.6
Hz, CH3)
3
3
CD2Cl2, 0 °C
7.90 (br s, 1H, Ha), 5.01 (br s,
H, Hb,c)
4.26 (sept, 2H, JHH)6.5 Hz, CH),
3.68 (sept, 2H, JHH)6.6 Hz,
3
3
2
1.50 (d, 12H, JHH)6.5 Hz, CH3)
CH), 1.21 (d, 12H, JHH)6.6
Hz, CH3)
CD2Cl2, -70 °C
DMSO-d6
8.25 (br s, 1H, Ha), 5.99 (br s,
H, Hb), 4.03 (br s, 1H, Hc)
10.15 (br s, 1H, Ha), 6.94 (br s,
H, Hb), 4.78 (br s, 1H, Hc)
10.09 (br s, 1H, Ha), 6.79 (br s,
H, Hb), 4.49 (br s, 1H, Hc)
9.86 (br s, 1H, Ha), 6.40 (br s,
H, Hb), 4.52 (br s, 1H, Hc)
7.02 (br s, 1H, Hb), 5.61 (br s,
H, Hc)
4.21 (m, 2H, CH), 1.46 (br s, 12H,
CH3)
3.64 (m, 2H, CH), 1.14 (br s,
12H, CH3)
3.67 (br s, 2H, CH), 1.12 (br s,
12H, CH3)
3.32 (s, 2H, ipso CH), 1.0-2.2
(unresolved, 40H)
1.36 (s, 18H)
1
4.29 (br s, 2H, CH), 1.42 (d, 12H,
3
1
JHH)6.4 Hz, CH3)
1c
1d
1e
DMSO-d6
4.04 (s, 2H, ipso CH), 1.0-2.2
(unresolved, 40H)
1
DMSO-d6
1.57 (s, 18H)
1
3
DMSO-d6
3.00 (d, 3H, JHH)4.8 Hz), 2.56
3.51 (unresolved, 6H), 3.08 (s,
3H, N2CH3)
3
1
(d, 3H, JHH)4.8 Hz)
dihalides
3
2
3
2
3
2
3
2
3
2
3
a
a
b
b
c
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
10.97 (s, 2H, Ha), 7.80 (m, 2H,
Hb)
11.08 (s, 2H, Ha), 7.77 (m, 2H,
Hb)
11.12 (s, 2H, Ha), 7.57 (d, 2H,
2.83 (d, 6H, JHH)5.1 Hz)
3
2.83 (d, 6H, JHH)5.4 Hz)
3.78 (m, 2H, CH), 1.14 (d, 12H,
JHH)6.4 Hz, CH3)
3.79 (m, 2H, CH), 1.15 (d, 12H,
JHH)6.3 Hz, CH3)
3.53 (br s, 2H, ipso CH), 1.0-2.2
(20H, unresolved)
3.55 (br s, 2H, ipso CH), 1.0-2.0
(20H, unresolved)
3
3
JHH))7.8 Hz, Hb)
11.17 (s, 2H, Ha), 7.59 (d, 2H,
3
3
JHH))8.4 Hz, Hb)
11.15 (s, 2H, Ha), 7.71 (d, 2H,
3
JHH))8.0 Hz, Hb)
c
11.21 (s, 2H, Ha), 7.74 (d, 2H,
3
JHH))7.6 Hz, Hb)
d
d
e
10.37 (s, 2H, Ha), 8.05
1.32 (s, 18H)
(
s, 2H, Hb)
10.41 (s, 2H, Ha), 7.99
s, 2H, Hb)
10.74 (s, 1H, Ha), 7.97 (m,
H, Hb1), 7.84 (m, 1H, Hb2)
1.33 (s, 18H)
(
3
3.11 (d, 3H, JHH)5.6 Hz), 2.81
3.43 (s, 3H, N2CH3)
3.44 (s, 3H, N2CH3)
3
1
(d, 3H, JHH)5.2 Hz)
3
e
10.82 (s, 1H, Ha), 7.91 (m, 1H,
Hb1), 7.79 (m, 1H, Hb2)
3.11 (d, 3H, JHH)5.2 Hz), 2.82
3
(d, 3H, JHH)5.6 Hz)
a
Spectra obtained at 400 MHz, 25 °C, unless otherwise noted. b Alkyl resonances of 1b assigned on the basis of a H COSY experiment (CD3CN, 25 °C).
1
Scheme 3. Proposed N-H Exchange Mechanism for 1a-d
sponding to a double bond and the C(8)-N(2) distance of
.3588(18) Å representing a bond length intermediate between
1
that of a single and a double bond. Significant π-delocalization
in the ligand NCNNCN unit is indicated by these bond lengths
as well as by the planarity of the chelate, which shows a mean
deviation from planarity of only 0.073 Å within the N4C2Pd
unit. The palladium-carbon bond lengths of the chelating ligand
are similar at 2.0219(14) Å for Pd-C(8) and 2.0114(13) Å for
Pd-C(9), suggesting no significant differences in the donor
abilities of the two carbon atoms.
the designation of the ligand as a carbene-imidoyl chelate. Bond
lengths between C(9) and neighboring nitrogens are nearly
identical at 1.326(2) and 1.3294(19) Å to N(4) and N(5),
respectively (Table 4), characterizing a resonance-stabilized
diaminocarbene moiety. However, C(8) exhibits unequal carbon-
nitrogen bond lengths consistent with a formally anionic imidoyl
carbon, with the C(8)-N(3) distance of 1.3069(19) Å corre-
To identify any structural features of (dicarbene)palladium
dihalide complexes that could potentially account for differences
in their catalytic activities (vide infra), we obtained X-ray
structures of complexes of all of the new ligands (Figure 3).
Dibromide complexes 3b-e were employed, because their
superior solubility properties relative to dichlorides 2b-e
allowed the growth of higher quality crystals. Selected structural
parameters of 3b-e are compiled in Table 5, along with
published data for the parent methylisocyanide-derived complex
(67) A possibly closer comparison in terms of carbene substitution pattern
would be the NH,NR-substituted benzannulated heterocyclic carbenes
5
9a-c
reported by Hahn and co-workers,
but no Pd-bound examples are
1
3
known. Pt complexes of these ligands show carbene C NMR signals at δ
67-169, but Pd-bound carbenes typically resonate significantly down-
23,33c
59c
1
field of their Pt congeners.

Modular Palladium Diaminocarbene Complexes
Organometallics, Vol. 25, No. 2, 2006 497
Table 3. 13C NMR Data for Palladium Diaminocarbene Complexesa
compound
precursors
solvent
Pd-C
R1
R2, R3
b
1a
DMSO-d6
CD3CN
132.1 (MeNC)
30.1
29.7
c
i
b
1b
133.7 ( PrNC)
50.7 (CH), 22.5 (CH3,
unresolved)
45.7 (CH), 22.5 (CH3, unresolved)
1
1
c
DMSO-d6
not detected
53.0 (ipso), 31.9, 25.1, 24.3
51.2 (ipso), 31.1, 24.3 (unresolved),
22.0
54.9 (CMe3), 28.9 (CH3)
54.7, 53.4 (CMe3), 28.6, 28.3 (CH3)
(unresolved)
d
CD3CN
CD2Cl2, -50 °C
not detected
190.1, 174.6 (carbene/imidoyl),
60.3 (CMe3), 29.9 (CH3)
59.4, 59.3 (CMe3), 29.7,
29.5 (CH3)
t
1
32.9, 131.9 ( BuNC)
191.7, 172.9 (carbene/imidoyl),
33.0, 130.9 (MeNC)
1
e
DMSO-d6
34.0, 29.7
36.6 (N2CH3), 30.0 (CNCH3), 29.7
(CNCH3)
1
dihalides
2
3
2
3
2
3
2
3
2
3
a
a
b
b
c
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
DMSO-d6
179.0
179.0
176.1
175.9
175.7
175.7
177.0
176.8
30.2
30.6
44.9 (CH), 21.8 (CH3)
45.3 (CH), 21.7 (CH3)
51.3 (ipso), 31.3, 24.7, 23.5
51.3 (ipso), 31.2, 24.7, 23.5
54.4 (CMe3), 28.0 (CH3)
54.8 (CMe3), 28.0 (CH3)
34.2, 30.7
c
d
d
e
182.6, 175.8
182.6, 175.7
38.2 (N2CH3)
38.1 (N2CH3)
e
34.2, 30.7
a
Spectra obtained at 101 MHz, 25 °C, unless otherwise noted. b Carbene resonances not detected. c Alkyl resonances of 1b assigned on the basis of a
1
13
H- C HMQC experiment (CD3CN, 25 °C).
Table 4. Selected Bond Lengths (Å) and Angles (deg) for 1b
Pd-C(8)
2.0219(14)
2.0114(13)
1.3069(19)
1.3588(18)
1.326(2)
1.3294(19)
1.4085(16)
2.0195(15)
2.0391(15)
1.140(2)
Pd-C(9)
C(8)-N(3)
C(8)-N(2)
C(9)-N(4)
C(9)-N(5)
N(3)-N(4)
Pd-C(4)
Pd-C(13)
C(4)-N(1)
C(13)-N(6)
1.148(2)
77.87(6)
94.16(6)
92.79(6)
C(8)-Pd-C(9)
C(8)-Pd-C(4)
C(9)-Pd-C(13)
C(4)-Pd-C(13)
N(3)-C(8)-N(2)
N(4)-C(9)-N(5)
sum of angles around C(8)
sum of angles around C(9)
C(7)-N(2)-C(8)-N(3)
C(7)-N(2)-C(8)-Pd
C(10)-N(5)-C(9)-N(4)
C(10)-N(5)-C(9)-Pd
mean dev from plane N4C2Pd
94.52(6)
117.84(13)
120.14(13)
359.9(2)
359.7(2)
-7.3(2)
176.11(10)
5.8(2)
Figure 2. Molecular structure of 1b, with thermal ellipsoids drawn
at the 50% probablility level.
2
a53 for comparison. Crystallographic data for the carbene
moieties of 3b-e reveal structural similarities with imidazole-
based NHC ligands. The Pd-Ccarbene bond lengths of 1.96-
179.36(11)
0.073 Å
1
.99 Å are very close to those observed in comparable cis-(bis-
23,24
NHC)PdX2 complexes (1.99-2.00 Å).
The Ccarbene-N
lecular steric interference. The only potential structural differ-
ence that can be discerned is a slight shortening of the Ccarbene-
Nterminal distances for 3c and 3d (0.01-0.02 Å) relative to the
other complexes, possibly resulting from a subtle electronic
influence of the larger alkyl groups (vide infra). However, these
distances are still within three standard deviations of the values
for 3b and 3e, and therefore the available data do not permit
meaningful analysis of such minor structural variations.
An unexpected structural feature of the methylhydrazine-
derived complex 3e is the syn configuration of the two methyl
groups adjacent to C(4). Although no other metal dihalide
complexes of the chelating ligand of 3e have been structurally
characterized, the structure of the platinum analogue of the
cationic “precursor” complex 1e has been reported, and it adopts
an anti configuration of these two methyl groups presumably
distances of 1.30-1.33 Å are indicative of resonance-stabilized
diaminocarbenes. These distances are slightly shorter than the
typical range of 1.34-1.37 Å for NHC ligands, implicating a
high degree of π-delocalization within the chelate ligand.
Substantial π-delocalization is also apparent from the small
deviations from planarity (0.015-0.041 Å) observed in the
N4C2Pd units of the complexes. The ligand geometry constrains
the Ccarbene-Pd-Ccarbene bite angles to approximately 80° for
all of the complexes, although the sum of angles around Pd is
still 360° in each case.
No substantial structural differences are evident among the
hydrazine-derived carbene ligands of 2a and 3b-d. The
dicarbene alkyl groups are oriented away from the palladium
center, and they exert no apparent steric influence on the
geometries of the ligand or the palladium coordination plane.
As indicated by torsion angles (Table 5), the bulkier Cy and
5
0
due to steric effects. We have not been able to obtain X-ray
quality crystals of 1e to confirm its structure, but we have
assumed the same configuration observed for the platinum
congener (i.e., that shown in Scheme 2) given that Pd-C bond
lengths are expected to differ little from Pt-C distances. The
t
Bu groups of 3c and 3d are rotated out of the ligand plane
slightly more than the less bulky groups of 2a and 3a, but this
is likely due to crystal-packing interactions rather than intramo-

4
98 Organometallics, Vol. 25, No. 2, 2006
Moncada et al.
Figure 3. Molecular structures of 3b-e, showing hydrogen bonding with solvent molecules. Thermal ellipsoids are drawn at the 50%
probability level. For 3d, the DMSO molecules were modeled as disordered, and only the dominant orientation is shown.
2
Table 5. Selected Bond Lengths (Å) and Angles (deg) for (Dicarbene)PdX Complexes
2
aa,b
3b
3cb
3d
3e
Distances
Pd-Ccarbene
1.948(5)
1.309(6)
1.327(7)
1.9721(15)
1.976(4)
1.329(5)
1.314(5)
1.969(8)
1.970(8)
C(2): 1.962(2)
1
.9771(15)
1.3293(19)
.3294(18)
1.324(2)
.319(2)
C(4): 1.991(2)
C(2): 1.329(3)
C(4): 1.332(3)
C(2): 1.323(3)
C(4): 1.319(3)
1.404(2)
Ccarbene-Ninternal
Ccarbene-Nterminal
1.330(10)
1.330(11)
1.302(10)
1.300(10)
1.401(10)
2.4933(12)
2.5103(13)
1
1
N-N
Pd-X
1.395(8)
2.387(1)
1.3942(17)
2.5029(3)
1.401(7)
2.5127(5)
Br(1): 2.4930(4)
Br(2): 2.4908(4)
2.5194(2)
Angles
C-Pd-C
79.5(3)
79.69(6)
79.8(2)
80.0(3)
80.23(9)
90.182(9)
360.0(1)
C(2): 118.4(2)
C(4): 123.79(19)
C(2): 360.0(2)
C(4): 360.0(2)
C(3)-N(3)-C(4): 132.37(19)
C(4)-N(4)-C(5): 132.54(19)
X-Pd-X
94.49(7)
360.0(4)
118.2(4)
93.446(7)
359.74(8)
119.93(13)
93.09(3)
360.1(3)
120.5(4)
91.36(4)
360.11(4)
120.8(7)
121.6(8)
359.8(11)
360.0(11)
sum of angles around Pd
N-C-N(carbene)
1
20.14(13)
360.0(2)
60.0(2)
sum of angles around Ccarbene
other
360.0(4)
359.9(6)
3
Torsion Angles
-4.5
C(R1)- Nterm-Ccarbene-Ninternal
C(R1)- Nterm-Ccarbene-Pd
0c
0c
-2.8(2)
.9(2)
176.67(10)
80.00(11)
6.8(16)
C(2): -0.7(3)
1
-2.7(16)
-167.9(8)
175.9(8)
C(4): 0.3(4)
172.7
C(2): -179.36(15)
C(4): -177.82(17)
1
Mean Deviation from Plane (Å)
0.040 0.015
N4C2Pd
0c
0.041
0.028
a
Data taken from ref 53. b Two halves of molecule related by crystallographic 2-fold rotation axis. c Required by crystallographic symmetry.
preference for the syn isomer observed in 3e indicates that the
terminal methyl group is subject to greater steric repulsions from
the bromide ligand than from the internal methyl group, whereas
the repulsions from the internal methyl group are apparently
more significant when an isocyanide ligand occupies the cis
coordination site. Another possible explanation for the syn

Modular Palladium Diaminocarbene Complexes
Organometallics, Vol. 25, No. 2, 2006 499
Table 6. Hydrogen-Bonding Interactions in Palladium
Carbene X-ray Structures
Table 7. Selection of Optimal Base for the Catalytic
a
Suzuki-Miyaura Cross-Coupling Reaction
D-H‚‚‚A
d(D‚‚‚A)
∠ (DHA)
1
3
b
b
N(4)-H‚‚‚O(1)
N(2)-H‚‚‚O(1)
N(3)-H‚‚‚O(2)
N(2)-H‚‚‚O(1)
N(3)-H‚‚‚O(2)
N(2)-H‚‚‚O(1)
2.9705(16)
2.7808(17)
2.7105(16)
2.761(11)
2.742(10)
2.720(2)
150.9
162.6
158.7
141.0
138.9
141.0
3
d
e
entry
base
K2CO3
Cs2CO3
CsF
yield (%)b
3
1
2
3
4
5
6
7
69
34
73
81
81
45
4
configuration of 3e is that this geometry permits a favorable
hydrogen bond-like interaction between the terminal N-H and
Br(2). However, the long N‚‚‚Br distances of 3e (N(4)‚‚‚Br(2)
K3PO4
K3PO4‚H2O
t
NaO Bu
3
.2098(18) Å; N(1)‚‚‚Br(1) 3.2903(18) Å) indicate that the H‚
none
68
‚
‚Br interactions are weak at best and unlikely to outweigh
a
Reaction conditions: 0.017 mmol of 3b, 1.7 mmol of PhBr, 2.04 mmol
69
steric interactions. Steric strain is apparent in the structure of
e, with the C(3)-N(3)-C(4) and C(5)-N(3)-C(4) angles
distorted to 132.37(19)° and 132.54(19)°, respectively (Table
). However, the carbene NCN unit is only slightly distorted,
of PhB(OH)2, 2.6 mmol of base, DMA, 120 °C, 24 h; reaction times not
3
optimized. b Yields determined by 1H NMR.
base,12,60,62 we first performed base optimization studies. Several
commonly used bases were examined, using the prototypical
coupling of bromobenzene with phenylboronic acid as a
screening reaction (Table 7). Complex 3b, with isopropyl
substituents and bromides as labile ligands, was employed for
these studies because initial screening identified it as a catalyst
with moderately high activity. The most effective reagent was
the mild base K3PO4 (Table 7, entry 4), which has also proved
5
with a N(3)-C(4)-N(4) angle of 123.79(19)°, and the Pd-C
and C-N distances are not signficantly affected. Thus, the donor
ability of the ligand does not appear to be disrupted by the steric
strain.
A common feature observed in the solid-state structures of
the palladium carbene complexes is hydrogen bonding involving
the acidic internal N-H groups. Precursor cation 1b exhibits
64
-
optimal in some of the most active palladium-phosphine and
an unusual hydrogen bond with the ClO4 anion (Figure 2).
1
7
palladium-NHC Suzuki catalysts. Other mild bases such as
The neutral dibromide complexes 3b, 3d, and 3e all display
hydrogen bonding with DMSO solvent molecules. Notably,
DMSO was the only solvent that yielded X-ray quality crystals
of these compounds. The structure of 3c, which was obtained
from a crystal grown from DMF, did not display any hydrogen-
bonding interactions, but the structure of dichloride analogue
71
61
K2CO3 and CsF gave somewhat lower yields (Table 7, entries
1
and 3). The base of choice for in situ generated Pd-NHC
1
2,13
catalysts is Cs2CO3,
but this was found ineffective in our
t
62
system (Table 7, entry 2), as was the stronger base NaO Bu
Table 7, entry 6). One possible explanation for the poor activity
(
using stronger bases is that they could initiate catalyst decom-
position by reaction with ligand NH groups. Very little cross-
coupling occurred in the absence of base (Table 7, entry 7),
reflecting that the base is an essential component of the catalytic
system.
2
c previously reported by us contains hydrogen-bonding DMSO
6
5
molecules. The observed N‚‚‚O distances (2.71-2.97 Å) and
calculated N-H‚‚‚O angles (139-163°) are within the normal
ranges for hydrogen bonds (Table 6), although the hydrogen
bond to ClO4 in 1b is almost in the “weak” category. The
prevalence of these interactions in these structures suggests that
hydrogen bonding plays an important role in solvation and
crystal growth of Chugaev-type carbene complexes containing
N-H groups.
Catalytic Suzuki-Miyaura Cross-Coupling Reactions. The
preceding synthetic studies yielded a convenient and straight-
forward method for the preparation of a series of palladium
dicarbene complexes with different alkyl substituents and halide
ligands. Our goal was to exploit this synthetic flexibility to
optimize the activity of Suzuki-Miyaura cross-coupling cata-
lysts through ligand variation. Our preliminary studies of
-
68
To probe the effect of ligand modification on catalytic
activity, we screened the entire series of (dicarbene)palladium
dihalide complexes obtained from our synthetic studies as
precatalysts for the coupling of bromobenzene with phenylbo-
ronic acid (Table 8). Substantial variations in yield were
observed, ranging from 31% to 95% at 24 h. No clear correlation
between the size of the ligand substituents and catalytic activity
was apparent among the hydrazine-derived complexes 2a-d
and 3a-d. Precatalysts containing secondary alkyl substituents
i
(
Pr: 2b, 3b; Cy: 2c, 3c) displayed somewhat higher activity
than the parent methyl-substituted complexes 2a and 3a, but a
t
65
drastic drop in yield occurred with Bu-substituted precatalysts
cyclohexyl-substituted catalyst 2c indicated that palladium
Chugaev carbene complexes are promising candidates for the
development of air- and moisture-tolerant Suzuki-Miyaura
cross-coupling reactions. Given that drastic variations in catalytic
activity have been observed in palladium Suzuki catalysts
2
d and 3d. Unexpectedly, the methylhydrazine-derived com-
plexes 2e and 3e exhibited the highest activity among all the
precatalysts tested. Our initially studied cyclohexyl-substituted
6
5
catalyst 2c gave the best yields among the hydrazine-derived
complexes. Little difference in activity was observed between
precatalysts containing chloride versus bromide ligands in most
cases, but the dichloride complexes gave slightly better yields
in the most active systems.
containing phosphine6
0,70
13,17
or NHC
ligands upon variation
of ligand substituents, we hypothesized that systematic screening
of the palladium dicarbene catalyst “library” might allow
identification of more active and/or air-stable catalysts.
Because catalyst activities in Suzuki-Miyaura cross-coupling
reactions are often highly sensitive to the nature of the added
Having identified 2e as the most promising precatalyst, we
investigated the functional group tolerance of this catalyst in
Suzuki-Miyaura cross-couplings of aryl bromides and chlorides
as well as its effectiveness in the presence of moisture and air.
Optimal yields were obtained by increasing the amount of
arylboronic acid from 1.2 equiv to 1.5 equiv and using a
(
68) Jeffrey, G. A. An Introduction to Hydrogen Bonding; Oxford
University Press: New York, 1997; p 12.
69) Similar N‚‚‚Br distances were observed for complexes 3b-3d; see
Table S2 (Supporting Information) for relevant data.
70) Kirchhoff, J. H.; Dai, C.; Fu, G. C. Angew. Chem., Int. Ed. 2002,
1, 1945-1947.
(
(
4
(71) Weissman, H.; Milstein, D. Chem. Commun. 1999, 1901-1902.

5
00 Organometallics, Vol. 25, No. 2, 2006
Moncada et al.
Table 8. Optimization of Catalytic Suzuki-Miyaura
arise from “double transmetalation” of the arylboron reagent
Cross-Coupling Activity by Systematic Ligand Variationa
73
followed by biaryl reductive elimination, and this side reaction
might be increased if Pd(0) intermediates in the catalytic cycle74
are diminished by aerobic oxidation to Pd(II). Indeed, substantial
quantities of homocoupling product (up to 11%) have been
observed in Suzuki-Miyaura cross-coupling reactions con-
7
5
ducted under air. Although larger quantities of homocoupling
products were detected in aerobic Suzuki reactions catalyzed
by 2e compared with those performed under nitrogen, the largest
amounts represented less than one catalytic turnover and only
1
% of the total product. Thus, byproduct formation does not
appear to be a significant problem in these aerobic Suzuki-
Miyaura cross-coupling reactions.
entry
precatalyst
R
R′
X
yield (%)b
1
2
3
4
5
6
7
8
9
2a
3a
2b
3b
2c
3c
2d
3d
2e
3e
Me
Me
H
H
H
H
H
H
H
H
Cl
Br
Cl
Br
Cl
Br
Cl
Br
Cl
Br
74
75
80
81
84
78
34
31
95
92
Yield versus Time in Catalytic Suzuki-Miyaura Cross-
Coupling Reactions. To gain further insights into the Suzuki-
Miyaura cross-coupling activities of the most promising cata-
lysts, the time course of the Suzuki coupling of bromobenzene
with phenylboronic acid was monitored for precatalysts 2c and
2e (Figure 4). For both precatalysts, the reaction was essentially
complete (97% yield) within 5 h. Importantly, no induction
periods were observed for coupling reactions using either
catalyst 2c or 2e, and 2e displayed a small amount of product
formation (3%) before heating. Induction periods can indicate
that the catalytically active species is a palladium(0) colloid
formed after initial decomposition of the ligated palladium
i
Pr
Pr
i
Cy
Cy
t
Bu
Bu
t
Me
Me
Me
Me
10
a
Reaction conditions: 0.017 mmol of precatalyst, 1.7 mmol of PhBr,
.04 mmol of PhB(OH)2, 2.6 mmol of base, DMA, 120 °C, 24 h; reaction
times not optimized. Yields determined by H NMR.
2
b
1
7
6
precatalyst. Such Pd(0) colloids are believed to be involved
temperature of 120 °C. The solubility properties of 2e neces-
sitated the use of dimethylacetamide (DMA) as a solvent, and
less polar solvents such as THF could not be used. Using 1
mol % of 2e under these conditions, aryl bromides containing
a range of functional groups underwent cross-coupling with
phenylboronic acid in good to excellent yields (Table 9).
Couplings of electron-poor (entries 1a-3a) and electron-neutral
entry 4a) aryl bromides generally gave 97-99% yield under
N2. Aryl bromides with electron-donating substituents were also
well tolerated, with a 98% yield obtained for 4-bromotoluene
in a number of “ligandless” catalyst systems for Suzuki-
77
Miyaura coupling. The yield versus time plots for precatalysts
2
e and 2c are quite similar, exhibiting maximum activity at the
beginning of the reaction followed by gradual attainment of a
plateau, in contrast to the sigmoidal plots reported for coupling
reactions in which Pd(0) colloids are the catalytic species.76 This
is consistent with an active catalyst that forms immediately and
contains an intact ligand. However, formation of palladium black
was observed at ∼1.5 h for the reaction catalyzed by 2e,
corresponding to the time at which the yield reached ∼90%
and began to level off. Thus, it is possible that colloidal
palladium(0) formed by decomposition of 2e is responsible for
some of the activity in the later stages of the reaction. No
palladium black formation was evident for catalyst 2c within
the 6 h reaction time.
(
(
6
entry 5a) and an 89% yield obtained for 4-bromoanisole (entry
a). The coupling of an ortho-substituted arylboronic acid was
also successfully carried out (entry 7a). Conducting these
reactions open to air in undried solvent led to identical or slightly
lower yields in couplings of electron-poor or electron-neutral
aryl bromides (entries 1b-4b), but substrates containing -Me
or -OMe substituents showed significant drops in yield under
aerobic conditions (entries 5b-7b). Because these substituents
are prone to oxidation at elevated temperatures, it is likely that
the oxidative stability of the substrate rather than that of the
catalyst is the limiting factor in these cases. Overall, the yields
obtained using catalyst 2e in Suzuki-Miyaura cross-coupling
Discussion
The synthetic results demonstrate that metal-templated ad-
dition of hydrazines to isocyanides can be used to prepare a
series of alkyl-substituted palladium dicarbene complexes in
high yields in only two steps, with the added advantages of
employing aqueous solvent under air and not requiring a separate
ligand synthesis. From the perspective of catalyst discovery,
the primary benefit of this approach is that it provides rapid
access to several variations of a modular ligand for catalytic
evaluation. However, the reactions involving methylhydrazine
reactions of aryl bromides are very similar to those previously
reported by us for 2c,65 although 2e provides better yields under
air in some cases (entries 3b, 5b). However, 2e does show
substantial improvements in activity with activated aryl chlorides
relative to 2c. Catalytic cross-coupling reactions of 4-chloroni-
trobenzene, 4-chlorobenzonitrile, and 4-chloroacetophenone with
phenylboronic acid provided yields of 92%, 93%, and 37% with
e (entries 8-10), whereas the same reactions using 2c as a
precatalyst gave respective yields of 79%, 25%, and 20%. Like
c, precatalyst 2e is ineffective in couplings of electron-rich
(
73) (a) Moreno-Ma n˜ as, M.; P e´ rez, M.; Pleixats, R. J. Org. Chem. 1996,
1, 1, 2346-2351. (b) Wong, M. S.; Zhang, X. L. Tetrahedron Lett. 2001,
42, 4087-4089. (c) Lei, A.; Zhang, X. Tetrahedron Lett. 2002, 43, 2525-
2
6
72
2
528.
2
(
74) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483.
aryl chlorides (entries 11, 12).
(
75) Alonso, D. A.; N a´ jera, C.; Pacheco, M. C. J. Org. Chem. 2002, 67,
The amount of biphenyl homocoupling product was measured
in all of the reactions in order to determine whether the use of
aerobic reaction conditions resulted in increased byproduct
formation (Table 9, last column). Homocoupling product can
5
588-5594.
(76) Eberhard, M. R. Org. Lett. 2004, 6, 2125-2128.
(77) (a) Reetz, M. T.; Westermann, E. Angew. Chem., Int. Ed. 2000, 39,
165-168. (b) Leadbeater, N. E.; Marco, M. Org. Lett. 2002, 4, 2973-
2976. (c) Alimardanov, A.; Schmieder-van de Vondervoort, L.; de Vries,
A. H. M.; de Vries, J. G. AdV. Synth. Catal. 2004, 346, 1812-1817. (d)
Bhattacharya, S.; Srivastava, A.; Sengupta, S. Tetrahedron Lett. 2005, 46,
3557-3560.
(
72) The latter example (4-chloroacetophenone + phenylboronic acid)
was not reported in ref 65.

Modular Palladium Diaminocarbene Complexes
Organometallics, Vol. 25, No. 2, 2006 501
Table 9. Functional Group Tolerance and Air/Moisture Tolerance of Suzuki-Miyaura Cross-Coupling Reactions Catalyzed by
Optimized Catalyst 2ea
a
b
Reaction conditions: 0.017 mmol of precatalyst, 1.7 mmol of PhBr, 2.6 mmol of PhB(OH)2, 2.6 mmol of K3PO4, DMA, 120 °C, 24 h. Reactions under
c
1
N2 conducted in anhydrous DMA; reactions under air conducted open to atmosphere in undried DMA. Yields determined by H NMR; isolated yields in
parentheses. TON ) moles biphenyl/moles catalyst; determined by GC. e None detected.
d
Figure 4. Yield versus time plots for Suzuki-Miyaura cross-coupling of bromobenzene with phenylboronic acid catalyzed by (a) 2c and
(b) 2e.
suggest that this synthetic route is probably limited in its ability
to provide carbene ligands with substantial steric bulk adjacent
to the metal coordination sphere. Such bulk is thought to play
an important role in catalytic cross-coupling reactions by
of the base used under catalytic Suzuki-Miyaura conditions,
and this might lead to decomposition and deposition of
palladium black as observed in the later stages of reactions with
catalyst 2e. However, the lack of induction periods or sigmoidal
yield versus time plots, which have been considered as evidence
of catalysis by colloidal palladium in palladacycle Heck coupling
1
6
increasing the rate of product-forming reductive elimination.
Whereas the methylhydrazine-derived precursor complex 1e is
expected to have an anti orientation of one terminal methyl
group that directs it toward the palladium center, the corre-
sponding dibromide complex does not retain this configuration,
apparently due to steric interactions with a halide ligand. Similar
steric interactions within the square coordination plane of
palladium are a likely reason for the failure to form dicarbene
complexes from reactions of methylhydrazine with bulkier
alkylisocyanides.
76
systems, supports catalysis by intermediates with intact though
possibly deprotonated carbene ligands.
The substantial differences in catalytic Suzuki-Miyaura
cross-coupling activity observed for the different palladium
dicarbene complexes are difficult to rationalize on the basis of
structural data. Ligand sterics are unlikely to be responsible, as
the alkyl groups are directed away from the substrate binding
sites, and the catalytic activities of the complexes do not
correlate with alkyl group bulk. No other significant structural
differences in the carbene moieties of the different complexes
were apparent. Ligand electronic effects are a possible origin
Another possible limitation of these dicarbene ligands is the
presence of acidic N-H groups. It is likely that these N-H
functionalities are deprotonated to some degree in the presence

5
02 Organometallics, Vol. 25, No. 2, 2006
Moncada et al.
of the differences in activity. The consensus mechanistic view
To our knowledge, the only other example of a carbene-ligated
Suzuki catalyst reported to function under air is a chelating
pincer-type NHC complex. Considering these precedents, it
is that increased σ-donation from ligands such as electron-rich
phosphines6
0-64
and NHCs
12-17
enhances Suzuki-Miyaura
82
cross-coupling activity by boosting the rate of aryl halide
oxidative addition and preventing ligand dissociation that could
lead to catalyst destruction.16 Increasing the size of an alkyl
group is generally considered to increase the electron density
is probable that chelation of palladium by the bidentate
diaminocarbene ligands enhances the stabilities of the catalysts
under aerobic conditions, perhaps by preventing the formation
of oxidatively unstable low-ligated intermediates. However,
chelation may also limit the activity that can be attained by
these catalysts, given that several studies of highly active
Suzuki-Miyaura catalysts have suggested that formation of
78
at the substituted atom via the inductive effect. Thus, larger
alkyl substituents might be expected to result in more electron-
rich and more strongly σ-donating carbene ligands. This is
consistent with the higher activities of the precatalysts containing
8
6
monoligated palladium intermediates is required for high
i
13,14,16,17,61,87
secondary alkyls ( Pr, Cy) compared with the parent methyl-
catalytic rates.
Thus, the room-temperature activity
substituted complexes 2a and 3a (Table 8). However, tert-butyl-
substituted complexes 2d and 3d do not fit this trend, as they
exhibited the poorest catalytic activities. One effect that could
counteract the inductive donation trend is the greater polariz-
ability of a larger alkyl group.79 This can result in a larger alkyl
substituent effectively acting as an electron-withdrawing group
in certain cases, particularly in reactions involving a buildup
and high-yield couplings of unactivated aryl chlorides attained
by these monodentate ligand-based systems may be out of reach
for catalysts containing nonlabile chelate ligands such as the
diaminocarbenes reported herein. This is in agreement with
reported examples of Suzuki-Miyaura cross-coupling reactions
employing chelated palladium(II)-NHC precatalysts, all of which
require high temperatures (>110 °C) and show limited activities
2
4,82,88,89
of negative charge such as gas-phase deprotonations of alco-
with aryl chlorides.
Overall, the optimized catalyst 2e
hols.7
9,80
Such a charge buildup could occur in these catalytic
compares favorably in terms of yields and substrate scope with
other aerobic Suzuki-Miyaura catalysts. To the best of our
knowledge, only four aerobic Suzuki-Miyaura systems have
been reported to achieve high yields for aryl bromides containing
systems if the dicarbene ligands are deprotonated. A plausible
explanation for the trend in catalytic activities is that the donor
abilities of the dicarbene ligands are influenced by opposing
inductive and polarizability effects. In this scenario, inductive
effects predominate for secondary alkyls, leading to greater
σ-donation by the carbene moieties, whereas the polarizibility
effect is dominant for tert-butyl groups, resulting in a more
weakly donating ligand. The dicarbene ligands of the most active
precatalysts, 2e and 3e, are more highly substituted than the
other dicarbenes due to the backbone methyl group, and
therefore they might be expected to have increased σ-donor
7
1,83,85
a comparable range of functional groups,
and 2e is free
from the problem of significant homocoupling side product
formation that has been observed in some aerobic Suzuki-
7
5
Miyaura catalysts.
Conclusion
A series of modular chelating diaminocarbene complexes of
palladium have been prepared using a facile, procedurally simple
synthetic method based on metal-templated addition of hydra-
zines to alkylisocyanides. Structural and spectroscopic data as
well as Suzuki-Miyaura cross-coupling activities indicate that
the new carbene ligands possess strong donor properties similar
to those of imidazole-based N-heterocyclic carbenes. Systematic
modification of the carbene substituents allowed rapid identi-
fication of a backbone-substituted palladium dicarbene complex
as the most promising Suzuki-Miyaura cross-coupling catalyst.
Although it does not exhibit the high catalytic activities in
couplings of electron-rich aryl chlorides that have been attained
by Suzuki-Miyaura catalysts containing monodentate carbene
or phosphine ligands, this optimized catalyst has the advantage
of maintaining high yields under air in many aryl bromide
coupling reactions without significant byproduct formation. The
catalyst optimization studies indicated that seemingly minor
variations in ligand electronic properties can drastically affect
catalytic activity, accentuating the importance of a modular
ligand design that allows systematic variation of ligand sub-
stituents for rapid catalyst screening. Future studies will seek
to extend this modular synthetic strategy to diaminocarbene
ligands that do not contain acidic N-H groups as well as more
1
3
ability. The C NMR data for precatalysts 2a-e and 3a-e do
not indicate substantial electronic differences among the carbene
ligands, with a fairly narrow range of carbene chemical shifts
observed (δ 176-183, Table 3). The striking outcome of this
study is that substantial differences in the catalytic activity of
the various complexes are observed despite the lack of
distinguishing structural or spectroscopic features. This suggests
that seemingly minor differences in ligand electronics can exert
significant effects on the rates of key reactions in a catalytic
cycle, and such effects are probably very difficult to predict.
Aside from their ease of synthesis, the primary advantage of
the new palladium dicarbene catalysts over the majority of
known Suzuki-Miyaura cross-coupling systems is their ability
to operate effectively under air. Only a few palladium catalysts
have been reported to perform Suzuki-Miyaura couplings under
7
1,75,81-85
aerobic conditions.
Most of these examples employ
chelating ligands,8 primarily involving nitrogen donors.
2,85
71,75,81
(
78) Carey, F. A.; Sundberg, R. J. AdVanced Organic Chemistry, 4th
ed.; Part A: Structure and Mechanisms; Kluwer Academic/Plenum Publish-
ers: New York, 2000; pp 204-215, 243-246.
(
79) Brauman, J. I.; Blair, L. K. J. Am. Chem. Soc. 1970, 92, 5986-
5
992.
80) Taft, R. W.; Taagepera, M.; Abboud, J. L. M.; Wolf, J. F.; DeFrees,
D. J.; Hehre, W. J.; Bartmess, J. E.; McIver, R. T., Jr. J. Am. Chem. Soc.
(
1
978, 100, 7765-7767.
(86) For kinetic evidence for the intermediacy of a palladium(0)-
monophosphine species in aryl bromide oxidative addition, see: Hartwig,
J. F.; Paul, F. J. Am. Chem. Soc. 1995, 117, 5373-5374.
(87) Stambuli, J. P.; Kuwano, R.; Hartwig, J. F. Angew. Chem., Int. Ed.
2002, 41, 4746-4748.
(
81) (a) Grasa, G. A.; Hillier, A. C.; Nolan, S. P. Org. Lett. 2001, 3,
1
077-1080. (b) Bedford, R. B.; Cazin, C. S. J. Chem. Commun. 2001,
1
540-1541.
(82) Loch, J. A.; Albrecht, M.; Peris, E.; Mata, J.; Faller, J. W.; Crabtree,
R. H. Organometallics 2002, 21, 700-706.
(88) Baker, M. V.; Skelton, B. W.; White, A. H.; Williams, D. J. Dalton
2001, 111-120.
(
83) (a) Tao, B.; Boykin, D. W. J. Org. Chem. 2004, 69, 4330-4335.
b) Li, J.-H.; Liu, W.-J. Org. Lett. 2004, 6, 2809-2811.
84) Gossage, R. A.; Jenkins, H. A.; Yadav, P. N. Tetrahedron Lett. 2004,
5, 7689-7691.
85) Xiong, Z.; Wang, N.; Dai, M.; Li, A.; Chen, J.; Yang, Z. Org. Lett.
004, 6, 3337-3340.
(
(89) Two reports have demonstrated high-yield Suzuki-Miyaura cou-
plings of aryl bromides and chlorides at 80 °C using palladium catalysts
generated in situ from bis-imidazolium salts (refs 25b,c). However, it is
not known whether chelated palladium intermediates are the active catalysts
in these systems.
(
4
2
(

Modular Palladium Diaminocarbene Complexes
Organometallics, Vol. 25, No. 2, 2006 503
i
structurally diverse examples derived from bulky or chiral
diamine precursors.
Synthesis of [Pd(C
8
H
17
N
4
)(CN Pr)
2
][ClO
4
] (1b). Isopropyliso-
cyanide (340 mg, 4.93 mmol) was added to a stirred solution of
PdCl , prepared in situ from PdCl (217 mg, 1.22 mmol) and
KCl (377 mg, 5.05 mmol) in 40 mL of H O at room temperature.
K
2
4
2
Experimental Section
2
Hydrazine hydrate (2.0 mL, 26 equiv) was then added to the
General Considerations. All syntheses were performed under
air. Methylisocyanide was synthesized by a literature procedure.90
Isopropylisocyanide (Strem, 99%), tert-butylisocyanide (Strem,
2+
resulting colorless solution of [Pd(CNCy)
solution. Excess LiClO
solution to precipitate the product, which was collected by filtration,
washed with water, and dried in vacuo over P . Recrystallization
of the product was achieved by slow diffusion of Et O into a CHCl
solution of the compound to yield yellow, needle-shaped crystals
533 mg, 85%). Anal. Calcd for C16 ClO Pd: C, 37.44, H,
.09, N, 16.37. Found: C, 37.41, H, 6.35, N, 15.95.
Synthesis of [Pd(C14 )(CNCy) ][ClO ] (1c). Cyclohexyl-
isocyanide (400 mg, 3.68 mmol) was added to a stirred solution of
PdCl , prepared in situ from PdCl (163 mg, 0.92 mmol) and
KCl (274 mg 3.68 mmol) in 30 mL of H O at room temperature.
Excess hydrazine hydrate (1.5 mL, 26 equiv) was added to the
4
] , affording a yellow
4
(1.043 g, 8 equiv) was added to the yellow
9
8%), cyclohexylisocyanide (Fluka, g98%), hydrazine hydrate
Acros), methylhydrazine (Aldrich, 98%), phenylhydrazine (East-
man, 97%), PdCl (Alfa, 99.9%), KCl (Spectrum, reagent), and
LiClO (Aldrich, 95+%) were used as received. CAUTION:
2
O
5
(
2
3
2
4
(
6
H
31
N
6
4
Perchlorate salts are potentially explosive, and they should be
handled with care and in small quantities. Solvents used for
H
25
N
4
2
4
syntheses and recrystallization: acetonitrile (EM Science), CHCl
Pharmco), CH Cl (Pharmco), Et O (Acros), DMSO (Fisher), and
3
(
2
2
2
K
2
4
2
hexane (Pharmco) were of reagent grade and were used without
purification. Water was purified by an E-pure system (Barnstead)
and had a resistivity of g17.6 MΩ-cm. Suzuki-Miyaura substrates
2
2+
resulting colorless solution of [Pd(CNCy)
precipitate, which was collected by filtration, washed with aqueous
LiClO and water, and dried in vacuo over P (455 mg, 73%).
Anal. Calcd for C28 ClO Pd: C, 49.93, H, 7.03, N, 12.48.
4
]
to give a yellow
4-bromoacetophenone (Aldrich), 4-bromonitrobenzene (Eastman),
4
-bromobenzene (Aldrich), 4-chlorobenzene (Aldrich), and 4-chlo-
4
2 5
O
91
ronitrobenzene (Eastman) were purified by literature procedures
H
47
N
6
4
from samples that had been in use >4 years. All other aryl halides
and arylboronic acids were purchased from Acros or Aldrich in
Found: C, 50.32, H, 6.65, N, 12.48.
t
Synthesis of [Pd(C10
H
21
N
4
)(CN Bu)
2
][ClO
4
] (1d). tert-Butyl-
the highest available purity and used as received. Anhydrous K
Aldrich, 97%), K PO ‚H O (Acros, c.p.), K CO (Aldrich, anhy-
drous reagent), NaO Bu (Acros, 98%), CsF (Acros, 99.9%), and
Cs CO (Acros, 99.5%) were used as received. For Suzuki-Miyaura
3 4
PO
isocyanide (305 mg, 3.63 mmol) was added to a stirred solution of
PdCl , prepared in situ from PdCl (163 mg, 0.92 mmol) and
KCl (274 mg, 3.67 mmol) in 30 mL of H O at room temperature.
Hydrazine hydrate (1.5 mL, 26 equiv) was added to the resulting
(
3
4
2
2
3
K
2
4
2
t
2
2
3
cross-coupling reactions, anhydrous DMA (Acros, septum-sealed
bottle) was used as received for reactions under inert atmosphere,
and undried DMA (Acros, 99+%) was used as received for aerobic
reactions.
NMR spectra were recorded on a Varian Unity INOVA 400 MHz
spectrometer. Reported chemical shifts are referenced to residual
solvent peaks. NMR solvents were purchased from Cambridge
Isotope Laboratories and were generally used as received. When
dry NMR solvents were needed, they were dried over degassed 4
Å molecular sieves and then vacuum transferred into a glass ampule
t
2+
colorless solution of [Pd(CN Bu)
Excess LiClO (391 mg, 4 equiv) was added to the yellow solution
to precipitate the product, which was collected by filtration, washed
with water, and dried in vacuo over P . Recrystallization of the
product was achieved by slow diffusion of Et O into a CHCl
solution of the compound to yield yellow crystals (352 mg, 67%).
Anal. Calcd for C20 ClO Pd: C, 42.18, H, 6.90, N, 14.76.
Found: C, 42.42, H, 7.20, N, 14.60.
Synthesis of [Pd(C )(CNMe)
cyanide (100 mg, 2.45 mmol) was added to a stirred solution of
PdCl , prepared in situ from PdCl (108 mg, 0.61 mmol) and
KCl (190 mg, 2.54 mmol) in 8 mL of H O at room temperature.
Excess methylhydrazine (65 µL, 2 equiv) was added to the resulting
4
]
to give a yellow solution.
4
2
O
5
2
3
H
39
N
6
4
5
H
11
N
4
2 4
][ClO ] (1e). Methyliso-
before use in the glovebox (CD
over P and vacuum transferred into a J Young NMR tube
containing the sample (CD Cl ). IR spectra were acquired from
3 6 7
CN, DMSO-d , DMF-d ) or stored
K
2
4
2
2 5
O
2
2
2
Nujol mulls on a Nicolet Prot e´ g e´ 460 FT-IR spectrometer. GC
analyses utilized a Hewlett-Packard 6850 gas chromatograph with
a 100% dimethylpolysiloxane capillary column (HP-1, Agilent
Technologies, 0.25 mm i.d. × 30 m) and a flame ionization detector.
For determination of concentrations by GC, multilevel calibration
plots were performed with stock solutions of analytes and internal
standard (diethylene glycol dibutyl ether) that approximated
experimental concentrations. Elemental analyses were performed
by Desert Analytics, Tucson, AZ.
2+
pale yellow solution of [Pd(CNMe)
Excess LiClO (400 mg, 6 equiv) was then added to precipitate
the product as an orange solid, which was collected by filtration,
washed with cold water, and dried in vacuo over P (218 mg,
6%). Anal. Calcd for C ClO Pd: C, 26.04, H, 4.13, N, 20.24.
Found: C, 25.86, H, 4.16, N, 19.86.
Synthesis of Pd(C )Cl (2a). Compound 1a (340 mg,
4
]
to give an orange solution.
4
2
O
5
8
9
H
17
N
6
4
4
H
10
N
4
2
0.848 mmol) was dissolved in hot 3 M aqueous HCl, and the
solution was then allowed to cool with stirring until a white
precipitate formed. The solid was filtered, washed with water, and
Synthesis of [Pd(C
nide (213 mg, 5.18 mmol) was added to a stirred solution of K
PdCl , prepared in situ from PdCl (200 mg, 1.13 mmol) and KCl
336 mg, 4.51 mmol) in 20 mL of H O at room temperature. Excess
hydrazine hydrate (1.0 mL, 15 equiv) was added to the resulting
4 9 4 2 4
H N )(CNMe) ][ClO ] (1a). Methylisocya-
2
-
dried in vacuo over P
Cl Pd: C, 16.48, H, 3.46, N, 19.22. Found: C, 16.55, H, 3.54, N,
19.07.
Synthesis of Pd(C H N )Br (3a). Compound 1a (332 mg,
2 5 4 10 4
O (225 mg, 92%). Anal. Calcd for C H N -
4
2
(
2
2
2+
colorless solution of [Pd(CNMe)
Dropwise addition of a saturated solution of LiClO
in the formation of an orange precipitate, which was collected by
filtration, washed with water, and dried in vacuo over P . The
product was recrystallized by dissolution in a minimum amount of
hot CH CN, followed by filtration and slow addition of Et O to
give yellow-orange crystals (293 mg, 65%). Anal. Calcd for
ClO Pd: C, 23.96, H, 3.77, N, 20.95. Found: C, 24.10,
H, 3.91, N, 20.77.
4
]
to give a yellow solution.
4
10
4
2
4
in H O resulted
2
0.828 mmol) was dissolved in hot 3 M aqueous HBr, and the
solution was then allowed to cool with stirring until a white
precipitate formed. The solid was filtered, washed with water, and
dried in vacuo over P O (287 mg, 91%). Anal. Calcd for C H N -
2 5
O
2
5
4
10
4
3
2
Br Pd: C, 12.63, H, 2.65, N, 14.73. Found: C, 12.8, H, 2.56, N,
2
14.47.
C H
8 15
N
6
4
Synthesis of Pd(C
8
H
18
N
4
)Cl
2
(2b). A 3 M aqueous solution of
CN solution (15 mL) of
HCl was added dropwise to a CH
3
compound 1b (260 mg, 0.506 mmol) until the solution became
colorless. The volume of the solution was reduced until a white
(
90) Schuster, R. E.; Scott, J. E.; Casanova, J. Org. Synth. 1966, 46,
5-77.
91) Armarego, W. L. F.; Chai, C. L. L. Purification of Laboratory
Chemicals, 5th ed.; Butterworth-Heinemann: New York, 2003.
7
2
precipitate formed. Et O was added dropwise to complete precipita-
(
tion of the solid, which was collected by filtration, washed with

5
04 Organometallics, Vol. 25, No. 2, 2006
Table 10. Crystal Data and Structure Refinement Details
Moncada et al.
1b
3b
3c
3d
3e
chem formula
C16H31ClN6O4Pd
C8H18Br2N4Pd‚
C14H26Br2N4Pd
C10H22Br2N4Pd‚
2C2H6SO
620.79
C5H12Br2N4Pd‚
C2H6SO
472.53
2
C2H6SO
fw
513.32
592.74
516.61
cryst syst
space group
cryst size (mm)
color, habit
orthorhombic
P212121
triclinic
P1h
monoclinic
C2/c
monoclinic
P21/c
triclinic
P1h
0.32 × 0.18 × 0.14
0.32 × 0.12 × 0.10
0.42 × 0.18 × 0.07
0.3 × 0.3 × 0.3
0.12 × 0.10 × 0.06
yellow needle
colorless needle
colorless plate
colorless
colorless prism
parallelepiped
slow diff ether/
DMSO
growth method
slow diff ether/
CHCl3
slow diff ether/
DMSO
slow diff ether/
DMF
slow diff ether/
DMSO
diffractometer
temp (K)
unit cell dimens
a (Å)
b (Å)
c (Å)
Bruker APEX
103(2)
Bruker APEX
103(2)
Bruker APEX
296(2)
Syntex P21
293(2)
Bruker APEX
103(2)
8.0840(5)
13.8728(9)
20.2548(13)
90
90
90
10.8099(8)
11.3178(9)
11.3765(9)
74.7190(10)
62.9710(10)
62.2700(10)
1095.04(15)
2
26.2920(12)
7.6568(3)
9.6383(4)
90
107.610(3)
90
11.698(2)
11.767(2)
21.873(6)
90
121.70(2)
90
7.5348(10)
9.0018(12)
10.5540(14)
83.427(2)
88.080(2)
81.682(2)
R (deg)
â (deg)
γ (deg)
3
volume (Å )
2271.5(3)
4
1849.38(14)
4
2561.6(9)
4
703.55(16)
2
Z
abs correction
multiscan
0.967
2.01 to 28.32
-10 e h e 10
multiscan
4.698
multiscan
5.324
psi-scan
4.021
multiscan
7.134
-
1
µ (mm
)
θ range (deg)
2.01 to 28.30
-14 e h e 14
-14 e k e 14
-14 e l e 14
13 623
5148 [0.0161]
R1 ) 0.0173
wR2 ) 0.0452
R1 ) 0.0179
wR2 ) 0.0455
3.25 to 28.30
-25 e h e 34
-8 e k e 10
-12 e l e 12
6130
2261 [0.0211]
R1 ) 0.0411
wR2 ) 0.0878
R1 ) 0.0476
wR2 ) 0.0894
2.05 to 28.00
0 e h e 15
-15 e k e 0
-28 e l e 24
6427
6148 [0.0826]
R1 ) 0.0616
wR2 ) 0.1664
R1 ) 0.1282
wR2 ) 0.2197
1.94 to 28.35
-10 e h e 10
-11 e k e 11
-13 e l e 14
14 048
14 048 [0.0000]
R1 ) 0.0445
wR2 ) 0.1208
R1 ) 0.0463
wR2 ) 0.1219
index ranges
-
18 e k e 18
26 e l e 27
-
no. reflns collected
no. indep reflns [Rint]
R indices (I > 2σ(I))
27 748
5444 [0.0143]
R1 ) 0.0149
wR2 ) 0.0394
R1 ) 0.0151
wR2 ) 0.0395
R indices (all data)
Et
Cl
1
2
O, and dried in vacuo (164 mg, 93%). Anal. Calcd for C
Pd: C, 27.64, H, 5.22, N, 16.12. Found: C, 27.97, H, 5.17, N,
5.75.
Synthesis of Pd(C
HBr was added dropwise to a CH
8
H
18
N
4
-
Et
Cl
14.52.
Synthesis of Pd(C10
of HBr was added dropwise to a CH
2
O, and dried in vacuo (253 mg, 96%). Anal. Calcd for C10
22 4
H N -
2
2
Pd: C, 31.97, H, 5.90, N, 14.92. Found: C, 31.97, H, 5.85, N,
8
H
18
4
N )Br
2
(3b). A 3 M aqueous solution of
CN solution (10 mL) of
H
22
4
N )Br
2
(3d). A 3 M aqueous solution
CN solution (25 mL) of
3
3
compound 1b (243 mg, 0.473 mmol) until a colorless solution was
compound 1d (400 mg, 0.702 mmol) until a colorless solution was
formed. The volume of the solution was reduced until a white
formed. The volume of the solution was reduced until a white
precipitate formed. Et
tion of the solid, which was collected by filtration, washed with
Et O, and dried in vacuo (137 mg, 66%). Anal. Calcd for C
Br Pd: C, 22.01, H, 4.16, N, 12.84. Found: C, 22.37, H, 4.46, N,
2.60.
Synthesis of Pd(C14
HCl was added dropwise to a CH
2
O was added dropwise to complete precipita-
precipitate formed. Et
tion of the solid, which was collected by filtration, washed with
Et O, and dried in vacuo (204 mg, 63%). Anal. Calcd for C10
Br Pd: C, 25.86, H, 4.77, N, 12.06. Found: C, 25.98, H, 4.74, N,
11.85.
Synthesis of Pd(C H N )Cl (2e). Compound 1e (100 mg, 0.241
2
O was added dropwise to complete precipita-
2
8 18 4
H N -
2
22 4
H N -
2
2
1
H
26
4
N )Cl
2
(2c). A 3 M aqueous solution of
CN solution (15 mL) of
5
12
4
2
3
mmol) was dissolved in hot 3 M aqueous HCl, and the resulting
solution was allowed to cool with stirring until a white precipitate
formed. The solid was filtered, washed with water, and dried in
vacuo over P O (51 mg, 70%). Anal. Calcd for C H N Cl Pd:
compound 1c (0.201 g, 0.298 mmol) until a pale yellow solution
was formed. The volume of the solution was reduced until a white
precipitate formed. Et
tion of the solid, which was collected by filtration, washed with
Et O, and dried in vacuo (83 mg, 65%). Anal. Calcd for C14
Cl Pd: C, 39.31, H, 6.13, N, 13.10. Found: C, 39.72, H, 6.11, N,
3.14.
Synthesis of Pd(C14
HBr was added dropwise to a CH
2
O was added dropwise to complete precipita-
2
5
5
12
4
2
C, 19.66, H, 3.96, N, 18.34. Found: C, 19.77, H, 3.83, N, 18.07.
2
H
26
N
4
-
Synthesis of Pd(C H N )Br (3e). Compound 1e (89 mg, 0.214
5
12
4
2
2
mmol) was dissolved in hot 3 M aqueous HCl, and the resulting
solution was allowed to cool with stirring until a white precipitate
formed. The solid was filtered, washed with water, and dried in
vacuo over P O (72 mg, 85%). Anal. Calcd for C H N Br Pd:
1
H
26
4
N )Br
2
(3c). A 3 M aqueous solution of
CN solution (15 mL) of
3
2
5
5
12
4
2
compound 1c (109 mg, 0.162 mmol) until a pale yellow solution
was formed. The volume of the solution was reduced until a white
C, 15.23, H, 3.07, N, 14.20. Found: C, 15.14, H, 2.90, N, 13.85.
X-ray Crystallographic Analyses. Crystal data and refinement
details for all X-ray crystallographic analyses are presented in Table
10. X-ray diffraction data for 1b, 3b, 3c, and 3e were collected on
a Bruker APEX diffractometer with a CCD detector using combina-
tions of æ and ω scans. Data integration employed the Bruker
SAINT software package.92 For 3d, data were obtained on a Syntex
P21 point-detector instrument using θ/2θ scans, and data reduction
employed REDUCE (UCLA crystallographic package). All X-ray
diffraction experiments employed graphite-monochromated Mo KR
radiation (λ ) 0.71073 Å). Structures were solved by direct methods
precipitate formed. Et
tion of the solid, which was collected by filtration, washed with
Et O, and dried in vacuo (60 mg, 72%). Anal. Calcd for C14
Br Pd: C, 32.56, H, 5.07, N, 10.84. Found: C, 33.01, H, 5.04, N,
0.60.
Synthesis of Pd(C10
HCl was added dropwise to a CH
2
O was added dropwise to complete precipita-
2
26 4
H N -
2
1
H
22
4
N )Cl
2
(2d). A 3 M aqueous solution of
CN solution (25 mL) of
3
compound 1d (400 mg, 0.702 mmol) until a colorless solution was
formed. The volume of the solution was reduced until a white
2
precipitate formed. Et O was added dropwise to complete precipita-
tion of the solid, which was collected by filtration, washed with
(92) SAINT-plus, Version 6.29; Bruker AXS: Madison, WI, 2001.

Modular Palladium Diaminocarbene Complexes
Organometallics, Vol. 25, No. 2, 2006 505
2
and refined by full-matrix least-squares on F using the SHELXTL
product was isolated and purified by extraction of the whole reaction
suite.93 Non-hydrogen atoms were assigned anisotropic temperature
factors, with hydrogen atoms included in calculated positions (riding
model). For 3d, the hydrogen-bound DMSO molecules were
modeled as disordered, with the sulfur atoms occupying two
possible positions for each DMSO. The occupancy factors of the
sulfurs in the dominant orientations refined to values of 0.838 and
mixture with CH
hexanes/ethyl acetate). In some reactions, the amount of homo-
2 2
Cl , followed by silica flash chromatography (4:1
coupling product was determined by GC analysis of the CH
extract.
2 2
Cl
Yield versus Time for Suzuki-Miyaura Cross-Coupling
Reactions. In a glovebox, K PO (478 mg, 2.25 mmol), bromoben-
3
4
0
.895 for the two different DMSO molecules.
General Procedure for Catalytic Suzuki-Miyaura Cross-
zene (158 µL, 1.5 mmol), and phenylboronic acid (2.25 mmol, 1.5
equiv) were added to a threaded vial containing a stir bar, followed
by addition of diethylene glycol dibutyl ether (GC internal standard,
40 µL) and a solution of the precatalyst (0.015 mmol) in anhydrous
DMA (3 mL). The vial was sealed with a screw cap containing a
PTFE-silicone septum and stirred briefly at room temperature to
mix the reagents. The vial was then placed in a preheated oil bath
at 120 °C. Aliquots (5 µL) of the reaction mixture were removed
Coupling Reactions. Base (2.57 mmol, 1.5 equiv), aryl halide (1.7
mmol), and arylboronic acid (2.04-2.57 mmol, 1.2-1.5 equiv)
were added to a flask, followed by addition of a solution of the
precatalyst (0.017 mmol) in DMA (5 mL). For reactions performed
2
under N , all manipulations were done in a drybox, anhydrous DMA
was employed, and the flask was sealed with a Teflon stopcock.
For aerobic reactions, all manipulations were done on the benchtop,
wet DMA was used, and the flask was connected to a reflux
condenser open to air. The flask was placed in a preheated oil bath
at 120 °C and stirred for 24 h. After cooling the reaction mixture,
2 2
after fixed times with a syringe and added to 50 µL of CH Cl .
These mixtures were filtered through a glass microfiber plug and
analyzed by GC.
Acknowledgment is made to the Donors of the American
Chemical Society Petroleum Research Fund (#40196-G1) for
support of this research. We thank Charles Campana (Bruker
AXS) for assistance in obtaining the X-ray structure of 3c and
Masood Khan (University of Oklahoma) for assistance in
obtaining the structures of 1b and 3b.
1
00 µL of diethylene glycol dibutyl ether (GC and NMR internal
standard) was added to the flask. A 200 µL aliquot of the reaction
mixture was then added to 10 mL of CH Cl . The organic layer
was extracted four times with 10 mL portions of water and then
2
2
dried over MgSO
residue was dissolved in CDCl
4
, and the CH
2
Cl
2
was removed in vacuo. The
1
3
and analyzed by H NMR
spectroscopy. The product peak assignments were based on
Supporting Information Available: Tabulated full IR spectral
data for reported compounds; tabulated structural data for possible
intramolecular N(H)‚‚‚Br interactions in 3b-e; crystallographic data
for 1b, 3b, 3c, 3d, and 3e in CIF format. This material is available
free of charge via the Internet at http://pubs.acs.org.
authentic samples or on published data.6
3,94
In some cases the
(93) SHELXTL, Version 6.14; SHELXS (structure solution, 1990);
SHELXL (structure refinement, 1997); XP (Version 5.1, graphics); Bruker
AXS: Madison, WI, 2000.
(
94) Okamoto, K.; Akiyama, R.; Kobayashi, S. Org. Lett. 2004, 6, 1987-
1
990.
OM050786F