Weil-defined N-heterocyclic carbene based ruthenium catalysts for direct amide synthesis from alcohols and amines

Article abstract of DOI:10.1021/om901020h

Well-defined N-heterocyclic carbene based ruthenium, complexes were developed as highly active catalysts for direct amide synthesis from alcohols and amines. A catalytic amount of a base such, as KO¹Bu was essential to initiate the catalytic cycle. Activity of the Ru complexes was comparable with the reported in situ Ru catalysts. These catalysts provided mechanistic insight suggesting a Ru hydride species as an active catalytic intermediate. The generation of the Ru hydride was critical for the amidation of free aldehydes.

Full text of DOI:10.1021/om901020h

1374 Organometallics 2010, 29, 1374–1378
DOI: 10.1021/om901020h
Well-Defined N-Heterocyclic Carbene Based Ruthenium Catalysts for
Direct Amide Synthesis from Alcohols and Amines
Yao Zhang, Cheng Chen, Subhash Chandra Ghosh, Yongxin Li, and Soon Hyeok Hong*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang
Technological University, Singapore 637371, Singapore
Received November 24, 2009
Well-defined N-heterocyclic carbene based ruthenium complexes were developed as highly active
catalysts for direct amide synthesis from alcohols and amines. A catalytic amount of a base such as
KOtBu was essential to initiate the catalytic cycle. Activity of the Ru complexes was comparable with
the reported in situ Ru catalysts. These catalysts provided mechanistic insight suggesting a Ru
hydride species as an active catalytic intermediate. The generation of the Ru hydride was critical for
the amidation of free aldehydes.
Introduction
Our group recently developed phosphine-free in situ gen-
erated N-hetercocyclic carbene (NHC) based ruthenium
catalysts from imidazolium salts, a base, pyridine, and
[Ru(p-cymene)Cl2]2.5 The result indicated that the NHC-
based ruthenium complexes synthesized from [Ru(p-cym-
ene)Cl2]2 such as 2,8a 3, and 48b might be real catalytic
intermediates for the direct amide synthesis (Figure 1). Iden-
tifying well-defined catalysts from in situ generated catalysts
is important to investigate the mechanism and improve
the activity further by rational design of catalysts. Herein,
we report the catalytic activity of the well-defined
NHC-based ruthenium complexes and the study of catalytic
intermediates.
The amide bond is a key functional group in organic and
biological chemistry.1 Several groups have reported direct
amide synthesis from alcohols and amines by liberating two
molecules of hydrogen using Ru-,2-5 Rh-,6 and Ag-based7
catalyst systems. Milstein and co-workers developed a Ru
catalyst, 1, for the amide synthesis using a hemilabile PNN
pincer ligand (Figure 1).2 In situ generated catalysts using a
commercially available ruthenium source and supporting
ligands with3 or without4,5 hydrogen acceptors have also
been reported. The direct acylation of amines with alcohols is
a highly atom economical transformation that evolves hy-
drogen as a sole byproduct with less waste than traditional
amide synthesis, often producing toxic chemical waste with
tedious procedures.2-7
Results and Discussion
However, there are many challenges in this reaction. All
reported ruthenium catalyst systems require elevated tempera-
ture under toluene reflux and give lower yields for sterically
hindered substrates and less basic aryl amines such as aniline.
It has also been shown that simpler in situ generated catalyst
systems from readily available materials have lower TON.5 To
improve current catalyst systems, it is essential to understand
the identity of catalytic intermediates and mechanisms.
Catalytic Activity of 2-4. On the basis of the reports
showing the high activity of 1,3-diisopropylimidazolium
bromide (5) on in situ generated ruthenium catalyst
systems,4,5 we synthesized complex 3 modifying the reported
procedure by using a Ag carbene.8 The structure was con-
firmed by X-ray crystallography (Figure 2). The structure of
3 is similar to that of the reported 4. To our surprise, when
complexes 2-4 were initially screened with 2-phenylethanol
(6) and benzylamine (7), they did not show any activity.
Mimicking the reported in situ conditions, bases such as NaH
and KOtBu were found necessary for catalytic activity
(Table 1). Weaker bases such as K2CO3 were not as effective
as NaH and KOtBu (entry 11, Table 1). Further optimization
demonstrated that only a catalytic amount of a base, 15-
20 mol %, is ideal for the catalysis (Table 1). The major role
of these bases was previously considered for in situ genera-
tion of NHCs from imidazolium salts. However, the current
results with well-defined precatalysts indicated that the role
of bases is more than generation of NHC and is related to
activation of the Ru complexes. To our delight, supporting
*Corresponding author. E-mail: hongsh@ntu.edu.sg.
(1) (a) Valeur, E.; Bradley, M. Chem. Soc. Rev. 2009, 38, 606.
(b) Cupido, T.; Tulla-Puche, J.; Spengler, J.; Albericio, F. Curr. Opin. Drug
Discovery Dev. 2007, 10, 768. (c) Bode, J. W. Curr. Opin. Drug Discovery
Dev. 2006, 9, 765. (d) Humphrey, J. M.; Chamberlin, A. R. Chem. Rev. 1997,
97, 2243.
(2) Gunanathan, C.; Ben-David, Y.; Milstein, D. Science 2007, 317,
790.
(3) (a) Naota, T.; Murahashi, S.-I. Synlett 1991, 693. (b) Watson, A. J.
A.; Maxwell, A. C.; Williams, J. M. J. Org. Lett. 2009, 11, 2667.
(4) Nordstrom, L. U.; Vogt, H.; Madsen, R. J. Am. Chem. Soc. 2008,
e
130, 17672.
(5) Ghosh, S. C.; Muthaiah, S.; Zhang, Y.; Xu, X.; Hong, S. H. Adv.
Synth. Catal. 2009, 351, 2643.
(6) Zweifel, T.; Naubron, J.-V.; Grutzmacher, H. Angew. Chem., Int.
€
Ed. 2009, 48, 559.
(8) (a) Herrmann, W. A.; Elison, M.; Fischer, J.; Kocher, C.; Artus,
G. R. J. Chem.;Eur. J. 1996, 2, 772. (b) Lo, C.; Cariou, R.; Fischmeister,
C.; Dixneuf, P. H. Adv. Synth. Catal. 2007, 349, 546.
(7) Shimizu, K.-i.; Ohshima, K.; Satsuma, A. Chem.;Eur. J. 2009,
15, 9977.
r
pubs.acs.org/Organometallics
Published on Web 02/04/2010
2010 American Chemical Society

Article
Organometallics, Vol. 29, No. 6, 2010 1375
Table 1. Optimization of Conditionsa
base
additive
Figure 1. Ru complexes for amide synthesis from alcohols.
entry Ru complex
base
mol % additive mol % yieldb (%)
1
2
3
4
5
6
7
8
3
3
3
3
3-I
3
3
3
3
3
3
2
2-I
4
2
2
2
2
0
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
NaH
K2CO3
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
5
10
15
15
20
40
60
100
20
20
15
15
15
20
20
20
20
7
82
93
93
89
60
50
10
93
0
97
89
72
46c
44c
42c
46c
9
10
11
12
13
14
15
16
17
18
NaBr
NaI
KBr
100
100
100
a 5 mol % catalyst, toluene, reflux, 24 h unless otherwise noted.
b Determined by GC using dodecane as an internal standard. c 80 °C,
24 h.
Substrate Scope. Complex 2, with smaller wingtip groups
of NHC, was chosen to expand the substrate scope, expect-
ing improvement for challenging sterically hindered sub-
strates. A range of amides were synthesized with good to
excellent yields with precatalyst 2 (Table 2). Excellent yields
were obtained for sterically nonhindered substrates (entries
1, 2). Modestly hindered substrates worked reasonably well
(entries 3, 4). Cyclic secondary amines such as 21 and 22 also
reacted smoothly, producing the corresponding amides with
good yields (entries 5, 6). In particular, five- to seven-
membered cyclic lactams, 29, 30, and 31, were synthesized
efficiently from R,ω-amino alcohols (entries 7-9). We stu-
died the electronic effect on alcohols using benzyl alcohol
derivatives. Slighlty reduced yields were observed with elec-
tron-deficient substrates (entries 10-12). However, rather
disappointingly, it also showed a similar limitation on steri-
cally bulky substrates and less basic aniline, demonstrating
challenges in this area (entries 13, 14).2-5
Catalytic Intermediates. With the benefit of the structu-
rally well-defined complex 2, we attempted to reveal the
mechanism and catalytic intermediates during catalysis.
1-Hexanol (10) and 1-pentylamine (19) were chosen for the
study, because the corresponding amide product 24 is com-
pletely soluble in toluene-d8 during catalysis. We first tried an
NMR reaction with the same catalytic conditions (5 mol %
2, 15 mol % KtOBu) in toluene-d8 to investigate catalytic
intermediates during catalytic reactions. Several interesting
features were observed. Even though complex 2 itself did not
have high solubility in toluene, it was immediately solubi-
lized by the addition of substrates in the presence of a base
with characteristic peaks of π-bound p-cymene, which shows
characteristic upfield shifts near 5 ppm in the 1H NMR
spectrum. This observation indicated that exchange of chlor-
ide with alkoxide is a rapid initiation step. Concurrent
Figure 2. Crystal structure of 3 with thermal ellipsoids drawn at
the 50% probability level. Hydrogen atoms are omitted for
clarity. Selected bond distances (A): Ru1-C1 2.0828(14),
Ru1-Cl1 2.4439(4), Ru1-C13 2.1701(14). Selected bond angles
(deg): C1-Ru1-C13 89.55(5), C1-Ru1-Cl1 89.87(4), Cl1-
Ru1-Cl2 83.006(13).
˚
ligands such as pyridine, acetonitrile, and phosphines, which
were required for improving activity of in situ generated
catalysts, were not necessary for the well-defined complexes
2-4.
Interestingly, even though NHC precursors that have
isopropyl wingtip groups such as 5 were reported to be
significantly superior than 1,3-dimethylimidazolium salt in
in situ catalyst systems,4,5 2 and 3 showed comparable
activity. The reason is not clear, but we think that there
might be less efficiency of NHC-Ru bond formation in in
situ generation with 1,3-dimethylimidazolium iodide (9).9,10
To improve the activity, we tried to exchange the chloride
ligands with bromide and iodide. However, complexes 2-I
and 3-I also did not show any improvement over 2 and 3.11
The use of silver salts such as AgBF4 to abstract chloride
ligands did not show any improvement either.
(9) It is reported that the NHC of 5 (pKa ∼22, in DMSO) is a little
more basic than that of 9 (pKa ∼21, in DMSO). See: Magill, A. M.;
Cavell, K. J.; Yates, B. F. J. Am. Chem. Soc. 2004, 126, 8717.
(10) For recent reviews on NHCs: (a) Arduengo, A. J., Bertrand, G.,
ꢀ
Eds. Chem. Rev. 2009, 109 (8), 3209. (b) de Fremont, P.; Marion, N.; Nolan,
S. P. Coord. Chem. Rev. 2009, 253, 862. (c) Hahn, F. E.; Jahnke, M. C.
Angew. Chem., Int. Ed. 2008, 47, 3122. (d) Nolan, S. P., Ed. N-Heterocyclic
Carbenes in Synthesis; Wiley-VCH: Weinheim, Germany, 2006. (e) Crab-
tree, R. H., Ed. Coord. Chem. Rev. 2007, 251 (5-6), 595.
(11) Synthesis of 2-Br was attempted; however, mixtures of mono-
and disubstituted bromo complexes were observed even in the presence
of excess (∼30 equiv) NaBr.

1376 Organometallics, Vol. 29, No. 6, 2010
Zhang et al.
Table 2. Direct Amide Synthesis Catalyzed by 2a
Scheme 1. Proposed Mechanism
disappeared along with many trace hydridic peaks, implying
decomposition of catalysts.12 Peaks from π-bound cymene
near 5-6 ppm also disappeared after a few hour heating.
With 2 and 10 without a base, no reaction was observed,
suggesting a base is required to generate the Ru hydride
complex. These observations strongly indicated that a ruthe-
nium hydride species is an active catalytic intermediate.
Proposed Mechanism. On the basis of the studies, it is
proposed that the role of a catalytic amount (at least 2 equiv
vs precatalyst) of a base is to stimulate the generation of the
ruthenium alkoxide species (Scheme 1). Subsequent β-hy-
drogen elimination can generate the Ru(II) dihydride spe-
cies. The generation of [Ru]H2 from [Ru]Cl2 with the help of
a base and the Ru(0)/Ru(II) cycle have been suggested in
catalytic alcohol dehydrogenation,13 N-alkylation of amines
with alcohols,14 and esterification of alcohols.15 In addition,
synthesis of the [(p-cymene)RuH2(PCy3)] complex from
[(p-cymene)RuCl2(PCy3)] with methanol and K2CO3 has
been reported.16 However, attempts to synthesize [(p-cymene)-
RuH2(IMe)] 2-H2 under the same conditions were not
successful, limiting clear characterization of the observed
Ru-H intermediate. Diminished catalytic activity from inc-
reased amount of a base from 20 mol % also supported the
role of a base and implied that deprotonation of all alcohols
is not necessary for alcohols to react with a catalytically
active intermediate.
a Catalyst 2 (5 mol %), KOtBu (15 mol %), toluene, reflux, 24 h unless
otherwise noted. b Isolated yields, average of two runs. c 20 mol %
KOtBu. d Mesitylene, 163 °C.
formation of ruthenium hydrides as singlets, shown at δ -6.6
ppm (major) and -7.7 ppm (minor) by 1H NMR spectros-
copy, was observed immediately after the addition of sub-
strates with KOtBu at ambient temperature. When the
reaction mixture was heated at 115 °C and the amide started
to form, two hydridic peaks disappeared and a major hydride
peak at δ -9.8 ppm was observed, along with many trace
weak hydridic peaks at about δ -10 to -20 ppm.12
Encouraged by the observations, we tried an NMR tube
reaction in toluene-d8 with a 1:3:3 ratio reaction of 2, 10, and
KOtBu. At room temperature, a major hydride peak was
observed at the same position observed in catalytic reactions
at δ -6.6 ppm. However upon heating to 115 °C, the hydride
peak disappeared and a new singlet at δ -9.8 ppm
was observed.12 With prolonged heating, 2-3 h, the peak
(13) Zhang, J.; Gandelman, M.; Shimon, L. J. W.; Rozenberg, H.;
Milstein, D. Organometallics 2004, 23, 4026.
(14) (a) Murahashi, S.-I.; Kondo, K.; Hakata, T. Tetrahedron Lett.
1982, 23, 229. (b) Grigg, R.; Mitchell, T. R. B.; Sutthivaiyakit, S.; Tongpe-
nyai, N. J. Chem. Soc., Chem. Commun. 1981, 611. (c) Watanabe, Y.; Tsuji,
Y.; Ige, H.; Ohsugi, Y.; Ohta, T. J. Org. Chem. 1984, 49, 3359. (d) Watanabe,
Y.; Morisaki, Y.; Kondo, T.; Mitsudo, T.-A. J. Org. Chem. 1996, 61, 4214.
(e) Ganguly, S.; Roundhill, D. M. Polyhedron 1990, 9, 2517. (f) Huh, K.-T.;
Tsuji, Y.; Kobayashi, M.; Okuda, F.; Watanabe, Y. Chem. Lett. 1988, 449.
(g) Naskar, S.; Bhattacharjee, M. Tetrahedron Lett. 2007, 48, 3367.
(h) Hollmann, D.; Tillack, A.; Michalik, D.; Jackstell, R.; Beller, M. Chem.
Asian J. 2007, 2, 403. (i) Tillack, A.; Hollmann, D.; Michalik, D.; Beller, M.
Tetrahedron Lett. 2006, 47, 8881. (j) Del Zotto, A.; Baratta, W.; Sandri, M.;
Verardo, G.; Rigo, P. Eur. J. Inorg. Chem. 2004, 524. (k) Hamid, M. H. S. A.;
Allen, C. L.; Lamb, G. W.; Maxwell, A. C.; Maytum, H. C.; Watson, A. J. A.;
Williams, J. M. J. J. Am. Chem. Soc. 2009, 131, 1766, and more references
therein.
(15) (a) Murahashi, S.-I.; Ito, K.; Naota, T.; Maeda, Y. Tetrahedron
Lett. 1981, 22, 5327. (b) Murahashi, S.-I.; Naota, T.; Ito, K.; Maeda, Y.; Taki,
H. J. Org. Chem. 1987, 52, 4319. (c) Zhao, J.; Hartwig, J. F. Organome-
tallics 2005, 24, 2441.
(12) The 1H NMR spectra were obtained at ambient temperature,
after the NMR tube was heated at 115 °C in an oil bath for the specified
time.
ꢀ
(16) Demerseman, B.; Mbaye, M. D.; Semeril, D.; Toupet, L.;
Bruneau, C.; Dixneuf, P. H. Eur. J. Inorg. Chem. 2006, 1174.

Article
Organometallics, Vol. 29, No. 6, 2010 1377
Scheme 2. Amidation of Aldehydea
during the discussed NMR studies, implied that the direct
amide formation from alcohol might occur through Ru-
bound aldehyde-like species, instead of free aldehyde. A
recent mechanistic study with a heterogeneous Ag catalyst
on the same transformation indicated that the reaction
proceeded through metal-bound aldehyde-like species, not
through a free aldehyde.7
To investigate further, we ran a reaction with a mixture of
6, 37, and 7 (1:1:1.2 ratio). The corresponding amides 8 and
33 were obtained in 10% and 47% yields, respectively,
suggesting that once a catalytically active species is gener-
ated, aldehydes could generate amides more favorably than
alcohols (Scheme 3). Although it is still not conclusive
whether a free aldehyde is generated during the amidation of
primary alcohols or not, our study clearly indicated that
generation of a ruthenium hydride is essential for the forma-
tion of amides from either alcohol or aldehyde.
a Determined by GC using dodecane as an internal standard, average
of two runs.
Scheme 3. Reactions of a Mixture of an Alcohol
and an Aldehydea
Conclusions
In conclusion, we have shown that well-defined N-hetero-
cyclic carbene based ruthenium complexes are active for the
direct amide synthesis of alcohols with a catalytic amount of
a base. The Ru complexes enabled us to approach a facile
mechanistic investigation, suggesting that formation of a Ru
hydride catalytic intermediate by alcohols and a catalytic
amount of a base is necessary for catalytic cycles.
a Determined by GC using dodecane as an internal standard, average
of two runs.
The proposed mechanism is similar to the mechanism
proposed for the Ru-catalyzed alkylation of amine using
the “borrowing hydrogen” methodology.14 We think that
the critical point is whether a hemiaminal intermediate
would be further oxidized to a corresponding amide or
would form an imine, which could be subsequently hydro-
genated to an amine by elimination of water. On the basis of
the reports on the alkylation of amine done with similar Ru
complexes with supporting phosphine ligands and the essen-
tial role of NHC ligands on the amide formation,4,5,14 we
believe that the more σ-donating NHC ligand has a critical
role to facilitate the oxidation over the elimination of water.
It was reported that in situ generated NHC-based Ru was
not active4 or was much less active5 in the amide formation of
aldehydes with amines, forming imines as major products,
even though aldehydes were proposed as intermediates
formed by dehydrogenation of alcohols. To rationalize the
results, it was proposed that Ru coordination on the gener-
ated aldehyde would be essential for the catalytic cycle.4,5
Indeed, we could not observe any free aldehyde during the
NMR studies, suggesting the short lifetime of free aldehyde,
if it is even generated.
However, our study on the catalytic intermediate indi-
cated that there might be another possible reason for the
limited activity of the aldehyde. It would be less efficient to
form active [Ru]H2 from [Ru]Cl2 and an aldehyde without
the help of primary alcohols. To see whether primary
alcohols are essential for the catalysis, we ran two reactions
of the amidation of an aldehyde with and without a pri-
mary alcohol (Scheme 2). Aldehyde itself did not efficiently
produce an amide from benzaldehyde (37) with benzylamine
(7) under the same reaction conditions using complex 2.
However, when we added 10 mol % of the primary alcohol 6
as an additive, the reaction smoothly generated the corre-
sponding amide, N-benzylbenzamide (33), demonstrating
that formation of a catalytically active species by an alcohol
is necessary for the amidation of aldehydes. However, the
observation of 9% of 38 that was sometimes observed in
trace amounts, less than 3%, in the reaction of benzyl alcohol
and benzyl amine, and no observation of free aldehyde
Experimental Section
General Considerations. Unless otherwise noted, all reactions
were carried out using standard Schlenk techniques or in an
argon-filled glovebox. Dichloromethane, diethyl ether, and
toluene were dried over a Pure Solv solvent purification system.
Deuterated solvents were purchased from Cambridge Isotope
Laboratories and dried over molecular sieves. NMR spectra
were recorded in CDCl3, CD2Cl2, or toluene-d8 using a Bruker
DPX300, AMX400, JEOL ECA400, or JEOL ECA400SL
spectrometer, and TMS (tetramethylsilane) was used as a re-
ference. Chemical shifts were reported in ppm and coupling
constants in Hz. Elemental analyses were performed by the
Elemental Analysis Laboratory of the Division of Chemistry
and Biological Chemistry at Nanyang Technological Univer-
sity. GC analyses were carried out with a 7980A GC system
from Agilent Technologies, equipped with an HP-5 column.
1,3-Dimethylimidazolium iodide (9),17 (1,3-dimethylimidazol-
2-ylidene)silver(I) iodide,18 1,3-diisopropylimidazolium bro-
mide (5),19 and compound 48b were prepared by literature
procedures. Other chemicals were purchased from commercial
suppliers and used as received without further purification.
Synthesis of 2. A mixture of (1,3-dimethylimidazol-2-
ylidene)silver(I) iodide (148.9 mg, 0.45 mmol) and [Ru(p-cym-
ene)Cl2]2 (137.8 mg, 0.23 mmol) was stirred in CH2Cl2 at room
temperature for 6 h. The white precipitate (AgI) was then
filtered through Celite. After removal of the solvent under va-
cuum, analytically pure product 2 was obtained by washing the
crude product with diethyl ether (3 Â 5 mL). Yield: 93% (168.3 mg,
0.42 mmol). 1H NMR (400 MHz, CD2Cl2): δ 7.03 (s, 2H,
CHimid), 5.39 (d, J = 5.96 Hz, 2H, CHpcym), 5.06 (d, J = 5.96
Hz, 2H, CHpcym), 3.96 (s, 6H, NCH3), 2.93 (septet, J = 6.88 Hz,
1H, CHisop pcym), 1.98 (s, 3H, CH3pcym), 1.25 (d, J = 6.84 Hz,
6H, CH3isop pcym). The formation of complex 2 was confirmed
(17) Chu, Y.; Deng, H.; Cheng, J.-P. J. Org. Chem. 2007, 72, 7790.
(18) Khramov, D. M.; Lynch, V. M.; Bielawski, C. W. Organome-
tallics 2007, 26, 6042.
(19) Starikova, O. V.; Dolgushin, G. V.; Larina, L. I.; Ushakov, P. E.;
Komarova, T. N.; Lopyrev, V. A. Russ. J. Org. Chem. 2003, 39, 1467.

1378 Organometallics, Vol. 29, No. 6, 2010
Zhang et al.
1
by comparing the chemical shifts of H NMR with reported
Synthesis of 3-I. A Schlenk tube was charged with complex 3
(83.4 mg, 0.18 mmol), NaI (539.6 mg, 3.6 mmol), and 5 mL of
THF. The reaction mixture was stirred at room temperature for
8 h. All volatiles were removed under vacuum. The residue was
dissolved in toluene, and the resulting suspension was passed
through a plug of Celite. All the volatiles were removed, and the
residue was washed with diethyl ether (3 Â 5 mL) to give 3-I as a
dark red powder. Yield: 68% (78.5 mg, 0.12 mmol). 1H NMR
(300 MHz, CD2Cl2): δ 7.19 (s, 2H, CHimid), 5.69 (d, J = 5.91 Hz,
2H, CHpcym), 5.52 (septet, J = 6.60 Hz, 2H, CHisop imid), 5.15
(d, J = 5.88 Hz, 2H, CHpcym), 3.29 (septet, J = 6.93 Hz, 1H,
CHisop pcym), 2.01 (s, 3H, CH3pcym), 1.44 (br, 12H, CH3isop imid),
1.32 (d, J = 6.96 Hz, 6H, CH3isop pcym). 13C{1H} NMR (100 MHz,
CD2Cl2): δ 167.6 (C-Ru), 120.1 (CHimid), 108.4 (Cqpcym), 99.8
(Cqpcym), 87.3 (CHpcym), 82.3 (CHpcym), 55.0 (CHisop imid), 32.0
(CHisop pcym), 25.7 (CH3isop imid), 25.1 (CH3isop imid), 23.2
(CH3isop pcym), 19.8 (CH3pcym). Anal. Calcd for C20H32Cl2I2N2-
values.8a
Synthesis of 2-I. A Schlenk tube was charged with complex 2
(67.7 mg, 0.17 mmol), NaI (509.7 mg, 3.4 mmol), and 5 mL of
THF. The reaction mixture was stirred at room temperature for
8 h. The solvent was removed under vacuum. The residue was
dissolved in toluene, and the resulting suspension was passed
through a plug of Celite. All the volatiles were removed, and the
residue was washed with diethyl ether (3 Â 5 mL) to give 2-I as a
dark red powder. Yield: 70% (69.8 mg, 0.12 mmol). 1H NMR
(400 MHz, CD2Cl2): δ 7.08 (s, 2H, CHimid), 5.59 (d, J = 5.60 Hz,
2H, CHpcym), 5.18 (d, J = 5.56 Hz, 2H, CHpcym), 4.04 (s, 6H,
CH3imid), 3.15 (septet, J = 6.88 Hz, 1H, CHisop pcym), 1.96 (s,
3H, CH3pcym), 1.23 (d, J = 6.88 Hz, 6H, CH3isop pcym). 13C{1H}
NMR (100 MHz, CD2Cl2): δ 170.4 (C-Ru), 124.4 (CHimid),
110.0 (Cqpcym), 99.9 (Cqpcym), 86.6 (CHpcym), 83.0 (CHpcym),
44.9 (CH3imid), 32.0 (CHisop pcym), 23.0 (CH3isop pcym), 19.2
(CH3pcym). Anal. Calcd for C16H24Cl2I2N2Ru (2-I CH2Cl2,
670.2): C, 28.68; H, 3.61; N, 4.18. Found: C, 28.41; H, 3.89;
N, 4.33.
Ru (3-I CH2Cl2, 726.3): C, 33.08; H, 4.44; N, 3.86. Found: C,
33.46; H, 4.01; N, 4.03.
3
3
General Procedure for Amide Synthesis. In an argon-filled
glovebox, a 10 mL oven-dried Schlenk tube was charged with
complex 2, 3, or 4 (0.025 mmol), base (0.075 mmol), and 0.6 mL
of toluene. The Schlenk tube was then taken out, and alcohol
(0.50 mmol) and amine (0.55 mmol) were added. The reaction
mixture was heated to reflux under a flow of argon to facilitate
removal of hydrogen for 24 h before being cooled to room
temperature. All the volatiles were removed under vacuum.
Purification of the crude product by flash chromatography
afforded amides. All the amides were identified by spectral
comparison with literature data.3-5
Synthesis of 3. A suspension of 1,3-diisopropylimidazolium
bromide (106.4 mg, 0.46 mmol) and Ag2O (64.0 mg, 0.28 mmol)
in CH2Cl2 was stirred at room temperature in the dark for 2 h.
The mixture was then filtered through a plug of Celite, and to the
filtrate was added [Ru(p-cymene)Cl2]2 (139.8 mg, 0.23 mmol).
The reaction mixture was stirred at room temperature for 2 h
and then filtered through Celite. The solvent was removed under
vacuum. Washing the crude product with diethyl ether
(3 Â 5 mL) can afford 3 as an orange powder. Yield: 90%
(189.8 mg, 0.41 mmol). 1H NMR (300 MHz, CD2Cl2): δ 7.15 (s,
2H, CHimid), 5.48 (d, J = 5.97 Hz, 2H, CHpcym), 5.34-5.25
(m, 2H, CHisop imid), 5.06 (d, J = 6.00 Hz, 2H, CHpcym), 2.94
(septet, J = 6.96 Hz, 1H, CHisop pcym), 2.01 (s, 3H, CH3pcym),
1.42 (br, 12H, CH3isop imid), 1.31 (d, J = 6.93 Hz, 6H,
CH3isop pcym). 13C{1H} NMR (100 MHz, CD2Cl2):δ172.2 (C-Ru),
119.5 (CHimdi), 107.4 (Cqpcym), 98.5 (Cqpcym), 86.9 (CHpcym),
82.0 (CHpcym), 52.5 (CHisop imid), 31.2 (CHisop pcym), 25.5
(CH3isop imid), 25.1 (CH3isop imid), 22.9 (CH3isop pcym), 19.2
Acknowledgment. The Singapore National Research
Foundation is acknowledged for financial support (NRF-
RF2008-05). Y.Z. and C.C. thank the Nanyang Techno-
logical University for graduate student scholarships.
Supporting Information Available: 1H and 13C NMR spectra
of new compounds and X-ray data for complex 3 in CIF format.
This material is available free of charge via the Internet at http://
pubs.acs.org.
(CH3pcym). Anal. Calcd for C20H32Cl4N2Ru (3 CH2Cl2,
3
543.4): C, 44.21; H, 5.94; N, 5.16. Found: C,44.68; H, 5.63;
N, 5.37.