N-heterocyclic carbene based ruthenium-catalyzed direct amide synthesis from alcohols and secondary amines: Involvement of esters

Article abstract of DOI:10.1021/jo201756z

A well-defined N-heterocyclic carbene based ruthenium complex was developed as a highly active precatalyst for the direct amide synthesis from alcohols and secondary amines. Notably, reaction of 1-hexanol and dibenzylamine afforded 60% of the corresponding amide using our catalytic system, while no amide formation was observed for this reaction with the previously reported catalytic systems. Unlike the previously reported amidation with less sterically hindered alcohols and amines, involvement of ester intermediates was observed (Figure presented).

Full text of DOI:10.1021/jo201756z

Article
pubs.acs.org/joc
N-Heterocyclic Carbene Based Ruthenium-Catalyzed Direct Amide
Synthesis from Alcohols and Secondary Amines: Involvement of
Esters
Cheng Chen,‡ Yao Zhang,‡ and Soon Hyeok Hong†,‡,*
†Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea
‡Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 637371, Singapore
S
* Supporting Information
ABSTRACT: A well-defined N-heterocyclic carbene based ruthenium
complex was developed as a highly active precatalyst for the direct amide
synthesis from alcohols and secondary amines. Notably, reaction of
1-hexanol and dibenzylamine afforded 60% of the corresponding amide
using our catalytic system, while no amide formation was observed for this
reaction with the previously reported catalytic systems. Unlike the
previously reported amidation with less sterically hindered alcohols and amines, involvement of ester intermediates was observed.
Our group reported (p-cymene)(NHC)RuX2 complexes
such as 1 and 2 as precatalysts for the direct amide synthesis
(Figure 1).6 When we attempted less sterically bulky NHC-
INTRODUCTION
■
Transition-metal-catalyzed oxidative amide synthesis directly
from alcohols and amines, without any oxidative preparation of
aldehydes, carboxylic acids, and acyl halides, has been recently
highlighted as a highly atom economical transformation that
generates hydrogen as the sole byproduct.1 Among the
reported catalytic systems, ruthenium complexes have been
most extensively studied.2−11
Although the direct amide synthesis has attractive advantages
over traditional amide syntheses, there are many challenges for
this emerging method to be widely used for the synthesis of
ubiquitous amides, such as limited substrate scope and harsh
reaction conditions.1 One of the challenges is the amidation of
secondary amines.1 The reported Ru catalysts showed limited
activity for the reactions between alcohols and linear secondary
amines, especially with sterically hindered ones, while they
showed excellent activity for less hindered primary amines.2−10
For example, no desired product has been observed with the
previous catalytic systems when dibenzylamine was used for the
amidation reaction (Scheme 1).3,5 Herein, we wish to address
Figure 1. Ru complexes for the direct amide synthesis from alcohols
and amines.
based 2 for the transformation of sterically hindered substrates
including secondary amines, no improvement was observed.
Although it was postulated that the arene group would be
dissociated during the catalysis,6,8,10 it was reported that
improvements could be achieved by changing a Ru precursor
[RuCl2(p-cymene)]2 with [RuCl2(benzene)]2 for less hindered
cyclic secondary amines such as piperidine and morpholine.5 As
an example, the [RuCl2(benzene)]2-based catalytic system
showed 90% yield on the amidation of morpholine with
2-phenylethanol (vs 63% with [RuCl2(p-cymene)]2), although
it still showed limitations on other steically more congested
secondary amines such as dibenzylamine.5 These observations
led us to explore the catalytic activity of Ru complex 3 for the
amidation of challenging secondary amines with alcohols.
Scheme 1. Reaction of 1-Hexanol and Dibenzylamine
RESULTS AND DISCUSSION
■
Complex 3 was synthesized by transmetalation from an NHC-
Ag complex, and the structure was confirmed by X-ray
the issue by reporting an NHC-based Ru complex as an active
precatalyst for the amide synthesis from alcohols and secondary
amines.
Received: August 24, 2011
Published: November 15, 2011
© 2011 American Chemical Society
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a
Table 1. Direct Amide Synthesis from Alcohols and Primary Amines Catalyzed by 3
a
b
c
Catalyst 3 (5 mol %), KOtBu (15 mol %), toluene, reflux, 24 h unless otherwise noted. Isolated yields. No ester was observed. 20 mol % KOtBu.
crystallography.12 Attempts to synthesize less sterically
congested 4 by the same procedure were not successful
presumably as a result of lower stability. Since no improvement
was previously reported on sterically bulky substrates with 2
over 1, we decided to pursue the amidation reaction only with
3.6,9 It has been consistently reported that 1,3-diisopropylimi-
dazoline showed the best activities on the NHC-promoted Ru-
catalyzed amide synthesis among the other NHCs.4−9
Reactions of alcohols and primary amines catalyzed by 3
were explored first (Table 1). The optimization of the catalytic
conditions was conducted with a reaction of 5a and 6a. It was
found that 15−20 mol % KOtBu or NaH and 5 mol % of 3 are
required for the catalysis, consistent with the previous report.6
It was suggested that the role of the strong base is to stimulate
the formation of Ru alkoxide species, which are further
transformed to an active Ru hydride catalytic intermediate.6,7
Good to excellent yields were obtained for both intermolecular
and intramolecular processes with precatalyst 3 (Table 1).
Catalytic activities of 3 on the amidation of primary amines
with alcohols were generally comparable with 1 and 2.6 No
ester was observed in the reactions in Table 1, consistent with
other NHC-Ru catalyzed amidation of less hindered primary
amines with alcohol.4,5
lower yields were obtained for electron-deficient substrates as
observed with complex 1 and 2 (entries 6−8).6 Excitingly, the
more bulky secondary amine, dibenzylamine, worked well in
the presence of 35 mol % of KOtBu (entries 9 and 10), while
previously reported catalysts were not active for the reaction of
a primary alcohol and dibenzylamine.3,5 A few bulky secondary
amines were tested, and moderate to good yields were obtained
(entries 11−13). Different from the cases of primary amines in
Table 1, we observed esters, formed by oxidative esterification
of alcohols 5, as a byproduct in some cases, especially when the
reaction was performed with sterically bulky secondary amines
(Table 2).13
To understand the rationale for the improvement on the
secondary amine, we first investigated the effect of the arene
ring of precatalysts 1 and 3. Initially, we suspected that less
hindered benzene compared to p-cymene would result in the
improvement for more hindered secondary amines. Noyori,
Ikariya, and co-workers discussed the arene effect in
[RuCl2(arene)]2 complexes for asymmetric transfer hydro-
genation.14 Noels and co-workers also reported the effect of the
arene on the RuCl2(arene)(PR3)-catalyzed ring-opening meta-
thesis polymerization.15 It has been reported in different cases
that dissociation of the arene ligand is necessary for catalytlic
activity of 18-electron RuCl2(arene)(L)-type complexes (L =
PR3 or NHC).15,16 In the case of the direct amidation catalyzed
by 1 and 2, it has been also suggested that arene ligand is fully
dissociated especially at the required reaction temperature of
110 °C.4−9 Indeed, free benzene or p-cymene was observed
Next, various secondary amines were tested for the amidation
reactions (Table 2). To our delight, 3 showed higher activity
for secondary amines with increased amount of KOtBu. Cyclic
secondary amines and less bulky noncyclic ones yielded
excellent yields (entries 1−5). The previously reported yields
for the reaction between a primary alcohol and N-benzyl
methylamine are 40−70%.4,5,8 In contrast, 3 can catalyze the
same reaction in 90% yield (entry 3). We studied the electronic
effect on alcohols using benzyl alcohol derivatives. Slightly
1
during catalysis when the reaction was monitored by H NMR
spectroscopy in toluene-d8 indicating the full dissociation of
arene rings. Therefore, we believe that the reduced steric effect
of the benzene ring of 3 should not be the reason. Next, we
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a
Table 2. Direct Amide Synthesis from Alcohols and Secondary Amines Catalyzed by 3
a
b
Complex 3 (5 mol %), KOtBu (35 mol %), 1 equiv alcohol and 1.1 equiv amine, toluene, reflux, 24 h unless otherwise noted. Isolated yields. Yields
c
d
in parentheses represent the yields of the corresponding ester from alcohol 5. 20 mol % KOtBu. 1 equiv alcohol and 2 equiv amine.
focused on the less electron-rich nature of benzene compared
to p-cymene. If full dissociation of the arene ring should occur
to generate the active catalytic intermediate, 3 can generate the
active catalytic intermediate, i.e., initiate the catalytic cycle faster
than with 1 because of the more electron-deficient arene ring.
Kinetic data showed that the reactions catalyzed by 3 were
faster than those catalyzed by 1 (23% by 1 vs 31% by 3 for the
reaction of entry 9 in Table 2, after 3 h, Figure 2), suggesting
that faster dissociation of benzene ring could be one of the
reasons of the improvement. However, the undramatic reaction
rate acceleration with 3 implied that there might be another
reason for the improvement.
Next, we noticed that the increased amount of KOtBu was
required. Previously, there was no significant formation of 9i
with 5 mol % complex 1 and 2 and 15−20 mol % of KOtBu.
The improved conversion in Figure 2, even with 1, strongly
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this study, compared to those used in the primary amine
amidations, implied that there might be another role of the
base. Product distribution depending on the amount of the base
was thoroughly investigated with the reaction between 5e and
8f catalyzed by 3 (Table 3). It was found that as the amount of
KOtBu increased up to 35 mol %, the yield of the desired
product 9i increased while that of the major byproduct 10
decreased, which means the increased amount of KOtBu either
decreased the formation of 10 or promoted the reaction
between 10 and 8f to give 9i (Table 3). The Ru-catalyzed
formation of esters from alcohols has been well documented.13
It was also reported as one of side reactions on the Ru-catalyzed
amide and cyclic imide syntheses from alcohols.3,8,17
A few catalytic amide formation reactions from esters and
amines have been reported including the very recent report
using dearomatized Ru-pincer complexes by Milstein and co-
workers.18 NHC-based Ru catalytic systems developed for the
amide synthesis from alcohols and amines were reported not
efficient for the amide formation from esters and amines.3−5
The less efficient amidation of esters under the reported
catalytic conditions using 15−20 mol % of a strong base were
confirmed again by entry 3 in Table 3.5 However, when an
increased amount of KOtBu was used, the amidation from ester
worked with moderate yields (entries 4−8, Table 4). The
optimal amount of the base, 0.3−0.5 equiv, was close to our
current conditions for the secondary amine amidation.
Figure 2. Comparison of reaction progress monitored by GC (entry 9
in Table 2).
implied that the increased amount of the strong base might be
the key of the improvement. The role of a catalytic amount of a
strong base was suggested to activate [Ru]Cl2-type precatalysts
by generating [Ru]H2 species from alkoxides and the
precatalysts.6 However, the increased amounts of the base in
Table 3. Reaction of 1-Hexanol and Dibenzylamine Catalyzed by 3 with Different Amounts of KOtBu
a
a
entry
KOtBu (equiv)
9i (%)
10 (%)
1
2
3
4
5
6
7
8
0.15
0.20
0.25
0.30
0.35
0.40
0.60
1.00
33
34
50
51
60
44
30
11
61
50
10
8
<3
<1
<1
<1
a
Isolated yields.
Table 4. Reaction of an Ester and Dibenzylamine Catalyzed by 3 with Different Amounts of KOtBu
a
entry
precatalyst
KOtBu (equiv)
yield for 9i (%)
1
3
3
3
3
3
3
3
3
3
3
0.00
0.10
0.20
0.30
0.35
0.40
0.45
0.50
0.60
1.00
0.40
<1
<1
6
2
3
4
39
46
59
44
40
31
10
<1
5
6
7
8
9
10
11
a
Isolated yields.
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General Procedure for Amide Synthesis. Inside an argon-filled
glovebox, compound 3 (10.0 mg, 0.025 mmol), KOtBu (8.4 mg, 0.075
mmol), and toluene (0.6 mL) were added to an oven-dried Schlenk
tube. The Schlenk tube was taken out of the glovebox before the
alcohol (0.5 mmol) and the amine (0.55 mmol) were added. Then
the mixture was heated to reflux under argon atmosphere for 24 h. The
reaction mixture was cooled down to room temperature, and the
solvent was removed in vacuo. The residue was purified by silica gel
flash column chromatography to afford the amide. N-Benzyl-2-
phenylacetamide (7a),5 N-hexyl-2-phenylacetamide (7b),5 piperidin-
2-one (7d),5 N-benzyl-2-methylbutanamide (7e),5 N-(heptan-2-yl)-2-
phenylacetamide (7f),9 2-phenyl-1-(piperidin-1-yl)ethanone (9a),9
1-morpholino-2-phenylethanone (9b),5 N-benzyl-N-methyl-2-phenyl-
acetamide (9c),5 N-benzyl-N-methylbenzamide (9f),22 N-benzyl-N-
methyl-4-methoxybenzamide (9g),22 and N-benzyl-N-methyl-4-fluo-
robenzamide (9h)22 were identified by spectral comparison with
literature data.
Therefore, we believe that in the case of sterically hindered
secondary amine amidation where direct amidation is less
efficient, involvement of an ester intermediate and its
conversion to the amide product with help of a catalytic
intermediate, presumably generated by a Ru−NHC complex
and an increased amount of a base, is essential for the
improvement. The exact nature of the catalytic intermediate
and the precise role of the increased amount of the base are
currently unclear. Revised pathways for the amidation of
alcohols with amines are suggested in Scheme 2.19 We are
Scheme 2. Proposed Pathways for the Direct Amidation of
Alcohols with Amines
N-Benzylfuran-2-carboxamide (7c). Purified by silica gel
chromatography using hexane/ethyl acetate (3:1) solvent mixture as
an eluent. White solid. Isolated yield: 80%. Mp 112−113 °C. 1H NMR
(CDCl3) δ 7.40 (s, 1 H), 7.20−7.38 (m, 5 H), 7.13 (m, 1 H), 6.74
(s, 1H), 6.49 (m, 1 H), 4.60 (d, 2H, J = 5.92 Hz). 13C NMR (CDCl3)
δ 158.4, 148.0, 144.1, 138.2, 128.9, 128.0, 127.8, 114.5, 112.3, 43.3.
HRMS-ESI (m/z): [M + H+] calcd for C12H12NO2, 202.0868; found,
202.0872.
N-Methyl-N-phenethyl-2-phenylacetamide (9d). Purified by
silica gel column chromatography using hexane/ethyl acetate (3:1)
solvent mixture as an eluent. Pale yellow clear oil. Yield: 87%, 1:1.1
1
mixture of rotamers. H NMR (CDCl3) (major rotamer) δ 7.02−7.38
currently investigating the amidation of esters with the NHC-
based Ru catalytic systems.
(m, 10 H), 3.68 (s, 2H), 3.60 (t, 2H, J = 7.56 Hz), 2.84 (s, 3H), 2.83
(t, 2H, J = 7.56 Hz); 1H NMR (CDCl3) (minor rotamer) δ 7.02−7.38
(m, 10 H), 3.49 (t, 2H, J = 7. 32 Hz), 3.44 (s, 2H), 2.98 (s, 3H), 2.72
(t, 2H, J = 7.32 Hz). 13C NMR (CDCl3) δ 171.1, 171.0, 139.2, 138.3,
135.4, 135.1, 129.0, 128.9, 128.8, 128.6, 127.0, 126.9, 126.8, 126.4,
52.2, 50.3, 41.5, 40.8, 36.7, 34.9, 33.8, 33.7. HRMS-ESI (m/z): [M + H+]
calcd for C17H20NO, 254.1545; found, 254.1547.
CONCLUSION
■
The direct amidation of alcohols with challenging secondary
amines was achieved with a well-defined N-heterocyclic carbene
based ruthenium complex. Involvement of ester intermediates
was suggested unlike the previous amidation with less sterically
hindered alcohols and amines. The scope and the nature of
catalysts for NHC-Ru catalyzed conversion from esters to
amides will be reported in due course.
N-Hexyl-N-methylhexanamide (9e). Purified by silica gel
column chromatography using hexane/ethyl acetate (5:1) solvent
mixture as an eluent. Colorless clear oil. Yield: 81%, 1:1.05 mixture of
1
rotamers. H NMR (CDCl3) (major rotamer) δ 3.25 (t, 2H, J = 7.60
Hz), 2.91 (s, 3H), 2.20−2.40 (m, 2H), 1.42−1.75 (m, 4H), 1.20−1.40
1
(m, 10H), 0.80−1.00 (m, 6H); H NMR (CDCl3) (minor rotamer) δ
3.35 (t, 2H, J = 7.52 Hz), 2.97 (s, 3H), 2.20−2.40 (m, 2H), 1.42−1.75
(m, 4H), 1.20−1.40 (m, 10H), 0.80−1.00 (m, 6H). 13C NMR (CDCl3) δ
173.2, 173.1, 50.2, 47.8, 35.5, 33.7, 33.5, 33.1, 31.9, 31.8, 31.7, 31.6,
28.6, 27.4, 26.6, 26.5, 25.3, 25.0, 22.7, 22.6, 14.2, 14.1. HRMS-ESI (m/z ):
[M + H+] calcd for C13H28NO, 214.2171; found, 214.2178.
EXPERIMENTAL SECTION
General Considerations. All reactions were carried out using
■
standard Schlenk techniques or in an argon-filled glovebox unless
1
otherwise mentioned. H and 13C NMR spectra were recorded at 400
N,N-Dibenzylhexanamide (9i). Purified by silica gel column
chromatography using hexane/ethyl acetate (10:1) solvent mixture as
an eluent. Pale yellow clear oil. Yield: 60%. 1H NMR (CDCl3) δ 7.02−
7.45 (m, 10 H), 4.60 (s, 2H), 4.44 (s, 2H), 2.41 (t, 2H, J = 7.56 Hz),
1.72 (pent, 2H, J = 7.56 Hz), 1.20−1.40 (m, 4H), 0.88 (t, 3H, J = 6.88
Hz); 13C NMR (CDCl3) δ 173.9, 137.7, 136.8, 129.1, 128.7, 128.4,
127.7, 127.5, 126.5, 50.1, 48.2, 33.4, 31.8, 25.3, 22.7, 14.1. HRMS-ESI
(m/z): [M + H+] calcd for C20H26NO, 296.2014; found, 296.2015.
N,N-Dibenzyl-2-phenylacetamide (9j). Purified by silica gel
column chromatography using hexane/ethyl acetate (7:1) solvent
mixture as an eluent. Pale yellow clear oil. Yield: 40%. 1H NMR
(CDCl3) δ 7.02−7.45 (m, 15 H), 4.61 (s, 2H), 4.43 (s, 2H), 3.79
(s, 2H); 13C NMR (CDCl3) δ 171.8, 137.5, 136.6, 135.2, 129.2, 129.0,
128.9, 128.8, 128.5, 127.9, 127.6, 127.1, 126.6, 50.4, 48.4, 41.2. HRMS-
ESI (m/z): [M + H+] calcd for C22H22NO: 316.1701, found, 316.1702.
N-Benzyl-N-ethylhexanamide (9k). Purified by silica gel col-
umn chromatography using hexane/ethyl acetate (7:1) solvent mixture
as an eluent. Pale yellow clear oil. Yield: 60%, 1:1.3 mixture of
and 100 MHz, respectively. Chemical shifts were reported in ppm and
coupling constants in Hz. GC analyses were carried out using
dodecane as an internal standard. Mass spectrometry was performed
using electrospray ionization (ESI) mode.
Materials. 1,3-Diisopropylimdazolium bromide,5 hexyl hexanoate
(10),20 phenethyl 2-phenylacetate (11),4 4-methoxybenzyl 4-methoxy-
benzoate (12),21 and compound 16 were prepared by the literature
procedures. Alcohols and amines were purchased from commercial
suppliers and used as received without further purification. Toluene
was dried over a solvent purification system.
Synthesis of 3. A suspension of 1,3-diisopropylimdazolium
bromide (106.4 mg, 0.46 mmol) and Ag2O (64.0 mg, 0.28 mmol)
in CH2Cl2 was stirred at room temperature in dark for 2 h. The
mixture was then filtered through a plug of Celite, followed by the
addition of [RuCl2(benzene)]2 (115.0 mg, 0.23 mmol). The reaction
mixture was stirred at room temperature for 4 h and then filtered
through Celite. The solvent was removed under vacuum. Washing the
crude product with diethyl ether (3 × 5 mL) afforded 3 as an orange
powder. Yield: 85% (156.8 mg, 0.39 mmol). Mp 219 °C dec; 1H NMR
(CD2Cl2) δ 7.17 (s, 2H), 5.53 (s, 6H), 5.35−5.50 (m, 2H), 1.25−1.55
(m, 12H); 13C NMR (CD2Cl2) δ 170.1, 119.7, 86.5, 52.8, 25.5, 24.6.
Anal. Calcd for C15H22Cl2N2Ru (3): C, 44.78; H, 5.51; N, 6.96.
Found: C, 44.65; H, 5.12; N, 6.64.
1
rotamers. H NMR (CDCl3) (major rotamer) δ 7.02−7.38 (m, 5 H),
4.56 (s, 2H), 3.23 (q, 2H, J = 7.17 Hz), 2.34 (t, 2H, J = 7.78 Hz),
1.50−1.80 (m, 2H), 1.16−1.42 (m, 4H), 1.02−1.15 (m, 3H), 0.75−
1.00 (m, 3H); 1H NMR (CDCl3) (minor rotamer) δ 7.02−7.38 (m, 5
H), 4.48 (s, 2H), 3.38 (q, 2H, J = 7.16 Hz), 2.27 (t, 2H, J = 7.78 Hz),
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1.50−1.80 (m, 2H), 1.16−1.42 (m, 4H), 1.02−1.15 (m, 3H), 0.75−
1.00 (m, 3H); 13C NMR (CDCl3) δ 173.4, 173.2, 138.3, 137.4, 129.0,
128.6, 128.1, 127.6, 127.3, 126.4, 50.7, 47.8, 41.7, 41.0, 33.5, 33.2, 31.9,
31.8, 25.4, 25.2, 22.7, 22.6, 14.2, 14.1, 13.9, 12.9. HRMS-ESI (m/z ):
[M + H+] calcd for C15H24NO, 234.1858; found, 234.1858.
(8) Dam, J. H.; Osztrovszky, G.; Nordstrøm, L. U.; Madsen, R.
Chem.−Eur. J. 2010, 16, 6820.
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(10) Prades, A.; Peris, E.; Albrecht, M. Organometallics 2011, 30,
1162.
N-Benzyl-N-phenethylhexanamide (9l). Purified by silica gel
column chromatography using hexane/ethyl acetate (7:1) solvent
mixture as an eluent. Pale yellow clear oil. Yield: 43%, 1:1.05 mixture
(11) For other metals, see: (a) Fujita, K.; Takahashi, Y.; Owaki, M.;
Yamamoto, K.; Yamaguchi, R. Org. Lett. 2004, 6, 2785. (b) Zweifel, T.;
Naubron, J. V.; Grutzmacher, H. Angew. Chem., Int. Ed. 2009, 48, 559.
̈
1
of rotamers. H NMR (CDCl3) (major rotamer) δ 7.02−7.40 (m,
(c) Shimizu, K.; Ohshima, K.; Satsuma, A. Chem.−Eur. J. 2009, 15,
10 H), 4.35 (s, 2H), 3.56 (t, 2H, J = 7.56 Hz), 2.85 (t, 2H, J = 7.56
Hz), 2.31 (t, 2H, J = 7.54 Hz), 1.55−1.75 (m, 2H), 1.20−1.40 (m,
4H), 0.80−1.00 (m, 3H); 1H NMR (CDCl3) (minor rotamer) δ
7.02−7.40 (m, 10 H), 4.61 (s, 2H), 3.43 (t, 2H, J = 7.56 Hz), 2.79 (t,
2H, J = 7.56 Hz), 2.22 (t, 2H, J = 7.78 Hz), 1.55−1.75 (m, 2H), 1.20−
1.40 (m, 4H), 0.80−1.00 (m, 3H); 13C NMR (CDCl3) δ 173.7, 173.5,
139.5, 138.4, 138.0, 137.2, 129.0, 129.0, 128.9, 128.9, 128.7, 128.6,
128.3, 127.7, 127.5, 126.9, 126.5, 52.0, 48.7, 48.5, 48.3, 35.2, 34.2, 33.5,
33.1, 31.8, 31.7, 25.3, 25.2, 22.7, 14.2, 14.1. HRMS-ESI (m/z): [M +
H+] calcd for C21H28NO, 310.2171; found, 310.2173.
9977.
(12) See Supporting Information for the X-ray crystallography data.
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2-Phenyl-N,N-dipropylacetamide (9m). Purified by silica gel
column chromatography using hexane/ethyl acetate (7:1) solvent
mixture as an eluent. Colorless clear oil. Yield: 44%. 1H NMR
(CDCl3) δ 7.15−7.40 (m, 5 H), 3.70 (s, 2H), 3.29 (t, 2H, J = 7.54
Hz), 3.18 (t, 2H, J = 7.78 Hz), 1.41−1.69 (m, 4H), 0.75−0.95
(m, 6H); 13C NMR (CDCl3) δ 170.7, 135.7, 128.8, 128.7, 126.8, 50.1,
47.7, 41.1, 22.3, 21.0, 11.6, 11.4. HRMS-ESI (m/z): [M + H+] calcd
for C14H22NO, 220.1701; found, 220.1696.
(16) Delaude, L.; Delfosse, S.; Richel, A.; Demonceau, A.; Noels, A.
F. Chem. Commum. 2003, 1526.
(17) Zhang, J.; Senthilkumar, M.; Ghosh, S. C.; Hong, S. H. Angew.
Chem., Int. Ed. 2010, 49, 6391.
(18) (a) Gnanaprakasam, B.; Milstein, D. J. Am. Chem. Soc. 2011,
133, 1682. (b) Ishihara, K.; Kuroki, Y.; Hanaki, N.; Ohara, S.;
Yamamoto, H. J. Am. Chem. Soc. 1996, 118, 1569. (c) Han, C.; Lee, J.
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(d) Kuroki, Y.; Ishihara, K.; Hanaki, N.; Ohara, S.; Yamamoto, H. Bull.
Chem. Soc. Jpn. 1998, 71, 1221.
ASSOCIATED CONTENT
■
S
* Supporting Information
X-ray data for complex 3 in CIF format and H and 13C NMR
1
spectra. This material is available free of charge via the Internet
at http://pubs.acs.org.
(19) For the detailed mechanisms of the related Ru-catalyzed
amidation, see refs 6 and 8.
(20) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. J. Am. Chem.
Soc. 2005, 127, 10840.
(21) Gowrisankar, S.; Neumann, H.; Beller, M. Angew. Chem., Int. Ed.
2011, 50, 5139.
AUTHOR INFORMATION
Corresponding Author
*E-mail: soonhong@snu.ac.kr.
■
(22) Li, J. M.; Xu, F.; Zhang, Y.; Shen, Q. J. Org. Chem. 2009, 74,
2575.
ACKNOWLEDGMENTS
■
This work is supported by the Research Settlement Fund for
the new faculty of Seoul National University. The Singapore
National Research Foundation is also acknowledged for
generous support of this research (NRF-RF2008-05). C.C.
and Y.Z. thank Nanyang Technological University for graduate
student scholarships. We are also grateful for Dr. Yongxin Li for
generous help with the X-ray crystallography.
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