Mild gold-catalyzed aerobic dehydrogenative coupling of amines and phenylglyoxal derivatives

Article abstract of DOI:10.1016/j.jorganchem.2014.05.017

A simple and efficient gold-catalyzed coupling of secondary amine with phenylglyoxal derivatives has been developed, which provides a practical synthetic strategy for the synthesis of substituted α-ketoamides under mild reaction conditions.

Full text of DOI:10.1016/j.jorganchem.2014.05.017

Accepted Manuscript
Mild Gold-Catalyzed Aerobic Dehydrogenative Coupling of Amines and Phenylglyoxal
Derivatives
Ying Shao , Zhuhong Wu , Chunbao Miao , Li Liu
PII:
S0022-328X(14)00245-9
10.1016/j.jorganchem.2014.05.017
JOM 18589
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 29 March 2014
Revised Date: 16 May 2014
Accepted Date: 17 May 2014
Please cite this article as: Y. Shao, Z. Wu, C. Miao, L. Liu, Mild Gold-Catalyzed Aerobic
Dehydrogenative Coupling of Amines and Phenylglyoxal Derivatives, Journal of Organometallic
Chemistry (2014), doi: 10.1016/j.jorganchem.2014.05.017.
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ACCEPTED MANUSCRIPT
Mild Gold-Catalyzed Aerobic Dehydrogenative Coupling of
Amines and Phenylglyoxal Derivatives **
Ying Shao, Zhuhong Wu, Chunbao Miao, Li Liu*
A simple and efficient gold-catalyzed coupling of secondary amine with phenylglyoxal
derivatives has been developed, which provides a practical synthetic strategy for the
synthesis of substituted α-ketoamides under mild reaction conditions.

ACCEPTED MANUSCRIPT
Highlights
A novel method for the synthesis of a-ketoamides is developed.
Arylglyoxal can react with secondary amines effectively by AuBr3 catalyst in air.
The scope of the present reaction is extended.
A radical involved mechanism is proposed.

ACCEPTED MANUSCRIPT
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Mild Gold-Catalyzed Aerobic Dehydrogenative Coupling of Amines and
Phenylglyoxal Derivatives
Ying Shao, Zhuhong Wu, Chunbao Miao, Li Liu 1
O
R1
N
O
5 mol% AuBr3
R1
R2
R2
H
Ar
Ar
CH2Cl2, 60oC, air
N
H
O
O
53%-93% yield

1
ACCEPTED MANUSCRIPT
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com
Mild Gold-Catalyzed Aerobic Dehydrogenative Coupling of Amines and
Phenylglyoxal Derivatives
Ying Shao, Zhuhong Wu, Chunbao Miao, Li Liu*
Key Laboratory of Advanced Catalytic Materials and Technology, School of Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R.
China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A simple and efficient gold-catalyzed coupling of secondary amine with phenylglyoxal
derivatives has been developed, which provides a practical synthetic strategy for the synthesis of
substituted α-ketoamides under mild reaction conditions.
Available online
2014 Elsevier Ltd. All rights reserved
.
Keywords:
α-ketoamide
gold-catalyzed
phenylglyoxal derivatives
secondary amine
———
* Corresponding author. Fax: +86 519 86330224.
E-mail address: liliuchem@gmail.com

2
Our initial studies focused on the phenylglyoxal
ACCEPTED MANUSCRIPT
1. Introduction
monohydrate (1a) and piperidine (2a) in the presense of 5
mol% AuCl in DCM at room temperature for 12 h. The
desired α-ketoamide 3a was obtained in 10% yield (Table 1,
entry 1). Among the gold catalysts tested (entries 2-5), AuBr3
was the best which was found to afford the desired product in
34% yield, but the yield was still low. Interestingly, Ag2CO3
was found to be almost as effective as AuBr3. No reaction
product was observed in the absence of catalyst (Table 1,
entry 6). The desired product 3a was obtained along with
phenyl(piperdine-1-yl)methanone in the presence of CuBr.
The transition-metal-catalyzed amidation reaction is a
widely used transformation that has been applied to the
synthesis of complex organic molecules and commodity
chemicals.1 α-Ketoamides are omnipresent among the most
abundant motifs in natural products and pharmaceuticals with
important biologically active properties.2 In addition, they also
used as useful precursors for synthesis of α-hydroxy acids, α-
amino acids and others.3 The development of synthesis α-
ketoamides has therefore attracted considerable attention.
Among these methods, transition metal-catalyzed double
carbonylative amination of aryl halides, aerobic oxidative
o
When the reaction temperature was increased to 60 C, the
obtained yield was promoted to 72% (entry 6). The reactions
showed lower yields when they were in other solvents such
as DCE, MeOH, H2O and toluene, even in higher reaction
temperature.
coupling reactions have been explored, especially the
4
formations involving secondary amine.
High reaction
temperature and phosphine, N-heterocyclic carbene (NHC) or
N-based ligands are usually required in these amidation
reactions (Scheme 1).5 Recently, Ji developed a novel copper-
catalyzed direct oxidative synthesis of α-ketoamides from aryl
methyl ketones.4e However, a general and simple catalytic
system on the direct accessing α-ketoamides is still a great
demand.
Table 1. Optimization of reaction conditions for the preparation
of 3a.a
Pd or Cu / ligand
+
Ar
X
H
CO, base
Buchwald
N
H
Xia & Sun
entry
catalyst
T(ºC)
solvent
yield(%)b
O
O
Cu / ligand
N
AuCl
AuCl3
25
25
25
25
25
25
25
25
60
60
60
60
60
80
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCE
10
17
34
0
+
1
2
Ar
Ar
Ar
N
H
Jiao
O
O
AuBr3
NaAuCl4·2H2O
CuI
O
3
Cu neat
+
+ O2
4
N
H
Ji
19
16
31
0
5
Scheme 1. Previous work on transition metal-catalyzed α-ketoamide
construction.
CuBr
6
Gold catalysts have recently gained growing attention and
have become an important tool for the organic synthesis,
owing to their soft lewis acidity and excellent reactivity. 6
Although many more reactions based on this theme are to be
developed, further expansion of gold chemistry demands
revelation of new reactivities. Recently, gold-catalyzed
coupling reactions involving Au(I)/Au(III) catalytic cycles
have been a hot research area in the presence of Selectfluor7
or PhI(OAc)28 as the external oxidants. However, the gold-
catalyzed oxidative coupling under aerobic oxidative
conditions is still a challenge. In 2012, the group of Zhu
developed a highly efficient homogeneous gold-catalyzed
oxidative C-C and C-P coupling methods by using air as the
sole oxidant under mild conditions.9 Wong and co-workers
uncovered an efficient aerobic gold-catalyzed amide synthesis
from aldehydes and amines with high functional group
tolerance in aqueous medium under mild reaction
conditions. 10 Herein, we report the example of gold(III)-
catalyzed phenylglyoxal derivatives and secondary amines to
give α-ketoamides under mild condition without ligand or
additive. 11
Ag2CO3
--
7
8
AuBr3
AuBr3
AuBr3
AuBr3
AuBr3
AuBr3
72
61
14
15
54
23
9
10
11
12
13
14
H2O
MeOH
Toluene
Toluene
a Standard reaction conditions: 1a (1.0 mmol), 2a (1.5 mmol), catalyst (5
mol%), solvent (2.0 mL) were heated in a sealed tube, 12 h. b Isolated
yield.
With the optimized reaction conditions in hand, we then
examined the scope of different phenylglyoxal derivatives and
amines. As shown in table 2, both electron-rich and electron-
deficient groups at different position (para-, meta-, and ortho-
position) of phenylglyoxal derivatives could be smoothly
transformed into the desired products with good yields. A
wide range of different groups at the aromatic moiety of
phenylglyoxal derivatives, such as halogen, trifluoromethyl,
and methoxy, generated the corresponding coupling products
2. Results and discussion

3
in 71-80% isolated yields (Table 2, 3a-3f). The substrates
bearing electron-withdrawing groups (3n-3q) was found
suitable to afford higher yield than phenylglyoxal derivatives
bearing electron-donating group (3r, Table 2). The results
indicated that the electronic effect of phenylglyoxal
derivatives would have influence on the α-ketoamides
synthesis. However, aliphatic glyoxal such as ethyl
glyoxalate with piperidine only gave 26% yield (GC yield)
of the product (3w). Further investigation of the substrate
scope involved a series of secondary amines was then
explored. Piperdine, morpholine and pyrrolidine worked well
in the reaction, provided the corresponding products in
moderate to good yields (3g-3r). It’s interesting to note that
the pyrrolidine displays higher reactivity compared to the
other amines. Acyclic amine such as diethylamine was also
suitable for the reaction to give 3s-3u in 54%-63% yields,
respectively. It is noteworthy that 2-[2-chloro-4(4-
chlorophenoxy)phenyl]-2-oxoacetaldehyde could also be
smoothly transformed into the desired product 3v in 71%
yield. No desired products were observed when using primary
amines including aniline.
ACCEPTED MANUSCRIPT
It
is
interesting
that
when
(R)-(+)-2-
(diphenylhydroxymethyl)pyrrolidine 2e, was used as
secondary amine to condense with 2-oxoacetaldehyde 1d, the
corresponding dehydroxy product 3x was obtained in 62%
yield (Scheme 2). We speculate that alkene was formed
after the amide bond formation due to dehydration the
tertiary alcohol, because of using 2e only in the same
system, 2e decomposed into benzophenone. In addition, the
structure of 3x was further confirmed by single-crystal X-ray
analysis (Figure 1).
O
O
N
standard conditon
H
Ph
Ph
Ph
O
N
O
Cl
Ph
Cl
H
HO
3x,
2e
1d
62%
Scheme 2. Gold-catalyzed Coupling of 1d and 2e.
Table 2. Gold-Catalyzed Coupling of Secondary Amine and
Glyoxals.a
O
O
R2
N
5 mol% AuBr3
R2
R3
Cl
H
R1
R3
R1
N
H
CH2Cl2, 60oC, air
O
O
3
1
2
O
O
O
N
Cl
N
N
O
O
O
3c, 75%
3a, 72%
3b, 71%
O
O
O
N
N
N
O
O
O
F3C
Cl
Br
Cl
3f, 80%
3e, 74%
3d, 71%
Figure 1. X-ray crystal structure of the product 3x.
O
O
O
O
O
O
O
O
O
In order to obtain the reaction mechanism, some
experiments were conducted. The transformation of 1a and 2a
was conducted in the presence of O2 and anhydrous solvent,
3a was obtained in 76% yield (equation 1). When the reaction
was performed in the presence of N2 and anhydrous DCM, no
product was detected (equation 2). Furthermore, it is
noteworthy that the reaction didn’t work when the
transformation of 1a and 2a was performed in the presence of
N
N
N
O
O
O
Cl
3g, 81%
3i, 73%
3h, 70%
O
O
O
N
N
N
O
O
O
Br
Cl
O2N
Cl
Cl
3l, 61%
3k, 81%
3j, 53%
O
O
O
N
N
N
O
O
O
3m, 93%
3o, 91%
3n, 87%
O
O
O
N
N
N
O
O
O
F3C
Cl
H3CO
Br
3r, 71%
3p, 80%
3q, 90%
O
O
O
N
N
N
O
O
O
Br
3u, 61%
3t, 54%
3s, 63%
O
O
Cl
N
O
N
O
O
O
Cl
3w, 26% c
3v, 71%
a
Reaction conditions: 1 (0.5 mmol), 2 (0.76 mmol), 5 mol% AuBr3 in
CH2Cl2 (2 mL) at 60 oC for 12 h in air; b Yield of isolated products;
Yield determined by GC.
c
H2O under N2 atmosphere. The results demonstrate that O2
plays the key role of oxidation to facilitate this chemical
process (equation 3). To gather further insight into our novel

4
gold-catalyzed direct amidation reactions,
A
rad
C
ic
C
al
E
sc
P
av
T
en
E
g
D
ers,MA
5
N
00
U
M
S
H
C
z
R
spectrometer in CDCl3 or DMSO-d6 solution and
I
P
T
such as TEMPO and 1,1-diphenylethylene, were employed in
the reaction and the reactions significantly suppressed, which
could indicate that this transformation involved radical
intermediates (Scheme 3).
the chemical shifts were reported in parts per million (δ)
relative to internal standard TMS (0 ppm). For HRMS
measurements, the mass analyzer is GC-TOFMS. Unless
otherwise noted, materials obtained from commercial
suppliers were used without further purification.
O
O
4.2. General procedure.
5 mol% AuBr3
H
N
Ph
CH2Cl2, 60oC, air
N
H
To a solution of AuBr3 (10.9 mg, 5 mol%), glyoxal derivative
1 (0.5 mmol) and secondary amine 2 (0.75 mmol) in CH2Cl2
(2 mL) in a 10 mL Schlenk tube. The resulting solution was
stirred at 60 ºC overnight. After cooling to room temperature,
the resulting mixture was filtered through a pad of celite. The
volatile compounds were removed in vacuum and the residue
was purified by column chromatography (SiO2, petroleum
ether/ethyl acetate =10:1- 4:1) to give compounds 3.
O
O
1a
2a
3a
No Scavenger
72%
TEMPO 1.0 equiv
5%
8%
1,1-diphenylethylene 1.0 equiv
Scheme 3. Radical Trapping Experiments.
1-phenyl-2-(piperidin-1-yl)ethanone-1,2-dione (3a)
On the basis of the above results and literatures,10, 12 the
proposed mechanism of this coupling reaction is depicted in
Scheme 4. We speculate that iminium 4 could be formed by
condensation, subsequently water addition to the iminium ion
to form a hemiaminal 5, and finally gold-catalyzed abstraction
of the alpha-proton by dioxygen (likely alkoxy radical 6
involving) to form the amide C=O bond. In the presence of O2,
the resulting Au(I) species can be re-oxidized to the
catalytically active Au(III) ion to complete the catalytic cycle.
1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 7.3 Hz, 2H), 7.64
(t, J = 7.3 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H), 3.72-3.70 (m,
2H), 3.30 (t, J = 5.5 Hz, 2H), 1.71-1.70 (m, 4H), 1.56-1.54
(m, 2H). 13C NMR (125 MHz, CDCl3) 191.9, 165.5, 134.7,
133.3, 129.6, 129.0, 47.1, 42.2, 26.2, 25.5, 24.4.
1-(2-chlorophenyl)-2-(piperidin-1-yl)ethane-1,2-dione (3b)
1H NMR (400 MHz, CDCl3) δ 7.89 (dd, J = 7.7 Hz, 1.4Hz,
1H), 7.52-7.49 (m, 1H), 7.45-7.39 (m, 2H), 3.66 (t, J = 5.6
Hz, 2H), 3.44 (t, J = 5.6 Hz, 2H), 1.71-1.68 (m, 6H). 13C
NMR (125 MHz, CDCl3) δ 190.1, 165.4, 134.3, 133.9, 133.3,
132.4, 130.9, 127.3, 46.9, 42.5, 25.6, 25.0, 24.4. HRMS (ESI)
calcd for C13H14ClNaNO2 ([M+Na]+): 274.0611, found
274.0606.
R2
N
O
R2
N
O
O
R2
R3
N
H
H
R3
R3
+H2O
R1
R1
R1
OH
O
-H2O
4
1
5
Au(III)
O2
Au(I)
R1
1-(3-chlorophenyl)-2-(piperidin-1-yl)ethane-1,2-dione (3c)
1H NMR (400 MHz, CDCl3) δ 7.94 (s, 1H), 7.82 (d, J = 7.8
Hz, 1H), 7.6 (d, J = 8.0 Hz, 1H), 7.46 (t, J = 7.8 Hz, 1H),
3.71-3.70 (m, 2H), 3.29 (t, J = 5.6 Hz, 2H), 1.72-1.70 (m,
4H), 1.57-1.54 (m, 2H). 13C NMR (125 MHz, CDCl3) δ 190.4,
164.7, 135.4, 134.9, 134.6, 130.3, 129.4, 127.8, 47.1, 42.3,
26.2, 25.5, 24.4. HRMS (ESI) calcd for C13H14ClNaNO2
([M+Na]+): 274.0611, found 274.0607.
R2
N
O
R2
O
H
N
R3
R3
R1
O
O
6
3
Scheme 4. Proposed mechanism.
3. Conclusions
1-(4-chlorophenyl)-2-(piperidin-1-yl)ethane-1,2-dione (3d)
1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.6 Hz, 2H), 7.48
(d, J = 8.6 Hz, 2H), 3.69 (t, J = 5.5 Hz, 2H), 3.28 (t, J = 5.6
Hz, 2H), 1.71-1.69 (m, 4H), 1.57-1.54 (m, 2H). 13C NMR
(125 MHz, CDCl3) δ 190.5, 164.9, 141.2, 131.7, 130.9, 129.4,
47.0, 42.2, 26.2, 25.4, 24.3.
In summary, we have described a simple and efficient gold-
catalyzed coupling of secondary amine with phenlglyoxal
derivatives under ligand-free conditions. This method
provides an avenue of the easy assembly of α-ketoamides.
Further studies on the reaction mechanism, scope and
synthetic applications are ongoing in our laboratory.
1-(4-bromophenyl)-2-(piperidin-1-yl)ethane-1,2-dione (3e)
1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.4 Hz, 2H), 7.66
(d, J = 8.4 Hz, 2H), 3.72-3.69 (m, 2H), 3.28 (t, J = 5.5 Hz,
2H), 1.71-1.69 (m, 4H), 1.59-1.57 (m, 2H). 13C NMR (125
MHz, CDCl3) 190.7, 164.9, 132.4, 132.1, 130.9, 130.1, 47.1,
42.3, 26.3, 25.5, 24.4.
4. Experimental
4.1. Materials and methods
All experiments were conducted under an air atmosphere.
All solvents were commercially avaliable. For column
1
1-(piperidin-1-yl)-2[4-(trifluoromethyl)phenyl]ethane-1,2-
dione (3f)
chromatography, 200-300 mesh silica gel was employed. H
NMR and 13C NMR were recorded on 300 MHz, 400MHz or

5
1H NMR (400 MHz, CDCl3) δ 8.07 (d, J =
A
8.
C
2 H
C
z
E
, 2
P
H
T
)
E
, 7
D
.77MA
1
N
-(
U
3-c
S
hl
C
or
R
op
I
henyl)-2-(pyrrolidin-1-yl)ethane-1,2-dione (3n)
P
T
(d, J = 8.2 Hz, 2H), 3.73-3.71 (m, 2H), 3.30 (t, J = 5.5 Hz,
2H), 1.71-1.70 (m, 4H), 1.59-1.55 (m, 2H). 13C NMR (125
MHz, CDCl3) δ 190.5, 164.6, 135.9, 135.8, 135.6, 129.9,
126.1, 126.0, 47.1, 42.4, 26.3, 25.5, 24.4. HRMS (ESI) calcd
for C14H14F3NaNO2 ([M+Na]+): 308.0874, found 308.0869.
1H NMR (400 MHz, CDCl3) δ 7.87 (t, J = 1.7 Hz, 1H), 7.87-
7.85 (m, 1H ), 7.58-7.56 (m, 1H), 7.44-7.40 (m, 1H), 3.62 (t, J
= 6.9 Hz, 2H), 3.42 (t, J = 6.7 Hz, 2H), 1.95-1.91 (m, 4H). 13C
NMR (125 MHz, CDCl3) δ 189.9, 164.0, 135.2, 134.6, 134.5,
130.3, 129.7, 128.1, 46.8, 45.4, 25.9, 23.9. HRMS (ESI)
calcd for C12H12ClNaNO2 ([M+Na]+): 260.0454, found
260.0449.
1-morpholino-2-phenylethane-1,2-dione (3g)
1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 7.2 Hz, 2H ), 7.63
(t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.7 Hz, 2H), 3.77-3.74 (m,
1-(4-chlorophenyl)-2-(pyrrolidin-1-yl)ethane-1,2-dione (3o)
1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.6 Hz, 2H ), 7.47
(d, J = 8.6 Hz, 2H), 3.64 (t, J = 6.9 Hz, 2H), 3.43 (t, J = 6.6
Hz, 2H), 1.97-1.92 (m, 4H). 13C NMR (125 MHz, CDCl3) δ
190.1, 164.2, 141.1, 131.8, 131.3, 129.3, 46.8, 45.4, 25.9,
23.9. HRMS (ESI) calcd for C12H12ClNaNO2 ([M+Na]+):
260.0454, found 260.0451.
4H), 3.62 (t, J = 4.8 Hz, 2H), 3.35 (t, J = 4.8 Hz, 2H). 13
C
NMR (125 MHz, CDCl3) 191.1, 165.4, 134.9, 133.0, 129.6,
129.1, 66.7, 66.6, 46.2, 41.6.
1-(3-chlorophenyl)-2-morpholinothane-1,2-dione (3h)
1H NMR (300 MHz, CDCl3) δ 7.94 (t, J = 7.7 Hz, 1H), 7.85-
7.82(m, 1H ), 7.64-7.60 (m, 1H), 7.49-7.44 (m, 1H), 3.80-3.77
(m, 4H), 3.66 (t, J = 4.8 Hz, 2H), 3.38 (t, J = 4.8 Hz, 2H). 13C
NMR (75 MHz, CDCl3) δ 189.6, 164.7, 135.5, 134.8, 134.7,
130.4, 129.4, 127.9, 66.7, 66.6, 46.3, 41.8. HRMS (ESI) calcd
for C12H12ClNaNO3 ([M+Na]+):276.0403, found 276.0401.
1-(4-bromophenyl)-2-(pyrrolidin-1-yl)ethane-1,2-dione (3p)
1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.6 Hz, 2H), 7.64
(d, J = 8.6 Hz, 2H), 3.64 (t, J = 7.0 Hz, 2H), 3.43 (t, J = 6.7
Hz, 2H), 1.97-1.92 (m, 4H). 13C NMR (125 MHz, CDCl3) δ
190.3, 164.2, 132.3, 131.9, 131.4, 130.1, 46.8, 45.4, 25.9,
23.9. HRMS (ESI) calcd for C12H12BrNaNO2 ([M+Na]+):
303.9949, found 303.9945.
1-(4-chlorophenyl)-2-morpholinothane-1,2-dione (3i)
1H NMR (300 MHz, CDCl3) δ 7.90 (d, J =8.6 Hz, 2H), 7.49
(d, J =8.6 Hz, 2H), 3.80-3.77 (m, 4H), 3.66 (t, J = 4.8 Hz,
2H), 3.38 (t, J = 4.8 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ
189.7, 164.9, 141.6, 131.5, 131.0, 129.5, 66.7, 66.6, 46.3,
41.7.
1-(pyrrolidin-1-yl)-2[4-(trifluoromethyl)phenyl]ethane-1,2-
dione (3q)
1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 8.1 Hz, 2H), 7.76
(d, J = 8.2 Hz, 2H), 3.67 (t, J = 7.0 Hz, 2H), 3.46 (t, J = 6.7
Hz, 2H), 1.98-1.93 (m, , 4H). 13C NMR (125 MHz, CDCl3) δ
189.9, 163.8, 135.8, 130.3, 125.9, 125.8, 124.5, 46.8, 45.5,
25.9, 23.9.
1-(2-chlorophenyl)-2-morpholinoethane-1,2-dione (3j)
1H NMR (300 MHz, CDCl3) δ 7.88 (dd, J =7.8, 1.6 Hz, 1H),
7.55-7.50 (m, 1H), 7.46-7.40 (m, 2H), 3.82-3.79 (m, 2H),
3.78-3.73 (m, 4H), 3.56 (t, J = 4.8 Hz, 2H). 13C NMR (75
MHz, CDCl3) δ 189.7, 165.5, 134.5, 133.6, 133.5, 132.3,
130.8, 127.4, 66.3, 66.2, 46.2, 41.9. HRMS (ESI) calcd for
C12H12ClNaNO3 ([M+Na]+): 276.0403, found 276.0403.
1-(4-methoxyphenyl)-2-(pyrrolidin-1-yl)ethane-1,2-dione (3r)
1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 9.0 Hz, 2H), 6.95
(d, J = 9.0 Hz, 2H), 3.88 (s, 3H), 3.63 (t, J = 6.7 Hz, 2H), 3.41
(t, J = 6.5 Hz, 2H), 1.96-1.92 (m, 4H). 13C NMR (125 MHz,
CDCl3) δ 190.3, 165.3, 164.8, 132.4, 126.0, 114.3, 55.6, 46.7,
45.2, 25.9, 24.1.
1-morpholino-2-(4-nitrophenyl)ethane-1,2-dione (3k)
1H NMR (400 MHz, CDCl3) δ 8.37 (d, J =8.9 Hz, 2H), 8.18
(d, J =8.9 Hz, 2H), 3.83-3.80 (m, 4H), 3.71 (t, J = 4.8 Hz,
2H), 3.44 (t, J = 4.8 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ
188.7, 164.0, 151.2, 137.5, 130.9, 124.2, 66.8, 66.7, 46.4,
42.0.
N,N-diethyl-2-oxo-2-phenylacetamide (3s)
1H NMR (300 MHz, CDCl3) δ 7.94 (d, J = 7.0 Hz, 2H),7.63
(t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.5 Hz, 2H), 3.57 (q, J = 7.2
Hz, 2H), 3.25 (q, J = 7.1 Hz, 2H), 1.29 (t, J = 7.2 Hz, 3H),
1.16 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 191.6,
166.7, 134.5, 133.3, 129.6, 128.9, 42.1, 38.8, 14.1, 12.8.
1-(4-bromophenyl)-2-morpholinothane-1,2-dione (3l)
1H NMR (300 MHz, CDCl3) δ 7.83 (d, J =8.5 Hz, 2H), 7.67
(d, J = 8.5 Hz, 2H), 3.80-3.77 (m, 4H), 3.66 (t, J = 4.8 Hz,
2H), 3.38 (t, J = 4.8 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ
189.5, 164.4, 132.1, 131.5, 130.6, 130.0, 66.3, 66.2, 45.9,
41.3.
2-(3-chlorophenyl)-N,N-diethyl-2-oxoacetamide (3t)
1H NMR (400 MHz, CDCl3) δ 7.93 (s, 1H), 7.81 (d, J = 7.7
Hz, 1H), 7.61-7.59 (m, 1H), 7.47-7.43 (m, 1H), 3.56 (q, J =
7.2 Hz, 2H), 3.24 (q, J = 7.1 Hz, 2H), 1.29 (t, J = 7.2 Hz, 3H),
1.17 (t, J = 7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 190.0,
160.0, 135.4, 134.9, 134.5, 130.3, 129.4, 127.9, 42.2, 39.0,
14.2, 12.8.
1-phenyl-2-(pyrrolidin-1-yl)ethane-1,2-dione (3m)
1H NMR (300 MHz, CDCl3) δ 7.99 (d, J = 7.1 Hz, 2H), 7.66-
7.61 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.5 Hz, 2H), 3.66 (t, J =
7.0 Hz, 2H), 3.42 (t, J = 6.8 Hz, 2H), 1.97-1.92 (m, 4H). 13C
NMR (75 MHz, CDCl3) δ 191.6, 164.9, 134.6, 132.9, 129.9,
128.9, 46.7, 45.2, 25.9, 24.0.
2-(4-bromophenyl)-N,N-diethyl-2-oxoacetamide (3u)
1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.5 Hz, 2H), 7.65
(d, J = 8.5 Hz, 2H), 3.55 (q, J = 7.2 Hz, 2H), 3.23 (q, J = 7.1

6
Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H), 1.16 (t, J
NMR (125 MHz, CDCl3) δ 190.4, 166.2, 132.4, 132.1, 131.0,
A
=
C
7.
C
1 H
E
z
P
, 3
T
H
ED MANUSCRIPT
). 13
C
(c) Tomita, D.; Yamatsugu, K.; Kanai, M.; Shibasaki, M. J. Am.
130.0, 42.2, 38.9, 14.2, 12.8.
Chem. Soc. 2009, 131, 6946. (d) Yang, L.; Wang, D.-X.; Huang, Z.-
T.; Wang, M.-X. J. Am. Chem. Soc. 2009, 131, 10390.
1-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-(piperidin-1-
yl)ethane-1,2-dione (3v)
4 (a) Grassot, J.-M.; Masson, G.; Zhu, J. Angew. Chem. Int. Ed. 2008, 46,
947. (b) Bouma, M.; Masson, G.; Zhu, J. J. Org. Chem. 2010, 75,
2748. (c) Zhang, C.; Jiao, N. J. Am. Chem. Soc. 2010, 132, 28. (d)
Zhang, C.; Xu, Z.; Zhang, L.; Jiao, N. Angew. Chem., Int. Ed. 2011,
50, 11088. (e) Du, F.-T.; Ji, J.-X. Chem. Sci. 2012, 3, 460. (f) Zhang,
C.; Zong, X.; Zhang, L.; Jiao, N. Org. Lett. 2012, 14, 3280.
5 (a) Iizuka, M.; Kondo, Y. Chem. Commun. 2006, 1739. (b) Fukuyama,
T.; Nishitani, S.; Inouye, T.; Morimoto, K.; Ryu, I. Org. Lett. 2006, 8,
1383. (c) Murphy, E. R.; Martinelli, J. R.; Zaborenko, N.; Buchwald,
S. L.; Jensen, K. F. Angew. Chem. Int. Ed. 2007, 46, 1734. (d) Liu, J.;
Zhang, R.; Wang, S.; Sun, W.; Xia, C. Org. Lett. 2009, 11, 1321.
6 (a) Hashmi, A. S. K. Chem. Rev., 2007, 107, 3180. (b) Jimenez-Nunez,
E.; Echavarren, A. M. Chem. Rev., 2008, 108, 3326. (c) Corma, A.;
Leyva-Pérez, A.; Sabater, M. J. Chem. Rev., 2011, 111, 1657.
7 (a) Peng, Y.; Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem. Soc., 2009,
131, 5062. (b) Zhang, G.; Peng, Y.; Cui, L.; Zhang, L. Angew. Chem.
Int. Ed. 2009, 48, 3112. (c) Tkatchouk, E.; Mankad, N. P.; Benitez,
D.; Goddard III, W. A.; Toste, F. D. J. Am. Chem. Soc. 2011, 133,
14293.
1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.4 Hz, 1H), 7.37
(d, J = 8.8 Hz, 2H), 7.20 (dd, J = 8.4, 1.8 Hz, 1H), 7.03 (d, J =
8.8 Hz, 2H), 6.78 (d, J = 1.8 Hz, 1H), 3.45 (t, J = 5.6 Hz, 2H),
3.35 (t, J = 5.6 Hz, 2H), 1.60-1.58 (m, 4H), 1.41-1.39 (m,
2H). 13C NMR (125 MHz, CDCl3) δ 188.9, 166.0, 158.5,
153.7, 141.5, 132.2, 130.6, 130.4, 124.4, 124.3, 121.4, 118.1,
46.8, 42.0, 25.7, 25.1, 24.3. HRMS (ESI) calcd for
C19H17Cl2NaNO3 ([M+Na]+): 400.0483, found 400.0478.
1-(4-chlorophenyl)-2-[2-(diphenylmethylene)pyrrolidin-1-
yl]ethane-1,2-dione (3x)
1H NMR (400 MHz, CDCl3) δ 7.43-7.40 (m, 2H), 7.28-7.26
(m, 4H), 7.17-7.14 (m, 2H), 7.11-7.08 (m, 2H), 6.86-6.82 (m,
4H), 3.91-3.81 (m, 2H), 2.69-2.62 (m, 2H), 2.13-2.03 (m, 2H).
13C NMR (125 MHz, CDCl3) δ 185.4, 164.8, 141.5, 139.4,
139.3, 136.4, 131.4, 130.9, 129.9, 128.5, 128.0, 127.9, 127.3,
45.7, 29.8, 21.0. HRMS (ESI) calcd for C25H20ClNaNO2
([M+Na]+): 424.1080, found 424.1079.
8 (a) Ball, L. T.; Lloyd-Jones, G. C.; Russell, C. A. Science 2012, 337,
1644. (b) Kar, A.; Mangu, N.; Kaiser, H. M.; Tse, M. K.; J.
Organomet. Chem. 2009, 694, 524. (c) Haro, T.; Nevado, C. J. Am.
Chem. Soc. 2010, 132, 1512.
Acknowledgements
9 (a) Xie, J.; Li, H.; Zhou, J.; Cheng, Y.; Zhu, C. Angew. Chem. Int. Ed.
2012, 51, 1252. (b) Xie, J.; Li, H.; Xue, Q.; Cheng, Y.; Zhu, C. Adv.
Synth. Catal. 2012, 354, 1646.
This work was supported by the National Natural Science
Foundation of China (grant No. 21302015), the Natural
Science Fundation for Colleges and Universities of Jiangsu
Province(grant No. 12KJB150005), and the Priority Academic
Program Development of Jiangsu Higher Education
Institutions (PAPD).
10 Li, G.-L.; Kung, K. K.-Y.; Wong, M.-K. Chem. Commun. 2012, 48,
4112.
11 During our investigation, one gold-catalyzed oxidative coupling
reaction of phenylglyoxal and piperidine was simply mentioned,
without substrate scope broadening and mechanism investigation,
see: Shi, S.; Wang, T.; Weingand, V.; Rudolph, M.; Stephen, A.;
Hashmi, K. Angew. Chem. Int. Ed. 2013, 52, 1.
Supplementary materials
Electronic Supplementary Information (ESI) available: [NMR
spectra data for all the compounds and the cif file of the
compound 3x (CCDC 962698 has been deposited at the
Cambridge Crystallographic Database Centre and is available
on request from the Director, CCDC, 12 Union Road,
Cambridge, CB2 1EZ, UK (Fax: +44-1223-336033; e-mail:
deposit@ccdc.cam.ac.uk or www.ccdc.cam.ac.uk)].
12 (a) Pina, C. D.; Falletta, E. Catal. Sci. Technol. 2011, 1, 1564. (b).
Wang, L.; Li, J.; Dai, W.; Lv, Y.; Zhang, Y.; Gao, S. Green Chem. 2014,
16, 2164.
Notes and references
1 (a) Kiss, G. Chem. Rev. 2001, 101, 3435. (b) Tafesh, A. M.; Weiguny, J.
Chem. Rev. 1996, 96, 2035. (c) Morimoto, T.; Kakiuchi, K. Angew.
Chem., Int. Ed. 2004, 43, 5580.
2 (a) Slee, D. H.; Laslo, K. L.; Elder, J. H.; Ollmann, I. R.; Gustchina, A.;
Kervinen, J.; Zdanov, A.; Wlodawer, A.; Wong, C.-H. J. Am. Chem.
Soc., 1995, 117, 11867. (b) Knust, H.; Nettekoven, M.; Pinard, E.;
Roche, O.; Rogers-Evans, M. PCT Int. Appl. WO 2009016087, 2009.
(c) Avolio, S.; Robertson, K.; Hernando, J. I. M.; Dimuzio, J.;
Summa, V. Bioorg. Med. Chem. Lett. 2009, 19, 2295.
3 (a) Zhang, Z.; Zhang, Q.; Ni, Z.; Liu, Q. Chem. Commun. 2010, 46,
1269. (b) Jesuraj, J. L.; Sivaguru, J. Chem. Commun. 2010, 46, 4791.

ACCEPTED MANUSCRIPT
Table 2. Gold-Catalyzed Coupling of Secondary Amine and Glyoxals.a
O
O
R2
N
5 mol% AuBr3
R2
R3
H
R1
R3
R1
N
H
CH2Cl2, 60oC, air
O
O
1
2
3
O
O
Cl
O
N
Cl
N
N
O
O
O
3c, 75%
3a, 72%
3b, 71%
O
O
O
N
N
N
O
O
O
F3C
Cl
Br
Cl
3f, 80%
3e, 74%
3d, 71%
O
O
O
O
O
O
O
O
O
N
N
N
O
O
O
Cl
3g, 81%
3i, 73%
3h, 70%
O
O
O
N
N
N
O
O
O
Br
O2N
Cl
Cl
3l, 61%
3k, 81%
3j, 53%
O
O
O
N
N
N
O
O
O
Cl
3m, 93%
3o, 91%
3n, 87%
O
O
O
N
N
N
O
O
O
F3C
Cl
H3CO
Br
3r, 71%
3p, 80%
3q, 90%
O
O
O
N
N
N
O
O
O
Br
3u, 61%
3t, 54%
3s, 63%
O
O
O
N
O
Cl
N
O
O
Cl
3w, 26% c
3v, 71%
a Reaction conditions: 1 (0.5 mmol), 2 (0.76 mmol), 5 mol% AuBr3 in CH2Cl2 (2 mL) at 60 oC for 12 h in air; b Yield of isolated
products; c Yield determined by GC.

ACCEPTED MANUSCRIPT
Supporting Information for
Mild Gold-Catalyzed Aerobic Dehydrogenative Coupling of Amines and Phenylglyoxal
Derivatives
Ying Shao, Zhuhong Wu, Chunbao Miao, Li Liu*
Key Laboratory of Advanced Catalytic Materials and Technology, School of Petrochemical Engineering,
Changzhou University, Changzhou 213164, P. R. China.
Fax: (+86) 519-86330224, E-mail: liliuchem@gmail.com
Contents:
Pages
NMR spectra of all new compounds 3a-3v and 3x
S2-S24
S1

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3a:
1H NMR (400 MHz, CDCl3) of 3a.
13C NMR (125 MHz, CDCl3) of 3a.
S2

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3b:
1H NMR (400 MHz, CDCl3) of 3b.
13C NMR (125 MHz, CDCl3) of 3b.
S3

ACCEPTED MANUSCRIPT
3c:
1H NMR (400 MHz, CDCl3) of 3c.
13C NMR (125 MHz, CDCl3) of 3c.
S4

ACCEPTED MANUSCRIPT
3d:
1H NMR (400 MHz, CDCl3) of 3d.
13C NMR (125 MHz, CDCl3) of 3d.
S5

ACCEPTED MANUSCRIPT
3e:
1H NMR (400 MHz, CDCl3) of 3e.
13C NMR (125 MHz, CDCl3) of 3e.
S6

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3f:
1H NMR (400 MHz, CDCl3) of 3f.
13C NMR (125 MHz, CDCl3) of 3f.
S7

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3g:
1H NMR (400 MHz, CDCl3) of 3g.
13C NMR (125 MHz, CDCl3) of 3g.
S8

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3h:
1H NMR (300 MHz, CDCl3) of 3h.
13C NMR (75 MHz, CDCl3) of 3h.
S9

ACCEPTED MANUSCRIPT
3i:
1H NMR (300 MHz, CDCl3) of 3i.
13C NMR (75 MHz, CDCl3) of 3i.
S10

ACCEPTED MANUSCRIPT
3j:
1H NMR (300 MHz, CDCl3) of 3j.
13C NMR (75 MHz, CDCl3) of 3j.
S11

ACCEPTED MANUSCRIPT
3k:
1H NMR (400 MHz, CDCl3) of 3k.
13C NMR (125 MHz, CDCl3) of 3k.
S12

ACCEPTED MANUSCRIPT
3l:
1H NMR (300 MHz, CDCl3) of 3l.
13C NMR (75 MHz, CDCl3) of 3l.
S13

ACCEPTED MANUSCRIPT
3m:
1H NMR (300 MHz, CDCl3) of 3m.
13C NMR (75 MHz, CDCl3) of 3m.
S14

ACCEPTED MANUSCRIPT
3n:
1H NMR (400 MHz, CDCl3) of 3n.
13C NMR (125 MHz, CDCl3) of 3n.
S15

ACCEPTED MANUSCRIPT
3o:
1H NMR (400 MHz, CDCl3) of 3o.
13C NMR (125 MHz, CDCl3) of 3o.
S16

ACCEPTED MANUSCRIPT
3p:
1H NMR (400 MHz, CDCl3) of 3p.
13C NMR (125 MHz, CDCl3) of 3p.
S17

ACCEPTED MANUSCRIPT
3q:
1H NMR (400 MHz, CDCl3) of 3q.
13C NMR (125 MHz, CDCl3) of 3q.
S18

ACCEPTED MANUSCRIPT
3r
1H NMR (400 MHz, CDCl3) of 3r.
13C NMR (125 MHz, CDCl3) of 3r.
S19