Au-complex containing phosphino and imidazolyl moieties as a bi-functional catalyst for one-pot synthesis of pyridine derivatives

Article abstract of DOI:10.1016/j.molcata.2016.09.008

The complex of Au-L1 containing imidazolyl ring and the phosphine-ligated-Au moiety was synthesized and applied as the efficient bi-functional catalyst for the one-pot sequential condensation/annulation reaction for the synthesis of pyridine derivatives. It was found that, as for Au-L1, the involved imidazolyl group acted as a Lewis base to catalyze the condensation of carbonyl compounds with propargylamine to form the imino intermediate, and the involved Au⁺-complex species with alkynophilicity corresponded to the subsequent activation of imino-tailed alkynyl to afford dehydropyridine intermediate. The latter proceeded auto-oxidation reaction to afford the pyridine derivatives. The observed sequential catalysis over Au-L1 proved more efficient than that over the mechanical mixtures of the Au-complex (Au-L2) and N-methylimidazole, because the free N-methylimidazole as an N-containing donor competed with the alkyne substrate to coordinate to Au-center. Moreover, Au-L1 exhibited good generality to a wide range of the substrates for the synthesis of 2,3-fused pyridine derivatives and 2-aryl(heteroaryl)-substituted pyridines.

Full text of DOI:10.1016/j.molcata.2016.09.008

Journal of Molecular Catalysis A: Chemical 424 (2016) 323–330
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Au-complex containing phosphino and imidazolyl moieties as a
bi-functional catalyst for one-pot synthesis of pyridine derivatives
Da Yang, Huan Liu, Dong-Liang Wang, Yong Lu, Xiao-Li Zhao, Ye Liu∗
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 3663
North Zhongshan Road, Shanghai 200062, P. R. China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 August 2016
Received in revised form 5 September 2016
Accepted 6 September 2016
Available online 8 September 2016
The complex of Au-L1 containing imidazolyl ring and the phosphine-ligated-Au moiety was synthesized
and applied as the efficient bi-functional catalyst for the one-pot sequential condensation/annulation
reaction for the synthesis of pyridine derivatives. It was found that, as for Au-L1, the involved imidazolyl
group acted as a Lewis base to catalyze the condensation of carbonyl compounds with propargylamine to
form the imino intermediate, and the involved Au+-complex species with alkynophilicity corresponded
to the subsequent activation of imino-tailed alkynyl to afford dehydropyridine intermediate. The latter
proceeded auto-oxidation reaction to afford the pyridine derivatives. The observed sequential catalysis
over Au-L1 proved more efficient than that over the mechanical mixtures of the Au-complex (Au-L2) and
N-methylimidazole, because the free N-methylimidazole as an N-containing donor competed with the
alkyne substrate to coordinate to Au-center. Moreover, Au-L1 exhibited good generality to a wide range
of the substrates for the synthesis of 2,3-fused pyridine derivatives and 2-aryl(heteroaryl)-substituted
pyridines.
Keywords:
Bi-functional catalyst
Sequential reactions
Gold complexes
Pyridine derivatives
One-pot synthesis
© 2016 Elsevier B.V. All rights reserved.
1. Introduction
(Scheme 2). Specifically, ␣,␤-unsaturated imines and alkynes are
the most widely applied substrates for this method [13–16].
Pyridine derivatives have gained considerable attention due
to their central role as the versatile building blocks in the syn-
thesis of natural products, active pharmaceuticals, and functional
materials with novel photo-/electrochemical or catalytic proper-
ties [1–3]. Historically, many pyridine derivatives syntheses rely
on the condensation of amines with carbonyl compounds with-
out involvement of transition metal catalyst [4–8]. For example,
ammonia (NH3) has served as the nitrogen source, including [5 + 1]
condensation with 1,5-dicarbonyls (Scheme 1-A) [9]. Ammonia is
also frequently used in the [2 + 2 + 1 + 1] Hantzsch pyridine synthe-
sis (Scheme 1-B) [10,11]. Other pyridine syntheses rely on vinyl
amines such as the [3 + 3] condensation of 1,3-dicarbonyl derivative
with vinylogous amide (Scheme 1-C) [12]. In these condensation
methods, auto-oxidation (dehydrogenation) is necessary for arom-
atization.
Although many synthesis routes to pyridine derivatives have
been developed [4], comparatively, the one-pot synthesis of
pyridines derivatives with high atom-economy by using easily
available starting materials is still challengeable but in great
demand [17–21]. Arcadi firstly reported a novel one-pot sequen-
tial amination/annulation reaction of carbonyl compounds and
propargylamine for the synthesis of pyridine derivatives [22]. It was
believed that the applied Au-catalyst not only catalyzed the con-
densation of carbonyl compounds and primary amines to afford
imino- moieties as a Lewis ␲-acid [22], but also activate alkynes
for the subsequent annulation due to its unique alkynophilicity
[23–32].
Highlighted by Arcadi’s elegant method, herein,
a novel
Au(I)-complex (Au-L1) containing the Lewis basic amino group
(imidazolyl) and the phosphine-ligated-Au-complex unit was
developed as a bi-functional catalyst for the one-pot sequential
reaction of ketones (or aldehydes) and propargylamine for the syn-
thesis of pyridine derivatives. The incorporated imidazolyl group
in Au-L1 was expected to behave as a base to catalyze the conden-
sation reaction and the phosphine-ligated-Au-complex unit was
responsible for the subsequent annulation (Scheme 3). For compar-
ison, the similar structured complex of Au-L2, in which the basicity
of imidazolyl group was quenched via quaternization of N-site, was
On the other hand, the [4 + 2] aza-Diels-Alder cycloaddition
reaction basically is another prevalent approach for the con-
struction of pyridine derivatives especially with alkynes as the
electron-deficient groups over the transition-metal catalysts [4]
∗
Corresponding author.
E-mail address: yliu@chem.ecnu.edu.cn (Y. Liu).
http://dx.doi.org/10.1016/j.molcata.2016.09.008
1381-1169/© 2016 Elsevier B.V. All rights reserved.

324
D. Yang et al. / Journal of Molecular Catalysis A: Chemical 424 (2016) 323–330
Scheme 1. Pyridine derivative synthesis via condensation of carbonyl compounds with amines.
Scheme 2. Pyridine derivative synthesis via [4 + 2] aza-Diels-Alder cycloaddition of ␣,␤-unsaturated imines with alkynes.

D. Yang et al. / Journal of Molecular Catalysis A: Chemical 424 (2016) 323–330
325
Scheme 3. Pyridine derivative synthesis via one-pot sequential reactions of carbonyl compounds and propargylamine catalyzed by Au-L1.
Table 1
The crystal data and structure refinement for L1, L2, Au-L1 and Au-L2.
L1
L2
Au-L1
Au-L2
Empirical formula
C19H15N2PS
334.36
Orthorhombic
Pca21
18.8043(5)
5.9555(2)
14.8202
90
C21H18F3N2O3PS2
498.46
Triclinic
P-1
8.0971(4)
9.4106(5)
18.3414(10)
86.612(2)
88.149(2)
67.998(2)
1293.46(12)
2
1.280
0.312
173(2)
0.71073
15199
C19H15AuClN2PS
566.78
Monoclinic
P21/c
10.3293(3)
12.1701(3)
15.6973(4)
90
104.1130(10)
90
1913.73(9)
4
1.967
8.024
296(2)
C21H18AuClF3N2O3PS2
730.88
Triclinic
P-1
8.0768(2)
9.5693(3)
18.1758(5)
81.4890(10)
86.7620(10)
65.3520(10)
1262.72(6)
2
1.922
6.208
296(2)
0.71073
14667
Formula weight
Crystal system
Space group
a (Å)
b (Å)
c (Å)
␣ (o)
␤ (o)
90
90
ꢀ (o)
V (Å3)
1659.70(8)
4
1.338
Z
dcalc (g cm−3
)
ꢁ (Mo-K␣) (mm−1
T (K)
)
0.291
296(2)
0.71073
18088
ꢂ (A)
Total reflections
0.71073
21825
Unique reflections (Rint
R1 [I > 2␴(I)]
wR2 (all data)
)
2831 (0.0350)
0.0294
0.0704
696
4534 (0.0387)
0.0503
0.1443
512
1.097
3368 (0.0233)
0.0271
0.0668
1080
1.066
4431 (0.0197)
0.0219
0.0571
704
1.112
F(000)
Goodness-of-fit on F2
1.057
applied as the reference catalyst in order to elucidate the advantage
of the bi-functional catalysis over Au-L1.
ment Analyzer. Gas chromatography (GC) was performed on
a SHIMADZU-2014 equipped with a DM-Wax capillary column
(30 m × 0.25 mm × 0.25 ␮m).
2. Experimental
2.2. Synthesis
2.1. Reagents and analysis
2.2.1. 1-(2-(diphenylphosphanyl)thiophen-3-yl)-1H-imidazole
(L1)
The chemical reagents were purchased from Shanghai Aladdin
Chemical Reagent Co. Ltd. and Alfa Aesar China, and used as
L1 was prepared according to the procedures reported by
Pitchumani [33] and us [34] with some modifications.
A solution of 3-bromothiophene (9.78 g, 60 mmol), imida-
zole (3.40 g, 50 mmol), l-proline (2.30 g, 20 mmol), K2CO3 (14.51 g,
105 mmol) and CuI (1.91 g, 10 mmol) in DMSO (150 mL) was stirred
vigorously at 110 ◦C for 24 h. Water (150 mL) was added to the sys-
tem after completion of the reaction. The mixture was extracted
received. The solvents were distilled and dried before use. 1H/31
P
NMR spectra (85% H3PO4 sealed in
a capillary tube as an
internal standard) were recorded on a Bruker ARX 400 spectrom-
eter at ambient temperature. 13C NMR spectra were recorded
on a Bruker ARX 500 spectrometer at ambient temperature.
CHN-elemental analysis was performed on a Vario EL III Ele-

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D. Yang et al. / Journal of Molecular Catalysis A: Chemical 424 (2016) 323–330
Fig. 1. The single crystal structures of L1, L2, Au-L1 and Au-L2.
11 mmol) dropwise. The resultant mixture was stirred overnight
along with the reaction temperature increasing to ambient. After
quenching the excess n-BuLi with deionized water, the mixture was
extracted with ethyl acetate (3 × 80 mL) and the combined organic
phase was concentrated by vacuum. The residue was purified by
column chromatography on silica gel, using petroleum ether/ethyl
acetate (2:1) as eluant, to give product of L1 as a yellow solid (1.59 g,
yield of 48%). The sample suitable for X-ray diffraction analysis
was obtained by slow volatilization of an ethyl acetate solution
containing L1. 1H NMR (ı, ppm, acetone-d6): 1H NMR (ı, ppm,
acetone-d6): 8.08 (s, 1H, NCHN), 7.88 (d, 1H, J = 4.0 Hz, CHimi), 7.70
(d, 1H, J = 4.0 Hz, CHimi), 7.58 (s, 1H, CHthio), 7.33-7.48 (m, 10H,
P(C6H5)2), 7.06 (s, 1H, CHthio). 13C NMR (ı, ppm, acetone-d6): 141.8
(d, J = 22.5 Hz), 137.2 (d, J = 5.0 Hz), 136.4 (d, J = 7.5 Hz), 133.1 (d,
J = 21.25 Hz), 132.62 (s), 129.5 (s), 129.2 (s), 128.8 (d, J = 7.5 Hz),
125.8 (d, J = 2.5 Hz), 120.1 (s). 31P NMR (ı, ppm, acetone-d6): −26.6
(s, PPh2). CHN-elemental analysis (%, found): C 68.32, H 4.85, N 8.06
(calcd., C 68.25, H 4.52, N 8.38).
21.80
17.13
1J Se = 761 Hz
31P-77
b
Selenide of L2
Selenide of L1
17.95
22.60
1J Se = 758 Hz
31P-77
a
30
25
20
15
10
5
0
-5
-10
Chemical Shift (ppm)
2.2.2. 1-(2-(diphenylphosphanyl)thiophen-3-yl)-3-methyl-1H-
imidazol-3-ium trifluoromethanesulfonate
(L2)
Fig. 2. 31P NMR spectra of the selenides of L1 and L2 (163 MHz): reacting elemental
selenium with L1 (a) and L2 (b) in CDCl3 at 70 ◦C for 10 h.
Under a nitrogen atmosphere, a solution of L1 (0.68 g, 2 mmol)
in dry dichloromethane was added dropwise with methyl-
trifluoromethanesulfonate (MeOTf, 0.33 g, 2 mmol) at −78 ◦C. The
obtained mixture was stirred overnight with the temperature
increasing to the ambient. After removal of solvent under vac-
uum, the residue was recrystallized in dichloromethane/petroleum
ether to give product of L2 as a white solid (0.42 g, yield of 68%).
The sample suitable for X-ray diffraction analysis was obtained by
recrystallization from dichloromethane/diethyl ether. 1H NMR (ı,
ppm, acetone-d6): 9.37 (s, 1H, NCHN), 8.08 (d, 1H, J = 4.0 Hz, CHimi),
with ethyl acetate (3 × 80 mL) and the combined organic phase was
concentrated by vacuum. The residue was purified by column chro-
matography on silica gel, using petroleum ether/ethyl acetate (1:1)
as eluant, to give product of 1-(thiophen-3-yl)-1H-imidazole as a
yellow solid (3.90 g, yield of 52%).
Under nitrogen atmosphere, a solution of 1-(thiophen-3-yl)-1H-
imidazole (1.50 g, 10 mmol) in dry CH2Cl2 (100 mL) was cooled to
−78 ◦C, then n-BuLi (2.5 M in hexane, 4.40 mL, 11 mmol) was added
dropwise. After stirring vigorously for 1 h, the obtained reaction
mixture was added with chlorodiphenylphosphine (PPh2Cl, 2.30 g,
7.87–7.89 (m, 2H, CHimi + thio), 7.57 (s, H, CHthio), 7.40–7.49 (m, 10H,

D. Yang et al. / Journal of Molecular Catalysis A: Chemical 424 (2016) 323–330
327
Table 2
The selected bond distances (Å) and bond angles (o) for L1, L2, Au-L1, and Au-L2.
Compound
Bond distance (Å)
Bond angle (o)
L1
P1-C1
P1-C7
P1-C13
1.8344(21)
1.8352(21)
1.8204(21)
∠C1P1C7 104.29(93)
∠C1P1C13 101.48(95)
∠C7P1C13 101.79 (96)
L2
P1-C1
P1-C7
P1-C16
1.8363(26)
1.8312(34)
1.8193(33)
∠C1P1C7 102.32(143)
∠C1P1C16 100.55(139)
∠C1P1C7 102.05(147)
Au-L1
Au-L2
Au-P
Au-Cl
2.2232(14)
2.2784(16)
∠P-Au-Cl 176.06(6)
Au-P
Au-Cl
2.2234(9)
2.2696(11)
∠P-Au-Cl 177.19(5)
Table 3
The reaction of 1,3-diphenylacetone and propargylamine catalyzed by Au(I)- complexesa.
Entry
Cat.
Sol.
Temp. (◦C)
Yield (%)b
1
2
3
4
5
6
7
8
Au-L1
Au-L1
Au-L1
Au-L1
Au-L1
Au-L1
Au-L1
Au-L1
C2H5OH
C2H5OH
C2H5OH
C2H5OH
DMF
75
46
71
90
95
35
37
32
6
71
53
75
92
50
100
120
140
120
120
120
120
120
120
120
120
120
THF
C6H5CH3
CH3COCH3
CH3OH
C2H5OH
C2H5OH
C2H5OH
C2H5OH
9
Au-L1
Au-L2
10
11c
12d
13d
Au-L2 + N-Methylimidazole
Au-L1 + AgOTf
Au-L2 + AgOTf
a
Cat. (Au-L1 or Au-L2, 0.025 mmol), 1,3-diphenylacetone (1 mmol), propargylamine (2 mmol), time 5 h.
GC yield.
N-Methylimidazole (0.025 mmol) was added.
AgOTf (0.025 mmol) was added.
b
c
d
P(C6H5)2), 4.15 (s, 3H, CH3). 13C NMR (ı, ppm, acetone-d6): 141.8
(d, J = 8.75 Hz), 137.53 (s), 135.07 (d, J = 7.5 Hz), 133.74 (s), 133.1 (d,
J = 20 Hz), 129.91 (s), 129.0 (d, J = 7.5 Hz), 126.28 (s), 124.19 (s), 36.22
(s). 31P NMR (ı, ppm, acetone-d6): −27.3 (s, PPh2). CHN-elemental
analysis (%, found): C 53.51, H 4.64, N 5.43 (calcd., C 53.43, H 4.28,
N 5.66).
(br, 1H, CHimi), 7.65–7.80 (m, 12H, P(C6H5)2 + CHthio), 4.16 (s, 3H,
CH3). 31P NMR (ı, ppm, acetone-d6): 12.7 (s, PPh2). CHN-elemental
analysis (%, found): C 34.63, H 2.59, N 3.85 (Calcd., C 34.51, H 2.48,
N 3.83).
2.3. X-ray crystallography
Intensity data were collected for L1 and L2 on a Bruker
SMARTAPEX II diffractometer using graphite monochromated Mo-
K␣ radiation (ꢂ = 0.71073 Å) at 296 K (or 173 K). Data reduction
included absorption corrections by the multi-scan method. The
structures were solved by direct methods and refined by full matrix
least-squares using SHELXS-97 (Sheldrick, 1990), with all non-
hydrogen atoms refined anisotropically. Hydrogen atoms were
added at their geometrically ideal positions and refined isotropi-
cally. The crystal data and refinement details are given in Table 1.
2.2.3. The Au(I)-complexes of Au-L1 and Au-L2
Under nitrogen atmosphere, ligand L1 (0.13 g, 0.4 mmol) dis-
solved in dry dichloromethane (2 mL) was added to a solution of
AuICl(tht) [tetrahydrothiophene-gold(I) chloride, 0.13 g, 0.4 mmol]
in dry dichloromethane (5 mL). The mixture was stirred for 30 min
at room temperature. Then n-hexane was added to precipitate
the white solid, which was dried under vacuum as the product
of Au-L1 in the yield of 83% (0.26 g). The sample suitable for
X-ray diffraction analysis was obtained by recrystallization from
dichloromethane/diethyl ether. 1H NMR (ı, ppm, acetone-d6): 8.19
(d, 1H, J = 4.0 Hz, CHthio), 7.63–7.77 (m, 10H, P(C6H5)2), 7.51 (d, 1H,
J = 4.0 Hz, CHthio), 7.46 (s, 1H, NCHN), 7.13 (br, 1H, CHimi), 6.99 (br,
1H, CHimi). 31P NMR (ı, ppm, acetone-d6): 15.5 (s, PPh2). CHN-
elemental analysis (%, found): C 40.31, H 2.59, N 4.68 (Calcd., C
40.26, H 2.67, N 4.94).
2.4. Measurement of coupling constant of the
1
31 77
phosphine-selenides ( J
)
P- Se
1
31
J
77
of the corresponding phosphine-
P- Se
The magnitude of
selenide in 31P NMR spectra (163 MHz) was measured according
to the reported method [35–37]. The corresponding phosphine-
selenides were prepared by reacting elemental selenium (with
7.63% 77Se) with each phosphine (L1 or L2) in the deuterated
solvent under appointed conditions (Fig. 2), which were directly
analyzed without isolation by a Bruker Avance 400 spectrometer
The Au(I)-complexes of Au-L2 was prepared with the yield of
78% by following the similar procedures as described above for Au-
L1. The sample suitable for X-ray diffraction analysis was obtained
by recrystallization from dichloromethane/diethyl ether. 1H NMR
(ı, ppm, acetone-d6): 9.46 (s, 1H, NCHN), 8.39 (br, 1H, CHimi), 7.90

328
D. Yang et al. / Journal of Molecular Catalysis A: Chemical 424 (2016) 323–330
Table 4
The generality of Au-L1 as the bifunctional catalyst for syntheses of the pyridine derivatives with the different scope of carbonyl compoundsa.
Entry
Carbonyl compound
Pyridine derivative
Time (h)
Yield (%)b
53
1
5
2
3
5
5
60
89
4
5
5
5
78
64
6
5
46
7
8
5
43
43
12
9
12
10
39
92
10
11
10
48
a
Cat. Au-L1 0.03 mmol, carbonyl compound 1.26 mmol, propargylamine 2.5 mmol, ethanol 5 mL, temp. 120 ◦C.
Isolated yield.
b
at ambient temperature to record an 31P NMR spectra (85% H3PO4
sealed in a capillary tube as an internal standard).
3. Results and discussion
3.1. Synthesis and characterization
2.5. General procedures for the synthesis of pyridine derivative
catalyzed by the Au(I)-complex
The ligands (L1, L2) and the corresponding Au(I)-complexes
(Au-L1, Au-L2) were prepared according to the reaction pathways
shown in Scheme 1. In 1-(thiophen-3-yl)-1H-imidazole parent
molecule, compared to the proton at 2-C position in imidazolyl ring,
the proton at 2ꢀ-C position in thiophenyl ring is more preferentially
to be substituted by PPh2 group due to the thermodynami-
cally stabilized carboanion by the neighbored S-atom with empty
d-orbital. Hence, by mixing n-BuLi, Ph2PCl and 1-(thiophen-3-yl)-
1H-imidazole at the equivalent amounts, one PPh2 group could be
selectively incorporated at 2ꢀ-C position of thiophenyl ring under
N2 atmosphere to afford L1. The subsequent quaternization of L1 by
MeOTf at −78 ◦C afforded the ionic ligand of L2 without N-electron-
rich character. When L1 and L2 were complexed respectively to
AuICl(tht) at the same P/Au molar ratio, the corresponding Au(I)-
complexes of Au-L1 and Au-L2 were obtained as the white solids
with the good yields (∼80%), which are stable in the solid state
at the ambient condition. The colourless crystals suitable for the
single-crystal X-ray diffraction analysis of L2, Au-L1 and Au-L2
were obtained by re-crystallization from dichloromethane/diethyl
ether, while L1 was obtained by slow volatilization of an ethyl
acetate solution.
To a safe glass pressure reactor was charged with a solution
of ketone (1 mmol) in ethanol (5 mL), propargylamine (2 mmol),
the isolated crystalline Au-complex pre-catalyst (0.025 mmol), and
AgOTf (0.025 mmol, if required) in sequential. The mixture was
heated in oil bath at the appointed conditions. After completion
of the reaction, the combined filtrate after washing the residue
with diethyl ether (3 × 3 mL) was analyzed by GC to determine
the conversion of ketone and selectivity to pyridine derivatives
(1-dodecane as the internal standard), which were calibrated by
the authentic samples. The temperature-programmed analysis for
the samples was performed on GC-SHIMADZU-2014 with a flame
ionization detector (FID). The analysis conditions were as follows:
Injector temperature, 250 ◦C; Detector temperature, 250 ◦C; Initial
oven temperature at 60 ◦C with retention time of 2 min and then
rising up to 240 ◦C with a temperature ramp of 10 ◦C min−1; Final
oven temperature 240 ◦C with retention time of 10 min. Alterna-
tively, the residue concentrated by vacuum was purified by column
chromatography on silica gel, using petroleum ether/ethyl acetate
as an eluent to yield the products of the pyridine derivatives.

D. Yang et al. / Journal of Molecular Catalysis A: Chemical 424 (2016) 323–330
329
Scheme 4. Co-catalysis of Au-L1 as a bifunctional catalyst for one-pot sequential condensation/annulation reaction for synthesis of pyridine derivatives.
The molecular structures (Fig. 1) indicated that the Au(I)-
centered vector of Au-L1 or Au-L2 is in a slightly distorted linear
configuration, which is diagonally coordinated by one Cl− and one
phosphine fragment. The bond distance of Au-P [2.2232(16) Å] in
Au-L1 is approximately equal to that [Au-P, 2.2234(9) Å] in Au-L2.
In Au-L1, the electron-rich N-atom in imidazolyl group was com-
pletely exposed without possible interaction to Au-center due to
the barrier of the bulky and rigid thiophenyl ring, indicating that
the individual functionalities of Au-P complex and imidazolyl could
keep intact without mutual interference.
to 2-benzyl-3-phenylpyridine (Entries 1–4). And 90% yield of 2-
benzyl-3-phenylpyridine was obtained at 120 ◦C after screening
ethanol as the optimal solvent (Entry 4, 95%). In contrast, under
the same reaction conditions, Au-L2 exhibited much lower activ-
ity towards the reaction with the product yield of 53% (Entry
10). The involvement of AgOTf (silver trifluoromethanesulfonate)
in Au-L1 or Au-L2 as a scavenger of Cl− ligand for the benefi-
cial formation of P-Au+ species [39,40] showed negligible effect
on their catalytic performance (Entries 12 and 13). While N-
methylimidazole was added additionally in Au-L2, the yield of
2-benzyl-3-phenylpyridine was improved up to 75%, but still much
lower than that obtained over Au-L1 (Entry 11 vs 3).
The coordinating ability of L1 and L2 was evaluated by
1
31
J
77
of the corresponding
P- Se
measuring the magnitude of
phosphine-selenide in 31P NMR spectra (163 MHz) [35–37]. An
As verified in Fig. 2 the coordination abilities of the phosphine
1
1
31
31
77
77
increased value of J
Seindicates the increased ␲-acceptor abil-
fragments in L1 and L2 are very similar (L1,
J
Se = 758 Hz;
P-
P-
1
31
77
ity (i.e., less ␴-donor ability) of the phosphine fragment. In L2,
although the positive-charged imidazolium was featured with the
strong electron-withdrawing effect, the coordinating ability of the
peripheral phosphine fragment was found similar to that in L1
L2, J
Se = 761 Hz). Hence, the different catalytic performance
P-
of Au-L1 and Au-L2 towards above reaction was not due to the
change of the coordinating ability of the involved phosphines in L1
and L2. Reasonably, the presence of N-containing moiety in the
mode of the intramolecular incorporation in Au-L1 contributed
to the high efficiency of this sequential condensation/annulation
reaction (Entry 3). Au-L1 was able to act as a unique bifunctional
catalyst in combination of the phosphine-ligated Au-complex (as
the transition metal catalyst) and the Lewis base organocatalyst
derived from imidazolyl group (Scheme 4). Due to the rigid and
bulky backbone of thiophenylimidazolyl moiety, the incorporated
imidazolyl, which was located remotely to the phosphine frag-
ment without competitive N-hemilabile ligation to Au-center, just
played the role of Lewis base to effectively catalyze the con-
densation of 1,3-diphenylacetone with propargylamine for the
formation of the imino intermediate with enamino tautomer (A).
Since the exclusive alkynophilicity of the Au-complex catalyst
[16,17], carbon–carbon triple bond was activated by P-Au+ species
through the ␲-coordination, and then attached by the carbon of
the enamino moiety through regioselective 6-endo-dig intramolec-
ular nucleophilic addition to give dehydropyridine intermediate
(B). The latter undergoes auto-oxidation reaction to afford the
pyridine derivatives. In contrast, Au-L2 without the incorporated
with indication of the similar 1
J
(L1, 1
J
Se = 758 Hz; L2,
31
77
31
77
P- Se
P-
1
31
77
J
Se = 761 Hz) (Fig. 2) [38]. Evidently, the positive-charged imi-
P-
dazolium in L2 had negligible electronic effect on the coordinating
ability of the phosphine fragment. As a result, the complexation of
L1 and L2 to AuICl(tht) consequently afforded the similar linear-
structured complexes of Au-L1 and Au-L2 with the identical Au
P
bond distances (Table 2).
3.2. Catalytic performance of Au-L1 and Au-L2 for one-pot
synthesis of pyridine derivatives
In this part, the developed Au(I)-complexes of Au-L1 and Au-L2
were applied as the pre-catalysts for the one-pot reaction of 1,3-
diphenylacetone and propargylamine for the efficient synthesis of
pyridine derivatives (Table 3).
Without the involvement of any auxiliary additive, under the
selected reaction conditions, over Au-L1 (2.5 mol%) the conversions
of 1,3-diphenylacetonewere steadily increased as the reaction tem-
perature increased from 70 to 140 ◦C along with 100% selectivity

330
D. Yang et al. / Journal of Molecular Catalysis A: Chemical 424 (2016) 323–330
Lewis base exhibited lower activity with the product yield of 53%
(Entry 10). Although, the sequential reaction efficiency over the
mechanical mixtures of Au-L2 and N-methylimidazole could be
improved to some extent (75% yield, Entry 11), it was still lower
than that over Au-L1. These results further confirmed that the
intramolecular combination of the Au-complex unit with the imi-
dazolyl ring by the stable chemical bonds in Au-L1 was not the
result of the simple mechanical mixture of the phosphine-ligated
Au-complex of Au-L2 and the Lewis base of N-methylimidazole.
In the mechanical mixtures of Au-L2 and N-methylimidazole, the
auxiliary N-methylimidazole as an N-containing donor with the
free mobility unavoidably competed with the alkyne substrate to
coordinate to Au-center, leading to the depressed condensation of
ketone and amine over the basic imidazole catalyst and the subse-
quent activation of alkyne for annulation over Au-L2 catalyst.
The generality of Au-L1 as the bi-functional catalyst for the syn-
theses of the pyridine derivatives was examined on the different
scope of carbonyl compounds. As shown in Table 4, under the
selected reaction conditions, Au-L1 universally exhibited accept-
able catalytic activities towards the sequential transformation.
The steric and electronic effects of the applied ketones had the
obvious influence on the reaction rate. The cycloalkanones with
Supplementary data
CCDC-1472858 (L1), 1472859 (L2), 1481287 (Au-L1), and
1481288 (Au-L2) contain the supplementary crystallographic of
the compounds synthesized in this paper. These data can be
obtained free of charge from the Cambridge Crystallographic
Database. The CIF files of them contain the experimental descrip-
tion and cryptographic data are also available free of charge via the
internet at http://pubs.asc.org.
Acknowledgment
This work was financially supported by the National Natu-
ral Science Foundation of China (Nos. 21473058, 21273077, and
21673077).
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