Heterogeneous gold(I)-catalysed annulation between 2-aminopyridines and propiolaldehydes leading to 3-acylimidazo[1,2-a]pyridines

Article abstract of DOI:10.3184/174751918X15314807595487

The heterogeneous annulation between 2-aminopyridines and propiolaldehydes was achieved in CH₂Cl₂ at 25 °C in the presence of 3 mol% of MCM-41-immobilised phosphine gold(I) complex (MCM-41-PPh₃-AuCl) and AgSbF₆

Full text of DOI:10.3184/174751918X15314807595487

JOURNAL OF CHEMICAL RESEARCH 2018
VOL. 42 JULY, 341–346
RESEARCH PAPER 341
Heterogeneous gold(I)-catalysed annulation between 2-aminopyridines and
propiolaldehydes leading to 3-acylimidazo[1,2-a]pyridines
Li Weia, Fang Yaoa,b, Feiyan Yia and Mingzhong Caia*
aKey Laboratory of Functional Small Organic Molecule, Ministry of Education and Department of Chemistry, Jiangxi Normal University, Nanchang 330022, P.R. China
bCollege of Chemical and Material Engineering, Quzhou University, Quzhou 324000, P.R. China
The heterogeneous annulation between 2-aminopyridines and propiolaldehydes was achieved in CH Cl2 at 25 °C in the presence of 3 mol%
of MCM-41-immobilised phosphine gold(I) complex (MCM-41-PPh3-AuCl) and AgSbF under air, yie2lding a variety of 3-acylimidazo[1,2-a]
pyridines in good yields. This heterogeneous gold(I) catalyst can be easily prepared 6by a simple procedure, recovered by filtration of the
reaction solution and recycled up to seven times without significant loss of activity.
Keywords: gold, annulation, imidazo[1,2-a]pyridine, propiolaldehyde, heterogeneous catalysis
Imidazo[1,2-a]pyridine as a key core is found in numerous
drugs and bioactive molecules, such as alpidem, saripidem,
necopidem, minodronic acids and zolpidem (Fig. 1).1 These
drug molecules have been considered as attractive synthetic
targets because of their excellent biological and pharmaceutical
properties, including antibacterial, anxiolytic, antiulcer, antiviral,
antiprotozoal, antiherpes and antiapoptotic activities.2–4 As a
result, many synthetic approaches have been developed for the
construction of imidazo[1,2-a]pyridine scaffolds.5 Traditional
methods include the heterocyclisation of 2-aminopyridines
with α-halocarbonyl compounds6–8 and multicomponent
coupling of 2-aminopyridines, aldehydes and ketones/alkynes/
isonitriles.9–11 Among a variety of new synthetic methods,
transition metal-catalysed cyclisation reactions with various
metals such as palladium,12 copper,13–16 silver17,18 and iron19 have
proved to be a powerful and useful tool for the construction of
imidazo[1,2-a]pyridines. Recently, Cao and co-workers reported
copper(I)-catalysed synthesis of functionalised imidazo[1,2-a]
Although these transition-metal-catalysed syntheses of
imidazo[1,2-a]pyridines are highly efficient, in all cases
homogeneous metal catalysts were used and the use of
expensive palladium and gold as well as difficult recovery and
non-recyclability of the metal catalysts make these methods
of limited synthetic utility from environmental and economic
points of view. In addition, homogeneous catalysis might result
in heavy metal contamination of the desired isolated product,
which is a particular drawback in the pharmaceutical industry.
Recycling of homogeneous catalysts is a task of great economic
and environmental importance, especially when expensive
and/or toxic heavy metal complexes are used in chemical
and pharmaceutical industries.28 The heterogenisation of the
existing homogeneous catalysts appears to be a logical solution
to these problems.29 There has been considerable interest in
the development of heterogeneous catalytic systems that can
be easily recycled whilst maintaining the inherent activity of
the catalytic centre. However, to the best of our knowledge,
no examples of heterogeneous transition metal-catalysed
construction of imidazo[1,2-a]pyridines have been described
until now, despite the practical benefits of heterogeneous
catalysis.
Mesoporous MCM-41 materials have recently been shown to
be powerful supports for immobilisation of homogeneous metal
catalysts such as palladium, rhodium, molybdenum, gold and
copper complexes.30–33 We have reported the synthesis of an
MCM-41-immobilised phosphine gold(I) complex (MCM-41-
PPh3-AuCl) and its successful application to direct Csp2–Csp bond
functionalisation of arylalkynes through a nitrogenation process
to form amides.34 In order to expand further our Au(I)-MCM-41
chemistry toolbox,32,34 we report here the first heterogeneous
gold(I)-catalysed annulation between 2-aminopyridines and
pyridinealdehydes/ketones
from
propiolaldehydes
and
2-aminopyridines by copper carbene oxidation using air as the
sole oxidant [Scheme 1(a)].20
During the last few decades, homogeneous catalysis of
organic transformations by gold complexes has become a
powerful tool for the synthesis of valuable building blocks.21
Gold-catalysed construction of heterocyclic compounds such
as furans,22 pyrroles,23 indoles,24 oxazoles25 and butenolides26
has attracted great interest due to their high efficiency and
mild reaction conditions, which strongly enriched the synthetic
methodologies of heterocycles. Recently, Cao et al. described
gold(I)-catalysed synthesis of 3-acylimidazo[1,2-a]pyridines
from propiolaldehydes and 2-aminopyridines by gold carbene
oxidation using air as oxidant [Scheme 1(b)].27
Fig. 1 Clinical medicines containing the imidazo[1,2-a]pyridine core structure.
* Correspondent. E-mail: caimzhong@163.com

342 JOURNAL OF CHEMICAL RESEARCH 2018
Previous work:
H
C O
R1
CuI (5 mol%), HOAc (5 mol%)
bipy (10 mol%)
O
O
N
R1
+
+
(a)
(b)
NH2
N
CH2Cl2, r.t. 12 h, air
R
R
N
N
R
1
3
2
H
C O
R1
PPh3AuCl (3 mol%)
AgSbF6 (3 mol%), HOAc (5 mol%)
N
R1
NH2
N
CH2Cl2, r.t. 12 h, air
R
3
2
1
This work:
H
C O
MCM-41-PPh3-AuCl (3 mol%)
R1
O
N
AgSbF (3 mol%), HOAc (5 mol%)
6
R1
+
(c)
NH2
N
CH2Cl2, r.t. 12 h, air
R
N
R
1
3
2
Recyclable gold catalyst
Scheme 1
O
H
H
O
O
PPh2
1. (EtO)3Si(CH2)3NHCNH
Toluene, reflux, 24 h
H
O
2. Me3SiCl, toluene, r.t., 24 h
MCM-41
OSiMe3
O
O
Me2SAuCl
DCM, r.t., 8 h
i
S
N
PPh2
N
H
O
H
Et
O
MCM-41-PPh3
OSiMe3
O
O
i
S
N
N
H
PPh2AuCl
O
H
Et
O
MCM-41-PPh3-AuCl
Scheme 2 Reprinted with permission of John Wiley and Sons, Copyright © 2017, Adv. Synth. Catal. 2017, 359, 3968 – 3976
propiolaldehydes leading to 3-acylimidazo[1,2-a]pyridines in
good yields under mild conditions [Scheme 1(c)].
0.38 mmol g–1 according to inductively coupled plasma atomic
emission spectroscopy (ICP-AES) measurements.
In our initial screening experiments, the reaction of
3-phenylpropiolaldehyde (1a) with 2-aminopyridine (2a)
was investigated to optimise the reaction conditions and the
results are summarised in Table 1. First, various supported
gold(I) catalysts were examined in CH2Cl2 at 25 ºC (Table 1,
entries 1–5). When MCM-41-PPh3-AuCl was used as catalyst,
the desired product 3a was isolated in moderate yield (Table
1, entry 1). Then various silver salts such as AgOTf, AgSbF6,
AgBF4 and AgOAc were tested as co-catalysts. It was found
that AgSbF6 as co-catalyst was the most efficient and gave
3a in 81% yield (Table 1, entry 3). When AgSbF6 alone was
used as catalyst the reaction did not take place, indicating that
Results and discussion
The MCM-41-immobilised phosphine gold(I) complex
(MCM-41-PPh3-AuCl) was prepared by a simple two-step
procedure as shown in Scheme 2.34 First, mesoporous MCM-
41 was condensed with 1-[4-(diphenylphosphino)phenyl]-3-[3-
(triethoxysilyl)-propyl]urea in toluene at 110 ºC, followed by
silylation with Me3SiCl to give Ph3P-functionalised MCM-41
(MCM-41-PPh3). Then the latter was reacted with Me2SAuCl
in dichloromethane (DCM) to afford the MCM-41-immobilised
phosphine gold(I) complex (MCM-41-PPh3-AuCl) as a grey
powder. The gold content of the complex was found to be

JOURNAL OF CHEMICAL RESEARCH 2018 343
the gold(I) catalyst plays a key role in the annulation reaction
(Table 1, entry 6). We next examined the effect of solvents on
the model reaction (Table 1, entries 7–13). When DMF, DMAc,
DMSO, MeCN, THF and dioxane were used as solvents, the
reaction afforded the desired 3a in 61–75% yields and toluene
as solvent gave a lower yield. So, CH2Cl2 as solvent was the best
choice (Table 1, entry 3). We attempted to improve the yield
by raising the reaction temperature. Unfortunately, the yield
decreased gradually on increasing the temperature from 25 to
60 ºC (Table 1, entries 14 and 15). Finally, the amount of the
catalyst was also screened. Reducing the amount of the catalyst
to 1.5 mol% resulted in a lower yield and a long reaction time
was required (Table 1, entry 16). Increasing the amount of the
catalyst could shorten the reaction time, but did not improve
the yield significantly (Table 1, entry 17). Thus, the optimised
reaction conditions for this transformation are MCM-41-PPh3-
AuCl/AgSbF6 (3 mol%) in CH2Cl2 at 25 ºC under air for 12 h
(Table 1, entry 3).
With the optimised conditions in hand, we next investigated
the scope and limitation of this heterogeneous gold(I)-
catalysed annulation reaction using a range of propiolaldehydes
1a–d and 2-aminopyridines 2a–h as the reactants; the results
are summarised in Table 2. Firstly, 3-phenylpropiolaldehyde
(1a) was used to explore the scope of the 2-aminopyridines.
As shown in Table 2, the annulation reactions of substituted
2-aminopyridines 2b–h with 1a proceeded smoothly
under the optimised conditions to afford the corresponding
3-benzoylimidazo[1,2-a]pyridines 3b–h in 66–89% yields
(Table 2, entries 2–8). The results indicated that the reaction
was compatible with a range of substituents in all positions
on the pyridine ring of the 2-aminopyridine. The halo groups
(chloro or bromo) on the pyridine ring remained intact under
the optimised conditions. We next examined the scope of
propiolaldehydes 1. The alkyl-substituted propiolaldehyde oct-
2-ynal (1b) proved to be also a suitable reactant and the reactions
with different 2-aminopyridines gave the desired imidazo-
[1,2-a]pyridine derivatives 3i–k in 63–72% yields (Table 2,
entries 9–11). Interestingly, the reaction was found to be perhaps
quite general as using 3-(trimethylsilyl)propiolaldehyde (1c) as
a reactant, the corresponding products 3l–p were produced in
60–68% yields (Table 2, entries 12–16). It is noteworthy that
when propiolaldehyde (1d) was used, the expected products
3q–s could be formed in 58–69% yields (Table 2, entries 17–19).
These results indicate that the heterogeneous gold(I) catalytic
system is applicable to aryl-, alkyl- and silyl-substituted as well
as terminal propiolaldehydes.
To determine whether the observed catalysis was due to the
heterogeneous catalyst MCM-41-PPh3-AuCl or to a leached
gold species in solution, we focused on the annulation reaction
of 3-phenylpropiolaldehyde (1a) with 2-aminopyridine (2a).
We filtered off the catalyst at 25 ºC after 5 h of reaction time
and allowed the filtrate to react further. We found that, after
removal of the catalyst, no further reaction was observed,
indicating that leached gold species from the catalyst (if any) are
not responsible for the observed activity. It was also confirmed
by ICP-AES analysis that no gold species could be detected
in the filtrate. These results suggest that the gold(I) complex
was stable during the reaction and the observed catalysis was
intrinsically heterogeneous.
A possible mechanism for this heterogeneous gold(I)-
catalysed annulation reaction of propiolaldehydes 1 with
2-aminopyridines 2 is outlined in Scheme 3. Firstly, HOAc-
promoted condensation of 1a and 2a takes place to form
intermediate A. Then coordination of the MCM-41-PPh3-
Table 1 Optimisation of the reaction conditionsa
Catalyst
Solvent
O
N
+
Ph
H
C O
NH2
N
Ph
N
1a
2a
3a
Entry
1
2
3
4
5
6
7
8
Catalyst
MCM-41-PPh3-AuCl
Solvent
Temp. (°C)
25
25
25
25
25
25
25
25
25
25
25
25
25
40
60
25
Yield (%)b
49
63
81
58
50
0
69
61
65
68
71
51
75
66
38
63
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DMF
DMAc
DMSO
MeCN
THF
Toluene
Dioxane
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MCM-41-PPh3-AuCl/AgOTf
MCM-41-PPh3-AuCl/AgSbF6
MCM-41-PPh3-AuCl/AgBF4
MCM-41-PPh3-AuCl/AgOAc
AgSbF6
MCM-41-PPh3-AuCl/AgSbF6
MCM-41-PPh3-AuCl/AgSbF6
MCM-41-PPh3-AuCl/AgSbF6
MCM-41-PPh3-AuCl/AgSbF6
MCM-41-PPh3-AuCl/AgSbF6
MCM-41-PPh3-AuCl/AgSbF6
MCM-41-PPh3-AuCl/AgSbF6
MCM-41-PPh3-AuCl/AgSbF6
MCM-41-PPh3-AuCl/AgSbF6
MCM-41-PPh3-AuCl/AgSbF6
MCM-41-PPh3-AuCl/AgSbF6
9
10
11
12
13
14
15
16c
17d
25
82
aAll reactions were performed using 1a (0.5 mmol), 2a (0.7 mmol), catalyst (3 mol%), HOAc (5 mol%), in solvent (3 mL) under air for 12 h.
bIsolated yield.
c1.5 mol% catalyst was used for 24 h.
d5 mol% catalyst was used for 8 h.

344 JOURNAL OF CHEMICAL RESEARCH 2018
Table 2 Heterogeneous gold(I)-catalysed synthesis of imidazo[1,2-a]pyridinesa
R1
MCM-41-PPh3-AuCl (3 mol%)
AgSbF6 (3 mol%), HOAc (5 mol%)
O
N
R1
+
R
H
C O
NH2
N
CH2Cl2, r.t. 12 h, air
R
N
3
1
2
Entry
1
2
3
4
R
Ph
Ph
Ph
Ph
Ph
Ph
R1
H
5-Me
4-Me
3-Me
4-Cl
Product
3a
3b
3c
3d
3e
3f
Yield (%)b
81
72
70
66
5
6
67
73
4-Br
7
8
9
Ph
Ph
4-EtOCO
4-F3C
3-Me
4-EtOCO
5-Me
H
3-Me
4-Me
5-Me
4-Br
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
89
84
63
65
72
64
68
60
67
63
58
62
n-C5H11
n-C5H11
n-C5H11
Me3Si
Me3Si
Me3Si
Me3Si
Me3Si
H
10
11
12
13
14
15
16
17
18
19
4-Me
4-Cl
5-Me
H
H
3s
69
aAll reactions were performed using 1 (0.5 mmol), 2 (0.7 mmol), MCM-41-PPh3-AuCl/AgSbF6 (3 mol%), HOAc (5 mol%), in CH2Cl2 (3 mL) at 25 °C under air for 12 h.
bIsolated yield.
+
Ph
H
C O
1a
N
2a
NH2
MCM-41-PPh3-AuCl
O
HOAc
N
A
bF
gS
6
Ph
Ph
N
N
3a
MCM-41
( )
A
N
PPh3
[Au]
air
MCM-41
MCM-41
PPh3
[Au]
PPh3
[Au]
( )
C
N
Ph
( )
B
Ph
N
N
MCM-41
N
PPh3
[Au]
Ph
N
N
Scheme 3

JOURNAL OF CHEMICAL RESEARCH 2018 345
3-Benzoylimidazo[1,2-a]pyridine (3a): White solid; m.p. 104–105 ºC
(lit.27 103–104 ºC); 1H NMR (400 MHz, CDCl3): δ 9.76 (d, J = 6.8 Hz,
1H), 8.21 (s, 1H), 7.88 (d, J = 7.2 Hz, 2H), 7.81 (d, J = 8.8 Hz, 1H),
7.63–7.52 (m, 4H), 7.16 (t, J = 7.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3): δ 184.8, 149.1, 145.7, 139.3, 132.0, 129.4, 128.9, 128.8, 128.6,
123.6, 117.8, 115.1.
3-Benzoyl-6-methylimidazo[1,2-a]pyridine (3b): White solid; m.p.
125–126 ºC (lit.27 126–127 ºC); 1H NMR (400 MHz, CDCl3): δ 9.58 (s,
1H), 8.16 (s, 1H), 7.90–7.85 (m, 2H), 7.71 (d, J = 8.8 Hz, 1H), 7.63–7.58
(m, 1H), 7.53 (t, J = 7.4 Hz, 2H), 7.41 (dd, J = 8.8, 1.6 Hz, 1H), 2.47 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 184.8, 148.1, 145.7, 139.5, 132.3,
131.9, 128.8, 128.6, 126.9, 126.8, 125.2, 117.0, 18.4.
3-Benzoyl-7-methylimidazo[1,2-a]pyridine (3c):27 Yellow oil;
1H NMR (400 MHz, CDCl3): δ 9.62 (d, J = 6.8 Hz, 1H), 8.15 (s, 1H),
7.90–7.84 (m, 2H), 7.61–7.49 (m, 4H), 6.99 (dd, J = 7.0, 1.4 Hz, 1H),
2.52 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 184.6, 149.6, 146.0, 141.1,
139.4, 131.9, 128.8, 128.5, 128.1, 124.6, 117.6, 116.4, 21.6.
AuSbF6 complex generated in situ from MCM-41- PPh3-AuCl
and AgSbF6 to the alkyne moiety in intermediate A affords an
MCM-41- bound phosphine-Au(I) alkyne complex B, which is
followed by an intramolecular 5-exo-dig cyclisation to give an
MCM-41-bound phosphine-Au(I) carbene complex C. Finally,
intermediate C undergoes carbene oxidation with oxygen
metathesis to afford the desired product 3a and regenerate the
MCM-41-PPh3-Au(I) complex.
The MCM-41-PPh3-AuCl complex can be easily separated
and recovered by simple filtration of the reaction solution.
We next examined the recycling of the catalyst by using the
annulation reaction of 3-phenylpropiolaldehyde (1a) with
2-amino-4-ethoxycarbonylpyridine (2g). After completion of
the reaction, the catalyst was recovered by simple filtration and
washed with 25–28 wt% NH3·H2O (2 × 5 mL), distilled water
(2 × 5 mL) and acetone (2 × 5 mL). After being air-dried, it was
reused directly without further purification. The recovered gold
catalyst was used in the next run and almost the same yield of
3g was observed for eight consecutive cycles (89, 88, 87, 87, 86,
85, 86 and 86% respectively). It is noteworthy that the reaction
catalysed by the recovered catalyst did not need the addition of
AgSbF6 because the MCM-41-PPh3-AuCl had been converted
into MCM-41-PPh3-AuSbF6 after the first cycle.
In conclusion, we have developed a novel and practical method
for the synthesis of 3-carbonyl-substituted imidazo[1,2-a]
pyridines through the annulation reaction of propiolaldehydes
with 2-aminopyridines by using an MCM-41-immobilised
phosphine gold(I) complex (MCM-41-PPh3-AuCl) and AgSbF6
as catalysts. The reactions generated a variety of imidazo[1,2-a]
pyridine derivatives in moderate to good yields under mild
conditions. Importantly, this heterogeneous gold(I) catalyst can
be easily recovered by simple filtration and recycled at least
seven times without significant loss of catalytic activity, thus
making this procedure economically and environmentally more
acceptable.
3-Benzoyl-8-methylimidazo[1,2-a]pyridine (3d): White solid; m.p.
1
123–124 ºC (lit.27 125–126 ºC); H NMR (400 MHz, CDCl3): δ 9.61
(d, J = 6.8 Hz, 1H), 8.18 (s, 1H), 7.90–7.85 (m, 2H), 7.63–7.58 (m, 1H),
7.53 (t, J = 7.4 Hz, 2H), 7.35 (d, J = 7.0 Hz, 1H), 7.06 (t, J = 7.0 Hz, 1H),
2.70 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 184.9, 149.2, 145.0, 139.4,
132.0, 128.9, 128.6, 128.5, 127.6, 126.6, 124.0, 115.2, 16.9.
3-Benzoyl-7-chloroimidazo[1,2-a]pyridine (3e):27 Yellow oil;
1H NMR (400 MHz, CDCl3): δ 9.68 (d, J = 7.2 Hz, 1H), 8.20 (s, 1H), 7.87
(d, J = 7.2 Hz, 2H), 7.82 (s, 1H), 7.63 (t, J = 7.2 Hz, 1H), 7.56–7.51 (m,
2H), 7.14 (dd, J = 7.4, 2.2 Hz, 1H);13C NMR (100 MHz, CDCl3): δ 184.8,
149.1, 146.0, 138.9, 136.1, 132.3, 129.1, 128.8, 128.7, 128.2, 116.9, 116.6.
3-Benzoyl-7-bromoimidazo[1,2-a]pyridine (3f):27 Yellow oil;
1H NMR (400 MHz, CDCl3): δ 9.61 (d, J = 7.2 Hz, 1H), 8.18 (s, 1H),
8.01 (d, J = 1.6 Hz, 1H), 7.87 (d, J = 7.2 Hz, 2H), 7.63 (t, J = 7.4 Hz,
1H), 7.57–7.50 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 184.8, 149.1,
145.8, 138.9, 132.3, 132.0, 129.3, 128.8, 128.7, 123.8, 119.0, 109.6.
3-Benzoyl-7-ethoxycarbonylimidazo[1,2-a]pyridine (3g): Yellow
oil; IR (neat): 3069, 2982, 1689, 1608, 1385, 1276, 1109 cm–1; 1H NMR
(400 MHz, CDCl3): δ 9.76 (d, J = 7.2 Hz, 1H), 8.51 (s, 1H), 8.31 (s, 1H),
7.90 (d, J = 7.2 Hz, 2H), 7.74–7.69 (m, 1H), 7.64 (t, J = 7.4 Hz, 1H),
7.58–7.54 (m, 2H), 4.47 (q, J = 7.2 Hz, 2H), 1.46 (t, J = 7.0 Hz, 3H);
13C NMR (100 MHz, CDCl3): δ 185.1, 167.7, 148.2, 146.3, 138.9, 132.4,
130.9, 128.9, 128.7, 128.5, 124.2, 119.8, 114.3, 62.1, 14.3; HRMS calcd
Experimental
All reagents were used as received without further purification.
The MCM-41-PPh3-AuCl complex was prepared according to our
previous procedure.34 The gold content was determined to be 0.38
mmol g–1 by ICP-AES. DCM was dried over P2O5 and distilled before
use. All reactions were carried out under air in oven-dried glassware
for C17H14N2O3 : [M+]: 294.1004; found: 294.1011.
+
3-Benzoyl-7-trifluoromethylimidazo[1,2-a]pyridine (3h):20 Yellow
1
oil; H NMR (400 MHz, CDCl3): δ 9.85 (d, J = 7.2 Hz, 1H), 8.32 (s,
1H), 8.11 (s, 1H), 7.90 (d, J = 7.2 Hz, 2H), 7.65 (t, J = 7.4 Hz, 1H), 7.56
(t, J = 7.6 Hz, 2H), 7.34–7.30 (m, 1H); 13C NMR (100 MHz, CDCl3): δ
185.1, 147.4, 146.1, 138.6, 132.6, 132.5, 130.8 (q, 2JC–F = 34.3 Hz), 129.6,
128.8, 128.7, 122.8 (q, 1JC–F = 271.0 Hz), 115.6 (q, 3JC–F = 4.7 Hz), 110.8
(q, 3JC–F = 2.8 Hz).
1
with magnetic stirring. H NMR spectra were recorded on a Bruker
Avance 400 spectrometer (at 400 MHz) with TMS as an internal
standard using CDCl3 as the solvent. 13C NMR spectra were recorded
on the Bruker Avance 400 spectrometer (at 100 MHz) using CDCl3
as the solvent. FTIR spectra were recorded using a PerkinElmer 782
Fourier transform spectrophotometer. HRMS spectra were recorded on
a Bruker MicroTOF-Q II spectrometer with micromass MS software
using electrospray ionisation. Gold content was determined using ICP-
AES on an Atomscan16 (TJA Corporation) instrument.
1-(8-Methylimidazo[1,2-a]pyridin-3-yl)hexan-1-one (3i):27 Yellow
1
oil; H NMR (400 MHz, CDCl3): δ 9.54 (d, J = 6.8 Hz, 1H), 8.34 (s,
1H), 7.29 (d, J = 7.2 Hz, 1H), 7.00 (t, J = 6.8 Hz, 1H), 2.92 (t, J = 7.6 Hz,
2H), 2.67 (s, 3H), 1.75–1.67 (m, 2H), 1.47–1.39 (m, 4H), 0.96 (t,
J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 190.8, 142.1, 127.9,
127.5, 126.6, 124.2, 115.0, 39.6, 31.6, 25.1, 22.5, 16.9, 13.7.
Synthesis of 3-benzoylimidazo[1,2-a]pyridine (3a); typical procedure
Ethyl 3-hexanoylimidazo[1,2-a]pyridine-7-carboxylate (3j): Yellow
oil; IR (neat): 2979, 2926, 2870, 1685, 1662, 1386, 1218, 1106 cm–1;
1H NMR (400 MHz, CDCl3): δ 9.70 (d, J = 7.2 Hz, 1H), 8.46 (s, 1H),
8.45 (s, 1H), 7.66 (dd, J = 7.2, 0.8 Hz, 1H), 4.45 (q, J = 7.2 Hz, 2H),
2.95 (t, J = 7.6 Hz, 2H), 1.81–1.71 (m, 2H), 1.47–1.37 (m, 7H), 0.94 (t,
J = 7.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 191.1, 164.5, 147.8,
143.7, 130.9, 128.3, 119.8, 114.1, 62.0, 39.8, 31.5, 24.8, 22.5, 14.2, 13.9;
A mixture of 3-phenylpropiolaldehyde (1a) (0.5 mmol), 2-aminopyridine
(2a) (0.7 mmol) and HOAc (5 mol%) was stirred in dry CH2Cl2 (3 mL) for
30 min at 25 ºC. Then MCM-41-PPh3-AuCl (39.5 mg, 0.015 mmol) and
AgSbF6 (5.2 mg, 0.015 mmol) were added and this mixture was stirred
at 25 ºC for 12 h under air. After completion of the reaction, the mixture
was diluted with ethyl acetate (15 mL) and filtered. The gold catalyst
was washed with 25–28 wt% NH3·H2O (2 × 5 mL), distilled water (2 ×
5 mL) and acetone (2×5 mL) and air-dried if to be reused. The filtrate
was quenched with water (10 mL) and the aqueous phase was extracted
with ethyl acetate (2 × 10 mL). The combined extract was dried over
anhydrous MgSO4. After removal of the solvent, the residue was
purified by column chromatography using petroleum ether (60–90
°C)/ethyl acetate (6:1) as eluent to afford the desired product 3a.
HRMS calcd for C16H20N2O3 : [M+]: 288.1474; found: 288.1469.
+
1-(6-Methylimidazo[1,2-a]pyridin-3-yl)hexan-1-one (3k):27 Yellow
oil; 1H NMR (400 MHz, CDCl3): δ 9.51 (s, 1H), 8.31 (s, 1H), 7.66 (d,
J = 9.2 Hz, 1H), 7.35 (d, J = 9.2 Hz, 1H), 2.90 (t, J = 7.4 Hz, 2H), 2.42
(s, 3H), 1.75–1.69 (m, 2H), 1.46–1.40 (m, 4H), 0.96 (t, J = 7.6 Hz, 3H);
13C NMR (100 MHz, CDCl3): δ 190.7, 149.2, 142.7, 139.0, 131.8, 126.7,
125.0, 116.8, 39.5, 31.6, 25.1, 22.5, 18.4, 13.7.

346 JOURNAL OF CHEMICAL RESEARCH 2018
Imidazo[1,2-a]pyridin-3-yl(trimethylsilyl)methanone (3l): Yellow
oil; IR (neat): 2925, 2823, 1661, 1515, 1487, 1322, 1253, 1164 cm–1;
1H NMR (400 MHz, CDCl3): δ 9.77 (d, J = 6.8 Hz, 1H), 8.42 (s, 1H),
7.83–7.76 (m, 1H), 7.55–7.49 (m, 1H), 7.08 (t, J = 7.0 Hz, 1H), 0.42
(s, 9H); 13C NMR (100 MHz, CDCl3): δ 167.7, 147.8, 145.0, 129.7,
129.0, 128.8, 117.5, 115.3, –1.6; HRMS calcd for C11H14N2OSi+: [M+]:
218.0875; found: 218.0863.
Received 12 March 2018; accepted 25 May 2018
Paper 1805311
https://doi.org/10.3184/174751918X15314807595487
Published online: 18 July 2018
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1165 cm–1; H NMR (400 MHz, CDCl3): δ 9.62 (s, 1H), 8.37 (s, 1H),
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1158 cm–1; H NMR (400 MHz, CDCl3): δ 9.63 (d, J = 7.2 Hz, 1H),
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1
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We thank the National Natural Science Foundation of China
(No. 21462021), the Natural Science Foundation of Jiangxi
Province of China (No. 20161BAB203086) and the Key
Laboratory of Functional Small Organic Molecule, Ministry of
Education (No. KLFS-KF-201704) for financial support.