Copper- A nd DMF-mediated switchable oxidative C-H cyanation and formylation of imidazo[1,2-: A] pyridines using ammonium iodide

Article abstract of DOI:10.1039/d0ob01838d

The cyanation and formylation of imidazo[1,2-a]pyridines were developed under copper-mediated oxidative conditions using ammonium iodide and DMF as a nontoxic combined cyano-group source and DMF as a formylation reagent. Mechanistic studies indicate that the cyanation of imidazo[1,2-a]pyridines proceeds through a two-step sequence: Initial iodination and then cyanation. The cyanation has a broad substrate scope and high functional group tolerance, and can be safely conducted on a gram scale. A novel copper-mediated formylation using the widely available DMF as the formylation reagent and environmentally friendly molecular oxygen as the oxidant has also been developed. This protocol also provided a convenient approach for the synthesis of clinically used saripidem. This journal is

Full text of DOI:10.1039/d0ob01838d

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: F. Ji, X. Li, S.
Wang, J. Zang, M. Liu and G. Jiang, Org. Biomol. Chem., 2020, DOI: 10.1039/D0OB01838D.
Volume 15
Number 47
21 December 2017
Pages 9945-10124
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
Accepted Manuscripts are published online shortly after acceptance,
rsc.li/obc
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
ISSN 1477-0520
PAPER
I . J. Dmochowski et al.
Oligonucleotide modifi cations enhance probe stability for
shall the Royal Society of Chemistry be held responsible for any errors
single cell transcriptome in vivo analysis (TIVA)
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
rsc.li/obc

Please do not adjust margins
Page 1 of 8
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB01838D
Journal Name
ARTICLE
Copper- and DMF-Mediated Switchable Oxidative C-H Cyanation
and Formylation of Imidazo[1,2-a]pyridines Using Ammonium
Iodide
enReceived 00th January
20xx,
Accepted 00th January
20xx
Xuan Li, Shoucai Wang, Jiawang Zang, Meichen Liu, Guangbin Jiang,* Fanghua Ji*
The cyanation and formylation of imidazo[1,2-a]pyridines were developed under copper-mediated oxidative conditions
using ammonium iodide and DMF as nontoxic combined cyano-group source and DMF as formylation reagent. Mechanistic
studies indicate that the cyanation of imidazo[1,2-a]pyridines proceeds through a two-step sequence: initial iodination and
then cyanation. The cyanation has a high broad substrate scope, high functional group tolerance, and can be safely
conducted on gram scale. A novel copper-mediated formylation using the widely available DMF as the formylation reagent
and environmentally friendly molecular oxygen as the oxidant has also been developed. This protocol also provided a
convenient approach for the synthesis of clinically used Saripidem.
DOI: 10.1039/x0xx00000x
www.rsc.org/
Introduction
Aryl nitriles are an ubiquitous structural motif frequently found in
Imidazo[1,2-a]pyridines are an important class of heterocycles in
medicinal chemistry and have attracted critical attention of chemists
for their application value.1 A number of clinically used drugs and
clinical candidates contain the core structure of imidazo[1,2-
a]pyridine, such as Saripidem, Necopidem, Alpidem, and Zolpidem
(Figure 1).2 It is not surprising, therefore, that great efforts have been
directed toward developing synthetic methods for the construction of
this privileged scaffold. Recently, Cao et al. reported a number of
successful synthetic strategies for the construction of functionalized
imidazo[1,2-a]pyridines.3 Jiang and Zhu et al. also described
efficient and elegant transformations to prepare imidazo[1,2-
a]pyridines.4
natural products, pharmaceuticals, agricultural chemicals, materials,
and dyes.5 Cyano unit is a key precursor for diverse functional
groups including amines, amidines, amides, tetrozoles, aldehydes, or
other carboxy derivatives.6 In the early years, the methods to
introduce a cyano group onto an aromatic ring were limited.7 As a
result,
a variety of new procedures have been extensively
investigated for the synthesis of aryl nitriles.8 In particular, metal-
catalyzed cyanation of aryl halides or (hetero)arenes with metal
cyano reagents, such as CuCN, KCN, NaCN, Zn(CN)2, TMSCN,
and K2Fe(CN)4, is considered to be highly promising.9 Despite of
their attractive features, these methods have some drawbacks: 1) the
employed cyano-group sources are highly toxic; 2) in order to
prevent the generation of hazardous HCN gas, careful handling is
generally needed; 3) metal waste is unavoidably produced in
stoichiometric amounts; 4) a careful control of the cyanide
concentration is required to maintain the catalyst activity. Owing to
the concept of “green chemistry”, the use of nonmetallic cyano-
group sources, especially combined cyano-group sources generated
in situ, has been scrutinized as an alternative approach in recent
years.10
Figure 1. Structures of Several Commercial Drugs Containing
Imidazo[1,2-a]pyridine Skeletons.
N
N
Cl
Cl
N
N
Cl
O
N
N
n-Pr
n-Pr
On the other hand, formylation of (hetero)arenes has attracted the
interest of organic chemists due to their remarkable application value
in synthetic chemistry. The traditional formylation methods such as
Vilsmeier-Haack, Reimer-Tiemann or Rieche and Friedel-Crafts
acylations are routinely employed for the preparation of
formylheteroarenes, which generally require the use of excess strong
bases or acids, high temperatures, and strict exclusion of moisture.11
Owing to the harsh reaction conditions, the development of more
efficient and facile formylation methods remains highly desirable. In
recent years, many elegant formylation processes have been
developed using DMSO, DMF, TMEDA, and anilines as the
carbonyl sources.12
O
n-Pr
Alpidem
Saripidem
N
N
N
N
O
N
N
i-Bu
O
Zolpidem
Necopidem
Guangxi Key Laboratory of Electrochemical and Magnetochemical Function
Materials, College of Chemistry and Bioengineering, Guilin University of
Technology, Guilin 541004, P. R. China, E-mail: jianggb@glut.edu.cn,
fanghuaji@glut.edu.cn, Fax: (+86) 773-899-1304
†Electronic Supplementary Information (ESI) available: General experimental
information, and NMR spectra. See DOI: 10.1039/x0xx00000x
Although significant progress has been made in these reasearch
fields, direct copper-mediated cyanation and formylation of
imidazo[1,2-a]pyridine using ammonium iodide and DMF as
nontoxic combined cyano-group source and DMF as formylation
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 8
ARTICLE
Journal Name
reagent have not been described yet. DMF is not only a common
solvent and industrial raw material but also an important carbon
source for C=O, CH3, CH2, CH and -CN formation.13 Owing to our
continuing interest in the construction of functionalized compounds
by employing simple and readily available starting materials,14 we
disclosed an efficient protocol on copper-mediated cyanation of
imidazo[1,2-a]pyridine C-H bonds using ammonium iodide and
DMF as the source of nitrogen and carbon atom of the cyano unit,
respectively. Meanwhile, we have also developed a convenient and
general method for C-3 formylation of imidazo[1,2-a]pyridines
using DMF as formylation reagent (Scheme 1).
7c
8
Cu(NO3)2.3H2O
Cu(NO3)2.3H2O
Cu(NO3)2.3H2O
Cu(NO3)2.3H2O
Cu(NO3)2.3H2O
Cu(NO3)2.3H2O
Cu(NO3)2.3H2O
Cu(NO3)2.3H2O
NH4I
NH4I
K2CO3
130
0
View Article Online
DOI: 10.1039/D0OB01838D
TFA
I2
130
130
140
110
100
130
130
50
82
0
9
NH4OAc
NH4I
10
11
12
13c
14d
HOAc
HOAc
HOAc
HOAc
HOAc
NH4I
23
0
NH4I
Scheme 1. Copper-Mediated Cyanation and Formylation of
Imidazo[1,2,a]pyridine.
NH4I
65
41
NH4I
N
N
N
Cu(II) / O2
Ar
R
Cu(II) / O2
aReaction conditions: 1a (0.2 mmol), [Cu] (2.0 equiv), NH4X (2.0 equiv), addtive (2.0
equiv), and DMF (2.0 mL) were added under O2 balloon. bIsolated yield. c[Cu] loading
is 1.0 equiv. dUnder air atmosphere.
Ar
R
DMF
N
Ar
R
+
N
with NH4I
N
without NH4I
CN
CHO
H
With the optimal conditions in hand, we next explored the scope
and limitations of our method (Table 2). In general, reaction of
imidazo[1,2-a]pyridines bearing electron-donating groups gave
slightly higher product yields than those containing electron-
withdrawing moieties (2a-2o). It is notable that a wide range of
functional groups were compatible with the optimal conditions.
Imidazo[1,2-a]pyridine substituted at different positions, having 6-
CH3, 7-CH3, 8-CH3 substitution, were all smoothly cyanated in good
yields (2b-2d). Polyaryl substrates such as 2-(naphthalen-2-
yl)imidazo[1,2-a]pyridine was readily cyanated (2p). Much to our
satisfaction, heteroaryl substrates and imidazo[1,2-a]pyridine
underwent the reaction in moderate yields (2q-2t). It was worth
noting that this cyanation process can be safely conducted on gram
scale when using substrate bearing electron-donating group as
starting material.
Results and discussion
Using 2-phenylimidazo[1,2-a]pyridine (1a) as a test substrate,
optimal conditions were first sought for the cyanation (Table 1).
After intensive screening of copper salts, we are pleased to find that
Cu(NO3)2·3H2O (2.0 equiv to 1a) was most effective for the
cyanation (Table 1, entries 1-5). For further investigation, we
focused on testing various additives to improve the product yield.
Fortunately, high yield was observed when acetic acid was used as
an additive (Table 1, entries 6-8). Interestingly, similar efficiency
was also obtained by the combined use of NH4OAc and I2, which
provided an important clue for the mechanistic details (Table 1,
entry 9). Furthermore, the temperature was found to be vital to the
reaction system, higher temprature or relatively lower temprature
was ineffective for the reaction (Table 1, entries 10-12). In addition,
when the copper salt loading was reduced to 1 equiv, 2a could be
obtained only in 65% yield (Table 1, entry 13). Then the reaction
was performed under air atmosphere, the desired product was
observed with lower yield (Table 1, entry 14).
In continuation of our interest in preparing imidazo[1,2-a]pyridine
derivatives by direct C-H functionalization, we next explored a novel
and facile copper-mediated C-3 formylation of imidazo[1,2-
a]pyridines utilizing DMF as formylation reagent and molecular
oxygen as the terminal oxidant (Table 3). A variety of substituted
imidazo[1,2-a]pyridines were tested under the optimized conditions.
Much to our satisfaction, the substrates with functional groups such
as fluoro, chloro, and bromo all gave the corresponding products in
moderate yields (3d-3f, 3j and 3k). To our delight, the substrates
with naphthalene, heterocyclic ring and 2-unsubstituted imidazo[1,2-
a]pyridine were also tolerated in the reaction system (3n-3p).
Furthermore, methyl imidazo[1,2-a]pyridine-2-carboxylate also gave
the desired product in 22% yield (3q). 2-Chloroimidazo[1,2-
a]pyridine and 2-bromoimidazo[1,2-a]pyridine also gave the
corresponding products in 30% and 27% yields (3r, 3s).
Table 1. Optimization of Reaction Conditions a
N
N
[Cu] (2 equiv.), Additive (2 equiv.)
NH4X
+
N
N
, 130 oC, O2 (balloon)
DMF
(2 equiv.)
CN
2a
H
1a
entry
[Cu]
NH4X
additive
T (oC) yieldb (%)
1
2
3
4
5
6
Cu(OAc)2
CuBr2
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
----
----
130
130
130
130
130
130
15
0
Table 2. Copper-Mediated Cyanation of Imidazo[1,2-a]pyridines a,b
Cu(NO3)2 3H2O (2 equiv.), O2
N
N
HOAc (2 equiv.), 130 o
C
R1
R2
CuI
----
0
R1
R2
NH4I
+
N
N
O
(2 equiv.)
CN
Me
H
1
2
CH
)
3
2
H
N(
CuCl2
----
0
Me
N
N
N
N
N
N
N
Cu(NO3)2.3H2O
Cu(NO3)2.3H2O
----
60
85
N
Me
CN
CN
2a
CN
CN
, 80%
2b
, 82%
2c
, 85%
, 87%
2d
HOAc
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Page 3 of 8
Organic & Biomolecular Chemistry
Journal Name
ARTICLE
2d
, 80%
N
To gain insight into the mechanism of the reaction, a variety of
control experiments were conducted as shown in ScVhieewmAerti3cl.e OFnirlisnte,
MeO
N
N
N
DOI: 10.1039/D0OB01838D
N
N
N
N
F
Cl
Ph
separately prepared 3-iodo-2-phenylimidazo[1,2-a]pyridine (4a)
underwent the cyanation with 88% yield when ammonium acetate
instead of its iodide salt was used to react under the otherwise
identical conditions (Scheme 3a). This result demonstrated that the
reaction proceeded in two steps via initial iodination and subsequent
cyanation. To probe the mechanism of the conversion of DMF into a
-CN unit, a series of labeling experiments were next carried out,
indicating that ammonium iodide plays a dual role to supply iodide
and nitrogen atom of the cyano unit (Scheme 3b, 3c). The results of
18O-labeling experiments proved that the oxygen atom in the
carbonyl group should be originated from molecular oxygen
(Scheme 3d and 3e). In addition, no products were obtained in the
presence of radical scavenger, such as BHT (2,6-di-tert-butyl-4-
methylphenol) and TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl),
which suggesting that the reaction probably proceeds through a
radical pathway (Scheme 3f).
CN
CN
CN
CN
2g
2h
, 65%
, 74%
2e
, 85%
N
2f
, 80%
F3C
N
N
N
Me
OMe
Ph
N
N
N
N
CN
CN
2j
CN
CN
2i
, 60%
2k
, 87%
, 90%
2l
, 82%
N
N
N
N
F
Cl
CF3
N
N
N
N
N
CN
2m
CN
2n
CN
2o
CN
2p
, 80%
S
, 75%
, 65%
, 78%
N
N
S
N
S
N
N
N
N
CN
2q
CN
CN
2r
CN
, 60%
2s
, 55%
, 60%
2t
,
45%
gram-scale reaction
Cu(NO3)2 H2O (2 equiv.), O2 (1 atm)
N
N
HOAc (2 equiv.), 130 o
C
OMe
OMe
NH4I
+
N
N
O
(2 equiv.)
CN
2k
, 7.2 mmol, 72%
H
CH
)
3
2
H
N(
1k
Scheme 3. Control Experiments
, 10 mmol
aReaction conditions: a mixture of 1 (0.2 mmol), Cu(NO3)2·3H2O (2.0 equiv), NH4I (2.0
equiv), HOAc (2.0 equiv) and DMF (2.0 mL) were added at 130 °C under O2 balloon.
bYields referred to isolated yields.
N
N
Cu(NO3)2 3H2O (2 equiv)
NH4OAc
a)
b)
c)
d)
+
N
N
HOAc (2 equiv)
DMF, 130 oC, O2
CN
, 88%
I
2a
Table 3. Copper-Mediated Formylation of Imidazo[1,2-a]pyridines
4a
O
13
H
N
N
a,b
Cu(NO3)2 3H2O (2 equiv)
,
2a
, 80%
+
+
H C
(
)2N
3
N
N
N
N
HOAc (2 equiv), NH4I (2 equiv)
130 oC, O2
Cu(NO3)2 3H2O (0.5 equiv.)
N
13CN
not detected
O2 , 130 o
C
N
H
R1
R2
R1
R2
N
1a
N
N
O
N
O
CHO
Cu(NO3)2 3H2O (2 equiv)
H
2a
,
, 83%
CH
)
3
15
H
N(
2
3
1
N
H C
(
)2HN
H
HOAc (2 equiv), NH4I (2 equiv)
130 oC, O2
3
CN15
not detected
N
N
N
N
H
F
OMe
Me
1a
N
N
N
N
N
N
Cu(NO3)2 3H2O (0.5 equiv)
DMF, 130 oC, O2
CHO
CHO
CHO
CHO
3b
3a
,
, 75%
+
H2O18(10 equiv)
N
3a
, 82%
, 85%
3c
, 80%
3d
, 70%
CHO18
not detected
N
N
N
N
H
N
Cl
Br
Ph
1a
CF3
N
N
N
N
N
Cu(NO3)2 3H2O (0.5 equiv)
CHO
CHO
CHO
CHO
e)
f)
(without O2)
3e
, 72%
DMF, 130 o
C
N
3g
3h, 50%
3f
, 70%
, 65%
N
N
N
CHO
no reaction
N
H
1a
Me
N
N
N
N
N
standard reaction conditions
for cyanation or formylation
N
Ph
Cl
F
N
N
N
CHO
, 75%
CHO
CHO
3k
, 68%
CHO
or
N
N
3l
radical scavenger
3i
, 80%
3j
, 65%
CN
2a
H
1a
CHO
3a
N
N
N
S
N
R1
H
N
N
N
N
2a
3a
i: BHT, , 0%; , 0%
F3C
CHO
, R1 = H, 35%
2a 3a
ii: TEMPO, , 0%; , 0%
CHO
, 45%
CHO
CHO
3p
3q
3r
3m
3o
, 40%
3n
, 63%
, R1 = 7-COOMe, 22%
, R1 = 7-Cl, 30%
, R1 = 6-Br, 27%
3s
aReaction conditions: a mixture of 1 (0.2 mmol), Cu(NO3)2·3H2O (0.5 equiv), and DMF
(2.0 mL) were added at 130 °C under O2 balloon. bYields referred to isolated yields.
The above results led us to propose a sequential cyanation
pathway that substrates are first iodinated and then cyanated under
the copper-mediated conditions (Scheme 4).16 It is assumed that
DMF is initially oxidized to intermediate A upon the reduction of
Cu(II) to Cu(I). Then, the reaction of A with ammonia can lead to
the formation of amidinyl species B, which is envisioned to release
the cyanide ion. On the other hand, an electrophilic substitution is
believed to involve the iodination of 1a giving intermediate C.
Finally, cyanation of intermediate C would take place presumably
upon the reaction with naked cyanide anion. The role of additive is
assumed to capture the released ammonia leading to its acetate salt.
A plausible mechanism of the formylation reaction has also been
proposed in Scheme 5. First, nucleophilic addition of 1a to species A
produced intermediate D, which was further oxidated into
As a synthetic application of this method, we successfully
converted our products 2n and 3e to the clinically used Saripidem
with 65% and 55% overall yields (Scheme 2). Compared with
previously reported procedures for the synthesis of Saripidem,15 our
synthetic strategy is much facile and convenient.
Scheme 2. Synthesis of Saripidem
1) LiAlH4, THF, 0 oC to rt
2) (n-PrCO)2O, DMAP
Et3N, DCM, 0 oC to rt
3) MeI, DMF, 5 oC to rt
N
Cl
N
CN
2n
65% yield over four steps
intermediate
E via a single electron-transfer (SET) process.
N
Cl
Intermediate E is trapped by dioxygen to give peroxy radical F.
Finally, intermediate F is converted into the desired formylation
product.
N
1) CH3NH2 HCl, NaHCO3
MeOH, 65 oC, 20 h
Saripidem
N
N
2) NaBH4, MeOH, 0 oC to rt
Cl
O
N
n-Pr
3) n-PrCOCl, NaHCO3, THF
CHO
3e
55% yield over four steps
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 8
ARTICLE
Journal Name
Scheme 4. Plausible Mechanism for Cyanation.
completed (monitored by TLC), the resulting mixture were cooled to
View Article Online
room temperature and diluted with EtOAc and aqueous NH3 solution
DOI: 10.1039/D0OB01838D
(3 M). Two layers were separated and aqueous layer was extracted
with EtOAc (3×10 mL). The combined organic layers were dried
over MgSO4, filtered and evaporated under vacuum. The desired
products 2 were obtained in the corresponding yields after purified
by column chromatography on silica gel with mixture of petroleum
ether and ethyl acetate.
NO3
2 Cu(NO3)2
[Cu]
NH
O
O
NH3
CH2
DMF
CN
H
N
CH
H
N
Me
2CuNO3
-HNO3
Me
B
A
1/2 O2
-H2O
NH I
NH
I
2
2
+ 2HOAc
2
4OAc +
N
4
N
N
N
I2
CuXn
General Procedure for Formylation
CN
Cyanation
/
Ph
Ph
Ph
N
Electrophilic
Iodination
N
H
I
CN
The mixture of 1 (0.2 mmol, 1.0 equiv) an Cu(NO3)2.3H2O (0.1
mmol, 0.5 equiv) was stirred in DMF (2.0 mL) in an oil bath at 130
oC in a 20 mL tube with a balloon O2. After the reaction was
completed (monitored by TLC), the resulting mixture were cooled to
room temperature and extracted with EtOAc (3×10 mL). The
combined organic layers were evaporated under vacuum. The
desired products 3 were obtained in the corresponding yields after
purified by column chromatography on silica gel with mixture of
petroleum ether and ethyl acetate. General Procedure for Synthesis
of 3
1a
C
Scheme 5. Plausible Mechanism for Formylation.
N
2 Cu(NO3)2
Ph
O
N
1a
H+
CH2
DMF
H
N
CH2
N
Me
2CuNO3
-HNO3
O
A
D
H
N
N
N
Experimental Procedure for Gram Scale Reaction.
[Cu], O2, SET
MeNHCHO
O2
Ph
Ph
Ph
N
N
N
CH2
CH2
CHO
A mixture of 2-(4-methoxyphenyl)imidazo[1,2-a]pyridine 1k
(10.0 mmol, 1.0 equiv), NH4I (20 mmol, 2.0 equiv), Cu(NO3)2.3H2O
(20 mmol, 2.0 equiv) and HOAc (20 mmol, 2.0 equiv) was stirred in
DMF (50 mL/mmol) at 130 oC in a 100 mL round-bottom flask with
a balloon O2. After the reaction was completed (monitored by TLC),
the resulting mixture were cooled to room temperature and diluted
with EtOAc and aqueous NH3 solution. Two layers were separated
and aqueous layer was extracted with EtOAc (3×10 mL). The
combined organic layers were dried over MgSO4, filtered and
evaporated under vacuum. The desired products 2k were obtained in
72% yield after purified by column chromatography on silica gel
with mixture of petroleum ether and ethyl acetate.
O
F
E
O
Conclusions
In summary, we have developed a new procedure of copper-
mediated cyanation of imidazo[1,2-a]pyridine using ammonium
iodide and DMF as nontoxic combined cyano-group source and
DMF as formylation reagent. Ammonium iodide plays a dual role to
supply iodide and nitrogen atom of the cyano unit. The reaction
features excellent functional group tolerance and can be safely
conducted on gram scale. This protocol is also recognized as a
convenient approach for the synthesis of Saripidem, which is
sedative and anxiolytic drug. Advantageously, the employment of O2
as a clean oxidant and DMF as formylation reagent significantly
improved the practicality of this C-H formylation transformation.
Our method is more convenient and environmentally friendly
compared to the traditional methods for the preparation of 3-
formylimidazo[1,2-a]pyridines. A detailed mechanistic investigation
and further application of DMF are currently underway in our
laboratory.
2-phenylimidazo[1,2-a]pyridine-3-carbonitrile (2a): Yield 37.2
1
mg (85%, white solid). H NMR (400 MHz, CDCl3) δ 8.26 (d, J =
6.8 Hz, 1H), 8.10 (d, J = 7.5 Hz, 2H), 7.66 (d, J = 9.1 Hz, 1H), 7.40
(m, 4H), 6.98 (t, J = 7.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)
δ 152.3, 145.8, 130.2, 129.1, 128.0, 127.7, 126.3, 124.6, 117.1,
113.7, 111.8, 92.8. HRMS Calcd (ESI-TOF) m/z: calcd for C14H10N3
[M+H]+, 220.0869; Found 220.0873.
7-methyl-2-phenylimidazo[1,2-a]pyridine-3-carbonitrile (2b):
1
Yield 38.2 mg (82%, yellow solid). H NMR (400 MHz, CDCl3) δ
8.10 (dd, J = 14.3, 7.2 Hz, 3H), 7.55-7.25 (m, 4H), 6.80 (d, J = 6.9
Hz, 1H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 153.5,
147.3, 140.4, 131.4, 130.0, 129.0, 127.3, 124.7, 117.3, 116.8, 113.1,
93.3, 21.6. HRMS Calcd (ESI-TOF) m/z: calcd for C15H12N3
[M+H]+, 234.1026; Found 234.1028.
Experimental section
General Information
All purchased reagents and solvents were used without further
6-methyl-2-phenylimidazo[1,2-a]pyridine-3-carbonitrile (2c):
Yield 40.5 mg (87%, white solid). H NMR (400 MHz, CDCl3) δ
1
purification unless otherwise noted. H and 13C NMR spectra were
1
recorded using a Bruker DRX-400 or Bruker DRX-600 spectrometer
using CDCl3 or DMSO-d6 as solvent. The chemical shifts are
referenced to signals at 7.26 and 77.0 ppm, respectively. TLC was
performed by using commercially prepared 100-400 mesh silica gel
plates and visualization was effected at 254 nm.
8.08 (d, J = 7.5 Hz, 2H), 8.04 (s, 1H), 7.55 (d, J = 9.1 Hz, 1H), 7.47-
7.31 (m, 3H), 7.19 (d, J = 8.9 Hz, 1H), 2.32 (s, 3H)；13C{1H} NMR
(100 MHz, CDCl3) δ 153.0, 145.8, 131.8, 131.4, 130.0, 129.0, 127.2,
125.0, 123.5, 117.4, 113.0, 93.5, 18.2. HRMS Calcd (ESI-TOF) m/z:
calcd for C15H11N3Na [M+Na]+, 256.0845; Found 256.0847.
General Procedure for Cyanation
8-methyl-2-phenylimidazo[1,2-a]pyridine-3-carbonitrile (2d):
Yield 37.2 mg (80%, white solid). H NMR (400 MHz, CDCl3) δ
1
The mixture of 1 (0.2 mmol, 1.0 equiv), NH4I (0.4 mmol, 2.0
equiv), Cu(NO3)2.3H2O (0.4 mmol, 2.0 equiv) and HOAc (0.4
mmol, 2.0 equiv) was stirred in DMF (2.0 mL/mmol) in an oil bath
8.23 (d, J = 7.3 Hz, 3H), 7.53 (t, J = 7.3 Hz, 2H), 7.49 (d, J = 6.7 Hz,
1H), 7.24 (d, J = 7.0 Hz, 1H), 6.99 (t, J = 6.8 Hz, 1H), 2.71 (s, 3H)
o
；
13C{1H} NMR (100 MHz, CDCl3) δ 152.8, 147.2, 131.5, 130.0,
at 130 C in a 20 mL tube with a balloon O2. After the reaction was
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Page 5 of 8
Organic & Biomolecular Chemistry
Journal Name
ARTICLE
129.0, 128.7, 127.4, 127.4, 123.3, 114.7, 113.1, 94.2, 16.9, 16.9.
2-([1,1'-biphenyl]-4-yl)imidazo[1,2-a]pyridine-3-carbonitrile
View Article Online
HRMS Calcd (ESI-TOF) m/z: calcd for C15H12N3 [M+H]+, (2l): Yield 48.4 mg (82%, yellow solid)D. O1HI: 10N.1M03R9/D(04O00B01M83H8zD,
234.1026; Found 234.1024.
CDCl3) δ 8.29 (d, J = 6.8 Hz, 1H), 8.20 (d, J = 8.0 Hz, 2H), 7.68 (t, J
= 8.5 Hz, 3H), 7.59 (d, J = 7.6 Hz, 2H), 7.39 (t, J = 7.4 Hz, 3H), 7.30
(t, J = 7.4 Hz, 1H), 7.01 (t, J = 6.9 Hz, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ 153.1, 146.9, 142.9, 140.3, 130.1, 128.9, 128.8,
127.8, 127.7, 127.6, 127.1, 125.6, 118.2, 114.8, 112.9, 93.9. HRMS
Calcd (ESI-TOF) m/z: calcd for C20H14N3 [M+H]+, 296.1182; Found
296.1179.
7-methoxy-2-phenylimidazo[1,2-a]pyridine-3-carbonitrile
(2e): Yield 42.3 mg (85%, white solid). 1H NMR (400 MHz, CDCl3)
δ 8.15 (dd, J = 10.7, 8.0 Hz, 3H), 7.51 (t, J = 7.3 Hz, 2H), 7.47 (d, J
= 6.8 Hz, 1H), 7.02 (s, 1H), 6.76 (d, J = 7.4 Hz, 1H), 3.92 (s, 3H)；
13C{1H} NMR (100 MHz, CDCl3) δ 160.7, 153.8, 148.7, 131.4,
130.0, 129.0, 127.1, 125.8, 113.2, 109.4, 95.9, 92.7, 55.9. HRMS
Calcd (ESI-TOF) m/z: calcd for C15H12N3O [M+H]+, 250.0975;
Found 250.0975.
2-(4-fluorophenyl)imidazo[1,2-a]pyridine-3-carbonitrile (2m):
1
Yield 37.9 mg (80%, white solid). H NMR (400 MHz, CDCl3) δ
8.36 (d, J = 6.2 Hz, 1H), 8.23-8.15 (m, 2H), 7.76 (d, J = 8.9 Hz, 1H),
7.48 (t, J = 7.8 Hz, 1H), 7.20 (t, J = 8.1 Hz, 2H), 7.10 (t, J = 6.7 Hz,
1H);13C{1H} NMR (100 MHz, CDCl3) δ 163.9 (d, JC-F = 249 Hz),
152.4, 146.8, 129.3 (d, JC-F = 9 Hz), 128.9, 127.5, 125.7, 118.1,
116.2 (d, JC-F = 21 Hz), 114.9, 112.7, 93.6. 19F NMR (471 MHz,
CDCl3) δ-109.5. HRMS Calcd (ESI-TOF) m/z: calcd for C14H9FN3
[M+H]+, 238.0775; Found 238.0776.
2,6-diphenylimidazo[1,2-a]pyridine-3-carbonitrile (2f): Yield
47.2 mg (80%, white solid). H NMR (400 MHz, CDCl3) δ 8.43 (s,
1
1H), 8.20-8.10 (m, 2H), 7.75 (dd, J = 9.3, 1.0 Hz, 1H), 7.64 (dd, J =
9.3, 1.8 Hz, 1H), 7.57-7.50 (m, 2H), 7.49-7.36 (m, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 152.7, 145.1, 134.9, 130.2, 129.2, 128.5,
128.4, 128.4, 128.0, 127.7, 126.3, 126.1, 121.7, 116.9, 111.9, 93.2.
HRMS Calcd (ESI-TOF) m/z: calcd for C20H14N3 [M+H]+,
296.1182; Found 296.1180.
2-(4-chlorophenyl)imidazo[1,2-a]pyridine-3-carbonitrile (2n):
1
Yield 37.9 mg (75%, white solid). H NMR (400 MHz, CDCl3) δ
6-fluoro-2-phenylimidazo[1,2-a]pyridine-3-carbonitrile
(2g):
8.35 (d, J = 5.4 Hz, 1H), 8.13 (d, J = 7.9 Hz, 2H), 7.75 (d, J = 8.9
Hz, 1H), 7.47 (d, J = 6.9 Hz, 3H), 7.10 (t, J = 6.6 Hz, 1H)；13C{1H}
NMR (100 MHz, CDCl3) δ 152.1, 146.8, 136.2, 129.7, 129.3, 129.0,
128.5, 125.7, 118.2, 114.9, 112.6, 93.9. HRMS Calcd (ESI-TOF)
m/z: calcd for C14H9ClN3 [M+H]+, 254.0480; Found 254.0484.
1
Yield 35.1 mg (74%, white solid). H NMR (400 MHz, CDCl3) δ
8.30 (s, 1H), 8.15 (d, J = 7.6 Hz, 2H), 7.73 (dd, J = 9.8, 4.8 Hz, 1H),
7.56-7.44 (m, 3H), 7.37 (t, J = 9.8 Hz, 1H);13C{1H} NMR (100
MHz, CDCl3) δ 154.3 (d, JC-F = 241 Hz), 154.1, 144.4, 131.0, 130.3,
129.1, 127.2, 120.7 (d, JC-F = 24 Hz), 118.8 (d, JC-F = 9 Hz), 113.0
(d, JC-F = 51 Hz), 112.2, 95.2. 19F NMR (471 MHz, DMSO-d6) δ -
136.7. HRMS Calcd (ESI-TOF) m/z: calcd for C14H9FN3 [M+H]+,
238.0775; Found 238.0773.
2-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridine-3-
1
carbonitrile (2o): Yield 37.3 mg (65%, white solid). H NMR (400
MHz, CDCl3) δ 8.38 (d, J = 6.8 Hz, 1H), 8.30 (d, J = 8.0 Hz, 2H),
7.76 (d, J = 7.5 Hz, 3H), 7.50 (t, J = 7.9 Hz, 1H), 7.12 (t, J = 6.9 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 151.5, 146.9, 134.6, 131.7
(q, JC-F = 33 Hz), 129.1, 127.5, 126.0 (q, JC-F = 4 Hz), 125.7, 123.9
(q, JC-F = 271 Hz), 118.4, 115.2, 112.3, 94.6. 19F NMR (471 MHz,
CDCl3) δ-62.9. HRMS Calcd (ESI-TOF) m/z: calcd for C15H9F3N3
[M+H]+, 288.0743; Found 288.0742
6-chloro-2-phenylimidazo[1,2-a]pyridine-3-carbonitrile (2h):
1
Yield 32.9 mg (65%, white solid). H NMR (400 MHz, CDCl3) δ
8.38 (s, 1H), 8.15 (d, J = 7.3 Hz, 2H), 7.68 (d, J = 9.5 Hz, 1H), 7.50
(q, J = 8.5, 7.7 Hz, 3H), 7.41 (d, J = 9.4 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 153.8, 145.2, 130.8, 130.4, 130.2, 129.1, 127.3,
123.6, 123.2, 118.4, 112.2, 94.3. HRMS Calcd (ESI-TOF) m/z: calcd
for C14H9ClN3 [M+H]+, 254.0480; Found 254.0487.
2-(naphthalen-2-yl)imidazo[1,2-a]pyridine-3-carbonitrile (2p):
1
Yield 41.9 mg (78%, white solid). H NMR (400 MHz, CDCl3) δ
2-phenyl-7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-
1
8.61 (s, 1H), 8.27 (d, J = 6.7 Hz, 1H), 8.20 (d, J = 8.8 Hz, 1H), 7.88
(d, J = 8.0 Hz, 2H), 7.82-7.76 (m, 1H), 7.69 (d, J = 9.1 Hz, 1H), 7.44
(d, J = 5.3 Hz, 2H), 7.37 (t, J = 8.1 Hz, 1H), 6.98 (t, J = 6.9 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 153.3, 146.9, 134.1, 133.3,
128.9, 128.8, 128.6, 127.8, 127.2, 127.2, 126.7, 125.6, 124.2, 118.2,
114.8, 112.9, 94.1. HRMS Calcd (ESI-TOF) m/z: calcd for
C18H11N3Na [M+Na]+, 292.0845; Found 292.0842.
carbonitrile (2i): Yield 34.4 mg (60%, white solid). H NMR (400
MHz, CDCl3) δ 8.46 (d, J = 7.0 Hz, 1H), 8.25-8.12 (m, 2H), 8.04 (s,
1H), 7.52 (m, 3H), 7.25 (d, J = 6.3 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ 154.7, 145.1, 130.7, 130.7(q, JC-F = 44 Hz), 130.5,
129.2, 127.4, 126.4, 122.6 (q, JC-F = 339 Hz), 116.0 (q, JC-F = 5 Hz),
111.9, 110.6 (q, JC-F = 4 Hz), 95.1. 19F NMR (471 MHz, CDCl3) δ-
64.0. HRMS Calcd (ESI-TOF) m/z: calcd for C15H9F3N3 [M+H]+,
288.0743; Found 288.0743
2-(p-tolyl)imidazo[1,2-a]pyridine-3-carbonitrile (2j): Yield
40.5 mg (87%, yellow solid). 1H NMR (400 MHz, CDCl3) δ 8.35 (d,
J = 6.4 Hz, 0H), 8.09 (d, J = 7.3 Hz, 1H), 7.74 (d, J = 8.8 Hz, 0H),
7.44 (t, J = 7.9 Hz, 0H), 7.32 (d, J = 7.5 Hz, 1H), 7.07 (t, J = 6.6 Hz,
0H), 2.43 (s, 1H) ； 13C{1H} NMR (100 MHz, CDCl3) δ 153.6,
146.8, 140.5, 129.7, 128.7, 128.4, 127.2, 125.6, 118.1, 114.6, 113.0,
93.5, 21.5. HRMS Calcd (ESI-TOF) m/z: calcd for C15H12N3
[M+H]+, 234.1026; Found 234.1029.
2-(thiophen-2-yl)imidazo[1,2-a]pyridine-3-carbonitrile (2q):
1
Yield 27.0 mg (60%, white solid). H NMR (400 MHz, CDCl3) δ
8.31 (d, J = 6.6 Hz, 1H), 7.91 (d, J = 3.7 Hz, 1H), 7.72 (d, J = 8.9
Hz, 1H), 7.50 (d, J = 5.0 Hz, 1H), 7.45 (t, J = 7.9 Hz, 1H), 7.19 (t, J
= 4.4 Hz, 1H), 7.08 (t, J = 6.7 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 148.5, 146.8, 134.4, 129.0, 128.4, 127.3, 125.6, 117.9,
114.86, 112.3, 92.7. HRMS Calcd (ESI-TOF) m/z: calcd for
C12H8N3S [M+H]+, 226.0433; Found 226.0433.
6-phenylimidazo[2,1-b]thiazole-5-carbonitrile (2r): Yield 24.7
mg (55%, white solid). H NMR (400 MHz, CDCl3) δ 7.98 (d, J =
2-(4-methoxyphenyl)imidazo[1,2-a]pyridine-3-carbonitrile
(2k): Yield 44.8 mg (90%, white solid). 1H NMR (400 MHz,
DMSO-d6) δ 8.62 (d, J = 6.7 Hz, 1H), 8.06 (d, J = 8.4 Hz, 2H), 7.82
(d, J = 9.0 Hz, 1H), 7.61 (t, J = 7.9 Hz, 1H), 7.23 (t, J = 6.8 Hz, 1H),
7.14 (d, J = 8.4 Hz, 2H), 3.85 (s, 3H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ 161.2, 152.6, 146.9, 130.2, 128.8, 127.3, 124.2, 117.7,
115.5, 115.1, 113.6, 92.7, 55.9. HRMS Calcd (ESI-TOF) m/z: calcd
for C15H11N3ONa [M+Na]+, 272.0794; Found 272.0799.
1
7.6 Hz, 2H), 7.55 (d, J = 4.4 Hz, 1H), 7.38 (dt, J = 15.3, 7.2 Hz, 3H),
6.98 (d, J = 4.5 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 155.8,
153.0, 131.5, 129.81, 129.0, 127.0, 126.7, 118.5, 115.1, 112.7, 94.5.
HRMS Calcd (ESI-TOF) m/z: calcd for C12H8N3S [M+H]+,
226.0433; Found 226.0436.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 6 of 8
ARTICLE
Journal Name
2-phenylbenzo[d]imidazo[2,1-b]thiazole-3-carbonitrile
(2s): 130.7, 128.8, 124.6, 120.7, 117.5, 115.5. HRMS CalVcidew(AErtSicIle-TOOnliFne)
1
Yield 33.0 mg (60%, white solid). H NMR (400 MHz, CDCl3) δ m/z: calcd for C14H10BrN2O [M+H]+, 300.9971; Found 300.9970.
DOI: 10.1039/D0OB01838D
8.10 (d, J = 8.2 Hz, 1H), 8.06-7.99 (m, 2H), 7.68 (d, J = 8.0 Hz, 1H),
7.53-7.31 (m, 5H); 13C{1H} NMR (100 MHz, CDCl3) δ 156.1,
151.5, 132.0, 131.3, 130.1, 129.9, 129.0, 127.1, 126.7, 126.2, 124.5,
113.5, 113.2, 94.6. HRMS Calcd (ESI-TOF) m/z: calcd for
C16H10N3S [M+H]+, 276.0590; Found 276.0589.
2-([1,1'-biphenyl]-4-yl)imidazo[1,2-a]pyridine-3-carbaldehyde
(3g): Yield 41.7 mg (70%, white solid). 1H NMR (400 MHz, CDCl3)
δ 10.13 (s, 1H), 9.67 (d, J = 6.8 Hz, 1H), 7.92 (d, J = 7.6 Hz, 2H),
7.85-7.71 (m, 3H), 7.63 (dd, J = 29.4, 8.2 Hz, 3H), 7.43 (d, J = 34.3
Hz, 3H), 7.12 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 179.5,
imidazo[1,2-a]pyridine-3-carbonitrile (2t): Yield 12.9 mg 157.9, 147.8, 142.7, 140.2, 131.3, 130.5, 130.3, 128.9, 128.8, 127.9,
1
(45%, white solid). H NMR (400 MHz, CDCl3) δ 8.39 (dt, J = 6.8, 127.6, 127.18, 120.8, 117.4, 115.3. HRMS Calcd (ESI-TOF) m/z:
1.2 Hz, 1H), 8.19 (s, 1H), 7.80 (dt, J = 9.2, 1.1 Hz, 1H), 7.49 (ddd, J calcd for C20H14N2ONa [M+Na]+, 321.0998; Found 321.0995.
= 9.1, 6.9, 1.2 Hz, 1H), 7.14 (td, J = 6.9, 1.2 Hz, 1H); 13C{1H} NMR
2-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridine-3-
carbaldehyde (3h): Yield 29.0 mg (50%, yellow solid). H NMR
(400 MHz, CDCl3) δ 10.07 (s, 1H), 9.67 (d, J = 6.9 Hz, 1H), 7.97 (d,
J = 7.8 Hz, 2H), 7.88-7.71 (m, 3H), 7.63 (t, J = 8.2 Hz, 1H), 7.18 (t,
(100 MHz, CDCl3) δ 147.2, 142.4, 128.3, 125.7, 118.7, 115.1, 111.1,
98.3. HRMS Calcd (ESI-TOF) m/z: calcd for C8H6N3 [M+H]+,
144.0556; Found 144.0553.
1
2-phenylimidazo[1,2-a]pyridine-3-carbaldehyde (3a): Yield J = 7.1 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 179.0, 156.3,
36.4 mg (82%, white solid). 1H NMR (400 MHz, CDCl3) δ 10.06 (s, 147.7, 135.9, 131.7 (q, JC-F = 33 Hz), 130.8, 130.1, 128.8, 125.8 (q,
1H), 9.65 (d, J = 6.8 Hz, 1H), 7.86-7.76 (m, 3H), 7.61-7.54 (m, 1H), JC-F = 4 Hz), 123.9 (q, JC-F = 335 Hz), 121.0, 117.6, 115.8. 19F
7.52 (m, 3H), 7.11 (t, J = 6.9 Hz, 1H); 13C{1H} NMR (100 MHz, NMR (471 MHz, CDCl3) δ-62.7. HRMS Calcd (ESI-TOF) m/z:
CDCl3) δ 179.6, 179.5, 158.3, 147.7, 132.4, 130.4, 129.8, 128.9, calcd for C15H10F3N2O [M+H]+, 291.0740; Found 291.0737.
128.8, 120.7, 117.4, 115.3. HRMS Calcd (ESI-TOF) m/z: calcd for
C14H10N2ONa [M+Na]+, 245.0685; Found 245.0688.
7-methyl-2-phenylimidazo[1,2-a]pyridine-3-carbaldehyde (3i):
Yield 37.8 mg (80%, white solid). H NMR (400 MHz, CDCl3) δ
1
2-(p-tolyl)imidazo[1,2-a]pyridine-3-carbaldehyde (3b): Yield 10.01 (s, 0H), 9.51 (d, J = 6.8 Hz, 0H), 7.87-7.78 (m, 1H), 7.61-7.47
40.1 mg (85%, white solid). 1H NMR (400 MHz, CDCl3) δ 10.07 (s,
1H), 9.65 (d, J = 6.7 Hz, 1H), 7.80 (d, J = 8.9 Hz, 1H), 7.73 (d, J =
7.7 Hz, 2H), 7.57 (t, J = 8.0 Hz, 1H), 7.34 (d, J = 7.7 Hz, 2H), 7.11
(t, J = 6.9 Hz, 1H), 2.45 (s, 3H)；13C{1H} NMR (100 MHz, CDCl3)
δ 179.6, 158.4, 147.7, 140.1, 130.4, 129.7, 129.6, 129.5, 128.8,
120.7, 117.4, 115.2, 21.4. HRMS Calcd (ESI-TOF) m/z: calcd for
C15H12N2ONa [M+Na]+, 259.0842; Found 259.0846.
(m, 1H), 6.96 (d, J = 6.9 Hz, 0H), 2.51 (s, 1H)；13C{1H} NMR (100
MHz, CDCl3) δ 179.2, 158.5, 148.2, 142.3, 132.4, 129.8, 128.9,
128.0, 120.6, 117.7, 116.2, 21.8. HRMS Calcd (ESI-TOF) m/z: calcd
for C15H12N2ONa [M+Na]+, 259.0842; Found 259.0847.
6-fluoro-2-phenylimidazo[1,2-a]pyridine-3-carbaldehyde (3j):
1
Yield 31.2 mg (65%, white solid). H NMR (400 MHz, CDCl3) δ
10.07 (s, 1H), 9.66 (dd, J = 4.4, 2.5 Hz, 1H), 7.88-7.69 (m, 3H),
2-(4-methoxyphenyl)imidazo[1,2-a]pyridine-3-carbaldehyde
7.60-7.38 (m, 4H); 13C{1H} NMR (100 MHz, CDCl3) δ 179.7, 158.6
(3c): Yield 40.3 mg (80%, white solid). 1H NMR (400 MHz, CDCl3) (d, JC-F = 4 Hz), 154.5 (d, JC-F = 239 Hz), 145.2, 132.1, 130.0, 129.7,
δ 9.97 (s, 1H), 9.56 (d, J = 6.8 Hz, 1H), 7.79-7.62 (m, 3H), 7.48 (t, J 129.0, 126.2, 121.7 (d, JC-F = 31 Hz), 117.7 (d, JC-F = 9 Hz), 116.1
= 8.2 Hz, 1H), 7.14-6.79 (m, 3H), 3.81 (s, 3H); 13C{1H} NMR (100 (d, JC-F = 43 Hz). 19F NMR (471 MHz, CDCl3) δ-135.2. HRMS
MHz, CDCl3) δ 179.5, 161.1, 158.2, 147.8, 131.2, 130.4, 128.8, Calcd (ESI-TOF) m/z: calcd for C14H10FN2O [M+H]+, 241.0772;
124.8, 120.5, 117.2, 115.1, 114.4, 55.4. HRMS Calcd (ESI-TOF) Found 241.0771.
m/z: calcd for C15H12N2O2Na [M+Na]+, 275.0791; Found 275.0786.
6-chloro-2-phenylimidazo[1,2-a]pyridine-3-carbaldehyde (3k):
1
2-(4-fluorophenyl)imidazo[1,2-a]pyridine-3-carbaldehyde
Yield 34.8 mg (68%, white solid). H NMR (400 MHz, CDCl3) δ
(3d): Yield 33.6 mg (70%, white solid). 1H NMR (400 MHz, CDCl3) 10.06 (d, J = 2.0 Hz, 1H), 9.74 (s, 1H), 7.85-7.79 (m, 2H), 7.74 (d, J
δ 10.04 (s, 1H), 9.66 (d, J = 6.8 Hz, 1H), 7.89-7.75 (m, 3H), 7.60 (t, = 9.4 Hz, 1H), 7.61-7.44 (m, 4H); 13C{1H} NMR (100 MHz, CDCl3)
δ 179.7, 179.7, 158.4, 146.0, 131.6, 130.1, 129.8, 129.0, 126.8,
123.5, 120.8, 117.6. HRMS Calcd (ESI-TOF) m/z: calcd for
C14H10ClN2O [M+H]+, 257.0476; Found 257.0476.
J = 7.9 Hz, 1H), 7.23 (t, J = 8.5 Hz, 2H), 7.14 (t, J = 6.9 Hz, 1H)；
13C{1H} NMR (100 MHz, CDCl3) δ 179.2, 163.9 (d, JC-F = 311 Hz),
157.2, 147.7, 131.7 (d, JC-F = 10 Hz), 130.6, 128.8, 128.5 (d, JC-F = 5
Hz), 120.7, 117.4, 116.1 (d, JC-F = 28 Hz), 115.4. 19F NMR (471
MHz, CDCl3) δ-110.7. HRMS Calcd (ESI-TOF) m/z: calcd for
C14H10FN2O [M+H]+, 241.0772; Found 241.0771.
2,6-diphenylimidazo[1,2-a]pyridine-3-carbaldehyde (3l): Yield
44.7 mg (75%, white solid). 1H NMR (400 MHz, CDCl3) δ 10.01 (s,
1H), 9.81 (t, J = 1.4 Hz, 1H), 7.80-7.73 (m, 4H), 7.58-7.53 (m, 2H),
7.49-7.39 (m, 5H), 7.38-7.32 (m, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 179.6, 158.5, 146.9, 136.4, 132.3, 130.7, 130.0, 129.9,
129.8, 129.3, 128.9, 128.4, 127.2, 126.2, 121.0, 117.2. HRMS Calcd
(ESI-TOF) m/z: calcd for C20H15N2O [M+H]+, 299.1179; Found
299.1177.
2-(4-chlorophenyl)imidazo[1,2-a]pyridine-3-carbaldehyde
(3e): Yield 36.8 mg (72%, white solid). 1H NMR (400 MHz, CDCl3)
δ 10.05 (s, 1H), 9.65 (dt, J = 6.8, 1.2 Hz, 1H), 7.84-7.74 (m, 3H),
7.60 (ddd, J = 8.8, 7.0, 1.4 Hz, 1H), 7.55-7.49 (m, 2H), 7.15 (td, J =
6.9, 1.3 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 179.1, 156.8,
147.7, 136.3, 131.0, 130.8, 130.6, 129.2, 128.8, 120.8, 117.5, 115.5.
HRMS Calcd (ESI-TOF) m/z: calcd for C14H10ClN2O [M+H]+,
257.0476; Found 257.0476.
2-phenyl-6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-
1
carbaldehyde (3m): Yield 26.1 mg (45%, white solid). H NMR
(400 MHz, CDCl3) δ 10.14 (s, 1H), 9.77 (d, J = 7.1 Hz, 1H), 8.10 (s,
1H), 7.84 (dd, J = 6.4, 3.3 Hz, 2H), 7.56 (dd, J = 5.0, 2.0 Hz, 3H),
7.29 (dd, J = 7.2, 1.9 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
180.2, 158.9, 146.1, 131.8 (q, JC-F = 34 Hz), 131.7, 130.3, 129.8,
2-(4-bromophenyl)imidazo[1,2-a]pyridine-3-carbaldehyde
(3f): Yield 39.1 mg (65%, white solid). 1H NMR (400 MHz, CDCl3)
δ 10.05 (s, 1H), 9.66 (dt, J = 6.8, 1.2 Hz, 1H), 7.82 (dd, J = 8.2, 1.4
Hz, 1H), 7.76-7.58 (m, 5H), 7.16 (td, J = 6.9, 1.3 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 179.1, 156.8, 147.7, 132.2, 131.2, 131.1,
129.6, 129.5, 129.1, 122.7 (q, JC-F = 271 Hz), 121.2, 115.2 (q, JC-F
=
5 Hz), 111.0 (q, JC-F = 3 Hz). 19F NMR (471 MHz, CDCl3) δ-64.0.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Page 7 of 8
Organic & Biomolecular Chemistry
Journal Name
ARTICLE
HRMS Calcd (ESI-TOF) m/z: calcd for C15H10F3N2O [M+H]+, 2H), 7.63 (d, J = 9.0 Hz, 1H), 7.51-7.40 (m, 2H), 7.27V-7ie.w20Art(icmle,O1nHlin)e,
291.0740; Found 291.0736.
6.83 (t, J = 6.9 Hz, 1H), 5.17 (s, 2H), 2.59D(Os,I:31H0.1),0329.2/D80(Ot,BJ01=8378.D4
Hz, 2H), 1.67 (h, J = 7.4 Hz, 2H), 0.95 (t, J = 7.4 Hz, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 173.6, 145.2, 144.8, 134.1, 132.8, 130.0,
128.9, 125.5, 125.4, 117.3, 116.0, 112.8, 38.6, 35.4, 33.6, 18.5, 13.9.
2-(naphthalen-2-yl)imidazo[1,2-a]pyridine-3-carbaldehyde
(3n): Yield 34.2 mg (63%, white solid). 1H NMR (400 MHz, CDCl3)
δ 10.18 (s, 1H), 9.69 (d, J = 6.8 Hz, 1H), 8.31 (s, 1H), 8.04-7.94 (m,
3H), 7.93-7.89 (m, 1H), 7.86 (d, J = 8.9 Hz, 1H), 7.65-7.49 (m, 3H),
1
2k from gram-scale: H NMR (500 MHz, CDCl3) δ 8.37 (d, J =
7.15 (td, J = 6.9, 1.3 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 6.7 Hz, 1H), 8.17 (d, J = 8.8 Hz, 2H), 7.75 (d, J = 9.2 Hz, 1H), 7.47
179.7, 158.0, 147.7, 133.9, 133.2, 130.6, 129.9, 129.6, 128.9, 128.8, (ddd, J = 8.6, 6.9, 1.3 Hz, 1H), 7.17-6.93 (m, 3H), 3.91 (s, 3H);
128.6, 127.8, 127.2, 126.8, 126.7, 121.0, 117.4, 115.4. HRMS Calcd 13C{1H} NMR (125 MHz, CDCl3) δ 161.2, 153.4, 146.9, 128.8,
(ESI-TOF) m/z: calcd for C18H13N2O [M+H]+, 273.1022; Found 128.7, 125.6, 123.9, 117.9, 114.5, 114.4, 113.2, 93.0, 55.4.
273.1021.
3-iodo-2-phenylimidazo[1,2-a]pyridine (4a): Yield 51.0 mg
1
2-(thiophen-2-yl)imidazo[1,2-a]pyridine-3-carbaldehyde (3o): (80%, white solid). H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 6.9
1
Yield 18.2 mg (40%, yellow solid). H NMR (400 MHz, CDCl3) δ Hz, 1H), 8.09 (d, J = 7.7 Hz, 2H), 7.65 (d, J = 9.1 Hz, 1H), 7.51 (t, J
10.32 (s, 1H), 9.64 (d, J = 6.8 Hz, 1H), 7.79 (d, J = 8.9 Hz, 1H), 7.66 = 7.7 Hz, 2H), 7.43 (d, J = 7.6 Hz, 1H), 7.33-7.26 (m, 1H), 6.94 (t, J
(dd, J = 3.7, 1.2 Hz, 1H), 7.62-7.53 (m, 2H), 7.21 (dd, J = 5.1, 3.6 = 6.7 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 148.1, 148.0,
Hz, 1H), 7.12 (td, J = 6.9, 1.3 Hz, 1H); 13C{1H} NMR (100 MHz, 133.5, 128.6, 128.4, 126.6, 125.7, 117.6, 113.3, 59.6. HRMS Calcd
CDCl3) δ 178.5, 151.2, 147.7, 134.7, 130.8, 129.2, 129.0, 128.8, (ESI-TOF) m/z: calcd for C13H10IN2 [M+H]+, 320.9883; Found
128.3, 120.0, 117.2, 115.4. HRMS Calcd (ESI-TOF) m/z: calcd for 320.9881.
C12H9N2OS [M+H]+, 229.0430; Found 229.0428.
Acknowledgements
imidazo[1,2-a]pyridine-3-carbaldehyde (3p): Yield 10.2 mg
(35%, white solid). 1H NMR (400 MHz, CDCl3) δ 9.96 (s, 1H), 9.50
This work was financially supported by Guangxi Natural Science
Fundation (2017GXNSFBA198224, 2018GXNSFAA281203 and
2018GXNSFBA050024), Guangxi Science and Technology Base
(d, J = 6.8 Hz, 1H), 8.34 (s, 1H), 7.81 (d, J = 9.0 Hz, 1H), 7.58 (ddd,
J = 8.8, 7.0, 1.3 Hz, 1H), 7.15 (t, J = 6.9 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 177.9, 149.4, 146.7, 130.2, 128.7, 125.0, 117.9,
and Special Fund for Talents (AD19110110) and Key Laboratory of
115.5. HRMS Calcd (ESI-TOF) m/z: calcd for C8H6N2ONa
Electrochemical and Magnetochemical Function Materials.
[M+Na]+, 169.0372; Found 169.0379.
Notes and references
methyl 3-formylimidazo[1,2-a]pyridine-7-carboxylate (3q):
Yield 8.9 mg (22%, white solid). H NMR (400 MHz, CDCl3) δ
1
10.03 (s, 1H), 9.53 (d, J = 7.0 Hz, 1H), 8.49 (s, 1H), 8.44 (s, 1H),
7.71 (dd, J = 7.1, 1.7 Hz, 1H), 4.02 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 178.4, 164.7, 148.5, 147.5, 131.1, 128.3, 125.5,
1 (a) A. A. Trabanco, G. Tresadern, G. J. Macdonald, J. A. Vega, A.
I. d. Lucas, E. Matesanz, A. García, M. L. Linares, S. A. A. d.
Diego, J. M. Alonso, D. Oehlrich, A. Ahnaou, W. Drinkenburg, C.
Mackie, J. I. Andrés, H. Lavreysen, J. M. Cid, J. Med. Chem.
120.0, 114.7, 53.0. HRMS Calcd (ESI-TOF) m/z: calcd for
C10H9N2O3 [M+H]+, 205.0608; Found 205.0610.
2012, 55, 2688-2701; (b) R. Ducray, C. D. Jones, F. H. Jung, I.
7-chloroimidazo[1,2-a]pyridine-3-carbaldehyde (3r): Yield
1
Simpson, J. Curwen, M. Pass, Bioorg. Med. Chem. Lett. 2011, 21,
4702-4704; (c) C. M. Marson, Chem. Soc. Rev. 2011, 40, 5514-
5533
10.8 mg (30%, white solid). H NMR (400 MHz, CDCl3) δ 9.94 (s,
1H), 9.43 (d, J = 7.2 Hz, 1H), 8.32 (s, 1H), 7.80 (d, J = 2.0 Hz, 1H),
7.27 (s, 0H), 7.13 (dd, J = 7.2, 2.1 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ 177.9, 149.4, 147.3, 136.8, 128.8, 125.0, 117.1,
117.0. HRMS Calcd (ESI-TOF) m/z: calcd for C8H6ClN2O [M+H]+,
181.0163; Found 181.0165.
2 (a) R. Ducray, I. Simpson, F. H. Jung, W. M. Nissink, P. W.
Kenny, M. Fitzek, G. E. Walker, L. T. Ward, K. Hudson, Bioorg.
Med. Chem. Lett. 2011, 21, 4698-4701; (b) G. Tresadern, J. M.
Cid, G. J. Macdonald, J. A. Vega, A. I. de Lucas, A. García, E.
Matesanz, M. L. Linares, D. Oehlrich, H. Lavreysen, I. Biesmans,
A. A. Trabanco, Bioorg. Med. Chem. Lett. 2010, 20, 175-179.
3 (a) H. Cao, X. Liu, L. Zhao, J. Cen, J. Lin, Q. Zhu, M. Fu, Org.
Lett. 2014, 16, 146-149; (b) H. Cao, H. Zhan, Y. Lin, X. Lin, Z.
Du, H. Jiang, Org. Lett. 2012, 14, 1688-1691; (c) C. Wang, S. Lei,
H. Cao, S. Qiu, J. Liu, H. Deng, C. Yan, J. Org. Chem. 2015, 80,
12725-12732; (d) S. Lei, Y. Mai, C. Yan, J. Mao, H. Cao, Org.
Lett. 2016, 18, 3582-3585; (e) S. Lei, H. Cao, L. Chen, J. Liu, H.
Cai, J. Tan, Adv. Synth. Catal. 2015, 357, 3109-3114; (f) C.
Wang, Y. Yu, Z. Su, X. Li, H. Cao, Org. Lett. 2019, 21, 4420-
4423; (g) Y. Liang, L. Teng, Y. Wang, Q. He, H. Cao, Green.
Chem. 2019, 21, 4025-4029.
6-bromoimidazo[1,2-a]pyridine-3-carbaldehyde (3s): Yield
1
12.0 mg (27%, white solid). H NMR (400 MHz, CDCl3) δ 9.96 (s,
1H), 9.68 (d, J = 1.8 Hz, 1H), 8.31 (s, 1H), 7.70 (d, J = 9.4 Hz, 1H),
7.63 (dd, J = 9.4, 1.9 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
178.0, 147.7, 146.6, 133.5, 128.8, 124.9, 118.4, 110.4. HRMS Calcd
(ESI-TOF) m/z: calcd for C8H6BrN2O [M+H]+, 224.9658; Found
224.9661.
1
Saripidem from 2n: Yield 44.3 mg (65%, white solid). H NMR
(400 MHz, CDCl3) δ 8.39 (d, J = 6.9 Hz, 1H), 7.68 (d, J = 8.3 Hz,
2H), 7.64 (d, J = 9.1 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.25 (dd, J =
9.1, 6.7 Hz, 1H), 6.84 (t, J = 6.8 Hz, 1H), 5.18 (s, 2H), 2.60 (s, 3H),
2.28 (t, J = 7.4 Hz, 2H), 1.68 (h, J = 7.4 Hz, 2H), 0.96 (t, J = 7.4 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 173.6, 145.2, 144.7, 134.1,
132.7, 130.1, 128.9, 125.5, 125.4, 117.3, 116.1, 112.8, 38.6, 35.4,
33.6, 18.5, 13.9. HRMS Calcd (ESI-TOF) m/z: calcd for
C19H21ClN3O [M+H]+, 342.1368; Found 342.1389.
4 (a) Y. Gao, M. Yin, W. Wu, H. Huang, H. Jiang, Adv. Synth.
Catal. 2013, 355, 2263-2273; (b) H. Wang, Y. Wang, D. Liang, L.
Liu, J. Zhang, Q. Zhu, Angew. Chem. Int. Ed. 2011, 50, 5678-
Saripidem from 3e: Yield 37.5 mg (55%, white solid).1H NMR
(500 MHz, CDCl3) δ 8.38 (d, J = 6.9 Hz, 1H), 7.68 (d, J = 8.4 Hz,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 8 of 8
ARTICLE
Journal Name
5681; (c) H. Wang, Y. Wang, C. Peng, J. Zhang, Q. Zhu, J. Am. 13 (a) X. Wu, Y. Zhao, H. Ge, J. Am. Chem. Soc. 2015, 137, 4924-
View Article Online
Chem. Soc. 2010, 132, 13217-13219.
4927; (b) Y. Li, D. Xue, W. Lu, C. WDanOgI:,1Z0..1-0T3.9/LDi0uO, BJ.01X83ia8oD,
Org.Lett. 2014, 16, 66-69; (c) J. Liu, H. Yi, X. Zhang, C. Liu, R.
Liu, G. Zhang, A. Lei, Chem. Commun. 2014, 50, 7636-7638; (d)
J. Zhu, Z. Zhang, C. Miao, W. Liu, W. Sun, Tetrahedron 2017,
73, 3458-3462; (e) S. Ding, N. Jiao, J. Am. Chem. Soc. 2011, 133,
12374-12377; (f) J. Muzart, Tetrahedron 2009, 65, 8313-8323; (g)
S Ding, N Jiao, Angew. Chem. Int. Ed. 2012, 51, 9226-9237; (h)
A. Batra, P. Singh, K. Singh, Eur. J. Org. Chem. 2016, 4927-
4947; (i) J. Bras, J. Muzart, Molecules 2018, 23, 1939-1952; (j) J.
Bras, J. Muzart, Weinheim: Wiley-VCH; 2017, 199-314; (k) M.
Heravi, M. Ghavidel, L. Mohammadkhani, RSC Adv. 2018, 8,
27832-27862.
5 A. Kleemann, J. Engel, B. Kutscher, D. Reichert, Pharmaceutical
Substance: Synthesis, Patents, Applications, 4th ed.; Georg
Thieme: Stuttgart, 2001.
6 (a) Z. Rappoport, Chemistry of the Cyano Group, Wiley, London,
1970; (b) R. C. Larock, Comprehensive OrganicTransformations:
A Guide to Functional Group Preparations, VCH, New York,
1989.
7 (a) T. Sandmeyer, Ber. Dtsch. Chem. Ges. 1884, 17, 1633-1635;
(b) C. Galli, Chem. Rev. 1988, 88, 765-792; (c) J. Lindley,
Tetrahedron 1984, 40, 1433-1456.
8 (a) W. Zhou, L. Zhang, N. Jiao, Angew. Chem. Int. Ed. 2009, 48,
7094-7097; (b) T. Oishi, K. Yamaguchi, N. Mizuno, Angew. 14 (a) F. Ji, J. Li, X. Li, W. Wu, H. Jiang, J. Org. Chem. 2018, 83,
Chem. Int. Ed. 2009, 48, 6286-6288; (c) W. Zhou, J. Xu, L.
Zhang, N. Jiao, Org. Lett. 2010, 12, 2888-2891; (d) J. He, K.
Yamaguchi, N. Mizuno, J. Org. Chem. 2011, 76, 4606-4610; (e)
Q. Wen, P. Lu, Y. Wang, Chem. Commun., 2015, 51, 15378-
15381; (f) A. B. Pawar, S. Chang, Chem. Commun., 2014, 50,
448-450; (g) R. Takise, K. Itami, J. Yamaguchi, Org. Lett. 2016,
18, 4428-4431; (h) B. Niu, C. You, B. Huang, M. Cai, Catalysis
Communications. 2019, 123, 11-16
104-112; (b) F. Ji, H. Peng, X. Zhang, W. Lu, S. Liu, H. Jiang, B.
Liu, B. Yin, J. Org. Chem. 2015, 80, 2092-2102; (c) F. Ji, X. Li,
W. Wu, H. Jiang, J. Org. Chem. 2014, 79, 11246-11253; (d) G.
Jiang, S. Wang, J. Zhang, J. Yu, Z. Zhang, F. Ji, Adv. Synth.
Catal. 2019, 361, 1798-1802; (e) S. Wang, K. Wang, X. Kong,
Shu. Zhang, G. Jiang, F. Ji, Adv. Synth. Catal. 2019, 361, 3986-
3990; (f) F. Ji, S. Wang, G. Jiang, China Patent NO. 2019-
10713629.
9 (a) J. Kim, H. J. Kim, S. Chang, Angew. Chem., Int. Ed. 2012, 51, 15 (a) N. Chernyak, V. Gevorgyan, Angew. Chem., Int. Ed. 2010, 49,
11948-11959; (b) G. Yan, J. Yu, L. Zhang, Chin. J. Org. Chem.
2012, 32, 294-303; (c) G. P. Ellis, T. M. Romney-Alexander,
2743-2746; (b) S. K. Guchhait, A. L. Chandgude, G.
Priyadarshani, J. Org. Chem. 2012, 77, 4438-4444.
Chem. Rev. 1987, 87, 779-794; (d) P. Anbarasan, T. Schareina, M. 16 (a) J. Kim, J. Choi, K. Shin, S. Chang, J. Am. Chem. Soc. 2012,
Beller, Chem. Soc. Rev. 2011, 40, 5049-5067.
134, 2528-2531; (b) J. Kim, H. Kim. S. Chang, Org.Lett. 2012,
14, 3924-3927; (c) H. Cao, S. Lei, N. Li, L. Chen, J. Liu, H. Cai,
S. Qiu, J. Tan, Chem. Commun. 2015, 51, 1823-1825.
10 (a) J. Kim, S. Chang, J. Am. Chem. Soc. 2010, 132, 10272-10274;
(b) G. Zhang, X. Ren, J. Chen, M. Hu, J. Cheng, Org. Lett. 2011,
13, 5004-5007; (c) J. Kim, J. Choi, K. Shin, S. Chang, J. Am.
Chem. Soc. 2012, 134, 2528-2531; (d) S. Xu, J, Teng, J.-T. Yu, S.
Sun, J. Cheng, Org. Lett. 2019, 21, 9919-9923.
11 (a) R. Lauchli, K. J. Shea, Org.Lett. 2006, 8, 5287-5289; (b) H.
Wynberg, Chem. Rev. 1960, 60, 169-184; (c) M. L. Bennasar, E.
Zulaica, D. Sole, S. Alonso, Tetrahedron 2007, 63, 861-866; (d)
A. R. Katritzky, K. Suzuki, S. K. Singh, H. Y. He, J. Org. Chem.
2003, 68, 5720-5723.
12 (a) Z. Zhang, Q. Tian, J. Qian, Q. Liu, T. Liu, L. Shi, G. Zhang, J.
Org. Chem. 2014, 79, 8182-8188; (b) X. Gao, X. Pan, J. Gao, H.
Jiang, G. Yuan, Y. Li, Org. Lett. 2015, 17, 1038-1041; (c) X. Pan,
Q. Liu, L. Chang, G. Yuan, RSC Adv. 2015, 5, 51183-51187; (d)
X. Gao, X. Pan, J. Gao, H. Huang, G. Yuan, Y. Li, Chem.
Commun. 2015, 51, 210-212; (e) X. Cui, Y. Zhang, Y. Deng, F.
Shi, Chem. Commun. 2014, 50, 189-191; (f) S. Ding, N. Jiao, J.
Am. Chem. Soc. 2011, 133, 12374-12377; (g) J. Chen, B. Liu, D.
Liu, S. Liu, J. Cheng, Adv. Synth. Catal. 2012, 354, 2438-2442;
(h) D. Zhao, Y. Wang, M. X. Zhu, Q. Shen, L. Zhang, Y. Du, J.
X. Li, RSC Adv. 2013, 3, 10272-10276; (i) W. Wu, W. Su, J. Am.
Chem. Soc. 2011, 133, 11924-11927; (j) W. Guo, J. Liao, D. Liu,
J. Li, F. Ji, W. Wu, H. Jiang, Angew. Chem. Int. Ed. 2017, 56,
1289-1293; (k) O. P. S. Patel, D. Anand, R. K. Maurya, P. P.
Yadav, J. Org. Chem. 2016, 81, 7626-7634; (l) H. Cao, S. Lei, N.
Li, L. Chen, J. Liu, H. Cai, S. Qiu, J. Tan, Chem. Commun., 2015,
51, 1823-1825; (m) I. B. Sayeed, V. L. Nayak, M. A. Shareef, N.
K. Chouhan, A. Kamal, Med. Chem. Commun., 2017, 8, 1000-
1006; (n) C. Patel, A. Thakur, G. Pereira, A. Sharma, Synth.
Commun. 2019, 49, 1836-1846
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins