Regioselective direct c-3 arylation of imidazo[1,2- a ]pyridines with aryl tosylates and mesylates promoted by palladium-phosphine complexes

Article abstract of DOI:10.1021/jo502386w

Direct C-3 arylation of imidazo[1,2-a]pyridines with aryl tosylates and mesylates has been accomplished by employing palladium(II) acetate associated with SPhos (2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl) or L1 (2-(2-(diisopropylphosphino)phenyl)-1-methyl-1H-indole). This catalyst system can be applied to a wide range of aryl sulfonates and shows excellent C-3 regioselectivity of imidazo[1,2-a]pyridine. These results represent the first examples of using tosylate- and mesylate-functionalized arenes as the electrophile partners for this regioselective direct arylation.

Full text of DOI:10.1021/jo502386w

Article
pubs.acs.org/joc
Regioselective Direct C‑3 Arylation of Imidazo[1,2‑a]pyridines with
Aryl Tosylates and Mesylates Promoted by Palladium−Phosphine
Complexes
Pui Ying Choy,† Kwan Chak Luk,† Yinuo Wu,†,‡ Chau Ming So,† Lai-lai Wang,*,§ and Fuk Yee Kwong*,†
†State Key Laboratory of Chirosciences and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic
University, Hung Hom, Kowloon, Hong Kong
‡School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
§State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of
Sciences, Lanzhou 730000, China
S
* Supporting Information
ABSTRACT: Direct C-3 arylation of imidazo[1,2-a]pyridines with
aryl tosylates and mesylates has been accomplished by employing
palladium(II) acetate associated with SPhos (2-dicyclohexylphosphi-
no-2′,6′-dimethoxybiphenyl) or L1 (2-(2-(diisopropylphosphino)-
phenyl)-1-methyl-1H-indole). This catalyst system can be applied to
a wide range of aryl sulfonates and shows excellent C-3
regioselectivity of imidazo[1,2-a]pyridine. These results represent
the first examples of using tosylate- and mesylate-functionalized arenes as the electrophile partners for this regioselective direct
arylation.
INTRODUCTION
■
Imidazo[1,2-a]pyridine scaffold is exemplified as one of the
most significant structural subunits in materials,1 agrochemical,2
and especially pharmaceutical products.3 They possess
important activities in antiviral, antimicrobial, herbicidal,
antitumor, and immunosuppressive agents.4 In particular, 3-
aryl-imidazo[1,2-a]pyridines are often found as the core
structures of various bioactive compounds, such as liver X
receptor (LXR) agonists,5 GABAAα2/α3 agonists,6 γ-secretase
modulators (GSMs),7 positive allosteric modulators (PAMs) of
metabotropic glutamate 2 receptor,8 TP-003,9 and kinase
inhibitors (Figure 1).10
Having the increased interest of this class of compound, we
envisage that the development of a direct and convergent
synthetic method for preparing such versatile 3-aryl-imidazo-
[1,2-a]pyridines would be valuable for drug development.
There have been scanty literature reports to-date for the
synthesis of 3-aryl-imidazo[1,2-a]pyridine derivatives. Relevant
organic transformations for accessing these compounds are the
condensation of 2-aminopyridine derivatives with α-halogen
ketones,11 aldehydes,2,12 alkynes,13 nitroolefins,14 or other
functional species (Figure 2).15 In 2012, Lei showed the
Figure 1. Examples of useful 3-aryl-imidazo[1,2-a]pyridine-containing
molecules.
silver-mediated C−H/N-H oxidative cyclization for preparing
arylimidazo[1,2-a]pyridines.16 Jiang and co-workers recently
reported a rapid transformation of pyridine to 3-arylimidazo-
diversified analogues (Figure 2).19 However, they usually
[1,2-a]pyridine derivatives via a copper-catalyzed aerobic
need the preactivation of organometallic nucleophiles or
dehydrogenative cyclization with ketone oxime esters (Figure
2).17 Recent advances of palladium-catalyzed cross-coupling, for
instance Suzuki reaction6,18 and decarboxylative coupling, offer
Received: October 17, 2014
convergent approaches to synthesize a number of these
© XXXX American Chemical Society
A
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Table 1. Initial Screening of the Palladium-Catalyzed Direct
a
Arylation of Imidazo[1,2-a]pyridine with ArOTs
b
entry
catalyst
solvent
base
% yield
1
Pd(OAc)2
PdCl2
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
toluene
dioxane
CH3CN
DMF
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K2CO3
90 (88)
32
2
3
Pd2(dba)3
Pd(TFA)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
44
4
80
5
61
6
K3PO4
88
7
Cs2CO3
79
8
KOAc
10
9
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
K3PO4·H2O
NR
NR
NR
20
10
c
11
Figure 2. Selected synthetic methods for preparation of 3-arylimidazo-
[1,2-a]pyridines.
12
d
13
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
NR
NR
67
e
14
require specific carboxylate substrates. A more streamlined and
attractive strategy is thus established in which the reaction can
proceed via C−H functionalization/arylation pathway.20
Although direct arylation of heterocycles has been successful,
direct C3-arylation of free imidazo[1,2-a]pyridines still has
room for further development.21 In 2006, Berteina-Raboin
employed 5 mol % of Pd(OAc)2 associated with 10 mol % of
PPh3 for the C3-arylation of imidazo[1,2-a]pyridines (Figure
2).22 Only aryl bromides were found applicable, and long
reaction times (∼48 h) were required to generate sufficient
yield. Bazin and Marchand reported coupling between 3-
haloimidazo[1,2-a]pyridines and arylboronic acids in the
presence of 4−8 mol % Pd(OAc)2 and PCy3·HBF4 salt (Figure
2).23 Recently, Doucet and co-workers disclosed a phosphine-
free Pd-catalyzed direct C-3 arylation of imidazo[1,2-a]-
pyridines with aryl bromides at low catalyst loading.24
Nevertheless, aryl bromides were the only suitable electro-
philes. In 2014, Zhan and Liu reported a facile synthesis of
arylimidazo[1,2-a]pyridines through oxidative coupling.25 In
fact, previous literature reports were mainly focused on aryl
halide electrophiles, as well as the 2-substituted imidazo[1,2-
a]pyridines. Thus, a catalyst system which allows general aryl
sulfonates and free imidazo[1,2-a]pyridines to serve as the
coupling partners is still in demand. In continuing our former
works on transition metal-catalyzed direct arylation26 and C−H
functionalization of heteroarenes,27 herein we report our
investigation of using aryl sulfonates as the electrophilic
partners for direct C−H arylation of imidazo[1,2-a]pyridines.
f
15
g
16
24
h
17
70
c
18
9
a
Reaction conditions: ArOTs (0.5 mmol), imidazo[1,2-a]pyridine (1.0
mmol), Pd(OAc)2 (0.01 mmol, 2 mol %), SPhos (0.04 mmol, 8 mol
%; Pd/L 1:4), base (1.5 mmol), and solvent (1 mL) were stirred at
120 °C under nitrogen for 18 h. Calibrated GC yields are reported,
using dodecane as the internal standard. The reaction was performed
at 80 °C. Pd/Ligand = 1:1. Pd/Ligand = 1:2. Pd/Ligand = 1:3. 1.0
mol % of Pd(OAc)2 was used. 1.5 mol % of Pd(OAc)2 was used.
b
c
d
e
f
g
h
Scheme 1. Ligand Screening for the Palladium-Catalyzed
Direct Arylation of Imidazo[1,2-a]pyridine
a
RESULTS AND DISCUSSION
■
We initially started our investigation by employing commer-
cially available imidazo[1,2-a]pyridine and 4-tert-butylphenyl
tosylate as the model substrates (Table 1). A series of well-
recognized and commercially available phosphines, as well as
our previously developed ligands, were initially screened
(Scheme 1). Poor conversion of aryl tosylate was observed
with BrettPhos, whereas CataCXium PCy did not promote this
direct arylation. A combination of Pd(OAc)2 with SPhos was
found to be the best catalyst of choice for this tosylate coupling.
L1 and XPhos showed comparable results while CM-phos gave
slightly lower yield.
a
Reaction conditions: 4-tert-butylphenyl tosylate (0.5 mmol), imidazo-
[1,2-a]pyridine (1.0 mmol), Pd(OAc)2 (2.0 mol %), L (8.0 mol %;
Pd/L 1:4), K3PO4·H2O (1.5 mmol) and t-BuOH (1 mL) were stirred
at 120 °C for 18 h. Yields were determined by GC analysis with
dodecane as the internal standard.
B
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We carried out a series of investigations to optimize the
reaction conditions (Table 1). Pd(OAc)2 showed superior
performance, and palladium(II) trifluoroacetate (Pd(TFA)2)
gave slightly lower conversion among other palladium sources
examined (Table 1, entries 1−4). A screening of commonly
used inorganic bases indicated that K3PO4 and K3PO4·H2O
were both suitable bases for this coupling process (Table 1,
entry 1 vs entries 5−8). The use of solvents, such as dioxane,
toluene, CH3CN, and DMF, in place of t-BuOH proved much
less effective (Table 1, entry 1 vs entries 9−12). The Pd/L ratio
of 1:4 afforded the best product yield whereas the ratio of 1:3
provided lower substrate conversions (Table 1, entry 1 vs
entries 13−15). The Pd/L ratio of 1:4 gave good yield possibly
because some of the ligands are required to serve as the
reductant to reduce Pd(II) to Pd(0) at the initial stage of the
catalysis. The ratio of Pd/L = 1:3 showed insufficient amount
of reductant, and thus the effective Pd(0) complex. A 2.0 mol %
amount of Pd(OAc)2 was sufficient to catalyze the arylation
(Table 1, entry 1 vs entries 16−17). Lowering the reaction
temperature to 80 °C led to poor substrate conversion (Table
1, entry 1 vs entry 18).
Table 2. Palladium-Catalyzed Direct Arylation of
Imidazo[1,2-a]pyridine with ArOTs
a
With the preliminary optimized reaction conditions in hand,
we next tested the generality of this catalyst system for the
direct arylation of imidazo[1,2-a]pyridine with aryl tosylates
(Table 2). A variety of aryl tosylates underwent the arylation
smoothly. To the best of our knowledge, there has been no
successful example of aryl tosylates reported to-date in the
direct arylation of imidazo[1,2-a]pyridines. Slightly lower yield
was afforded when this direct arylation of imidazo[1,2-
a]pyridine was performed under air (entry 1). In the presence
of SPhos, various electronically neutral aryl tosylates could be
efficiently coupled to give the corresponding products in good-
to-excellent yields (entries 1, 3, 5, and 7). Although functional
groups such as methoxy (entry 13), fluoro (entry 19), keto
(entry 20), and ester (entries 16 and 21) were compatible
under the catalyst system of Pd(OAc)2 and SPhos, moderate-
to-good product yields were obtained. It should be noted that
no desired product was observed when 3-cyanophenyl or 4-
cyanophenyl tosylate was used as coupling substrate. Upon
replacing the ligand SPhos with L1 (condition B), coupling of
3-cyanophenyl or 4-cyanophenyl tosylate with imidazo[1,2-
a]pyridine proceeded smoothly (entries 15 and 18). In fact, the
substrate scope of direct arylation with L1 was found
comparable to SPhos (entries 2, 4, 6, and 8) while functional
groups ester (entries 17 and 22), keto (entry 23), and even
cyano groups (entries 15 and 18) could be tolerated to afford
the product in improved yields. Yet, heterocyclic quinolyl
tosylate gave better yield when SPhos was employed (entries 9
and 10). We also examined the multiheteroatom-containing
aryl sulfonates, such as benzo[d]thiazol-6-yl 4-methylbenzene-
sulfonate and benzo[d]thiazol-6-yl methanesulfonate. However,
they were found not successful as coupling partners in this
reaction. Only monoheteroatom-containing aryl tosylate was
found suitable to afford the desirable product. When
naphthalen-1-yl tosylate was applied as coupling partner, 12%
yield was obtained. For bromo-group compatibility, we
additionally tested 3-bromophenyl tosylate. A 4:1 ratio of the
products 2-[3-(4-tolylsulfonyloxy)]imidazo[1,2-a]pyridine and
2-(3-bromophenyl)imidazo[1,2-a]pyridine, respectively, were
observed from GC-MS analysis.
a
Reaction conditions: ArOTs (0.5 mmol), imidazo[1,2-a]pyridines
(1.0 mmol), Condition A: Pd(OAc)2 (0.01 mmol, 2.0 mol %), SPhos
(0.04 mmol, 8.0 mol %; Pd/L 1:4), K3PO4 (1.5 mmol) and t-BuOH
(1.0 mL) were stirred at 120 °C under nitrogen for 18 h. Condition B:
Pd(OAc)2 (0.01 mmol, 2.0 mol %), L1 (0.04 mmol, 8.0 mol %; Pd/L
1:4), K3PO4·H2O (1.5 mmol) and t-BuOH (1 mL) were stirred at 120
b
c
°C under nitrogen for 18 h. Isolated yields are reported. K3PO4·H2O
was used as base. The reaction was performed under air. K2CO3 was
used as base. ArOTs (1.0 mmol) and imidazo[1,2-a]pyridines (0.5
mmol) were used.
d
e
f
functionalized arenes as the electrophilic coupling partners
(Table 3). Essentially no coupling products were observed
when the use of Pd−SPhos complex was initially attempted.
Further detailed screening revealed that XPhos, SPhos, and
BrettPhos did not promote the reaction. Only L1 was found
capable to facilitate this coupling process, and the desired
product was afforded in satisfactory yield under the same
reaction conditions as in Table 2, entry 2. With this effective
ligand L1 in hand, various aryl mesylates were then evaluated.
No examples of direct arylation of imidazo[1,2-a]pyridines
with aryl mesylates were reported. To expand the substrate
scope further, we next probed the possibility of using mesylate-
C
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Table 3. Palladium-Catalyzed Direct Arylation of
Imidazo[1,2-a]pyridines with ArOMs
CONCLUSION
■
a
We have reported the first general palladium-catalyzed direct
arylation of imidazo[1,2-a]pyridines with aryl tosylates and
mesylates. The Pd−SPhos catalyst system is effective for the
coupling of a range of tosylate-functionalized substrates.
Particularly noteworthy is that we also showed the first
successful examples of aryl mesylate coupling when the Pd−
L1 catalyst system was employed. Having the Pd−SPhos and
new Pd−L1 systems, the coupling of both functionalized aryl
tosylates and a range of aryl mesylates can be accomplished,
respectively.
EXPERIMENTAL SECTION
■
General Information. Unless otherwise noted, all reagents were
purchased from commercial suppliers and used without purification.
All the reactions were performed in Rotaflo (England) resealable
screw-cap tubes (approximately 10 mL volume) in the presence of a
Teflon-coated magnetic stirrer bar (4 mm × 10 mm). Dioxane and
toluene were freshly distilled over sodium under nitrogen.28 t-BuOH
was first distilled over sodium and stored with calcium hydride under
nitrogen. Thin layer chromatography was performed on precoated
silica gel 60 F254 plates. Silica gel (230−400 mesh) was used for
1
column chromatography. H NMR spectra were recorded on a 400
MHz spectrometer. Spectra were referenced internally to the residual
proton resonance in CDCl3 (δ 7.26 ppm), or with TMS (δ 0.00 ppm)
as the internal standard. Chemical shifts (δ) are reported as part per
million (ppm) in δ scale downfield from TMS. 13C NMR spectra were
recorded on a 100 MHz spectrometer, and the spectra were referenced
to CDCl3 (δ 77.0 ppm, the middle peak). Coupling constants (J) are
reported in hertz (Hz). Mass spectra (EI-MS and ES-MS) were
recorded on a mass spectrometer. High-resolution mass spectra
(HRMS) were obtained on a ESIMS mass spectrometer. GC-MS
analysis was conducted on a GCD system. GC yields are according to
the authentic samples/dodecane calibration standard from the GC-
FID system.
General Procedures for Reaction Condition Screenings.
Palladium source (2.0 mol %), ligand (8.0 mol %), aryl tosylates
(0.5 mmol), and base (1.5 mmol) were loaded into a Schlenk tube
equipped with a Teflon-coated magnetic stir bar. The tube was
evacuated and flushed with nitrogen for three times. Imidazo[1,2-
a]pyridines (1.0 mmol, 101 μL) and the solvent (1.0 mL) were then
added with stirring at room temperature for several minutes. The tube
was then placed into a preheated oil bath (120 °C or indicated in
Table 1) and stirred for 18 h. After completion of reaction, the
reaction tube was allowed to cool to room temperature. Ethyl acetate
(∼10 mL), dodecane (114 μL, internal standard), and water (∼3 mL)
were added. The organic layer was subjected to GC analysis. The GC
yield obtained was previously calibrated with the authentic sample/
dodecane calibration curve.
a
Reaction conditions: ArOMs (0.5 mmol), imidazo[1,2-a]pyridines
General Procedures for Direct C−H Bond Arylation:
Palladium-Catalyzed Direct Arylation of Imidazo[1,2-a]-
pyridines. Condition A: Pd(OAc)2 (2.0 mol %, 0.0022 g), SPhos
(8.0 mol %, 0.0164 g), aryl tosylates (0.5 mmol), and base (1.5 mmol)
were loaded into a Schlenk tube equipped with a Teflon-coated
magnetic stir bar. The tube was evacuated and flushed with nitrogen
for three times. Imidazo[1,2-a]pyridines (1.0 mmol, 101 μL) and the
solvent t-BuOH (1.0 mL) were then added with stirring at room
temperature for several minutes. The tube was then placed into a
preheated oil bath (120 °C) and stirred for 18 h. After completion of
reaction as judged by GC analysis, the reaction tube was allowed to
cool to room temperature and ethyl acetate then added for dilution.
The organic layer was separated, and the aqueous layer was washed
with ethyl acetate. The filtrate was concentrated under reduced
pressure. The crude products were purified by flash column
chromatography on silica gel (230−400 mesh) to afford the desired
product.
(1.0 mmol), Pd(OAc)2 (0.01 mmol, 2.0 mol %), L1 (0.04 mmol, 8.0
mol %; Pd/L 1:4), K3PO4·H2O (1.5 mmol) and t-BuOH (1 mL) were
b
stirred at 120 °C under nitrogen for 18 h. Isolated yields are reported.
c
d
K2CO3 was used as base. ArOMs (1.0 mmol) and imidazo[1,2-
a]pyridines (0.5 mmol) were used.
Good product yields were afforded for electronically neutral
aryl mesylates (entries 1−4). Functionalized aryl mesylates
containing nitrile (entries 8 and 9), keto (entry 10), and
benzodioxolyl groups (entry 5) were shown tolerable under this
system. When highly sterically hindered 2,4,6-trimethylphenyl
mesylates were tested, only hydrolyzed phenolic side product
was observed and no desired coupling product was afforded.
Condition B: Pd(OAc)2 (2.0 mol %, 0.0022 g) and L1 (8.0 mol %,
0.0129 g) were loaded into a Schlenk tube equipped with a Teflon-
D
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coated magnetic stir bar. The tubes were evacuated and backfilled with
nitrogen (three cycles). Precomplexation was applied by adding freshly
distilled dichloromethane (1.0 mL) and Et3N (0.05 mL) into the tube.
The palladium complex stock solution was stirred and warmed using a
hair drier for 1 to 2 min until the solvent started boiling. The solvent
was then evaporated under high vacuum. Aryl mesylates/tosylates (0.5
mmol) and base (1.5 mmol) were loaded into the tube, and the system
was further evacuated and flushed with nitrogen for three times.
Imidazo[1,2-a]pyridines (1.0 mmol, 101 μL) and the solvent t-BuOH
(1.0 mL) were then added with stirring at room temperature for
several minutes. The tube was then placed into a preheated oil bath
(120 °C) and stirred for 18 h. After completion of reaction, the
reaction tube was allowed to cool to room temperature, quenched with
water, and diluted with ethyl acetate. The organic layer was separated,
and the aqueous layer was washed with ethyl acetate. The filtrate was
concentrated under reduced pressure. The crude products were
purified by flash column chromatography on silica gel (230−400
mesh) to afford the desired product.
3-(4-(tert-Butyl)phenyl)imidazo[1,2-a]pyridine (Table 2, entries 1
and 2; Table 3, entry 1).24a EA:hexane = 1:2, Rf = 0.4, Table 2: 88%
(110 mg), Table 3: 60% (75 mg); 1H NMR (400 MHz, CDCl3) δ 1.38
(s, 9H), 6.77 (t, J = 6.8 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H), 7.47−7.55
(m, 4H), 7.65 (s, 1H), 7.67 (s, 1H), 8.32 (d, J = 6.4 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 31.3, 34.7, 112.4, 118.1, 123.4, 124.1,
125.7, 126.1, 126.3, 127.7, 132.1, 145.9, 151.3.
3-(3,4-Dimethylphenyl)imidazo[1,2-a]pyridine (Table 2, entries 3
and 4; Table 3, entry 3).25 EA:hexane = 1:2, Rf = 0.4, Table 2: 79%
(88 mg), Table 3: 72% (80 mg); 1H NMR (400 MHz, CDCl3) δ 2.32
(s, 6H), 6.77 (t, J = 6.8 Hz, 1H), 7.16 (t, J = 7.2 Hz, 1H), 7.26 (s, 2H),
7.30 (s, 1H), 7.64 (s, 1H), 7.67 (s, 1H), 8.29 (d, J = 6.8 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 19.6, 19.8, 112.4, 118.0, 123.4, 124.1,
125.4, 125.8, 126.5, 129.2, 130.4, 131.8, 136.9, 137.5, 145.7.
3-(3,5-Dimethylphenyl)imidazo[1,2-a]pyridine (Table 2, entries 5
and 6; Table 3, entry 4).25 EA:hexane = 1:2, Rf = 0.4, Table 2: 81%
(90 mg), Table 3: 72% (80 mg); 1H NMR (400 MHz, CDCl3) δ 2.36
(s, 6H), 6.74 (t, J = 6.8 Hz, 1H), 7.02 (s, 1H), 7.11−7.14 (m, 3H),
7.62 (s, 1H), 7.64 (s, 1H), 8.29 (d, J = 6.8 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 21.3, 112.3, 118.1, 123.5, 124.0, 125.7, 125.9, 129.0,
129.8, 132.3, 138.8, 145.9.
3-(Naphthalen-2-yl)imidazo[1,2-a]pyridine (Table 2, entries 7
and 8; Table 3, entry 2).24a EA:hexane = 1:2, Rf = 0.3, Table 2: 87%
(106 mg), Table 3: 73% (89 mg); 1H NMR (400 MHz, CDCl3) δ 6.82
(s, 1H), 7.22 (t, J = 7.2 Hz, 1H), 7.54 (s, 2H), 7.63 (d, J = 8.4 Hz,
1H), 7.71 (d, J = 8.8 Hz, 1H), 7.80 (s, 1H), 7.88 (s, 2H), 7.95 (d, J =
8.4 Hz, 1H), 8.00 (s, 1H), 8.42 (d, J = 6.0 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 112.5, 118.1, 123.2, 124.2, 125.6, 126.4 (overlapped),
126.5, 126.6, 127.7, 127.8, 128.9, 132.7, 133.4, 146.1.
(s, 1H), 7.14−7.21 (m, 2H), 7.43 (t, J = 8.0 Hz, 1H), 7.66 (d, J = 9.2
Hz, 1H), 7.70 (s, 1H), 8.35 (d, J = 7.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 55.2, 112.4, 113.4, 113.6, 118.1, 120.1, 123.4, 124.1, 125.4,
130.1, 130.4, 132.4, 146.0, 160.0.
3-(Imidazo[1,2-a]pyridin-3-yl)benzonitrile (Table 2, entries 15;
Table 3, entry 8).24a EA:hexane = 1:2, Rf = 0.30, Table 2: 64% (70
mg), Table 3: 43% (47 mg); 1H NMR (400 MHz, CDCl3) δ 6.88 (t, J
= 6.8 Hz, 1H), 7.24 (t, J = 7.2 Hz, 1H), 7.60−7.82 (m, 6H), 8.27 (d, J
= 6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 113.1, 113.4, 118.0,
118.3, 122.7, 123.2, 124.8, 130.0, 130.6, 130.7, 131.1, 131.7, 133.3,
146.4.
Ethyl 3-(imidazo[1,2-a]pyridin-3-yl)benzoate (Table 2, entries 16
and 17). EA:hexane = 1:2, Rf = 0.30, yellow viscous oil, 71% (94 mg);
1H NMR (400 MHz, CDCl3) δ 1.32 (s, 3H), 4.32 (d, J = 5.6 Hz, 2H),
6.75 (s, 1H), 7.13 (s, 1H), 7.50−7.66 (m, 4H), 8.00 (s, 1H), 8.16 (s,
1H), 8.23 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.3, 61.3, 112.8,
118.3, 123.1, 124.5, 124.7 (overlapped), 129.0, 129.3, 131.5, 132.1,
+
132.9, 146.3, 166.0; HRMS: calcd for C16H15N2O2 : 267.1134, found
267.1131.
4-(Imidazo[1,2-a]pyridin-3-yl)benzonitrile (Table 2, entry 18;
Table 3, entry 9).24a EA:hexane = 1:2, Rf = 0.30, Table 2: 74% (80
mg), Table 3: 52% (57 mg); 1H NMR (400 MHz, CDCl3) δ 6.92 (td,
J = 6.8 Hz, 1H), 7.30 (d, J = 7.6 Hz, 1H), 7.71−7.74 (m, 3H), 7.81−
7.83 (m, 3H), 8.38 (d, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3)
δ 111.2, 113.4, 118.5, 118.7, 123.1, 125.2, 127.6, 133.1, 134.0, 134.2.
3-(4-Fluorophenyl)imidazo[1,2-a]pyridine (Table 2, entry 19).24a
EA:hexane = 1:2, Rf = 0.20, 58% (61 mg); 1H NMR (400 MHz,
CDCl3) δ 6.80 (t, J = 6.0 Hz, 1H), 7.18−7.24 (m, 3H), 7.50−7.54 (m,
2H), 7.66 (s, 1H), 7.68 (s, 1H), 8.23 (d, J = 6.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 112.6, 116.3 (d, J = 21 Hz), 118.3, 123.0, 124.2,
124.6, 125.3 (d, JCF = 3 Hz), 130.0 (d, JCF = 8 Hz), 132.5, 146.0, 162.5
(d, JCF = 247); 19F NMR (400 MHz, CDCl3) δ −112.7.
(4-(Imidazo[1,2-a]pyridin-3-yl)phenyl)(phenyl)methanone (Table
2, entry 20; Table 3, entry 10). EA:hexane = 1:2, Rf = 0.25, pale yellow
1
oil, Table 2: 46% (69 mg), Table 3: 47% (70 mg); H NMR (400
MHz, CDCl3) δ 6.88 (t, J = 6.4 Hz, 1H), 7.25 (t, J = 7.9 Hz, 1H), 7.51
(t, J = 7.6 Hz, 2H), 7.61 (t, J = 7.2 Hz, 1H), 7.68−7.71 (m, 3H), 7.81
(s, 1H), 7.83 (d, J = 7.2 Hz, 2H), 7.94 (d, J = 8.4 Hz, 2H), 8.43 (d, J =
6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 113.1, 118.4, 123.4,
124.7, 124.9, 127.1, 128.4, 130.0, 131.1, 132.6, 133.3, 133.6, 136.7,
137.4, 146.8, 195.8; HRMS: calcd for C20H 15N2O+: 299.1184, found
299.1181.
Ethyl 4-(Imidazo[1,2-a]pyridin-3-yl)benzoate (Table 2, entries 21
1
and 22). EA:hexane = 1:2, Rf = 0.3, colorless oil, 68% (90 mg); H
NMR (400 MHz, CDCl3) δ 1.38 (t, J = 7.2 Hz, 3H), 4.38 (q, J = 6.8
Hz, 2H), 6.82 (t, J = 6.8 Hz, 1H), 7.19 (t, J = 8.0 Hz, 1H), 7.59−7.66
(m, 3H), 7.73 (s, 1H), 8.12 (d, J = 8.4 Hz, 2H), 8.34 (d, J = 6.8 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 14.1, 60.9, 112.8, 118.2, 123.1,
124.6, 126.9, 129.5, 130.3, 133.3, 133.4, 146.5, 165.8; HRMS: calcd for
6-(Imidazo[1,2-a]pyridin-3-yl)quinoline (Table 2, entries 9 and
10). EA, Rf = 0.2, pale yellow viscous oil, 79% (97 mg); 1H NMR (400
MHz, CDCl3) δ 6.80 (t, J = 6.8 Hz, 1H), 7.18 (t, J = 8.0 Hz, 1H),
7.38−7.41 (q, J = 4.0 Hz, 1H), 7.64 (d, J = 9.2 Hz, 1H), 7.76 (s, 1H),
7.82−7.84 (dd, J = 7.2, 1.6 Hz, 1H), 7.90 (s, 1H), 8.12, (d, J = 8.4 Hz,
1H), 8.17 (d, J = 8.8 Hz, 1H), 8.35 (d, J = 7.2 Hz, 1H), 8.88−8.90 (dd,
J = 2.8, 1.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 112.9, 118.3,
121.8, 123.2, 124.6, 124.9, 126.1, 127.4, 128.5, 129.1, 130.5, 133.3,
+
C16H15N2O2 : 267.1134, found 267.1136.
(7-(Imidazo[1,2-a]pyridin-3-yl)naphthalen-2-yl)(phenyl)-
methanone (Table 2, entry 23). EA:hexane = 1:2, Rf = 0.25, pale
yellow viscous oil, 82% (143 mg); 1H NMR (400 MHz, CDCl3) δ 6.87
(t, J = 6.8 Hz, 1H), 7.24 (t, J = 8.0 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H),
7.62 (t, J = 7.6 Hz, 1H), 7.70−7.73 (m, 2H), 7.84−7.87 (m, 3H),
7.95−8.07 (m, 4H), 8.29 (s, 1H), 8.48 (d, J = 7.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 112.8, 118.2, 123.2, 124.6, 125.1, 125.7, 126.3,
126.6, 128.1, 129.0, 129.9, 130.4, 131.4 (overlapped), 132.3, 133.3,
135.0, 135.3, 137.5, 146.4, 196.2; HRMS: calcd for C24H17N2O+:
349.1341, found 349.1330.
+
135.9, 146.4, 147.6, 150.8; HRMS: calcd for C16H12N3 : 246.1026,
found 246.1025.
3-(Benzo[d][1,3]dioxol-5-yl)imidazo[1,2-a]pyridine (Table 2, en-
tries 11 and 12; Table 3, entry 5). EA:hexane = 1:2, Rf = 0.35,
colorless oil, Table 2: 61% (73 mg), Table 3: 62% (74 mg); 1H NMR
(400 MHz, CDCl3) δ 6.03 (s, 2H), 6.76−6.80 (td, J = 6.8, 0.8 Hz,
1H), 6.93−7.01 (m, 3H), 7.14−7.19 (m, 1H), 7.61 (s, 1H), 7.63 (d, J
= 9.2 Hz, 1H), 8.24 (d, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3)
δ 101.3, 108.5, 108.9, 112.3, 118.0, 121.9, 122.7, 123.9, 125.3, 132.0,
3-(p-Tolyl)imidazo[1,2-a]pyridine (Table 3, entry 7).22 EA:hexane
= 1:2, Rf = 0.20, 71% (74 mg); 1H NMR (400 MHz, CDCl3) δ 2.43 (s,
3H), 6.79 (t, J = 6.0 Hz, 1H), 7.16−7.21 (m, 2H), 7.35−7.41 (m, 3H),
7.65 (d, J = 8.0 Hz, 2H), 8.32 (d, J = 6.8 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 21.3, 112.3, 118.0, 123.3, 124.0, 124.9, 125.7, 128.5,
128.8, 128.9, 129.0, 132.1, 138.9, 145.9.
+
145.7, 147.6, 148.2. HRMS: calcd for C14H11N2O2 : 239.0821, found
239.0820.
3-(Naphthalen-1-yl)imidazo[1,2-a]pyridine.24a EA:hexane = 1:1,
Rf = 0.20, colorless oil, 12% (15 mg); 1H NMR (400 MHz, CDCl3) δ
6.71 (t, J = 7.6 Hz, 1H), 7.21−7.25 (m, 1H), 7.44 (t, J = 8.0 Hz, 1H),
7.51−7.62 (m, 4H), 7.73 (t, J = 8.4 Hz, 2H), 7.80 (s, 1H), 7,95−8.00
3-(3-Methoxyphenyl)imidazo[1,2-a]pyridine (Table 2, entries 13
and 14; Table 3, entry 6).19 EA:hexane = 1:2, Rf = 0.35, Table 2: 79%
(88 mg), Table 3: 50% (56 mg); 1H NMR (400 MHz, CDCl3) δ 3.86
(s, 3H), 6.80 (t, J = 6.8 Hz, 1H), 6.94−6.97 (dd, J = 8.0 Hz, 1H), 7.09
E
DOI: 10.1021/jo502386w
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The Journal of Organic Chemistry
Article
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 112.2, 118.0, 124.1, 124.2,
125.2, 125.6, 126.4, 126.9, 128.7, 129.1, 129.6, 132.0, 133.9, 145.9.
H.; Biesmans, I.; Trabanco, A. A. Bioorg. Med. Chem. Lett. 2010, 20,
175−179.
(9) Fradley, R. L.; Guscott, M. R.; Bull, S.; Hallett, D. J.; Goodacre, S.
C.; Wafford, K. A.; Garrett, E. M.; Newman, R. J.; O’Meara, G. F.;
Whiting, P. J.; Rosahl, T. W.; Dawson, G. R.; Reynolds, D. S.; Atack, J.
R. J. Psychopharmacol. 2007, 21, 384−391.
(10) (a) Follot, S.; Debouzy, J.-C.; Crouzier, D.; Enguehard-
Gueiffier, C.; Gueiffier, A.; Nachon, F.; Lefebvre, B.; Fauvelle, F.
Eur. J. Med. Chem. 2009, 44, 3509−3518. (b) Colletti, S. L.; Frie, J. L.;
Dixon, E. C.; Singh, S. B.; Choi, B. K.; Scapin, G.; Fitzgerald, C. E.;
Kumar, S.; Nichols, E. A.; O’Keefe, S. J.; O’Neill, E. A.; Porter, G.;
Samuel, K.; Schmatz, D. M.; Schwartz, C. D.; Shoop, W. L.;
Thompson, C. M.; Thompson, J. E.; Wang, R.; Woods, A.; Zaller,
D. M.; Doherty, J. B. J. Med. Chem. 2003, 46, 349−352. (c) Katz, J.;
Jewell, J.; Jung, J.; Kattar, S.; Hou, Y.; Maccoss, R.; Ito, S. PCT Int.
Appl. WO 2010017047 A1, 2010.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H NMR, 13C NMR, 19F NMR, and HRMS spectra.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: fuk-yee.kwong@polyu.edu.hk.
*E-mail: wll@licp.cas.cn.
Notes
■
The authors declare no competing financial interest.
(11) (a) Djerassi, C.; Pett, G. R. J. Am. Chem. Soc. 1954, 76, 4470−
4472. (b) Elliott, A. J.; Guzik, H.; Soler, J. R. J. Heterocycl. Chem. 1982,
́
19, 1437−1440. (c) Stasyuk, A. J.; Banasiewicz, M.; Cyranski, M. K.;
ACKNOWLEDGMENTS
■
Gryko, D. T. J. Org. Chem. 2012, 77, 5552−5558. (d) Bangade, V. M.;
Reddy, B. C.; Thakur, P. B.; Babu, B. M.; Meshram, H. M. Tetrahedron
Lett. 2013, 54, 4767−4771.
We thank the Research Grants Council of Hong Kong (GRF:
PolyU5010/13P) and State Key Laboratory of Chirosciences
for financial support. F.Y.K. thanks the Croucher Foundation
for the Croucher Senior Research Fellowship (2013). Grateful
to Prof. Albert S. C. Chan’s research group (PolyU Hong
Kong) for sharing of GC-FID and GC-MS instruments.
(12) (a) DiMauro, E. F.; Kennedy, J. M. J. Org. Chem. 2007, 72,
1013−1016. (b) Adib, M.; Sheikhi, E.; Rezaei, N. Tetrahedron Lett.
2011, 52, 3191−3194. (c) Yan, H.; Wang, Y.; Pan, C.; Zhang, H.;
Yang, S.; Ren, X.; Li, J.; Huang, G. Eur. J. Org. Chem. 2014, 2754−
2763.
(13) (a) Wu, Z.; Pan, Y.; Zhou, X. Synthesis 2011, 2255−2260.
(b) Dixon, L. I.; Carroll, M. A.; Gregson, T. J.; Ellames, G. J.;
Harrington, R. W.; Clegg, W. Org. Biomol. Chem. 2013, 11, 5877−
5884.
(14) (a) Yan, H.; Yang, S.; Gao, X.; Zhou, K.; Ma, C.; Yan, R.;
Huang, G. Synlett 2012, 23, 2961−2964. (b) Nair, D. K.; Mobin, S. M.;
Namboothiri, N. N. Org. Lett. 2012, 14, 4580−4583.
(15) (a) Collins, M. R.; Huang, Q.; Ornelas, M. A.; Scales, S. A.
Tetrahedron Lett. 2010, 3528−3530. (b) Marhadour, S.; Marchand, P.;
Pagniez, F.; Bazin, M.-A.; Picot, C.; Lozach, O.; Ruchaud, S.; Antoine,
M.; Meijer, L.; Rachidi, N.; Pape, P. L. Eur. J. Med. Chem. 2012, 543−
556. (c) Liu, G.; Cong, X.; He, J.; Luo, S.; Wu, D.; Lan, J. J. Chem. Res.
2012, 36, 687−690.
REFERENCES
■
(1) Bae, J. S.; Lee, D. W.; Lee, D. H.; Jeong, D. S. PCT Int. Appl.
WO2007011163A1, 2007.
(2) Egner, U.; Gerbling, K. P.; Hoyer, G.-A.; Kruger, G.; Wegner, P.
̈
Pestic. Sci. 1996, 47, 145−158.
(3) (a) Rupert, K. C.; Henry, J. R.; Dodd, J. H.; Wadsworth, S. A.;
Cavender, D. E.; Olini, G. C.; Fahmy, B.; Siekierka, J. Bioorg. Med.
Chem. Lett. 2003, 13, 347−350. (b) Moraski, G. C.; Markley, L. D.;
Hipskind, P. A.; Boshoff, H.; Cho, S.; Franzblau, S. G.; Miller, M. J.
ACS Med. Chem. Lett. 2011, 2, 466−470.
(4) (a) Langer, S. Z.; Arbilla, S.; Benavides, J.; Scatton, B. Adv.
Biochem. Psychopharmacol. 1990, 46, 61−72. (b) Rival, Y.; Grassy, G.;
Taudou, A.; Ecalle, R. Eur. J. Med. Chem. 1991, 26, 13−18. (c) Rival,
Y.; Grassy, G.; Michel, G. Chem. Pharm. Bull. 1992, 40, 1170−1176.
(d) Kaminsky, J. J.; Doweyko, a. M. J. Med. Chem. 1997, 40, 427−436.
(e) Katritzky, A. R.; Xu, Y. J.; Tu, H. J. Org. Chem. 2003, 68, 4935−
4937. (f) Jain, A. N. J. Med. Chem. 2004, 47, 947−961. (g) Harrison,
T. S.; Keating, G. M. CNS Drugs 2005, 19, 65−89. (h) Puerstinger, G.;
Paeshuyse, J.; Declercq, E.; Neyts, J. Bioorg. Med. Chem. Lett. 2007, 17,
390−393. (i) Gueiffier, E. C.; Gueiffier, A. Mini-Rev. Med. Chem. 2007,
7, 888−899. (j) Hanson, S. M.; Morlock, E. V.; Satyshur, K. A.;
Czajkowski, C. J. Med. Chem. 2008, 51, 7243−7252. (k) Li, A.-R.;
Johnson, M. G.; Liu, J.; Chen, X.; Du, X.; Mihalic, J. T.; Deignan, J.;
Gustin, D. J.; Duquette, J.; Fu, Z.; Zhu, L.; Marcus, A. P.; Bergeron, P.;
McGee, L. R.; Danao, J.; Lemon, B.; Carabeo, T.; Sullivan, T.; Ma, J.;
Tang, L.; Tonn, G.; Collins, T. L.; Medina, J. C. Bioorg. Med. Chem.
Lett. 2008, 18, 688−693. (l) Hsua, N.; Jha, S. K.; Coleman, T.; Frank,
M. G. Behav. Brain Res. 2009, 201, 233−236.
(5) Singhaus, R. R.; Bernotas, R. C.; Steffan, R.; Matelan, E.; Quinet,
E.; Nambi, P.; Feingold, I.; Huselton, C.; Wilhelmsson, A.; Goos-
Nilsson, A.; Wrobel, J. Bioorg. Med. Chem. Lett. 2010, 20, 521−525.
(6) Goodacre, S. C.; Street, L. J.; Hallett, D. J.; Crawforth, J. M.;
Kelly, S.; Owens, A. P.; Blackaby, W. P.; Lewis, R. T.; Stanley, J.;
Smith, A. J.; Ferris, P.; Sohal, B.; Cook, S. M.; Pike, A.; Brown, N.;
Wafford, K. A.; Marshall, G.; Castro, J. L.; Atack, J. R. J. Med. Chem.
2006, 49, 35−38.
(16) He, C.; Hao, J.; Xu, H.; Mo, Y.; Liu, H.; Han, J.; Lei, A. Chem.
Commun. 2012, 48, 11073−11075.
(17) Huang, H.; Ji, X.; Tang, X.; Zhang, M.; Li, X.; Jiang, H. Org. Lett.
2013, 15, 6254−6257.
(18) (a) Enguehard, C.; Renou, J.-L.; Collot, V.; Hervet, M.; Rault,
S.; Gueiffier, A. J. Org. Chem. 2000, 65, 6572−6575. (b) Crawforth, J.
M.; Goodacre, S. C.; Hallett, D. J.; Harrison, T.; Owens, A. P.; Rowley,
M.; Teall, M. R. PCT Int. Appl. WO 2001038326 A2, 2001.
(c) Bilodeau, M. T.; Fraley, M. E.; Wu, Z. PCT Int. Appl. WO
2003092595 A2, 2003. (d) Masuda, N.; Miyamoto, S.; Kikuchi, S.;
Samizu, K.; Sato, F.; Shiina, Y.; Hamaguchi, W.; Seo, R.; Mihara, T.
PCT Int. Appl. WO 2012133607 A1, 2012.
(19) Nandi, D.; Jhou, Y.-M.; Lee, J.-Y.; Kuo, B.-C.; Liu, C.-Y.; Huang,
P.-W.; Lee, H. M. J. Org. Chem. 2012, 77, 9384−9390.
(20) Yamaguchi, J.; Yamaguchi, A. D.; Itami, K. Angew. Chem., Int. Ed.
2012, 51, 8960−9009.
(21) Selected examples for using palladium-catalysis, see: (a) Toure,
B. B.; Lane, B. S.; Sames, D. Org. Lett. 2006, 8, 1979−1982.
(b) Kumar, P. V.; Lin, W.-S.; Shen, J.-S.; Nandi, D.; Lee, H. M.
Organometallics 2011, 30, 5160−5169. (c) Ke, C.-H.; Kuo, B.-C.;
Nandi, D.; Lee, H. M. Organometallics 2013, 32, 4775−4784. (d) Lee,
J.; Chung, J.; Byun, S. M.; Kim, B. M.; Lee, C. Tetrahedron 2013, 69,
5660−5664. Selected examples for using other transition-metal-
catalysis, see: (e) Yang, H.; Yang, L.; Li, Y.; Zhang, F.; Liu, H.; Yi, B.
Catal. Commun. 2012, 26, 11−14. (f) Cao, H.; Zhan, H.; Lin, Y.; Lin,
X.; Du, Z.; Jiang, H. Org. Lett. 2012, 14, 1688−1691. (g) Liu, Y.; He,
L.; Yin, G.; Wu, G.; Cui, Y. Bull. Korean Chem. Soc. 2013, 34, 2340−
2342. (h) Liu, B.; Huang, Y.; Lan, J.; Song, F.; You, J. Chem. Sci. 2013,
4, 2163−2167.
(7) Bischoff, F.; Berthelot, D.; De Cleyn, M.; Macdonald, G.; Minne,
G.; Oehlrich, D.; Pieters, S.; Surkyn, M.; Trabanco, A. A.; Tresadern,
G.; Brandt, S. V.; Velter, I.; Zaja, M.; Borghys, H.; Masungi, C.;
Mercken, M.; Gijsen, H. J. M. J. Med. Chem. 2012, 55, 9089−9106.
(8) Tresadern, G.; Cid, J. M.; Macdonald, G. J.; Vega, J. A.; de Lucas,
A. I.; García, A.; Matesanz, E.; Linares, M. L.; Oehlrich, D.; Lavreysen,
F
DOI: 10.1021/jo502386w
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(22) Koubachi, J.; Kazzouli, S. E.; Berteina-Raboin, S.; Mouaddib, A.;
Guillaumet, G. Synlett 2006, 3237−3242.
(23) Marhadour, S.; Bazin, M.-A.; Marchand, P. Tetrahedron Lett.
2012, 297−300.
(24) (a) Fu, H. Y.; Chen, L.; Doucet, H. J. Org. Chem. 2012, 77,
4473−4478. (b) Laroche, J.; Beydoun, K.; Guerchais, V.; Doucet, H.
Catal. Sci. Technol. 2013, 3, 2072−2080.
(25) Wang, S.; Liu, W.; Cen, J.; Liao, J.; Huang, J.; Zhan, H.
Tetrahedron Lett. 2014, 1589−1592.
(26) (a) So, C. M.; Lau, C. P.; Kwong, F. Y. Chem.Eur. J. 2011, 17,
761−765. (b) Yeung, P. Y.; Chung, K. H.; Kwong, F. Y. Org. Lett.
2011, 13, 2912−2915. (c) Lee, D. S.; Choy, P. Y.; So, C. M.; Wang, J.;
Lau, C. P.; Kwong, F. Y. RSC Adv. 2012, 2, 9179−9182. (d) Yuen, O.
Y.; So, C. M.; Wong, W. T.; Kwong, F. Y. Synlett 2012, 23, 2714−
2718.
(27) (a) Choy, P. Y.; Lau, C. P.; Kwong, F. Y. J. Org. Chem. 2011, 76,
80−84. (b) Wu, Y.; Li, B.; Mao, F.; Li, X.; Kwong, F. Y. Org. Lett.
2011, 13, 3258−3261. (c) Wu, Y.; Choy, P. Y.; Mao, F.; Kwong, F. Y.
Chem. Commun. 2013, 49, 689−691. (d) Yuen, O. Y.; Choy, P. Y.;
Chow, W. K.; Wong, W. T.; Kwong, F. Y. J. Org. Chem. 2013, 78,
3374−3378. (e) Wu, Y.; Wang, J.; Mao, F.; Kwong, F. Y. Chem.
Asian J. 2014, 9, 26−47.
(28) Armarego, W. L. F.; Perrin, D. D. In Purification of Laboratory
Chemicals, 4th ed.; Butterworth-Heinemann: Oxford, UK, 1996.
G
DOI: 10.1021/jo502386w
J. Org. Chem. XXXX, XXX, XXX−XXX