Copper-catalyzed intermolecular oxidative cyclization of haloalkynes: Synthesis of 2-halo-substituted imidazo [1,2-α]pyridines, imidazo [1,2-α]pyrazines and imidazo [1,2-α]pyrimidines

Article abstract of DOI:10.1002/adsc.201300157

An efficient copper-catalyzed method for the synthesis of 2-haloimidazopyridines with aminopyridines and haloalkynes using molecular oxygen as oxidant in a one-pot manner has been developed. In this process, the reaction appears to be very general and suitable for the construction of a variety of 2-halo-substituted imidazopyridines, imidazopyrazines and imidazopyrimidines. The intermolecular oxidative diamination of haloalkynes was achieved for the first time. Importantly, the mild reaction conditions and the efficient conversion of the alkyl-substituted haloalkynes are great improvements over the existing methods. Moreover, the resultant 2-haloimidazo- [1,2-α]pyridines could be efficiently converted to other functionalized imidazopyridine products via substitution, coupling reactions and other transformations, which further indicates potential applications of this method in synthetic and pharmaceutical chemistry.

Full text of DOI:10.1002/adsc.201300157

FULL PAPERS
DOI: 10.1002/adsc.201300157
Copper-Catalyzed Intermolecular Oxidative Cyclization of Halo-
alkynes: Synthesis of 2-Halo-substituted Imidazo
N
N
ACHTUNGTRENNUNG
Yang Gao,a Meizhou Yin,a Wanqing Wu,a,* Huawen Huang,a
and Huanfeng Jianga,*
a
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, Peopleꢀs
Republic of China
Fax : (+86)-20-8711-2906; e-mail: cewuwq@scut.edu.cn or jianghf@scut.edu.cn
Received: February 23, 2013; Revised: June 24, 2013; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300157.
Abstract: An efficient copper-catalyzed method for ing methods. Moreover, the resultant 2-haloimidazo-
the synthesis of 2-haloimidazopyridines with amino-
ACHTUNGTREN[NGNU 1,2-a]pyridines could be efficiently converted to
pyridines and haloalkynes using molecular oxygen as other functionalized imidazopyridine products via
oxidant in a one-pot manner has been developed. In substitution, coupling reactions and other transfor-
this process, the reaction appears to be very general mations, which further indicates potential applica-
and suitable for the construction of a variety of 2- tions of this method in synthetic and pharmaceutical
halo-substituted imidazopyridines, imidazopyrazines chemistry.
and imidazopyrimidines. The intermolecular oxida-
tive diamination of haloalkynes was achieved for the
first time. Importantly, the mild reaction conditions Keywords: aerobic oxidative cyclization; Cu-cata-
and the efficient conversion of the alkyl-substituted lyzed reaction; diamination; haloalkynes; imidazo-
haloalkynes are great improvements over the exist- pyridines
Introduction
strategies to construct molecules of this class.[6] While
Mosby[7a] and Kickhoffen[7b] opened the way to the
The imidazo
imidazo[1,2-a]pyrimidine skeletons are of great im- thetic methods for imidazo
portance in the area of pharmaceuticals and are also have been developed.[7] The normal approach to the
ACHTUNGTRENNUNG[1,2-a]pyridine, imidazoCAHTUNGTRENNNUG
A
ACHTUNGTRENNUNG
versatile building blocks for natural products, bioac- synthesis of imidazoACHTUNTRGNEUNG[1,2-a]pyridine is based on the in-
tive compounds, and drugs.[1] Accompanied by an ex- termolecular cyclization of 2-aminopyridines and
tensive range of bioactivities such as antiviral, anti- other precursors[8] such as a-bromoaldehydes,[8a] 1,3-
bacterial, fungicidal, and anti-inflammatory proper- diones,[8b] alkynes[8c–e] and nitroolefins.[8f] Other ele-
ties, the significance of these scaffolds in the drug dis- gant methods involve copper-catalyzed intramolecular
covery sector is well appreciated.[2] Common imidazo- dehydrogenative aminooxygenation or direct intramo-
À
ACHTUNGTRENNUNG[1,2-a]pyridine-derived drugs (Figure 1) include lecular C H amination using aminopyridine as a di-
alpidem, which is used to treat anxiety and insom- recting group.[9] Despite the achievements in this fas-
nia.[3] The imidazopyrimidine-derived drug I was re- cinating research area, the further development of ef-
cently identified as a full antagonist of the androgen ficient and practical procedures that enhance the
receptor, demonstrating excellent in-vivo tumor product diversity with easily accessible starting mate-
growth inhibition in castration-resistant prostate rials under mild reaction conditions to construct these
cancer (CRPC).[4] Also imidazopyridazine-derived frameworks remains highly desirable.
drug II as an AKT kinase inhibitor was used in the
On the other hand, haloalkynes are one of the most
treatment of neoplasms.[5] Their importance has important intermediates and versatile building blocks,
stimulated considerable attention from organic chem- especially as several mild and convenient methods
ists and encouraged the development of new synthetic have been developed and thus have increased the at-
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
ÞÞ
These are not the final page numbers!

Yang Gao et al.
FULL PAPERS
Figure 1. Imidazolepyridine, imidazopyrazine, imidazopyri-
midine-based drugs.
tractiveness of this class of compounds in organic syn-
thesis.[10] However, their halide atoms are usually dis-
carded, rendering these transformations non-atom
economic.[11] Therefore, to achieve the efficient trans-
Figure 2. The formation of imidazopyridine structure.
formations of haloalkynes while retaining the reactive imidazoACTHNUTRGNE[NUG 1,2-a]pyridines via a copper-catalyzed oxida-
halide substituents of the starting material is still a big tive cyclization reaction of o-aminopyridines and hal-
challenge. Recently, nucleophilic addition of haloal- oalkynes. A variety of 2-halo-substituted imidazopyri-
kynes and tandem carbon-carbon or/and carbon- dine, imidazopyrazine, imidazopyrimidine products
hetero bond formations via transition metal-catalyzed were obtained with high regioselectivity under mild
cross-coupling reactions have been applied to the syn- reaction conditions (Figure 2). Furthermore, the resul-
thesis of various heterocycles (Scheme 1a).[12] Further- tant 2-halo-substituted products could be easily func-
more, a series of transition metal-catalyzed nucleo- tionalized via elegant cross-coupling reactions,[14] thus
philic addition reactions of haloalkynes has been dis- making the nitrogen-containing heterocyclic products
closed in our group and by others to realize the di- a valuable synthon.
functionalization of terminal alkynes.[8k,13] Base on the
previous work, we envisoned that the intermolecular
oxidative diamination of haloalkynes could be ach- Results and Discussion
ieved via a transition metal-catalyzed nucleophilic ad-
À
dition followed by C N bond formation, in which the Our initial investigations of this Cu-catalyzed inter-
reactive halide substituent of the starting material was molecular oxidative cyclization reaction focused on
retained (Scheme 1b). Herein, we disclose a new and the cyclization of 2-aminopyridine (1a) with 1-bromo-
convenient protocol to construct 2-halo-substituted 2-phenylacetylene (2a) using CuACHTNURTGEN(UNG OTf)2 as catalyst in
Scheme 1. Synthesis of heterocycle compounds from haloalkynes.
2
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

Copper-Catalyzed Intermolecular Oxidative Cyclization of Haloalkynes
Table 1. Optimization of reaction conditions.[a]
Table 2. Synthesis of 2-bromoimidazoACTHNUTRGNEUNG
[1,2-a]pyridines.[a,b]
Entry [Cu]
Additive Solvent
Yield [%][b]
1
2
3
4
Cu
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
CuBr2
Cu(OAc)2
G
Cs2CO3
LiBr
NaOAc
HOPiv
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DMF
1,4-dioxane 50
toluene
1,4-dioxane 68
THF
DMSO
DMF
trace
58
10
36
82 (80)
72
47
58
60
65
5
–
–
–
–
–
–
–
–
–
–
–
–
6[c]
7
8
9
CuCl2
CuBr
CuCl
10[d]
11
12
13
14
15
16
Cu
Cu
Cu
Cu
Cu
N
n.d.
n.d.
trace
trace
[a]
Unless otherwise specified, all reactions were carried out
using 1a (0.3 mmol, 1.5 equiv.) and 2a (0.2 mmol,
1 equiv.) with catalyst (20 mol%) and additive (1 mmol)
in MeCN (2 mL) at 608C under 1 atm O2 for 12 h.
Determined by GC using dodecane as the internal stan-
dard. Data in parentheses are the yield of isolated prod-
uct. n.d=not detected.
[b]
[c]
[d]
[a]
[b]
1 equivalent of Cu
mosphere.
ACHTUGNRTEN(NUGN OTf)2 was used instead of an O2 at-
Reaction conditions: 2-aminopyridine 1a (0.3 mmol), bro-
moalkyne 2 (0.2 mmol), and Cu(OTf)2 (20 mol%) in
MeCN (2 mL) at 608C under 1 atm O2 for 12 h.
AHCTUNGTRENNUNG
At 808C for 6 h.
Isolated yield.
MeCN under an O2 atmosphere at 608C. Gratifyingly,
the desired 2-bromo-3-phenylimidazo[1,2-a]pyridine
N
Under the optimized reaction conditions, various
(3a) was obtained in 60% GC yield after 6 h. On pro- bromoalkynes
2
were tested to access the 2-
longing the reaction time to 12 h, a higher GC yield bromoimidazoAHCTUNGTERNGN[UN 1,2-a]pyridines (Table 2). In general,
(82%) was obtained (Table 1, entry 5). To further im- either electron-withdrawing or electron-donating sub-
prove the yields, various additives were examined; stituent groups or halogen groups, such as Me, OMe,
neither base nor acid additives could improve the F, Cl, and Br, on the aromatic ring of bromoalkyne
yields, such as Cs2CO3, NaOAc, LiBr and HOPiv were well tolerated in the reactions. Notably, Me- and
(Table 1, entries 1–4). Also base additives were found MeO-substituted bromoalkynes afforded lower yields,
to cause the homocoupling of the bromoalkyne in the indicating that the electron-deficient bromoalkynes
presence of the Cu catalyst. Next, different copper were more favorable for this transformation. The
salts were tested. Both Cu(I) catalysts (CuCl, CuBr) structures of 3e and 3f were further confirmed by X-
and Cu(II) catalysts [Cu
the desired products under an O2 atmosphere, and phenylacetylenes with substituents at the ortho, meta,
Cu(OTf)2 proved to be optimal (entries 7–11). The or para position of the aromatic ring could react
(OAc)2, CuBr2] could afford ray diffraction (Figure 3).[15] Meanwhile, 1-bromo-2-
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
solvent was found to have a dramatic impact on the smoothly to afford the desired products 3f and 3g in
efficiency of the reaction (entries 12–16). Notably, tol- 71% and 59% isolated yields, respectively. Important-
uene and THF were found to be totally inefficient ly, alkyl-substituted bromoalkynes could also be trans-
and MeCN was identified as the most suitable formed into the corresponding products 3l–3q in mod-
medium for the formation of 3a. Thus, the optimal erate to good yields. Moreover, various 2-aminopyri-
catalytic system for this copper-catalyzed aerobic oxi- dines with different substituents were found to be
dative cyclization of haloalkyne was: 1a (0.3 mmol), suitable reaction partners for this transformation. 2-
2a (0.2 mmol), Cu
ACHTUNGTRENNUNG
at 608C under 1 atm O2 atmosphere for 12 h.
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3
ÞÞ
These are not the final page numbers!

Yang Gao et al.
FULL PAPERS
Figure 3. X-ray structures of compounds 3e and 3f.
went this oxidative cyclization reaction to form the Table 3. Synthesis of 2-bromo-substituted imidazopyrazine,
imidazopyrimidine and imidazoisoquinoline skeletons.[a,b]
corresponding products 3i, 3j, 3m in good yields.
However, 2-amino-6-methylpyridine (3k) was found
to be totally inefficient for this reaction, which might
be due to the steric hindrance of the 6-methyl group.
Halogen groups substituted on the aromatic ring of 2-
aminopyridine were also well tolerated (3p and 3q),
which provided the possibility for further functionali-
zation.
To further demonstrate the synthetic potential of
this methodology, various o-amino-nitrogen-contain-
ing heterocycles were introduced to this oxidative cyc-
lization reaction (Table 3). Apart from 2-aminopyri-
dines, anthranilic-substituted pyridazines, pyrazines,
isoquinolines and pyrimidines could also be trans-
formed to the cyclization products (4a–4j) in moder-
ate to good yields (52–76%). Gratifyingly, all the
tested substrates could react with both alkyl- and
aryl-substituted bromoalkynes to afford the desired
products under the optimized conditions. To the best
of our knowledge, there are only few examples of
using o-amino-nitrogen-containing heterocycles in the
oxidative cyclization reaction.
Next, the iodine-substituted (5a–5g) and chloro-
substituted (5h and 5i) imidazoACTHUNTGRNEUNG[1,2-a]pyridines were
[a]
[b]
Reaction conditions: 1b (0.3 mmol), bromoalkyne
2
obtained in moderate to good yields by switching one
of the reaction partners from bromoalkyne to chlor-
oalkyne and iodoalkyne (Table 4). In general, chlor-
oalkyne afforded lower yields of the desired products,
compared with iodoalkyne. This result might, in part,
(0.2 mmol), and Cu(OTf)2 (20 mol%) in MeCN (2 mL)
AHCTUNGTRENNUNG
at 608C under 1 atm O2 for 12 h.
Isolated yield.
be caused by different atomic radii and the electron- Moreover, compound 7c containing a higly conjugat-
withdrawing ability of the halogen atom. ed structure was successfully synthesized after three-
Halogenated aromatics are kown to be efficient re- step modifications (Scheme 3). The practicality of this
action partners for a variety of classic coupling reac- copper-catalyzed oxidative cyclization reaction should
tions.[16] To investigate the synthetic utility of the lead to potential utilities in optoelectronic materi-
products, we studied Suzuki, Kumada, and Sonoga- als.[17]
shira reactions using the obtained 2-haloimidazo
[1,2-
According to the above results and the previous re-
a]pyridines as reaction partners (Scheme 2). And the ports,[18] the possible reaction mechanism for this
corresponding arylation 6a, 6b, 6e and alkynylation copper-catalyzed oxidative cyclization reaction is pro-
6c, 6d products could be achieved in excellent yields. posed (Scheme 4). The reaction was likely to be initi-
4
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

Copper-Catalyzed Intermolecular Oxidative Cyclization of Haloalkynes
Table 4. Synthesis of 2-haloimidazoACTHNUTRGNEUNG
[1,2-a]pyridines.[a,b]
Scheme 3. Synthesis of compound 7c.
[a]
Reaction conditions: 2-aminopyridine 1a (0.3 mmol),
haloalkyne 2 (0.2 mmol), and Cu(OTf)2 (20 mol%) in
AHCTUNGTRENNUNG
MeCN (2 mL) at 608C under 1 atm O2 for 12 h.
Isolated yield.
[b]
Scheme 4. Proposed mechanism.
ated by the coordination of 2-aminopyridine to
Cu
ry insertion of haloalkyne occurred to form the new
(OTf)2, providing intermediate 9.[19] Then, migrato-
ACHTUNGTRENNUNG
2
[20]
À
CACHTUNGTRENNUNG
AHCTUNGTRENNUNG
mediate 11.[21] Finally, the reductive elimination of 11
afforded the cyclization product 12.[22] Although an-
other mechanistic scenario involving single electron
transfer might also be possible, the radical-trapping
experiments indicated that the radical scavengers,
such as TEMPO and 1,1-diphenylethylene did not
retard the present reaction. Thus, the organocopper
pathway was more preferred for this transformation.
Scheme 2. Investigation of the synthetic utility of the 2-
bromoimidazo[1,2-a]pyridine products.
ACHTUNGTRENNUNG
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
5
ÞÞ
These are not the final page numbers!

Yang Gao et al.
FULL PAPERS
Conclusions
ESI-HR-MS: m/z=273.0025, calcd. for C13H9BrN2 (M+
H)+: 273.0021.
2-Bromo-3-(4-fluorophenyl)imidazo
White solid; mp 170–1718C; IR (KBr): n=2930, 2859, 1645,
1578, 1516, 1378, 1237, 1166, 894, 787, 750, 671 cmÀ1
ACHTUNGERTN[NUNG 1,2-a]pyridine (3b):
In summary, we have developed a new and efficient
method to construct various 2-halo-substituted
;
imidazo
imidazoACHTUNGTRENNUNG
N
ACHTUNGTREN[NUNG 1,2-a]pyrazines and
1H NMR (400 MHz, CDCl3): d=8.05 (t, J=9.6 Hz, 1H),
7.61 (t, J=8.5 Hz, 1H), 7.59–7.53 (m, 2H), 7.32–7.22 (m,
3H), 6.84 (td, J=6.9, 0.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=162.8 (d, J=248.3 Hz), 144.6, 131.7 (d, J=
8.3 Hz), 125.2, 123.6, 123.0, 122.4, 117.3, 116.5, 116.3, 113.1;
ESI-HR-MS: m/z=290.9925, calcd. for C13H8BrFN2 (M+
H)+: 290.9927.
dative cyclization reaction of haloalkynes. The mild
reaction conditions and the efficient conversion of the
alkyl-substituted haloalkynes are great improvements
over existing methods. Also the intermolecular oxida-
tive diamination of haloalkynes was achieved for the
2-Bromo-3-(4-chlorophenyl)imidazoACTHNUTRGNEUNG[1,2-a]pyridine (3c):
first time. Moreover, the resultant 2-haloimidazoACTHUNTGRNEUNG[1,2-
White solid; mp 179–1808C; IR (KBr): n=2927, 2856, 1653,
a]pyridines could be efficiently converted to other
functionalized imidazopyridine products through sub-
stitution, cross-coupling reactions and other transfor-
mations. Therefore, this reaction is an attractive
1
1611, 1502, 1387, 1228, 1164, 924, 752, 673 cmÀ1; H NMR
(400 MHz, CDCl3): d=8.07 (d, J=6.9 Hz, 1H), 7.59 (d, J=
9.1 Hz, 1H), 7.54–7.48 (m, 4H), 7.26–7.20 (m, 1H), 6.83 (t,
J=6.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=144.7,
134.9, 130.8, 129.5, 126.0, 125.3, 122.9, 122.4, 121.0, 117.3,
113.2; ESI-HR-MS: m/z=306.9640, calcd. for C13H8BrClN2
(M+H)+: 306.9632.
method to prepare 2-halo-substituted imidazoACTHNUGTRNEUNG[1,2-
a]pyridine skeletons and should find potential appli-
cations in the preparation of more complex and sig-
nificant pharmaceuticals.
2-Bromo-3-(4-bromophenyl)imidazoACTHNUTRGNEUNG[1,2-a]pyridine (3d):
White solid; mp 187–1888C; IR (KBr): n=2924, 2853, 1698,
1
1607, 1500, 1347, 1226, 1161, 914, 749, 670 cmÀ1; H NMR
Experimental Section
(400 MHz, CDCl3): d=8.08 (d, J=6.9 Hz, 1H), 7.69 (d, J=
8.5 Hz, 2H), 7.62 (d, J=9.1 Hz, 1H), 7.45 (d, J=8.5 Hz,
2H), 7.28–7.21 (m, 1H), 6.84 (t, J=6.9 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=144.7, 132.5, 131.1, 126.5, 125.3,
123.1, 123.0, 122.5, 121.0, 117.4, 113.2; ESI-HR-MS: m/z=
350.9126, calcd. for C13H8Br2N2 (M+H)+: 350.9128.
General Methods
TLC was performed by using commercially prepared 100–
400 mesh silica gel plates (GF254) and visualization was ef-
fected at 254 nm. All the haloalkynes were prepared accord-
ing to the literature. Other reagents were purchased as re-
agent grade and used without further purification. Melting
points were measured with a Bꢂchi B-545 melting point in-
strument and are uncorrected. IR spectra were obtained as
potassium bromide pellets or as liquid films between two
potassium bromide pellets. 1H and 13C NMR spectra were
recorded on a 400 MHz spectrometer using CDCl3 as sol-
vent and TMS as an internal standard. The chemical shifts
were referenced to signals at 0.00 and 77.0 ppm, respective-
ly.
2-Bromo-3-(4-methoxyphenyl)imidazo
(3e): White solid; mp 162–1638C; IR (KBr): n=2917, 2849,
1677, 1583, 1499, 1347, 1249, 1169, 931, 739, 670 cmÀ1
ACHTUNGTREN[NGNU 1,2-a]pyridine
;
1H NMR (400 MHz, CDCl3): d=8.05 (d, J=6.8 Hz, 1H),
7.57 (d, J=9.0 Hz, 1H), 7.46 (d, J=8.7 Hz, 2H), 7.18 (dd,
J=18.4, 10.6 Hz, 1H), 7.07 (d, J=8.7 Hz, 2H), 6.78 (t, J=
6.8 Hz, 1H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3): d=
160.0, 131.0, 129.1, 124.8, 123.1, 122.0, 119.5, 117.1, 114.6,
114.0, 112.8, 55.3; ESI-HR-MS: m/z=303.0126, calcd. for
C14H11BrN2O (M+H)+: 303.0127.
2-Bromo-3-(3-chlorophenyl)imidazoACTHNUTRGNEUNG[1,2-a]pyridine (3f):
White solid; mp 170–1718C; IR (KBr): n=2927, 2856, 1653,
1636, 1521, 1387, 1228, 1164, 924, 763, 678 cmÀ1; H NMR
1
General Procedure for the Synthesis of 2-Bromo-
imidazoACHTUNGTRENNUNG[1,2-a]pyridines
(400 MHz, CDCl3): d=8.10 (d, J=6.9 Hz, 1H), 7.61–7.51
(m, 2H), 7.52–7.38 (m, 3H), 7.27–7.18 (m, 1H), 6.83 (t, J=
6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=144.6, 134.9,
130.4, 129.3, 129.2, 128.9, 127.6, 125.4, 122.9, 122.5, 120.6,
117.2, 113.2; ESI-HR-MS: m/z=306.9637, calcd for
C13H8BrClN2 (M+H)+: 306.9632.
A mixture of 2-aminopyridine 1a (0.3 mmol, 1.5 equiv.), 1-
bromo-2-phenylacetylene 2a (0.2 mmol, 1 equiv.) and
CuACHTUNGTRENNUNG(OTf)2 (20 mol%) was stirred in MeCN (2 mL) at 608C
under an oxygen atmosphere for 12 h. And then the 10 mL
of water were added to quench the reaction. The aqueous
solution was extracted with diethyl ether (3ꢃ10 mL) and
the combined extract was dried with anhydrous MgSO4. The
solvent was removed and the crude product was separated
by flash column chromatography on silica gel to give the
pure product.
2-Bromo-3-(2,4-dimethylphenyl)imidazo
(3g): Light yellow solid; mp 151–1528C; IR (KBr): n=2919,
2851, 1678, 1597, 1503, 1345, 1216, 1159, 925, 754, 675 cmÀ1
ACHTUNGTREN[NGNU 1,2-a]pyridine
;
1H NMR (400 MHz, CDCl3): d=7.60 (dd, J=5.5, 4.4 Hz,
2H), 7.24–7.20 (m, 3H), 7.16 (d, J=7.8 Hz, 1H), 6.77 (dd,
J=10.2, 4.3 Hz, 1H), 2.42 (s, 3H), 2.08 (s, 3H); 13C NMR
(100 MHz, CDCl3): d=144.4, 140.0, 138.8, 131.5, 131.5,
127.2, 124.7, 123.5, 122.6, 122.1, 117.0, 112.7, 21.3, 19.3; ESI-
HR-MS: m/z=301.0329, calcd. for C15H13BrN2 (M+H)+:
301.0334.
2-Bromo-3-phenylimidazo
solid; mp 156–1578C; IR (KBr): n=2924, 2853, 1698, 1607,
1500, 1347, 1230, 1161, 914, 749, 670 cmÀ1 1H NMR
ACHTUNGTNER[NUNG 1,2-a]pyridine (3a): White
;
(400 MHz, CDCl3): d=8.07 (d, J=6.9 Hz, 1H), 7.58–7.47
(m, 5H), 7.46–7.40 (m, 1H), 7.20–7.15 (m, 1H), 6.76 (td, J=
6.9, 0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=144.3,
129.3, 128.9, 128.7, 127.2, 124.9, 122.9, 121.9, 116.9, 112.8;
2-Bromo-6-chloro-3-(4-chlorophenyl)imidazo
dine (3h): White solid; mp 189–1908C; IR (KBr): n=2930,
2863, 1657, 1630, 1511, 1376, 1241, 1152, 918, 752, 673 cmÀ1
ACHTUNGTREN[NUNG 1,2-a]pyri-
;
6
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

Copper-Catalyzed Intermolecular Oxidative Cyclization of Haloalkynes
1H NMR (400 MHz, CDCl3): d=8.09 (s, 1H), 7.55 (d, J=
8.5 Hz, 3H), 7.49 (d, J=8.5 Hz, 2H), 7.21 (d, J=8.3 Hz,
1H); 13C NMR (100 MHz, CDCl3): d=135.4, 131.7, 131.6,
130.8, 129.7, 126.7, 121.8, 120.9, 117.7, 116.8, 116.5; ESI-HR-
MS: m/z=340.9246, calcd. for C13H7BrCl2N2 (M+H)+:
340.9242.
127.0, 122.7, 122.0, 121.0, 120.6, 112.5, 31.4, 28.7, 27.0, 23.3,
22.4, 16.8, 13.9; ESI-HR-MS: m/z=295.0807, calcd. for
C14H19BrN2 (M+H)+: 295.0804.
2-Bromo-7-chloro-3-hexylimidazo
G
(3p):
White solid; mp 143–1458C; IR (KBr): n=2928, 2857, 1702,
1
1607, 1502, 1347, 1256, 1161, 914, 749, 725 cmÀ1; H NMR
2-Bromo-8-methyl-3-phenylimidazo
N
(3i):
(400 MHz, CDCl3): d=7.81 (d, J=7.3 Hz, 1H), 7.51 (d, J=
1.6 Hz, 1H), 6.83 (dd, J=7.3, 2.0 Hz, 1H), 2.88 (t, J=
7.5 Hz, 2H), 1.65–1.55 (m, 2H), 1.38–1.24 (m, 6H), 0.88 (t,
J=6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=143.6,
130.5, 123.0, 122.5, 122.2, 115.9, 114.1, 31.4, 28.7, 27.0, 23.1,
22.4, 13.9; ESI-HR-MS: m/z=315.0256, calcd. for
C13H16BrClN2 (M+H)+: 315.0258.
White solid; mp 158–1598C; IR (KBr): n=2927, 2895, 1654,
1587, 1523, 1368, 1240, 1175, 854, 787, 674 cmÀ1; H NMR
(400 MHz, CDCl3): d=7.95 (dd, J=16.5, 7.3 Hz, 1H), 7.49
(s, 4H), 7.49–7.42 (m, 1H), 7.01 (d, J=6.8 Hz, 1H), 6.71 (t,
J=6.9 Hz, 1H), 2.62 (s, 3H); 13C NMR (100 MHz, CDCl3):
d=145.0, 129.6, 129.1, 128.3, 127.8, 127.1, 124.0, 122.5, 121.5,
121.0, 113.0, 16.9; ESI-HR-MS: m/z=287.0180, calcd. for
C14H11BrN2 (M+H)+: 287.0178.
2-Bromo-6-chloro-3-hexylimidazo
G
(3q):
White solid; mp 147–1498C; IR (KBr): n=2930, 2857, 1699,
1
2-Bromo-7-methyl-3-phenylimidazo
N
(3j):
1577, 1500, 1347, 1226, 1160, 920, 749, 723 cmÀ1; H NMR
White solid; mp 155–1568C; IR (KBr): n=2928, 2897, 1656,
(400 MHz, CDCl3): d=7.90 (s, 1H), 7.46 (s, 1H), 7.10 (dd,
J=9.5, 1.5 Hz, 1H), 2.86 (t, J=7.5 Hz, 2H), 1.66–1.55 (m,
2H), 1.40–1.23 (m, 6H), 0.87 (t, J=6.7 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=142.3, 125.0, 122.7, 122.5, 121.0,
120.5, 117.4, 31.3, 28.7, 26.8, 23.2, 22.4, 13.9; ESI-HR-MS:
m/z=315.0252, calcd. for C13H16BrClN2 (M+H)+: 315.0258.
1
1589, 1524, 1369, 1242, 1175, 854, 787, 670 cmÀ1; H NMR
(400 MHz, CDCl3): d=8.00 (d, J=7.1 Hz, 1H), 7.60–7.51
(m, 4H), 7.47 (dd, J=5.7, 2.5 Hz, 1H), 7.34 (s, 1H), 6.63 (d,
J=6.9 Hz, 1H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3):
d=145.0, 129.6, 129.1, 128.8, 127.8, 127.1, 124.0, 122.5, 121.5,
121.0, 113.0, 16.9; ESI-HR-MS: m/z=287.0182, calcd. for
C14H11BrN2 (M+H)+: 287.0178.
2-Bromo-7-chloro-3-hexylimidazo
White solid; mp 169–1708C; IR (KBr): n=2975, 2900, 2360,
1638, 1507, 1384, 1213, 1051, 751, 727 cmÀ1 1H NMR
ACHTUNGERTN[NUNG 1,2-b]pyridazine (4a):
2-Bromo-3-hexylimidazo
mp 124–1258C; IR (KBr): n=2928, 2857, 1699, 1567, 1500,
1347, 1226, 1161, 914, 749 cmÀ1 1H NMR (400 MHz,
A
;
(400 MHz, CDCl3): d=7.80 (d, J=9.4 Hz, 1H), 7.03 (d, J=
9.4 Hz, 1H), 3.02–2.98 (m, 2H), 1.76–1.67 (m, 2H), 1.40–
1.29 (m, 6H), 0.89 (t, J=7.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=146.9, 136.5, 128.3, 125.7, 123.2, 118.0, 31.4, 28.8,
26.8, 22.9, 22.5, 14.0; ESI-HR-MS: m/z=316.0216, calcd. for
C12H15BrClN3 (M+H)+: 316.0210.
;
CDCl3): d=7.89 (d, J=6.9 Hz, 1H), 7.54 (d, J=9.1 Hz, 1H),
7.19–7.13 (m, 1H), 6.84 (td, J=6.8, 0.9 Hz, 1H), 2.91 (t, J=
7.5 Hz, 2H), 1.68–1.59 (m, 2H), 1.41–1.23 (m, 6H), 0.88 (t,
J=7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=144.1,
123.8, 122.7, 121.8, 117.2, 112.5, 31.5, 28.8, 27.0, 23.2, 22.5,
14.0; ESI-HR-MS: m/z=2281.0645, calcd. for C13H17BrN2
(M+H)+: 281.0647.
2-Bromo-7-chloro-3-phenylimidazo
White solid; mp 177–1798C; IR (KBr): n=2974, 2901, 2360,
1637, 1507, 1384, 1213, 1051, 751, 670 cmÀ1 1H NMR
ACHTUNGERTN[NUNG 1,2-b]pyridazine (4b):
;
2-Bromo-3-hexyl-6-methylimidazo
U
(3m):
(400 MHz, CDCl3): d=7.88 (d, J=9.4 Hz, 1H), 7.83 (d, J=
7.4 Hz, 2H), 7.54 (t, J=7.5 Hz, 2H), 7.47 (t, J=7.4 Hz, 1H),
7.11 (t, J=8.7 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=
147.3, 137.0, 129.4, 129.2, 128.9, 128.5, 126.2, 126.0, 119.4;
ESI-HR-MS: m/z=307.9583, calcd. for C12H7BrClN3 (M+
H)+: 307.9584.
White solid; mp 136–1388C; IR (KBr): n=2917, 2836, 1699,
1578, 1500, 1347, 1216, 1161, 910, 750, 720 cmÀ1; H NMR
1
(400 MHz, CDCl3): d=7.68 (s, 1H), 7.48 (d, J=9.2 Hz, 1H),
7.05 (d, J=9.1 Hz, 1H), 2.89 (dd, J=14.6, 7.1 Hz, 2H), 2.38
(s, 3H), 1.64 (dt, J=15.1, 7.4 Hz, 2H), 1.36 (dd, J=22.6,
7.6 Hz, 6H), 0.92 (d, J=6.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=143.0, 127.2, 122.4, 121.6, 120.5, 116.4, 31.5, 28.8,
27.0, 23.2, 22.6, 18.4, 14.0; ESI-HR-MS: m/z=295.0809,
calcd. for C14H19BrN2 (M+H)+: 295.0804.
2-Bromo-7-chloro-3-hexylimidazoACHTUNTRGNEUNG[1,2-c]pyrimidine (4c):
White solid; mp 161–1628C; IR (KBr): n=2978, 2360, 1640,
1
1505, 1384, 1214, 1054, 753, 722 cmÀ1; H NMR (400 MHz,
CDCl3): d=7.79 (d, J=9.4 Hz, 1H), 7.03 (t, J=8.1 Hz, 1H),
2.98 (t, J=7.5 Hz, 2H), 1.69 (dd, J=14.4, 7.1 Hz, 2H), 1.40–
1.21 (m, 6H), 0.88 (t, J=6.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=146.8, 136.4, 128.2, 125.6, 123.2, 117.9, 31.3, 28.7,
26.7, 22.9, 22.4, 13.9; ESI-HR-MS: m/z=316.0213, calcd. for
C12H15BrClN3 (M+H)+: 316.0210.
2-Bromo-8-fluoro-3-hexylimidazo
N
(3n):
White solid; mp 140–1418C; IR (KBr): n=2929, 2857, 1699,
1557, 1500, 1349, 1236, 1160, 915, 749, 723 cmÀ1; H NMR
1
(400 MHz, CDCl3): d=7.74 (d, J=6.8 Hz, 1H), 6.88 (dd, J=
9.6, 8.2 Hz, 1H), 6.79 (td, J=7.2, 4.6 Hz, 1H), 2.91 (t, J=
7.6 Hz, 2H), 1.69–1.55 (m, 2H), 1.40–1.20 (m, 6H), 0.89 (t,
J=6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=150.84 (d,
J=253.1 Hz), 136.58 (d, J=28.4 Hz), 123.78, 121.90, 119.15
(d, J=4.9 Hz), 111.7 (d, J=6.8 Hz), 106.65 (d, J=16.3 Hz),
31.40, 28.75, 26.95, 23.50, 22.47, 13.95; ESI-HR-MS; m/z=
299.0550, calcd. for C13H16BrFN2 (M+H)+: 299.0553.
2-Bromo-7-chloro-3-phenylimidazoACTHNUTRGNEUNG[1,2-c]pyrimidine (4d):
White solid; mp 167–1688C; IR (KBr): n=2975, 2360, 1637,
1
1500, 1385, 1211, 1058, 754, 673 cmÀ1; H NMR (400 MHz,
CDCl3): d=7.88 (d, J=9.4 Hz, 1H), 7.83 (d, J=7.4 Hz, 2H),
7.55 (t, J=7.5 Hz, 2H), 7.47 (t, J=7.4 Hz, 1H), 7.11 (d, J=
9.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=147.3, 137.0,
129.4, 129.2, 128.5, 127.4, 126.2, 126.1, 123.5, 119.4; ESI-HR-
MS: m/z=307.9587, calcd. for C12H7BrClN3 (M+H)+:
307.9584.
2-Bromo-3-hexyl-8-methylimidazo
(3o):
White solid; mp 137–1398C; IR (KBr): n=2927, 2856, 1701,
1578, 1500, 1348, 1216, 1163, 917, 750, 720 cmÀ1; H NMR
1
(400 MHz, CDCl3): d=7.75 (d, J=6.8 Hz, 1H), 6.94 (d, J=
6.9 Hz, 1H), 6.74 (t, J=6.9 Hz, 1H), 2.88 (t, J=7.5 Hz, 2H),
2.57 (s, 3H), 1.68–1.54 (m, 2H), 1.39–1.26 (m, 6H), 0.88 (dd,
J=9.2, 4.7 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=144.5,
2-Bromo-3-hexylimidazoACTHGNUTERNNU[G 1,2-a]pyrazine (4e): White solid;
mp 131–1338C; IR (KBr): n=2974, 2901, 2360, 1637, 1384,
1
1213, 1051, 751, 724 cmÀ1; H NMR (400 MHz, CDCl3): d=
8.99 (s, 1H), 7.93 (d, J=4.4 Hz, 1H), 7.85 (d, J=4.3 Hz,
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
7
ÞÞ
These are not the final page numbers!

Yang Gao et al.
FULL PAPERS
1H), 2.94 (t, J=7.6 Hz, 2H), 1.71–1.60 (m, 2H), 1.40–1.22
(m, 6H), 0.89 (t, J=6.7 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=142.8, 129.8, 124.6, 124.2, 115.7, 31.4, 28.8, 27.0,
23.0, 22.5, 14.0; ESI-HR-MS: m/z=282.0603, calcd. for
C12H16BrN3 (M+H)+: 282.0600.
2-Iodo-8-methyl-3-phenylimidazo
G
(5b):
White solid; mp 145–1478C; IR (KBr): n=2930, 2890, 1656,
1585, 1521, 1369, 1243, 1176, 854, 787, 676 cmÀ1; H NMR
1
(400 MHz, CDCl3): d=7.94 (d, J=7.0 Hz, 0H), 7.55–7.51
(m, 1H), 7.47–7.40 (m, 0H), 7.34 (s, 0H), 6.57 (dd, J=7.1,
1.1 Hz, 0H), 2.39 (s, 1H); 13C NMR (100 MHz, CDCl3): d=
147.2, 136.0, 129.9, 129.1, 128.9, 128.8, 128.5, 127.1, 122.3,
115.4, 115.3, 93.1, 21.2; ESI-HR-MS: m/z=335.0038, calcd.
for C14H11IN2 (M+Na)+: 335.0039.
2-Iodo-7-methyl-3-phenylimidazo
cous liquid; IR (KBr): n=2927, 2895, 1657, 1589, 1523,
1369, 1242, 1175, 854, 787, 677 cmÀ1 1H NMR (400 MHz,
CDCl3): d=7.92 (t, J=5.8 Hz, 1H), 7.55–7.48 (m, 4H),
7.48–7.41 (m, 1H), 7.33 (s, 1H), 6.56 (dd, J=7.1, 1.4 Hz,
1H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3): d=147.2,
136.0, 129.9, 129.1, 128.9, 128.8, 128.5, 127.1, 122.3, 115.4,
115.3, 93.1, 21.2; ESI-HR-MS: m/z=335.0036, calcd. for
C14H11IN2 (M+Na)+: 335.0039.
2-Bromo-3-phenylimidazo
solid; mp 159–16058C; IR (KBr): n=2976, 2360, 1630, 1320,
1236, 1186, 1129, 974, 834, 652 cmÀ1 1H NMR (400 MHz,
ACHTUNGTNER[NUNG 1,2-a]pyrimidine (4f): White
;
CDCl3): d=8.56 (d, J=2.0 Hz, 1H), 8.45 (d, J=6.8 Hz, 1H),
7.62–7.54 (m, 4H), 7.50 (dd, J=8.5, 4.6 Hz, 1H), 6.92 (dd,
J=6.3, 4.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=150.1,
147.2, 130.6, 129.4, 129.3, 126.4, 124.4, 121.1, 109.4; ESI-HR-
MS: m/z=273.9978, calcd. for C12H8BrN3 (M+Na)+:
273.9974.
2-Bromo-3-hexylimidazo
solid; mp 138–1408C; IR (KBr): n=2977, 2360, 1660, 1501,
1319, 1193, 1031, 976, 839, 720 cmÀ1 1H NMR (400 MHz,
ACHTUNGTNER[NUNG 1,2-a]pyrimidine (4g): White
;
CDCl3): d=8.52–8.49 (m, 1H), 8.26 (dd, J=6.8, 1.2 Hz,
1H), 6.94 (dd, J=6.5, 4.2 Hz, 1H), 2.91 (t, J=7.5 Hz, 2H),
1.67–1.59 (m, 2H), 1.38–1.25 (m, 6H), 0.88 (t, J=6.7 Hz,
3H); 13C NMR (100 MHz, CDCl3): d=148.8, 146.8, 130.2,
124.3, 121.0, 108.9, 31.4, 28.7, 27.1, 23.0, 22.4, 13.9; ESI-HR-
MS: m/z=282.0605, calcd. for C12H16BrN3 (M+H)+:
282.0600, found .
3-Hexyl-2-iodoimidazo
N
Viscous
liquid; IR (KBr): n=2938, 2849, 1679, 1567, 1490, 1348,
1
1236, 1160, 915, 729 cmÀ1; H NMR (400 MHz, CDCl3): d=
7.90 (d, J=6.9 Hz, 1H), 7.55 (d, J=9.1 Hz, 1H), 7.15–7.09
(m, 1H), 6.80 (td, J=6.8, 0.7 Hz, 1H), 2.90 (t, J=7.6 Hz,
2H), 1.67–1.57 (m, 2H), 1.43–1.28 (m, 6H), 0.90 (t, J=
7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=146.5, 126.5,
123.6, 122.6, 117.1, 112.3, 93.4, 31.5, 28.8, 27.2, 24.5, 22.5,
14.0; ESI-HR-MS: m/z=329.0512, calcd. for C13H17IN2 (M+
H)+: 329.0509.
2-Bromo-3-(2,4-dimethylphenyl)imidazo
(4h): White solid; mp 156–1578C; IR (KBr): n=2978, 2358,
1641, 1389, 1015, 1237, 1192, 779, 726 cmÀ1 1H NMR
ACHTUNGTREN[NUGN 1,2-a]pyrimidine
;
(400 MHz, CDCl3): d=8.57 (dd, J=3.5, 1.6 Hz, 1H), 7.94
(dd, J=6.8, 1.2 Hz, 1H), 7.25–7.14 (m, 3H), 6.89 (dd, J=6.4,
4.2 Hz, 1H), 2.42 (s, 3H), 2.09 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=149.7, 147.2, 140.5, 138.7, 131.7, 131.4, 130.9,
127.4, 125.1, 122.4, 121.1, 109.2, 21.3, 19.4; ESI-HR-MS: m/
z=302.0285, calcd. for C14H12BrN3 (M+H)+: 302.0287.
6-Chloro-2-iodo-3-phenylimidazo
N
(5e):
White solid; mp 149–1518C; IR (KBr): n=2928, 2857, 1702,
1577, 1500, 1347, 1226, 1161, 914, 745, 672 cmÀ1; H NMR
1
(400 MHz, CDCl3): d=8.07 (d, J=1.0 Hz, 1H), 7.60–7.48
(m, 6H), 7.14 (dd, J=9.5, 1.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=145.1, 129.9, 129.4, 129.3, 128.8, 127.6, 127.4,
126.2, 121.4, 120.9, 117.4, 94.4; ESI-HR-MS: m/z=354.9498,
calcd. for C13H8ClIN2 (M+H)+: 354.9493.
2-Bromo-3-hexylimidazoACTHNUTRGENU[GN 2,1-a]isoquinoline (4i): White
solid; mp 166–1678C; IR (KBr): n=3054, 2927, 2856, 2360,
1
1577, 1512, 1376, 1161, 894, 787 cmÀ1; H NMR (400 MHz,
CDCl3): d=8.58 (d, J=8.0 Hz, 1H), 7.66 (dd, J=7.5, 3.7 Hz,
2H), 7.62–7.57 (m, 1H), 7.55–7.49 (m, 1H), 7.04 (d, J=
7.3 Hz, 1H), 2.87 (t, J=7.5 Hz, 2H), 1.67–1.57 (m, 2H),
1.39–1.27 (m, 6H), 0.88 (dd, J=9.3, 4.7 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=141.7, 128.7, 128.2, 128.1, 126.8,
123.8, 123.0, 122.9, 120.2, 118.7, 113.2, 31.4, 28.7, 27.7, 23.2,
22.5, 14.0; ESI-HR-MS: m/z=331.0808, calcd. for
C17H19BrN2 (M+H)+: 331.0804.
8-Fluoro-2-iodo-3-phenylimidazo
[1,2-a]pyridine
(5f):
White solid; mp 153–1558C; IR (KBr): n=2924, 2857, 1685,
1577, 1500, 1348, 1237, 1161, 914, 745, 673 cmÀ1; H NMR
1
(400 MHz, CDCl3): d=7.87 (d, J=6.6 Hz, 1H), 7.60–7.47
(m, 5H), 6.93–6.84 (m, 1H), 6.69 (td, J=7.3, 4.6 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=150.6 (d, J=253.5 Hz),
139.4 (d, J=28.4 Hz), 130.0, 129.4, 129.2, 128.6, 127.8, 119.5
(d, J=5.2 Hz), 111.9 (d, J=6.7 Hz), 107.4 (d, J=16.1 Hz),
93.4; ESI-HR-MS: m/z=338.9785, calcd. for C13H8FIN2
(M+Na)+: 338.9788.
2-Bromo-3-phenylimidazo
solid; mp 183–1858C; IR (KBr): n=3054, 2927, 1731, 1577,
1512, 1376, 1161, 894, 787 cmÀ1 1H NMR (400 MHz,
ACHTUNGTRNE[NUNG 2,1-a]isoquinoline (4j): White
;
3-Butyl-2-iodoimidazoACTHUNGTERNNU[G 1,2-a]pyridine (5g): Viscous liquid;
CDCl3): d=8.67 (d, J=8.0 Hz, 1H), 7.86 (d, J=7.4 Hz, 1H),
7.69 (d, J=7.8 Hz, 1H), 7.64 (t, J=7.4 Hz, 1H), 7.57 (q, J=
7.8 Hz, 5H), 7.49 (dd, J=8.7, 4.7 Hz, 1H), 7.03 (d, J=
7.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=142.3, 129.8,
129.3, 129.1, 129.0, 128.6, 128.5, 127.5, 126.8, 124.3, 123.4,
123.0, 120.7, 119.2, 113.6; ESI-HR-MS: m/z=323.0175,
calcd. for C17H12BrN2 (M+H)+: 323.0178.
IR (KBr): n=2928, 2857, 1699, 1567, 1500, 1347, 1226, 1160,
1
915, 725 cmÀ1; H NMR (400 MHz, CDCl3): d=7.89 (d, J=
6.9 Hz, 1H), 7.53 (d, J=9.1 Hz, 1H), 7.13–7.08 (m, 1H),
6.79 (td, J=6.8, 0.8 Hz, 1H), 2.89 (t, J=7.6 Hz, 2H), 1.65–
1.54 (m, 2H), 1.46–1.35 (m, 2H), 0.95 (t, J=7.3 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=146.4, 126.4, 123.5, 122.5,
117.0, 112.3, 93.3, 29.3, 24.1, 22.2, 13.8; ESI-HR-MS: m/z=
301.0198, calcd. for C11H13IN2 (M+H)+: 301.0196.
2-Iodo-3-phenylimidazoACTHUNRGTNE[NUG 1,2-a]pyridine (5a): White solid;
mp 139–1418C; IR (KBr): n=2925, 2850, 1697, 1605, 1498,
2-Chloro-3-phenylimidazoACTHNGUTRENNU[G 1,2-a]pyridine (5h): White
1
1342, 1221, 11 63, 912, 750, 670 cmÀ1; H NMR (400 MHz,
solid; mp 115–1178C; IR (KBr): n=2935, 2857, 1715, 1638,
1
CDCl3): d=8.04 (d, J=6.9 Hz, 1H), 7.61–7.43 (m, 6H), 7.16
(ddd, J=9.0, 6.8, 1.1 Hz, 1H), 6.73 (td, J=6.9, 0.9 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=146.8, 129.9, 129.1, 129.0,
128.2, 126.8, 124.8, 123.0, 117.0, 112.7, 93.6; ESI-HR-MS: m/
z=320.9985, calcd. for C13H9IN2 (M+H)+: 320.9983.
1500, 1348, 1226, 1160, 918, 749 cmÀ1; H NMR (400 MHz,
CDCl3): d=8.15 (d, J=6.9 Hz, 1H), 7.60–7.52 (m, 5H), 7.46
(dd, J=8.8, 4.5 Hz, 1H), 7.24 (t, J=7.8 Hz, 1H), 6.82 (t, J=
6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=143.1, 133.8,
129.2, 129.1, 128.8, 127.1, 125.1, 123.1, 119.5, 117.2, 112.9;
8
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

Copper-Catalyzed Intermolecular Oxidative Cyclization of Haloalkynes
ESI-HR-MS: m/z=229.0530, calcd. for C13H9ClN2 (M+H)+:
8-Fluoro-3-phenyl-2-[(trimethylsilyl)ethynyl]imidazoACHTUNGTRENNUNG[1,2-
229.0527.
a]pyridine (7a): White solid; mp 162–1638C; IR (KBr): n=
2937, 2859, 1710, 1557, 1500, 1349, 1236, 1160, 915, 750,
2-Chloro-3-(4-ethylphenyl)imidazo
White solid; mp 116–1178C; IR (KBr): n=2936, 2858, 1710,
1635, 1501, 1346, 1227, 1162, 918, 749 cmÀ1 1H NMR
N
(5i):
673 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=7.84 (d, J=
6.9 Hz, 1H), 7.49–7.42 (m, 2H), 7.38–7.28 (m, 2H), 7.24 (t,
J=7.4 Hz, 1H), 6.69 (dd, J=9.7, 7.8 Hz, 1H), 6.52 (td, J=
7.3, 4.6 Hz, 1H), À0.00 (s, 9H); 13C NMR (100 MHz,
CDCl3): d=151.2 (d, J=253.5 Hz), 137.2 (d, J=28.3 Hz),
129.5, 128.9, 128.6, 127.6, 126.7, 119.6 (d, J=5.1 Hz), 112.1
(d, J=6.7 Hz), 107.7 (d, J=16.1 Hz), 98.2, 98.0, À0.4; ESI-
HR-MS: m/z=309.1216, calcd. for C18H17FN2Si (M+H)+:
309.1217.
(400 MHz, CDCl3): d=8.14 (d, J=6.9 Hz, 1H), 7.57 (d, J=
9.1 Hz, 1H), 7.48 (d, J=8.2 Hz, 2H), 7.38 (d, J=8.1 Hz,
2H), 7.25–7.19 (m, 1H), 6.81 (t, J=6.9 Hz, 1H), 2.74 (q, J=
7.6 Hz, 2H), 1.31 (t, J=7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=145.13, 129.22, 128.67, 128.28, 127.34, 124.99,
124.34, 123.23, 117.16, 112.84, 77.32, 77.00, 76.68, 28.71,
15.30; ESI-HR-MS: m/z=257.0846, calcd. for C15H13ClN2
(M+H)+: 257.0840.
2-Ethynyl-8-fluoro-3-phenylimidazoACTHNUTRGNEUNG[1,2-a]pyridine (7b):
Viscous liquid; IR (KBr): n=3303, 2917, 2249, 1677, 1583,
8-Methyl-2,3-diphenylimidazoACTHNUGRTNEUNG[1,2-a]pyridine (6a): White
1
1499, 1347, 1249, 931, 739, 670; H NMR (400 MHz, CDCl3):
solid; mp 153–1558C; IR (KBr): n=2925, 2893, 1656, 1589,
1
d=8.02 (d, J=6.9 Hz, 1H), 7.65 (d, J=7.2 Hz, 2H), 7.56 (t,
J=7.5 Hz, 2H), 7.48 (t, J=7.4 Hz, 1H), 6.94 (dd, J=9.6,
7.9 Hz, 1H), 6.75 (td, J=7.3, 4.6 Hz, 1H), 3.15 (s, 1H);
13C NMR (100 MHz, CDCl3): d=151.4 (d, J=253.8 Hz),
137.3 (d, J=28.1 Hz), 130.0, 129.2, 129.2, 128.9, 127.4, 125.9,
119.7 (d, J=5.2 Hz), 112.2 (d, J=6.7 Hz), 107.9 (d, J=
16.1 Hz), 80.2, 77.1; ESI-HR-MS: m/z=237.0825, calcd. for
C15H9FN2 (M+H)+: 237.0822.
1524, 1369, 1242, 1175, 854, 766, 670; H NMR (400 MHz,
CDCl3): d=7.87 (d, J=7.0 Hz, 1H), 7.71–7.67 (m, 2H), 7.52
(ddt, J=15.0, 8.1, 4.2 Hz, 6H), 7.33–7.25 (m, 3H), 6.62 (d,
J=6.1 Hz, 1H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3):
d=145.0, 133.8, 130.7, 129.8, 129.5, 128.8, 128.3, 128.0, 127.5,
127.1, 122.6, 120.5, 115.7, 115.2, 21.3; ESI-HR-MS: m/z=
285.1389, calcd. for C20H16N2 (M+H)+: 285.1386.
2,3-DiphenylimidazoACTHNUTRGNEUNG
[1,2-a]pyridine (6b):[16] White solid;
8-Fluoro-2-[(8-fluoro-3-phenylindolizin-2-yl)buta-1,3-
diynyl]-3-phenylimidazoACTHNURTGNEU[GN 1,2-a]pyridine (7c): White solid;
mp 151–1538C; IR (KBr): n=2938, 2856, 1698, 1607, 1500,
1
1347, 1226, 1161, 914, 749, 670; H NMR (400 MHz, CDCl3):
mp 212–2138C; IR (KBr): n=2918, 2846, 1670, 1583, 1490,
d=7.91 (d, J=6.9 Hz, 1H), 7.69–7.64 (m, 3H), 7.52–7.39 (m,
5H), 7.29–7.20 (m, 3H), 7.15 (dd, J=8.3, 7.4 Hz, 1H), 6.67
(t, J=6.7 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=144.6,
142.2, 134.0, 130.6, 129.7, 129.4, 128.7, 128.1, 127.9, 127.3,
124.5, 123.1, 120.9, 117.4, 112.1; ESI-HR-MS: m/z=
271.1247, calcd. for C21H18N2 (M+H)+: 271.1249.
1
1347, 1249, 1169, 931, 739, 670; H NMR (400 MHz, CDCl3):
d=8.05 (d, J=6.9 Hz, 2H), 7.65 (d, J=7.2 Hz, 4H), 7.58 (t,
J=7.5 Hz, 4H), 7.50 (t, J=7.3 Hz, 2H), 6.99–6.91 (m, 2H),
6.77 (dt, J=11.8, 6.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d=151.3 (d, J=254.5 Hz), 137.6 (d, J=28.4 Hz), 131.7,
129.5, 129.4, 128.8, 127.1, 125.5, 119.8 (d, J=4.9 Hz), 112.5
(d, J=6.5 Hz), 108.3 (d, J=16.1 Hz), 77.2, 75.4; ESI-HR-
MS: m/z=471.1412, calcd. for C30H16F2N4 (M+H)+:
471.1415.
3-Phenyl-2-(phenylethynyl)imidazo
G
(6c):
White solid; mp 144–1468C; IR (KBr): n=2931, 2855, 2200,
1607, 1500, 1347, 1226, 1161, 914, 749, 670; 1H NMR
(400 MHz, CDCl3): d=8.31 (d, J=7.0 Hz, 1H), 7.78 (d, J=
7.3 Hz, 2H), 7.66 (d, J=9.1 Hz, 1H), 7.60 (t, J=7.6 Hz,
2H), 7.54–7.46 (m, 3H), 7.35–7.32 (m, 3H), 7.29–7.22 (m,
1H), 6.85 (t, J=6.7 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d=144.9, 131.6, 129.1, 128.8, 128.7, 128.4, 128.2, 127.8, 126.7,
125.5, 123.3, 123.0, 117.9, 113.1, 91.9, 83.5, 29.7; ESI-HR-
MS: m/z=295.1232, calcd. for C21H14N2 (M+H)+: 295.1229.
Acknowledgements
The authors thank the National Natural Science Foundation
of China (21202046 and 20932002), the National Basic Re-
search Program of China (973 Program) (2011CB808600),
7-Chloro-3-phenyl-2-(phenylethynyl)imidazoACTHNUTRGNE[UNG 1,2-a]pyri-
dine (6d): White solid; mp 155–1578C; IR (KBr): n=2941,
2856, 2200, 1608, 1502, 1348, 1226, 1161, 914, 749, 670;
1H NMR (400 MHz, CDCl3): d=8.29 (s, 1H), 7.73 (d, J=
7.2 Hz, 2H), 7.58 (dd, J=15.5, 8.1 Hz, 3H), 7.51–7.46 (m,
3H), 7.33–7.29 (m, 3H), 7.20 (dd, J=9.5, 1.8 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=143.2, 131.6, 129.2, 129.0,
128.7, 128.5, 128.2, 128.1, 127.6, 126.8, 122.7, 121.5, 121.1,
118.2, 92.3, 83.0; ESI-HR-MS: m/z=329.0844, calcd. for
C21H13ClN2 (M+H)+: 329.0840.
the
Guangdong
Natural
Science
Foundation
(S2012040007088), China Postdoctoral Science Foundation
(2012T50673 and 2011M501318) and the Fundamental Re-
search Funds for the Central Universities (2012ZP0003 and
2012ZB0011) for financial support.
References
3-Hexyl-2,7-diphenylimidazoACTHNUTRGNEUGN[1,2-c]pyrimidine (6e): White
solid; mp 169–1718C; IR (KBr): n=2928, 2849, 2212, 1607,
1500, 1347, 1226, 1161, 914, 750, 663; H NMR (400 MHz,
[1] a) K. C. Rupert, J. R. Henry, J. H. Dodd, S. A. Wads-
worth, D. E. Cavender, G. C. Olini, B. Fahmy, J. Sie-
kierka, Bioorg. Med. Chem. Lett. 2003, 13, 347; b) S. M.
Hanson, E. V. Morlock, K. A. Satyshur, C. Czajkowski,
J. Med. Chem. 2008, 51, 7243; c) M. H. Wiegand, Drugs
2008, 68, 2411; d) Y. Katsura, S. Nishino, Y. Inoue, M.
Tomoi, H. Takasugi, Chem. Pharm. Bull. 1992, 40, 371;
e) R. R. Singhaus, R. C. Bernotas, R. Steffan, E. Mate-
lan, A. Wilhelmsson, A. Goos-Nilsson, J. Wrobel,
Bioorg. Med. Chem. Lett. 2010, 20, 521.
1
CDCl3): d=8.21 (d, J=9.2 Hz, 1H), 8.05 (dd, J=7.9, 1.6 Hz,
2H), 7.93–7.90 (m, 2H), 7.57 (dt, J=16.0, 8.7 Hz, 6H), 7.44
(t, J=7.4 Hz, 1H), 3.38–3.29 (m, 2H), 1.51 (dt, J=14.6,
7.1 Hz, 2H), 1.41–1.30 (m, 5H), 0.91 (t, J=7.0 Hz, 4H);
13C NMR (100 MHz, CDCl3): d=151.6, 136.9, 135.6, 130.1,
129.1, 128.8, 128.2, 128.0, 127.0, 126.7, 124.5, 116.2, 31.4,
29.2, 27.4, 23.5, 22.6, 14.0; ESI-HR-MS: m/z=356.2125,
calcd. for C24H25N3 (M+H)+: 356.2121.
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
9
ÞÞ
These are not the final page numbers!

Yang Gao et al.
FULL PAPERS
[2] F. Couty, G. Evano, in: Comprehensive Heterocyclic
Chemistry III, Vol. 11, (Eds.: A. R. Katritzky, C. A.
Ramsden, E. F. V. Scriven, R. J. K. Taylor), Elsevier,
Oxford, 2008, pp 409–499, and references cited therein.
[3] a) J. Saletu, B. Grunberger, L. Linzmayer, Int. Clin.
Psychopharmacol. 1986, 1, 145; b) A. Berson, V. Desca-
toire, A. Sutton, D. Fau, B. Maulny, N. Vadrot, G. Feld-
mann, B. Berthon, T. Tordjmann, D. Pessayre, J. Phar-
macol. Exp. Ther. 2001, 299, 793.
[4] A. Linton, P. Kang, M. Ornelas, S. Kephart, Q. Y. Hu,
M. Pairish, Y. Jiang, C. X. Guo, J. Med. Chem. 2011,
54, 7705.
[5] V. Pogacic, A. N. Bullock, O. Fedorov, P. Filippakopou-
los, C. Gasser, A. Biondi, S. Meyer-Monard, S. Knapp,
J. Schwaller, Cancer Res. 2007, 67, 6916.
[6] For selected recent examples, see: a) N. Chernyak, V.
Gevorgyan, Angew. Chem. 2010, 122, 2803; Angew.
Chem. Int. Ed. 2010, 49, 2743; b) N. Denora, V. Laquin-
tana, M. G. Pisu, R. Dore, L. Murru, A. Latrofa, G.
Trapani, E. Sanna, J. Med. Chem. 2008, 51, 6876; c) V.
Laquintana, N. Denora, A. Lopedota, H. Suzuki, M.
Sawada, M. Serra, G. Biggio, A. Latrofa, G. Trapani, G.
Liso, Bioconjugate Chem. 2007, 18, 1397.
[7] a) W. L. Mosby, Heterocyclic Systems with Bridgehead
Nitrogen Atoms, (Ed.: A. Weissberger), Interacience
Publishers, Inc., New York, N.Y., 1961, p 460 ff; b) B.
Kickhoffen, Arch. Pharm. 1955, 288, 473; c) J. G. Lom-
bardino, J. Org. Chem. 1965, 30, 2403.
[8] a) A. Gueiffier, M. Lhassani, A. Elhakmaoui, R.
Snoeck, G. Andrei, O. Chavignon, J.-C. Teulade, A.
Kerbal, E. M. Essassi, J.-C. Debouzy, M. Witvrouw, Y.
Blache, J. Balzarini, E. De Clercq, J.-P. Chapat, J. Med.
Chem. 1996, 39, 2856; b) L. Ma, X. Wang, W. Yu, B.
Han, Chem. Commun. 2011, 47, 11333; c) C. He, J.
Hao, H. Xu, Y. P. Mo, H. Y. Liu, J. J. Han, A. W. Lei,
Chem. Commun. 2012, 48, 11073; d) J. Zeng, Y. J. Tan,
M. L. Leow, X.-W. Liu, Org. Lett. 2012, 14, 4386; e) N.
Chernyak, V. Gevorgyan, Angew. Chem. 2010, 122,
2803; Angew. Chem. Int. Ed. 2010, 49, 2743; f) R. L.
Yan, H. Yan, C. Ma, Z. Y. Ren, X. A. Gao, G. S.
Huang, Y. M. Liang, J. Org. Chem. 2012, 77, 2024; g) G.
Tresadern, J. M. Cid, G. J. Macdonald, J. A. Vega, A. I.
Lucas, A. Garcꢄa, E. Matesanz, M. L. Linares, D. Oehl-
rich, H. Lavreysen, I. Biesmans, A. A. Trabanco,
Bioorg. Med. Chem. Lett. 2010, 20, 175; h) A. J. Sta-
syuk, M. Banasiewicz, M. K. Cyranski, D. T. Gryko, J.
Org. Chem. 2012, 77, 5552; i) T. Donohoe, M. Kabe-
shov, A. Rathi, I. Smith, Org. Biomol. Chem. 2012, 10,
1093; j) T. Donohoe, M. Kabeshov, A. Rathi, I. Smith,
Synlett 2010, 19, 2956; k) P. Starkov, F. Rota, J.
D’Oyley, T. Sheppard, Adv. Synth. Catal. 2012, 354,
3217.
121, 9717; Angew. Chem. Int. Ed. 2009, 48, 9553;
d) A. S. Dudnik, V. Gevorgyan, Angew. Chem. 2010,
122, 2140; Angew. Chem. Int. Ed. 2010, 49, 2096;
e) D. L. Usanov, H. Yamamoto, J. Am. Chem. Soc.
2011, 133, 1286; f) Y. Ano, M. Tobisu, N. Chatani, J.
Am. Chem. Soc. 2011, 133, 12984; g) J. Hein, J. Tripp,
L. Krasnova, K. Sharpless, V. Fokin, Angew. Chem.
2009, 121, 8162; Angew. Chem. Int. Ed. 2009, 48, 8018.
[11] a) K. A. DeKorver, M. C. Walton, T. D. North, R. P.
Hsung, Org. lett. 2011, 13, 18; b) A. Arcadi, S. Cacchi,
G. Fabrizi, F. Marinelli, L. M. Parisi, J. Org. Chem.
2005, 70, 6213; c) Z. W. Chen, W. Zeng, H. F. Jiang,
L. X. Liu, Org. Lett. 2012, 14, 5385.
[12] a) S. H. Wang, P. H. Li, L. Yu, L. Wang, Org. Lett.
2011, 13, 5968; b) P. Huang, Q. Yang, Z. Y. Chen, Q. P.
Ding, J. S. Xu, Y. Y. Peng, J. Org. Chem. 2012, 77, 8092;
c) H. Xu, Y. Zhang, J. Huang, W. Chen, Org. Lett.
2010, 12, 3704.
[13] a) Y. Li, X. Liu, D. Ma, B. Liu, H. Jiang, Adv. Synth.
Catal. 2012, 354, 2683; b) Z. W. Chen, J. H. Li, H. F.
Jiang, S. F. Zhu, Y. B. Li, C. R. Qi, Org. Lett. 2010, 12,
3262; c) Y. Wang, B. Lu, L. Zhang, Chem. Commun.
2010, 46, 9179; d) A. Leyva-Pꢆrez, P. Rubio-Marquꢆs,
S. Al-Deyab, S. Al-Resayes, A. Corma, ACS Catal.
2011, 1, 601.
[14] a) H. Doucet, J.-C. Hierso, Angew. Chem. 2007, 119,
850; Angew. Chem. Int. Ed. 2007, 46, 834; b) T. Hun-
dertmark, A. F. Littke, S. L. Buchwald, Org. Lett. 2000,
2, 1729; c) Z. Novꢇk, P. Nemes, A. Kotschy, Org. Lett.
2004, 6, 4917; d) N. Miyaura, A. Suzuki, Chem. Rev.
1995, 95, 2457; e) A. F. Littke, G. C. Fu, J. Org. Chem.
1999, 64, 10; f) B. M. Choudary, S. Madhi, N. S. Chow-
dari, M. L. Kantam, B. Sreedhar, J. Am. Chem. Soc.
2002, 124, 14127; g) Y. Aratono, T. Matsumoto, T. Ta-
kayanagi, T. Kumada, K. Komaguchi, T. Miyazaki, J.
Phys. Chem. A 2000, 104, 1968; h) T. C. Zebovitz, R. F.
Heck, J. Org. Chem. 1977, 42, 3907.
[15] CCDC 921214 and CCDC 921213 contain the supple-
mentary crystallographic data for this paper (com-
pounds 3e and 3f). These data can be obtained free of
charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
[16] C. Enguehard, J.-L. Renou, V. Collot, M. Hervet, S.
Rault, A. Gueiffier, J. Org. Chem. 2000, 65, 6572.
[17] a) R. L. Christensen, K. C. Hultzsch, J. Phys. Chem. A
2004, 108, 8229; b) S. A. Locknar, L. A. Peteanu, Z. G.
Shuai, J. Phys. Chem. A 1999, 103, 2197; c) R. L. Chris-
tensen, H. A. Frank, J. Phys. Chem. A 2008, 112, 12629;
d) A. P. Kulkarni, C. J. Tonzola, A. Babel, S. A. Je-
nekhe, Chem. Mater. 2004, 16, 4556.
[18] a) H. J. Kim, S. H. Cho, S. Chang, Org. Lett. 2012, 14,
1424; b) B. G. Zhao, H. F. Du, S. L. Cui, Y. A. Shi, J.
Am. Chem. Soc. 2010, 132, 3523; c) B. G. Zhao, X. G.
Peng, S. L. Cui, Y. A. Shi, J. Am. Chem. Soc. 2010, 132,
11009; d) Y.-F. Wang, X. Zhu, S. Chiba, J. Am. Chem.
Soc. 2012, 134, 3679; e) W. Wang, Y. Shen, X. Meng,
M. Zhao, Y. Chen, B. Chen, Org. Lett. 2011, 13, 4514.
[19] a) E. S. Sherman, P. H. Fuller, D. Kasi, S. R. Chemler,
J. Org. Chem. 2007, 72, 3896; b) A. Iglesias, E. G.
Perez, K. Muniz, Angew. Chem. 2010, 122, 8286;
Angew. Chem. Int. Ed. 2010, 49, 8109; c) B. Yao, Q.
Wang, J. Zhu, Angew. Chem. 2012, 124, 5260; Angew.
[9] a) H. G. Wang, Y. Wang, C. L. Peng, J. C. Zhang, Q.
Zhu, J. Am. Chem. Soc. 2010, 132, 13217; b) H. G.
Wang, Y. Wang, D. D. Liang, L. Y. Liu, J. C. Zhang, Q.
Zhu, Angew. Chem. 2011, 123, 5796; Angew. Chem. Int.
Ed. 2011, 50, 5678.
[10] For selected examples for the application of haloal-
kynes, see: a) I. V. Seregin, V. Ryabova, V. Gevorgyan,
J. Am. Chem. Soc. 2007, 129, 7742; b) A. Trofimov, N.
Chernyak, V. Gevorgyan, J. Am. Chem. Soc. 2008, 130,
13538; c) F. Besseliꢅvre, S. Piguel, Angew. Chem. 2009,
10
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

Copper-Catalyzed Intermolecular Oxidative Cyclization of Haloalkynes
Chem. Int. Ed. 2012, 51, 5170; d) F. C. Sequeira, B. W.
Turnpenny, S. R. Chemler, Angew. Chem. 2010, 122,
6509; Angew. Chem. Int. Ed. 2010, 49, 6365.
b) A. King, L. Huffman, A. Casitas, M. Costas, X.
Ribas, S. Stahl, J. Am. Chem. Soc. 2010, 132, 12068;
c) S. Zhang, L. Liu, Y. Fu, Q. Guo, Organometallics
2007, 26, 4546; d) A. Casitas, A. King, T. Parella, M.
Costas, S. Stahl, X. Ribas, Chem. Sci. 2010, 1, 326; e) R.
Giri, J. Hartwig, J. Am. Chem. Soc. 2010, 132, 15860.
[22] a) T. P. Zabawa, D. Kasi, S. R. Chemler, J. Am. Chem.
Soc. 2005, 127, 11250; b) P. A. Sibbald, C. F. Rosewall,
R. D. Swartz, F. E. Michael, J. Am. Chem. Soc. 2009,
131, 15945.
[20] a) P. H. Fuller, J.-W. Kim, S. R. Chemler, J. Am. Chem.
Soc. 2008, 130, 17638; b) Y. Fukudome, H. Naito, T.
Hata, H. Urabe, J. Am. Chem. Soc. 2008, 130, 1820;
c) R. G. Cornwall, B. G. Zhao, Y. A. Shi, Org. Lett.
2011, 13, 434.
[21] For a discussion of mechanisms involving CuACTHNUTRGNE(UNG III) inter-
mediates, see: a) S. Ley, A. Thomas, Angew. Chem.
2003, 115, 5558; Angew. Chem. Int. Ed. 2003, 42, 5400;
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
11
ÞÞ
These are not the final page numbers!

FULL PAPERS
12 Copper-Catalyzed Intermolecular Oxidative Cyclization of
Halo-alkynes: Synthesis of 2-Halo-substituted ImidazoACTHNUTRGNEU[GN 1,2-
a]pyridines, Imidazo
a]pyrimidines
ACHUTGTNREN[UNG 1,2-a]pyrazines and ImidazoACHUTNGTREN[NUGN 1,2-
Adv. Synth. Catal. 2013, 355, 1 – 12
Yang Gao, Meizhou Yin, Wanqing Wu,* Huawen Huang,
Huanfeng Jiang*
12
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!