Silver-catalyzed isocyanide-alkyne cycloaddition: A general and practical method to oligosubstituted pyrroles

Article abstract of DOI:10.1002/anie.201302024

Ag₂CO₃ is the key: The transition-metal-catalyzed cycloaddition of isocyanides and unactivated terminal alkynes has been realized with Ag₂CO₃ as a unique and robust catalyst (see scheme). The protocol is highly

Full text of DOI:10.1002/anie.201302024

Angewandte
Chemie
DOI: 10.1002/anie.201302024
Cycloaddition
Silver-Catalyzed Isocyanide-Alkyne Cycloaddition: A General and
Practical Method to Oligosubstituted Pyrroles**
Jianquan Liu, Zhongxue Fang, Qian Zhang,* Qun Liu, and Xihe Bi*
Oligosubstituted pyrroles are important as components in
natural products, pharmaceuticals, and functional materials,
and also serve as valuable intermediates in organic syn-
thesis.[1,2] In the past, substantial advances in the development
of transition-metal-catalyzed synthetic methods for these
compounds have been achieved.[3] Compared to the tradi-
tional-metal-free reactions,[4] most of these protocols showed
high efficiency with remarkable functional-group tolerance.
However, the synthetic methods reported so far largely relied
on elaborately designed substrates that are not readily
accessible.[5,6] Thus, the direct assembly of pyrroles from
basic chemicals remains an important research objective.[7]
Isocyanides[8] and alkynes[9] are two classes of commercially
available and versatile starting materials. The atom-economic
nature of the reaction makes the cycloaddition of these
substrates an ideal route to oligosubstituted pyrroles
(Scheme 1). However, such reactions are mostly limited to
2005.[10b,c] With regard to the more abundant unactivated
terminal alkynes, a catalytic protocol remains elusive.[11]
Herein, we wish to report a novel silver-catalyzed isocya-
nide–alkyne cycloaddition, which works with a broad range of
alkynes, particularly unactivated terminal alkynes.
The search for a robust catalyst that achieves the cyclo-
addition of isocyanides with unactivated terminal alkynes has
always been met with challenges, that is 1) the facile
homocoupling of terminal alkynes (Glaser–Hay coupling)
under oxidative conditions,[12] and 2) the easy dimerization of
isocyanides to produce imidazoles in the presence of a base or
transition-metal catalyst.[13] Recently, a rapidly growing
number of reports on alkyne-involving organic reactions
that make use of silver salts as the catalyst have been
reported.[14] One advantage of silver catalysis is the avoidance
of the Glaser–Hay coupling commonly encountered with
terminal alkynes. A typical example is the recent pioneering
work of Lei and co-workers, who reported the Ag2CO3-
mediated oxidative cyclization of terminal alkynes with 1,3-
dicarbonyl compounds or 2-aminopyridines,[15] in which no
homocoupling products were observed. In addition, the silver-
catalyzed cycloadditions of isocyanides with aldehydes or a,b-
unsaturated carbonyl compounds are known.[16] On the basis
of these precedents and our continued efforts in metal-
catalyzed cyclizations,[17] we envisaged that Ag2CO3 might be
the right catalyst for the cycloaddition of isocyanides with
terminal alkynes. Delightfully, 2,3-disubstituted pyrrole 3a
was isolated in 82% yield from the reaction of ethyl
isocyanoacetate (1a) and phenylacetylene (2a) in DMF at
808C, with only a small amount of imidazole 4 [7%; Eq. (1)].
To our knowledge, this is the first example of a transition-
metal-catalyzed cycloaddition of isocyanides with unactivated
terminal alkynes.[10,11]
Scheme 1. Isocyanide–alkyne cycloaddition.
the use of electron-deficient alkynes under base or copper
catalysis, and are hitherto underexploited.[10,11] Copper catal-
ysis is the sole, synthetically useful transition-metal-catalyzed
version reported so far, stemming from the seminal, inde-
pendent work of the groups of Yamamoto and de Meijere in
[*] J. Liu, Z. Fang, Prof. Q. Zhang, Prof. Q. Liu, Prof. X. Bi
Department of Chemistry, Northeast Normal University
Changchun 130024 (China)
E-mail: bixh507@nenu.edu.cn
zhangq651@nenu.edu.cn
Prof. X. Bi
Encouraged by this finding, we continued our investiga-
tions by optimizing the reaction conditions (Table 1). A
variety of silver salts were initially examined for the reaction
of 1a and 2a in DMFat 808C (entries 1–8). The counter anion
of the silver salts turned out to play a critical role in the
product distribution of pyrrole 3a and imidazole 4. For
example, although AgOAc, AgOTf, Ag2O, AgF, and AgNO2
State Key Laboratory of Elemento-organic Chemistry, Nankai
University
Tianjin 300071 (China)
[**] This work was supported by NSFC (21172029, 21202016, 31101010)
and FRFCU (11CXPY005).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201302024.
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
Table 1: Screening of reaction conditions.[a]
Entry
[Ag]
Solvent
T
[8C]
t
Yield [%][b]
3a 4
[min]
1
2
3
4
5
6
7
8
AgOAc
AgOTf
Ag2O
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
1,4-dioxane
(CH2Cl)2
DMSO
CH3CN
1,4-dioxane
1,4-dioxane
1,4-dioxane
80
80
80
80
80
80
80
80
80
80
80
80
80
40
25
30
30
30
30
30
30
30
30
30
30
30
30
30
24 h
24 h
0
0
80
84
86
82
81
0
trace
trace
trace
0
0
0
AgF
AgNO2
AgNO3
AgBF4
AgClO4
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
–
0
0
9
90
78
trace
13
78
87
0
10
11
12
13
14
15
trace
trace
0
trace
trace
Ag2CO3
Ag2CO3
88
93
[a] Reactions were performed on 1.0 mmol scale, at a concentration of
0.25m (with respect to 1a). [b] Yields of isolated products. DMF=N,N-
dimethylformamide, DMSO=dimethyl sulfoxide.
all catalyzed the reaction to afford imidazole 4 in high yields
(81–86%), only the latter three silver salts led to trace
amounts of pyrrole 3a (entries 1–5). Remarkably, no reaction
took place with AgNO3, AgBF4, and AgClO4 catalysts
(entries 6–8). These results clearly demonstrate that Ag2CO3
is a unique and robust catalyst for the cycloaddition of 1a and
2a.[18] A better ratio of 3a (90%) to 4 (trace) was achieved
when 1,4-dioxane was employed as solvent (entries 9–12).
Interestingly, no homocoupling of phenylacetylene (2a) was
observed, which is consistent with the observation of Lei and
co-workers.[15] The necessity of using Ag2CO3 was confirmed
in a control experiment (entry 13). The reaction temperature
also distinctly influenced the product distribution. A decrease
in the temperature from 80 to 408C or 258C afforded
imidazole 4 as the major product (entries 14 and 15,
respectively).
With the optimal conditions in hand (10 mol% Ag2CO3,
1,4-dioxane, 808C; see Table 1, entry 9), the scope of the
reaction with regard to the terminal alkyne and isocyanide
components was investigated (Scheme 2). Ethyl isocyanoace-
tate 1a effectively reacted with arylalkynes (2b–2e) within
40–120 min to give the corresponding 2,3-disubstituted pyr-
roles (3b–3e) in high yields. Specifically, the free amino group
at the meta position of the phenyl ring of 2d was well
tolerated. Electron-rich and electron-poor heteroarylalkynes
that contain 2-thienyl and 2-pyridyl groups (2 f and 2g,
respectively) were also subjected to the cycloaddition, leading
to the corresponding products 3 f and 3g, respectively, in high
yields. These high product yields demonstrate the superior
catalytic activity of the current silver catalyst system.[11] Next,
we focused our attention on investigating the scope of
terminal alkynes by using a range of aliphatic alkynes (2h–
2o). To our delight, these reactions efficiently afforded the
2,3-disubstituted pyrroles (3h–3o) in good to high yields
within 30–60 min. Several representative functional groups,
Scheme 2. Scope of terminal alkynes.
including cyclopropyl, alkynyl, hydroxyalkyl, alkenyl, alkoxy,
and acetyl, were well tolerated. These functionalities in the
pyrrole products might be useful for further synthetic
modifications. The results of our study impressively illustrate
the negligible influence of the intrinsic electronic character of
aliphatic alkynes, that is, whether they are electron-rich or
electron-poor, on their cycloadditions with isocyanoacetates.
Also worthy of note is the observation that in place of ethyl
isocyanoacetate (1a), both toluenesulfonylmethyl isocyanide
(TosMIC, 1b) and benzyl isocyanide (1c) readily participated
in the cycloaddition with phenylacetylene 2a, giving rise to
products 3p and 3q in 83 and 87% yield, respectively. Thus,
the silver-catalyzed cycloaddition of isocyanides with a broad
range of unactivated terminal alkynes provides a powerful
method for the synthesis of 2,3-disubstituted pyrroles.[19]
Structurally, products 3 contain one nonsubstituted 5-
position and an ester group at the 2-position of the pyrrole
ring. Such a-nonsubstituted pyrrole-2-carboxylates have been
widely utilized in the preparation of pyrrole alkaloids,
porphyrins, polypyrroles, and BODIPY dyes.[20] To unravel
the synthetic potential of the method, the reaction of ethyl
isocyanoacetate 1a and propargyl alcohol 2k was carried out
on a gram scale (Scheme 3). To our delight, the corresponding
3-hydroxymethyl pyrrole 3l was isolated in 77% yield.
Furthermore, the high-yielding conversion of 3l to ethyl 3-
formyl-1H-pyrrole-2-carboxylate 5 was achieved in the pres-
ence of 1.5 equivalents of pyridinium chlorochromate
(PCC).[21] Notably, formylation at the 3-position of pyrroles
2
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
Scheme 3. Experiment on a gram scale and further synthetic deriva-
tion.
is hard to realize through the most commonly used Vilsmeier–
Haack reaction, which preferentially introduces the formyl
group at the 2-position rather than the 3-position of the
pyrrole ring.[22]
Some critical mechanistic information for the reaction of
a terminal alkyne with an isocyanide was collected by
experimental investigations (Scheme 4). Firstly, silver acety-
lide[23] 6 could efficiently react with ethyl isocyanoacetate 1a
Scheme 5. Mechanistic proposal for the cycloaddition of isocyanides
and terminal alkynes.
precedents.[11,13] The initial step is the formation of a silver–
acetylide intermediate 6 through the agostic interaction (I)
between phenylacetylene and Ag2CO3, resulting in the trans-
fer of a proton (H+) to Ag2CO3 with the release of
AgHCO3.[24] Subsequent 1,1 insertion of the isocyanide into
À
the metal carbon bond takes place, giving the acetylenic
imido complex A,[25] which readily undergoes protonolysis
with AgHCO3 to result in the acetylenic imide B and
regenerates Ag2CO3 as the active species in the catalytic
cycle. This step accounts for the destination of the acetylenic
hydrogen observed in the above deuterium-labeling experi-
ment [Scheme 4, Eq. (2)]. Subsequently, a possible interac-
tion (II) between intermediate B and Ag2CO3 occurs, giving
the metallic 2H-pyrrolenine species C through the intra-
molecular cyclization of acetylenic imide.[5 h] Intermediate C
then experiences a subsequent 1,5-hydrogen shift and proto-
nation by the AgHCO3 to yield 3a, thus completing the
catalytic cycle for Ag2CO3.
Scheme 4. Mechanistic investigations.
without the aid of Ag2CO3 as catalyst, giving pyrrole 3c in
78% yield [Eq. (2)]. This result suggests that silver acetylide
could be the intermediate in the reaction. Furthermore, the
deuterium-labeling experiments clearly revealed the source
of the a-hydrogen atom on pyrroles 3. When deuterated 4-
ethynylanisole ([D]-2c, 78% deuterium content) was reacted
with 1a, the deuterium atom was exclusively incorporated at
the a-position of pyrrole 3c to an extent of 59% [Eq. (3)].
This outcome is different from the experiment of de Meijere
and co-workers, in which equal incorporation of deuterium at
positions 4 and 5 (43% each) was observed,[11] hence implying
a different catalytic mechanism for the Ag2CO3 catalyst. In
addition, an elevated temperature of 1208C was necessary for
the reaction of the deuterated substrate [D]-2c, thus indicat-
To examine the generality of the silver-catalyzed isocya-
nide–alkyne cycloaddition, we further investigated the scope
of internal alkynes that have been previously used in base- or
copper-catalyzed procedures.[10] An array of ethoxylcarbonyl-
and benzoyl-activated internal alkynes reacted well with ethyl
isocyanoacetate 1a under the Ag2CO3-catalyed conditions
(Scheme 6), generally affording 2,3,4-trisubstituted pyrroles
(8a–8k) in high yields (up to 96%) with good functional-
group tolerance. The structures of pyrroles 8, substituted with
electron-withdrawing groups (EWGs) at positions 2 and 4,
were established with the aid of a 2D HMBC experiment on
product 8a. Notably, triethyl 2,3,4-pyrrole tricarboxylate 8l,
the precursor of a naturally occurring pyrrole acid in
melanosomes,[26] was obtained in 90% yield by the cyclo-
addition of ethyl isocyanoacetate 1a with diethyl acetylene-
dicarboxylate 7l. However, 1,2-diphenylacetylene, a non-
activated internal alkyne, did not react with ethyl isocyanoa-
cetate 1a under identical conditions. Consequently, a plausible
mechanism for the silver-catalyzed reactions of electron-
deficient internal alkynes involves the cycloaddition of a-
metallated isocyanides to acetylenes, similar to the copper
catalysis.[10,11]
À
ing that the C H bond cleavage of terminal alkynes was
involved in the rate-limiting step. With 2.0 equivalents of D2O
added to the reaction of 4-ethynylanisole 2c and 1a under the
standard conditions, approximately equal incorporation of
deuterium at positions 4 and 5 (16% each) was obtained
[Eq. (4)].
A plausible reaction mechanism (Scheme 5) is proposed
on the basis of the above experiments and literature
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
Fan, J. Peng, M. T. Hamann, J.-F. Hu, Chem. Rev. 2008, 108, 264 –
287.
[3] a) N. T. Patil, Y. Yamamoto, Arkivoc 2007, 10, 121 – 141; b) N. T.
Patil, Y. Yamamoto, Chem. Rev. 2008, 108, 3395 – 3442.
[4] Name Reactions in Heterocyclic Chemistry (Ed.: J. J. Li), Wiley,
Hoboken, 2005.
[5] For examples of intramolecular cyclizations, see: a) B. M. Trost,
J.-P. Lumb, J. M. Azzarelli, J. Am. Chem. Soc. 2011, 133, 740 –
743; b) M. Yamagishi, K. Nishigai, T. Hata, H. Urabe, Org. Lett.
2011, 13, 4873 – 4875; c) H. M. Peng, J. Zhao, X. Li, Adv. Synth.
Catal. 2009, 351, 1371 – 1377; d) A. Aponick, C.-Y. Li, J. Malinge,
E. F. Marques, Org. Lett. 2009, 11, 4624 – 4627; e) P. W. Davies,
N. Martin, Org. Lett. 2009, 11, 2293 – 2296; f) L. Ackermann, R.
Sandmann, L. T. Kaspar, Org. Lett. 2009, 11, 2031 – 2034; g) J. T.
Kim, A. V. Kelꢀin, V. Gevorgyan, Angew. Chem. 2003, 115, 102 –
105; Angew. Chem. Int. Ed. 2003, 42, 98 – 101; h) A. V. Kelꢀin,
A. W. Sromek, V. Gevorgyan, J. Am. Chem. Soc. 2001, 123,
2074 – 2075.
[6] For examples of intermolecular cyclizations, see: a) S. Rakshit,
F. W. Patureau, F. Glorius, J. Am. Chem. Soc. 2010, 132, 9585 –
9587; b) A. Mizuno, H. Kusama, N. Iwasawa, Angew. Chem.
2009, 121, 8468 – 8470; Angew. Chem. Int. Ed. 2009, 48, 8318 –
8320; c) E. Merkul, C. Boersch, W. Frank, T. J. J. Mꢁller, Org.
Lett. 2009, 11, 2269 – 2272; d) Y.-F. Wang, K. K. Toh, S. Chiba, K.
Narasaka, Org. Lett. 2008, 10, 5019 – 5022; e) T. J. Harrison, J. A.
Kozak, M. Corbella-Panꢂ, G. R. Dake, J. Org. Chem. 2006, 71,
4525 – 4529.
[7] a) S. Michlik, R. Kempe, Nat. Chem. 2013, 5, 140 – 144; b) D.
Srimani, Y. Ben-David, D. Milstein, Angew. Chem. 2013, 125,
4104 – 4107; Angew. Chem. Int. Ed. 2013, 52, 4012 – 4015.
[8] A. V. Gulevich, A. G. Zhdanko, R. V. A. Orru, V. G. Nenaj-
denko, Chem. Rev. 2010, 110, 5235 – 5331.
Scheme 6. Scope of internal alkynes.
[9] Acetylene Chemistry (Eds.: F. Diederich, P. J. Stang, R. R.
Tykwinski), Wiley-VCH, Weinheim, 2005.
In conclusion, we have discovered Ag2CO3 as a unique
and robust catalyst for the cycloaddition of isocyanides with
a variety of alkynes, providing a general and practical method
for the regioselective construction of synthetically useful 2,3-
disubstituted and 2,3,4-trisubstituted pyrroles. For the first
time, the transition-metal-catalyzed cycloaddition of isocya-
nides with unactivated terminal alkynes has been realized. A
novel mechanism involving the catalytic cycle between
Ag2CO3 and AgHCO3 is proposed that satisfactorily accounts
for the origin of the hydrogen atom on the pyrrole ring. In
view of the broad scope of substrates, excellent functional-
group tolerance, high reaction efficiencies, and high product
yields, the silver-catalyzed isocyanide–alkyne cycloaddition
can be expected to find wide synthetic applications.
[10] a) H. Saikachi, T. Kitagawa, H. Sasaki, Chem. Pharm. Bull. 1979,
27, 2857 – 2861; b) S. Kamijo, C. Kanazawa, Y. Yamamoto, J.
Am. Chem. Soc. 2005, 127, 9260 – 9266; c) O. V. Larionov, A.
de Meijere, Angew. Chem. 2005, 117, 5809 – 5813; Angew. Chem.
Int. Ed. 2005, 44, 5664 – 5667; d) Q. Cai, F. Zhou, T. Xu, L. Fu, K.
Ding, Org. Lett. 2011, 13, 340 – 343; e) M. Adib, B. Mohammadi,
E. Sheikhi, H. R. Bijanzadeh, Chin. Chem. Lett. 2011, 22, 314 –
317.
[11] Only one report involving the tedious in situ preparation of
copper acetylides is known to date, see: A. V. Lygin, O. V.
Larionov, V. S. Korotkov, A. de Meijere, Chem. Eur. J. 2009, 15,
227 – 236.
[12] A. S. Hay, J. Org. Chem. 1962, 27, 3320 – 3321.
[13] a) C. Kanazawa, S. Kamijo, Y. Yamamoto, J. Am. Chem. Soc.
2006, 128, 10662 – 10663; b) R. Grigg, M. I. Lansdell, M.
Thornton-Pett, Tetrahedron 1999, 55, 2025 – 2044.
Received: March 11, 2013
Published online: && &&, &&&&
[14] Silver in Organic Chemistry (Eds.: M, Harmata), Wiley, Hobo-
ken, 2010.
[15] a) C. He, S. Guo, J. Ke, J. Hao, H. Xu, H. Chen, A. Lei, J. Am.
Chem. Soc. 2012, 134, 5766 – 5769; b) C. He, J. Hao, H. Xu, Y.
Mo, H. Liu, J. Han, A. Lei, Chem. Commun. 2012, 48, 11073 –
11075.
Keywords: alkynes · cycloaddition · isocyanides ·
oligosubstituted pyrroles · silver carbonate
.
[16] a) T. Hayashi, Y. Uozumi, A. Yamazaki, M. Sawamura, H.
Hamashima, Y. Ito, Tetrahedron Lett. 1991, 32, 2799 – 2802.
[17] a) Z. Wang, X. Bi, P. Liao, X. Liu, D. Dong, Chem. Commun.
2013, 49, 1309 – 1311; b) Z. Wang, X. Bi, P. Liao, R. Zhang, Y.
Liang, D. Dong, Chem. Commun. 2012, 48, 7076 – 7078; c) T.
Xiong, Y. Li, X. Bi, Y. Lv, Q. Zhang, Angew. Chem. 2011, 123,
7278 – 7281; Angew. Chem. Int. Ed. 2011, 50, 7140 – 7143; d) Y.
Wang, X. Bi, D. Li, P. Liao, Y. Wang, J. Yang, Q. Zhang, Q. Liu,
Chem. Commun. 2011, 47, 809 – 811; e) K. Wang, X. Bi, S. Xing,
P. Liao, Z. Fang, X. Meng, Q. Zhang, Q. Liu, Y. Ji, Green Chem.
2011, 13, 562 – 565.
[1] For a general recent review on the reactivity of pyrrole
heterocycles, see: B. A. Trofimov, N. A. Nedolya in Comprehen-
sive Heterocyclic Chemistry III, Vol. 3 (Eds.: G. Jones, C. A.
Ramsden), Elsevier, Amsterdam, 2008, p. 45.
[2] For reviews regarding the prevalence and biological importance
of pyrrole heterocycles, see: a) C. T. Walsh, S. Garneau-Tsodi-
kova, A. R. Howard-Jones, Nat. Prod. Rep. 2006, 23, 517 – 531;
b) F. Bellina, R. Rossi, Tetrahedron 2006, 62, 7213 – 7256; c) H.
4
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
[18] Although the exact role of the counter anion of silver salts
remains unclear presently, the alkalinity of Ag2CO3 may account
for the observed unique catalytic activity. For related references,
see: a) S. Mitsuda, T. Fujiwara, K. Kimigafukuro, D. Monguchi,
A. Mori, Tetrahedron 2012, 68, 3585 – 3590; b) M. S. Shmidt,
I. A. Perillo, M. Gonzꢃlez, M. M. Blanco, Tetrahedron Lett. 2012,
53, 2514 – 2517.
[19] For the biological importance of 2,3-disubstituted pyrroles, see
for example: a) W. W. Wilkerson, W. Galbraith, K. Gans-Brangs,
M. Grubb, W. E. Hewes, B. Jaffee, J. P. Kenney, J. Kerr, N. Wong,
J. Med. Chem. 1994, 37, 988 – 998; b) W. W. Wilkerson, R. A.
Copeland, M. Covington, J. M. Trzaskos, J. Med. Chem. 1995, 38,
3895 – 3901.
[21] For the synthesis of 3-formylpyrroles, see: A. R. Kelly, M. H.
Kerrigan, P. J. Walsh, J. Am. Chem. Soc. 2008, 130, 4097 – 4104.
[22] J. R. Garabatos-Perera, B. H. Rotstein, A. Thompson, J. Org.
Chem. 2007, 72, 7382 – 7385.
[23] A. Vitꢂrisi, A. Orsini, J.-M. Weibel, P. Pale, Tetrahedron Lett.
2006, 47, 2779 – 2781.
[24] For a review on carboxylate-assisted transition-metal-catalyzed
À
C H bond functionalizations, see: L. Ackermann, Chem. Rev.
2011, 111, 1315 – 1345.
[25] E. Barnea, T. Andrea, M. Kapon, J.-C. Berthet, M. Ephritikhine,
M. S. Eisen, J. Am. Chem. Soc. 2004, 126, 10860 – 10861.
[26] S. Ito, K. Wakamatsu, K. Glass, J. D. Simon, Anal. Biochem.
2013, 434, 221 – 225.
[27] This Communication is published back-to-back with the follow-
ing study: M. Gao, C. He, H. Chen, R. Bai, B. Cheng, A. Lei,
Angew. Chem. DOI: 10.1002/ange.201302604; Angew. Chem.
Int. Ed. DOI: 10.1002/anie.201302604.
[20] N. Ono, T. Okujima in Isocyanide Chemistry: Applications in
Synthesis and Material Science First Edition (Ed.: V. G. Nenaj-
denko), Wiley-VCH, Weinheim, 2012, p. 385.
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
Cycloaddition
J. Liu, Z. Fang, Q. Zhang,* Q. Liu,
X. Bi*
&&&& — &&&&
Silver-Catalyzed Isocyanide-Alkyne
Cycloaddition: A General and Practical
Method to Oligosubstituted Pyrroles
Ag2CO3 is the key: The transition-metal-
catalyzed cycloaddition of isocyanides
and unactivated terminal alkynes has
been realized with Ag2CO3 as a unique
and robust catalyst (see scheme). The
protocol is highly efficient, allowing
a broad range of terminal and internal
alkynes to react under base- and ligand-
free conditions, generating synthetically
useful oligosubstituted pyrroles in high
yields.
6
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!