Facile synthesis of pyrroles via Rh(II)-catalyzed transannulation of 1-tosyl-1,2,3-triazoles with silyl or alkyl enol ethers

Article abstract of DOI:10.1016/j.tetlet.2014.09.134

A novel Rh(II)-catalyzed transannulation of 1-tosyl-1,2,3-triazoles with silyl or alkyl enol ethers has been developed, which enables the facile synthesis of substituted pyrroles in a regiocontrollable manner. Moreover, the methodology could be extended to access 3-pyrrolin-2-one derivatives with silyl ketene acetals used as the reaction partner.

Full text of DOI:10.1016/j.tetlet.2014.09.134

Tetrahedron Letters xxx (2014) xxx–xxx
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Facile synthesis of pyrroles via Rh(II)-catalyzed transannulation
of 1-tosyl-1,2,3-triazoles with silyl or alkyl enol ethers
Juan Feng a,b, Yuanhao Wang a, Qingong Li a, Renwang Jiang b, Yefeng Tang a,c,d,
⇑
a The Department of Pharmacology & Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China
b The Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China
c Collaborative Innovation Center for Biotherapy, Tsinghua University, Beijing 100084, China
d Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel Rh(II)-catalyzed transannulation of 1-tosyl-1,2,3-triazoles with silyl or alkyl enol ethers has been
developed, which enables the facile synthesis of substituted pyrroles in a regiocontrollable manner.
Moreover, the methodology could be extended to access 3-pyrrolin-2-one derivatives with silyl ketene
acetals used as the reaction partner.
Received 20 August 2014
Revised 25 September 2014
Accepted 29 September 2014
Available online xxxx
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Triazole
Pyrrole
Enol ether
Cycloaddition
3-Pyrrolin-2-one
Pyrroles are privileged structural motifs widely distributed in
natural products, pharmaceutics, agrochemicals, and functional
materials.1 Development of new methods for their synthesis has
attracted huge efforts from synthetic community.2 Among the
various strategic bond disconnections of pyrroles,3 the [3+2] cyclo-
addition is particularly attractive because of its highly convergent
and economic nature.4 In 2007, Gevorgyan reported a novel Rh(II)-
catalyzed formal [3+2] cycloaddition of pyridotriazoles with termi-
nal alkynes, which led to the formation of indolizine derivatives
[Eq. 1, Scheme 1a].5 This pioneer work opens the new avenue to uti-
lize triazole as the precursor for generating Rh(II)-iminocarbene,6 a
versatile intermediate which is capable of promoting various
interesting transformations.7 Subsequently, Murakami8 and
Gevorgyan,9 respectively, achieved the nickel- and rhodium-
catalyzed formal [3+2] cycloadditions of 1-sulfonyl 1,2,3-triazoles
with alkynes [Eq. 2]. More recently, both of the inter- and
intramolecular [3+2] cycloadditions of 1-sulfonyl 1,2,3-triazoles
with allenes were independently developed by Sarpong10 and
Murakami,11 respectively [Eq. 3].
Ni(0)-catalyzed cycloadditions are only compatible with the inter-
nal alkynes. Moreover, for the unsymmetric internal alkynes
[R1–R2, Eq. 2], the reactions led to a mixture of regioisomers with
no selectivity. Comparably, while the Rh(II)-catalyzed reactions
worked well with electron-rich terminal alkynes, they are not
applicable to other kinds of substrates, such as electron-deficient
terminal alkynes and internal alkynes. The use of allenes as the
[2C] component in this type of cycloadditions was proved to be
an effective way by affording improved reactivity and regioselec-
tivity. However, the preparation of allenes is sometimes laborious,
which discounts its practicality. Within this context, the develop-
ment of more general, efficient, and practical [3+2] cycloadditions
for accessing substituted pyrroles remains a synthetic challenge.
Recently, we reported a novel Rh(II)-catalyzed cycloaddition of
1-sulfonyl 1,2,3-triazoles with 1,3-dienes, which allowed to access
two different types of azaheterocycles, 2,5-dihydroazepines and
2,3-dihydropyrroles, respectively, via formal [4+3] and [3+2] cyc-
loadditions.12 Of note, in the cycloaddition with 2-TIPSO-1,3-diene,
substantial amounts of the [3+2] adduct were obtained [Eq. 4],
which gradually transformed into the corresponding pyrrole deriv-
atives through the elimination of TIPSOH during the course of
chromatography. This observation inspired us to explore a more
general strategy for the synthesis of pyrroles with silyl enol ethers
used as the [2C] component, as depicted in Eq. 5 (Scheme 1b). Thus,
the Rh(II)-iminocarbene C, readily generated from triazoles A upon
treatment with Rh(II)-catalyst, could undergo nucleophilic attack
All of the above-mentioned seminal works largely enrich the
current toolbox of methods for accessing substituted pyrroles,
however, their applicability is compromised to some extent for
the inherent reactivity and selectivity issues. For examples, the
⇑
Corresponding author. Tel.: +86 10 62784677.
E-mail address: yefengtang@tsinghua.edu.cn (Y. Tang).
http://dx.doi.org/10.1016/j.tetlet.2014.09.134
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Feng, J.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.09.134

2
J. Feng et al. / Tetrahedron Letters xxx (2014) xxx–xxx
1a: Formal [3+2] cycloadditions of triazoles with C-C double and triple bonds
topic. Notably, besides the alkyl enol ethers, the more readily
available silyl enol ethers were also proved to be suitable [2C]
component in our scenario, thus largely extending the synthetical
utility of the title reaction.
CO2Me
CO2Me
formal [3+2]
ref 5
+
N
R1
(1)
In align with our previous work,12 we commenced our investi-
gations by treatment of the triazole 1a and TIPS-protected enol
ether 2aa in the presence of 1% Rh2(oct)4 in 1,2-DCE at 100 °C for
1 h (Scheme 2). Gratifyingly, the expected reaction worked
smoothly to afford the dihydropyrrole 3aa, which, without isola-
tion, was directly treated with TsOH (2.0 equiv) to yield the desired
product 4a in 79% yield. Encouraged by this promising result, we
performed a simple evaluation of the effect of the silyl protecting
groups on the reaction. It turned out that, although the less steri-
cally hindered TMS-enol ether was amenable to the reaction, its
instable nature discounted its practical utility. To our delight, the
TBS-enol ether 2ab, which had the compromise steric effect as well
as stability, proved to be an ideal substrate for the reaction by
affording 4a in 92% yield.
N
N
N
N
R1
R2/R1
Cl
Cl
Ar
Ar
N
formal [3+2]
ref 8 and 9
+
+
R1
R2
(2)
(3)
NTs
Ar
Ar
R1/R2
N
Ts
Me
formal [3+2]/
isomerization
N
N
NTs
R1
ref 10 and 11
R1
N
Ts
1b: Formal[3+2] cycloadditions of triazoles with silyl and alkyl enol ethers
Ph
With the optimal conditions secured, we then turn to evaluate
the generality of the transformations (Table 1). First of all, various
1,1-disubstituted TBS- or TIPS-protected enol ethers were exam-
ined with 1a employed as the triazole partner. It was shown that
most of the aryl-substituted enol ethers, either bearing electron-
withdrawing or electron-donating substituents, could undergo
the transformations smoothly to afford the corresponding products
(4a–f) in good to excellent yields. The only exception was the
reaction leading to 4c, which gave only moderate yield, probably
due to the existence of some competitive reactions arising from
the cyanide group. Next, the transannulations were also extended
to the alkyl-substituted enol ethers, as exemplified by the reactions
delivering 4g–i. In agreement of the previous observations,
both TBS- and TIPS-protected enol ethers are amenable to the
N
N
N
formal [3+2]
ref 12
(4)
(5)
OTIPS
+
N
Ts
Ph
Ar
N
TIPSO
Ts
Ar
R1
formal [3+2]/
elimination
OR
R2
δ− δ+
R1
N
+
NTs
ref 13 and
this work
R2
N
B
A
F
Ts
RhII
-N2
-OR
R1
OR
Ar
R1
RhLn
B
OR
R2
δ+
LnRh
R2
NTs
NTs
δ−
N
Ar
Ar
Ts
C
D
E
Scheme 1. Formal [3+2] cycloadditions of triazoles with C-C double or triple bonds.
Table 1
Scope of the transannulations with 1,1-disubstituted silyl enol ethersa,b
Rh2(oct)4(1%)
with the silyl enol ether B to afford the zwitterionic intermediate
D. Subsequently, nucleophilic attack of the N atom of the imine
moiety to the resulted oxocarbenium followed by the release of
Rh(II)-catalyst leads to the formation of the dihydropyrrole E,
which could be transformed into the pyrrole F through the
elimination of ROH. We envisioned that the electron-donating nat-
ure of silyl enol ether together with its dipolar character would
benefit both the reactivity and selectivity of the new version of
[3+2] cycloadditions. It should be pointed out that when this
design was executed in our lab, a formal [3+2] cycloaddition of
1-sulfonyl 1,2,3-triazoles with alkyl enol ethers was reported by
Lee and co-workers.13 Herein, we disclose our own progress on this
N
DCE, 100 oC, 1-4 h;
then TsOH, rt, 3 h
Ts
N
OR
N
N
Ts
+
R1
R2
R2
R1
2
4
1
Ts
Ts
Ts
Ts
N
N
N
N
Ph
Ph
Ph
Ph
Me
F
NC
4d: 93% (R = TBS)
75% (R = TIPS)
4a: 92% (R = TBS)
4b: 72% (R = TBS)
72% (R = TIPS)
4c: 34% (R = TBS)
42% (R = TIPS)
79% (R = TIPS)
Ts
N
Ts
N
Ts
N
Ts
N
Ph
Ph
Ph
Me
Ph
OMe
MeO
4e: 70% (R = TBS)
68% (R = TIPS)
4g: 86% (R = TBS)
69% (R = TIPS)
4f: 85% (R = TBS)
90% (R = TIPS)
4h: 83% (R = TBS)
25% (R = TIPS)
Ts
CF3
N
Ts
N
Ts
N
OR1
Ts
Ph
Ts
Ph
Rh2(oct)4(1%)
N
N
F
DCE, 100 oC, 1 h
MeO2C
OR1
Ph
Ph
4i: 71% (R = TBS)
4j: 82% (R = TMS)
4k: 91% (R = TBS)
4l: 72% (R = TBS)
3aa: R = TIPS
F
F
2aa: R = TIPS
2ab: R = TBS
3ab : R = TBS
Ts
Ts
N
N
Ts
N
79% for 2aa
92% for 2ab
Ts
TsOH, rt
3 h
N
Ph
Ph
+
N
N
tBu
MeO
Ts
OMe
4p: 96% (R = TBS)
N
4m: 75% (R = TBS)
4n: 65% (R = TBS)
Ts
N
F
4o: 93% (R = TBS)
1a
4a
a
The reaction was run with
1 (0.2 mmol), 2 (0.4 mmol), and Rh2(oct)4
(0.002 mmol) in DCE (1.0 mL) at 100 °C.
Scheme 2. Preliminary results for the transannulation of 1-tosyl-1,2,3-triazoles
with 1,1-disubstituted enol ethers. oct = octanoate.
b
Refers to the isolated yield.
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J. Feng et al. / Tetrahedron Letters xxx (2014) xxx–xxx
3
Table 2
transformations, however, the former generally gave better results
Scope of the transannulations with 1,2-disubstituted alkyl enol ethersa,b,c
than the latter, particularly for the alkyl-substituted substrates
(e.g., 4g and 4h). Notably, for the substrate bearing an electron-
withdrawing carboxylate group, the reaction also worked well by
affording the corresponding product 4j in 82% yield. Finally, the
scope of the triazole partners was explored with an array of
4-Ar-1-tosyl-1,2,3-triazoles. Not surprisingly, all of the reactions
gave satisfying results (4k–p), showing little electronic or steric
effect.
Rh2(oct)4(1%)
DCE, 1 00 oC, 1-4 h;
th en TsOH, rt, 3 h
R2
N
N
N
Ts
N
Ts
OEt
+
R2
R1
R1
1
5
7
N
Ts
N
Ts
N
Ts
N
Ts
Besides the 1,1-disubstituted silyl enol ethers, we also
attempted the substrates with 1,2-disubstituted pattern. To our
disappointment, when the TBS-protected silyl ether 5aa (prepared
as a mixture of Z/E isomers in ratio of 1:0.9, 2.5 equiv) was
employed with 1a as the reaction partner, only a moderate yield
(40%) of the expected product 7a was obtained. We envisioned that
the increasing steric hindrance of the 1,2-disubstituted silyl enol
ether might decrease its nucleophilicity toward the Rh(II)-imino-
carbene intermediate. For this end, we turned to examine the less
steric alkyl enol ethers in the reaction. To our delight, while the
methyl enol ether 5ab (Z/E = 1:1) failed to give the desired product
in satisfying yield, the ethyl-derived substrate 5ac (Z/E = 20:1) dis-
played superior reactivity by affording 3,4-disubstituted pyrrole 7a
in yield of 90% (Scheme 3). Although a full rationalization of the
distinct behaviors among the above-examined silyl and alkyl enol
ethers (5aa, 5ab, and 5ac) remains yet to be achieved,14 these
observations indicated that both the steric and electronic features
of the enol ethers had profound influence on the reaction.15
With the suitable protecting group for the 1,2-disubstituted enol
ethers identified, we then evaluated the generality of the transfor-
mations. As shown in Table 2, an array of 4-Ar-1-tosyl 1,2,3-triazoles
bearing either electron-donating or withdrawing substituents
smoothly underwent the one-pot two step transformation with
5ac to afford the corresponding 3,4-disubstituted pyrroles 7a–e in
acceptable to good yields (47–90%). Comparably, the reaction seems
to be sensitive to the variants on the enol ether partner. Indeed,
while the substrates bearing an electron-deficient substituent were
amenable to the reactions (e.g., 7f and 7g), those ones carrying an
electron-donating aromatic ring failed to give the product in
synthetically useful yields (e.g., 7h). Furthermore, the reactions
could also be extended to the alkyl substituted enol ethers, as dem-
onstrated by the reactions leading to 7i–k. However, this type of
substrates showed relatively low reactivity and only resulted in
the corresponding products with moderate yields (30–60%).
To further extend the substrate scope, we also examined vari-
ous other types of substituted enol ethers (Table 3). As shown,
MeO
Me
F
7a: 90%
7b: 65%
7d: 56%
7c: 47%
Cl
F3
C
MeO
N
Ts
Ts
N
N
Ts
N
Ts
Cl
7e: 63%
7f: 55%
7g: 60%
7h : <5%
Me
Me
Me
Me
N
N
N
Ts
Ts
7i : 54%
Ts
7j: 60%
7k: 30%
a
The reaction was run with
(0.002 mmol) in DCE (1.0 mL) at 100 °C.
Refers to the isolated yield.
In most of the cases, the alkyl enol ethers were prepared as a mixture of Z/E
isomers, and used directly without further separation.
1 (0.2 mmol), 5 (0.4 mmol), and Rh2(oct)4
b
c
the ethyl vinyl ether 8a was turned out to be suitable substrates
by furnishing the monosubstituted pyrroles 9a in an excellent yield
(Table 3, entry 1). Besides, the cyclic 2,3-dihydrofuran 8b
and 3,4-dihydro-2H-pyran 8c could respectively lead to the disub-
stituted pyrroles 9b and 9c (entries 2 and 3), although the former
showed superior reactivity than the latter. Moreover, several
trisubstituted cyclic enol ethers 8d–f were evaluated, among
which, the more strained 1-ethoxycycloheptene (8e) and
1-ethoxycyclooctene (8f) afforded the better yields than the
1-ethoxycyclohexene (8d) (entries 4–6). Finally, it was found that
by giving a low yield of 9g (entry 7), most likely attributed to the
acyclic trisubstituted enol ether 8g exhibited poor reactivity unfa-
vorable steric effect associated with this type of substrates.
Finally, we also explored the possibility of employing the silyl
ketene acetals as the [2C] component in the transformations.16
As the proof-of-concept cases, three representative silyl ketene
acetals 10a–c (R = H, Me or Ph) were chosen as substrates. Interest-
ingly, the corresponding transannulation products 13a–c did form
at the beginning,17 however, they were found to be unstable and
readily underwent the deprotection of the silyl group followed
by double bond isomerization (Scheme 4) to afford the 3-pyrro-
lin-2-ones 11a–c as final products. Given that 3-pyrrolin-2-one
Ts
N
Rh2(oct)4(1%)
OR
DCE, 100 oC, 1 h
RO
5aa: R = TBS; Z:E = 1:0.9
5ab: R = Me; Z:E = 1:1
5ac: R = Et; Z:E = 20:1
6aa: R = TBS
6ab: R = Me
6ac: R = Et
represents
a key structural element in various bioactive
molecules,18 this transformation provides a new avenue to access
+
40% for 5aa
<5% for 5ab
90% for 5ac
TsOH, rt
1 h
the related aza-heterocycles.19
N
N
N
In summary, we have successfully developed a highly efficient
method for the synthesis of substituted pyrroles via a novel
Rh(II)-catalyzed transannulation of 1-tosyl-1,2,3-triazoles with
silyl or alkyl enol ethers. Moreover, the method could also be
extended to the synthesis of 3-pyrrolin-2-ones by employing silyl
ketene acetals as the reaction partner. Several advantages of the
described methodology, including the readily available starting
material, high efficiency, broad substrate scope, and controllable
regioselectivity, render it an alternative to the current toolbox of
Ts
1a
Ts
N
7a
Scheme 3. Preliminary results for the transannulations of 1-tosyl-1,2,3-triazoles
with 1,2-disubstituted silyl or alkyl enol ethers.
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4
J. Feng et al. / Tetrahedron Letters xxx (2014) xxx–xxx
Table 3
Supplementary data
Scope of transannulations with other types of substituted alkyl enol
ethersa,b
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.09.
134.
R2
Rh2(oct)4(1%)
R1
DCE, 100 oC, 1-4 h;
N
R1
N
N
Ts
N
then TsOH, rt, 3 h
Ts
+
Ph
R2
OR
1a
References and notes
8
9
Pyrroles
Entry
1
Enol ethers
Yields
1. For selected reviews, see: (a) Walsh, C. T.; Garneau-Tsodikova, S.; Howard-
Jones, A. R. Nat. Prod. Rep. 2006, 23, 517; (b) Fan, H.; Peng, J.; Hamann, M. T.; Hu,
J. Chem. Rev. 2008, 108, 264; (c) Heugebaert, T. S. A.; Roman, B. I.; Stevens, C. V.
Chem. Soc. Rev. 2012, 41, 5626; (d) Kathirav, M. K.; Salake, A. B.; Chothe, A. S.;
Dudhe, P. B.; Watode, R. P.; Mukta, M. S.; Gadhwe, S. Bioorg. Med. Chem. 2012,
20, 5678.
2. For reviews on pyrrole synthesis, see: (a) Gilchrist, T. L. J. Chem. Soc., Perkin
Trans. 1 1999, 2849; (b) Balme, G. Angew. Chem. Int. Ed. 2004, 43, 6238; (c)
Schmuck, C.; Rupprecht, D. Synthesis 2007, 3095; (d) Patil, N. T.; Yamamoto, Y.
Arkivoc 2007, 10, 121.
N
Ts
OEt
83%
Ph
8a
9a
HO
n
O
n
N
Ts
Ph
82%
24%
2
9b: n = 1
9c: n = 2
8b: n = 1
8c: n = 2
3c
3. For selected recent examples of pyrrole synthesis, see: (a) Rakshit, S.; Patureau,
F. W.; Glorius, F. J. Am. Chem. Soc. 2010, 132, 9585; (b) Trost, B. M.; Lumb, J.-P.;
Azzarelli, J. M. J. Am. Chem. Soc. 2011, 133, 740; (c) Huestis, M. P.; Chan, L.;
Stuart, D. R.; Fagnou, K. Angew. Chem. Int. Ed. 2011, 50, 1338; (d) Chen, F.; Shen,
T.; Cui, Y.; Jiao, N. Org. Lett. 2012, 14, 4926; (e) Michlik, S.; Kempe, R. Nat. Chem.
2013, 5, 140; (f) Reddy, B. V. S.; Reddy, M. R.; Rao, Y. G.; Yadav, J. S.; Sridhar, B.
Org. Lett. 2013, 15, 464.
4. (a) Lourdusamy, E.; Yao, L.; Park, C.-M. Angew. Chem. Int. Ed. 2010, 49, 7963; (b)
Ng, E. P. J.; Wang, Y.-F.; Chiba, S. Synlett 2011, 783; (c) Jun, X.; Xia, X. D.; Zeng, T.
T.; Feng, Z. J.; Chen, J. R.; Lu, L. Q.; Xiao, W. J. Angew. Chem. Int. Ed. 2014, 53,
5653.
Ph
OEt
N
n
n
Ts
8c
9d
4c
5
6
8d: n = 1
8e: n = 2
8f: n = 3
9d: n = 1
9e: n = 2
9f: n = 3
20%
72%
94%
Ph
Me
Me
Ph
7c
N
Ts
17%
EtO
8g (
Ph
5. Chuprakov, S.; Hwang, F. W.; Gevorgyan, V. Angew. Chem. Int. Ed. 2007, 46,
4757.
:
= 9:1)
Z E
9g
c 0.005 mmol Rh2(oct)4 was used.
6. For leading reviews, see: (a) Chattopadhyay, B.; Gevorgyan, V. Angew. Chem. Int.
Ed. 2012, 51, 862; (b) Gulevich, A. V.; Gevorgyan, V. Angew. Chem. Int. Ed. 2013,
52, 1371; (c) Davie, H. M. L.; Alford, J. S. Chem. Soc. Rev. 2014, 43, 5151.
7. For recent examples, see: (a) Shi, Y.; Gevorgyan, V. Org. Lett. 2013, 15, 5394; (b)
Alford, J. S.; Spangler, J. E.; Davies, H. M. L. J. Am. Chem. Soc. 2013, 135, 11712;
(c) Parr, B. T.; Green, S. A.; Davies, H. M. J. J. Am. Chem. Soc. 2013, 135, 4716; (d)
Zibinsky, M.; Fokin, V. V. Angew. Chem. Int. Ed. 2013, 52, 1507; (e) Spangler, J. E.;
Davies, H. M. L. J. Am. Chem. Soc. 2013, 135, 6802; (f) Chuprakov, S.; Kwok, S. W.;
Fokin, V. V. J. Am. Chem. Soc. 2013, 135, 4652; (g) Miura, T.; Tanaka, T.; Hiraga,
K.; Stewart, S. G.; Murakami, M. J. Am. Chem. Soc. 2013, 135, 13652; (h) Miura,
T.; Tanaka, T.; Biyajima, T.; Yada, A.; Murakami, M. Angew. Chem. Int. Ed. 2013,
52, 3883; (i) Parr, B. T.; Davies, H. M. L. Angew. Chem. Int. Ed. 2013, 52, 10044; (j)
Liu, R. H.; Zhang, M.; Winston-McPherson, G.; Tang, W. P. Chem. Commun. 2013,
4376; (k) Chuprakov, S.; Worrell, B. T.; Selander, N.; Sit, R. K.; Fokin, V. V. J. Am.
Chem. Soc. 2014, 136, 195; (l) Miura, T.; Funakoshi, Y.; Murakami, M. J. Am.
Chem. Soc. 2014, 136, 2272; (m) Yang, J.; Zhu, C.; Tang, X.; Shi, M. Angew. Chem.
Int. Ed. 2014, 53, 5142.
a
The reaction was run with 1a (0.2 mmol), 8 (0.4 mmol), and Rh2(oct)4
(0.002 mmol) in DCE (1.0 mL) at 100 °C.
b
Refers to the isolated yield.
Rh2(oct)4(1%)
O
DCE, 100 oC, 1 h;
R
R
N
N
then TsOH, rt, 3 h
N
Ts
+
N
Ts
TBSO
OEt
Ph
Ph
1a
10a: R = H
10b: R = Me
10c: R = Ph
11a: R = H (57%)
11b: R = Me (60%)
11c: R = Ph (54%)
8. Miura, T.; Yamauchi, M.; Murakami, M. Chem. Commun. 2009, 1470.
9. Chattopadhyay, B.; Gevorgyan, V. Org. Lett. 2011, 13, 3746.
10. Schultz, E. E.; Sarpong, R. J. Am. Chem. Soc. 2013, 135, 4696.
11. Miura, T.; Hiraga, K.; Biyajima, T.; Nakamuro, T.; Murakami, M. Org. Lett. 2013,
15, 3298.
12. Shang, H.; Wang, Y.; Tian, Y.; Feng, J.; Tang, Y. F. Angew. Chem. Int. Ed. 2014, 53,
5662.
13. Kim, C.; Park, S.; Eom, D.; Seo, B.; Lee, P. H. Org. Lett. 2014, 16, 1900.
14. For an illustrative reference, see: Burfeindt, J.; Patz, M.; Müller, M.; Mayr, H. J.
Am. Chem. Soc. 1998, 120, 3629.
deprotection/
[3+2]
OEt
isomerization
OTBS
Ts
TBSO
R
-OEt
R
N
N
Ts
Ph
Ph
12
13
15. It was proved that the geometry of the 1,2-disubstituted enol ethers had
influence on the reaction outcomes. The cis-isomer generally showed better
reactivity than the trans-isomer in the reaction.
Scheme 4. Transannulation of 1-tosyl 1,2,3-triazoles with silyl ketene acetals.
16. When this Letter was in preparation, a similar transformation was disclosed by
Li and co-workers. For the reference, see: Ran, R.-Q.; He, J.; Xiu, S.-D.; Wang, K.-
B.; Li, C.-Y. Org. Lett. 2014, 16, 3704.
17. The intermediacy of 13a–c were partly proved by the isolation and
characterization of 13a.
18. (a) Gurjar, M. K.; Joshi, R. A.; Chaudhuri, S. R.; Joshi, S. V.; Barde, A. R.; Gediya, L.
K.; Ranade, P. V.; Kadam, S. M.; Naik, S. J. Tetrahedron Lett. 2003, 44, 4853; (b)
Boiadjiev, S. E.; Woydziak, Z. R.; McDonagh, A. F.; Lightner, T. A. Tetrahedron
2006, 62, 7043; (c) Feng, Z.; Chu, F.; Guo, Z.; Sun, P. Bioorg. Med. Chem. Lett.
2009, 19, 2270.
19. For other selected examples of synthesis of 3-pyrrolin-2-one derivatives, see:
(a) Faul, M. M.; Winneroski, L. L.; Krumrich, C. A. J. Org. Chem. 1998, 63, 6053;
(b) Murai, M.; Miki, K.; Ohe, K. J. Org. Chem. 2008, 73, 9174; (c) Greger, J. G.;
Yoon-Miller, S. J. P.; Bechtold, N. R.; Flewelling, S. A.; MacDonald, J. P.; Downey,
C. R.; Cohen, E. A.; Pelkey, E. T. J. Org. Chem. 2011, 76, 8203; (d) Awuah, E.;
Capretta, A. J. Org. Chem. 2011, 76, 3122; (e) Qian, J.-L.; Yi, W.-B.; Cai, C.
Tetrahedron Let. 2013, 54, 7100.
methods for the synthesis of pyrroles and relevant derivatives.
Applications of the method in the total synthesis of bioactive mol-
ecules are underway in this laboratory.
Acknowledgments
We gratefully acknowledge the financial supports from the
NSFC (21102081 and 21272133), New Teachers’ Fund for Doctor
Stations Ministry of Education (20110002120011), Scientific
Research Foundation for the Returned Overseas Chinese Scholars,
Ministry of Education (20121027968), Beijing Natural Science
Foundation (2132037) and Tsinghua-Giti Project.
Please cite this article in press as: Feng, J.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.09.134