Functionalized pyrroles from vinylaziridines and alkynes via rhodium-catalyzed domino ring-opening cyclization followed by C[dbnd]C bond migration

Article abstract of DOI:10.1016/j.tet.2019.01.022

Rhodium(I)-catalyzed intermolecular cycloadditions of alkynes with vinyl aziridines bearing a conjugated carbonyl group in the olefin moiety followed by the double migration resulted in the formation of pyrrole derivatives in a one pot fashion.

Full text of DOI:10.1016/j.tet.2019.01.022

Accepted Manuscript
Functionalized pyrroles from vinylaziridines and alkynes via rhodium-catalyzed
domino ring-opening cyclization followed by C=C bond migration
Shu-Hao Wan, Shiuh-Tzung Liu
PII:
S0040-4020(19)30048-1
https://doi.org/10.1016/j.tet.2019.01.022
TET 30074
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 23 October 2018
Revised Date: 6 January 2019
Accepted Date: 11 January 2019
Please cite this article as: Wan S-H, Liu S-T, Functionalized pyrroles from vinylaziridines and alkynes
via rhodium-catalyzed domino ring-opening cyclization followed by C=C bond migration, Tetrahedron
(2019), doi: https://doi.org/10.1016/j.tet.2019.01.022.
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Functionalized pyrroles from vinylaziridines
and alkynes via rhodium-catalyzed domino
ring-opening cyclization followed by C=C
bond migration
Leave this area blank for abstract info.
Shu-Hao Wan and Shiuh-Tzung Liu
Department of Chemistry, National Taiwan University, Taipei, Taiwan 106

1
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Tetrahedron
journal homepage: www.elsevier.com
Functionalized pyrroles from vinylaziridines and alkynes via rhodium-catalyzed
domino ring-opening cyclization followed by C=C bond migration
Shu-Hao Wan and Shiuh-Tzung Liu
Department of Chemistry, National Taiwan University, Taipei, Taiwan, 106
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Rhodium(I)-catalyzed intermolecular cycloadditions of alkynes with vinyl aziridines bearing a
conjugated carbonyl group in the olefin moiety followed by the double migration resulted in the
formation of pyrrole derivatives in a one pot fashion.
2009 Elsevier Ltd. All rights reserved
.
Available online
Keywords:
Cycloaddition
Aziridine
Pyrrole
Isomerization
Rhodium
———
Corresponding author. Tel.: +0-000-000-0000; fax: +0-000-000-0000; e-mail: author@university.edu

2
Tetrahedron
ACCEPTED MANUSCRIPT
1. Introduction
Transition-metal catalysis toward the development of effective
methods for carbon−carbon and carbon−heteroatom bond
formation have been received much attention in particular for
those of the synthesis of heterocycles. Quite a number of readily
available compounds have been prepared in this regard. Among
them, vinyl-substituted aziridines 1 are known as valuable
substrates for transition-metal-catalyzed [3+2], [3+3], [3+4] or
[5+2] annulation reactions with alkynes for five, six or seven
membered hetercycles, respectively.1-5 In the [3+2] annulations,
vinyl-aziridine acts as a three atom component for the five-
member ring leaving the vinyl group unreacted, rendering the
vinyldihydropyrrole product 2 (Scheme 1). However, this
compound readily undergoes hydrolysis in the presence of a
Lewis acid, giving γ–amino ketone 3.3 In fact, these two steps
leading to 3 can be carried out in a one-pot fashion. In this
context, not much effort has addressed about the double bond
migration leading to the pyrrole 4. Here, we would like to report
the preparation of vinyldihydropyrroles via the rhodium
catalyzed cycloaddition and the double bond isomerization
reaction leading to the corresponding pyrroles in a one-pot
fashion.
Scheme 2. Cycloaddition followed by isomerization to yield
pyrroles
The isomerization was studied by monitoring the reaction in
CDCl3 with H1-NMR spectroscopy. Upon addition of a base,
compound 6a was converted into 8a as evidenced by the
disappearance of the signal corresponding to Hγ and a upfield
shift of Hα to 2.7 ppm with the integration of 2H (Figure 1a and
b). The NOE experiment showed the interaction between Hε and
Hβ, not Hα. Thus, the stereochemistry of compound 8a is
established as shown in Scheme 2.7 We also believed that the
ester functionality in the molecule may also assist the double
bond migration, presumably due to the increasing acidity of Hγ.8
Finally, the isomerization proceeded further to yield the pyrrole
9a by adjusting the medium to an acidic condition (Figure 1c).
Table 1 summarizes the study of isomerization with various
bases. Most organic bases assist this isomerization, but 1,4-
diazabicyclo[2.2.2]octane (DABCO) appears to be the most
efficient one.
Table 1. Optimization of isomerization of 6a into 7 and 9aa
Scheme 1. Cycloaddition of vinyl aziridines with alkynes
2. Results and discussion
entry
Base (amount)
iPr2NH (1 eq)
Pyrrolidine (1 eq)
Et3N (1 eq)
t (oC)
50
50
50
50
50
50
50
50
rt
7
9a
The starting substrate 5 in a mixture of E/Z forms was
obtained according to the reported method.1c Reaction of E/Z-5
with phenylacetylene in the presence of [Rh(NBD)2]BF4 in 1,2-
dichloroethane at ambient temperature proceeded smoothly. By
monitoring the reaction, we found that the E-isomer was
transformed into dihydropyrrole 6a within 0.5 h, but the Z-isomer
remained in the solution. However, upon standing a longer time,
the Z-isomer was eventually converted into 6a, indicating that the
E form is more reactive than the Z isomer. Such a selectivity is
similar to those reported in cycloadditions.1c,1d,6 The trans
1
85%
trace
11%
99%
7%
15%
99%
89%
trace
93%
99%
99%
84%
43%
trace
2
3
4
Pyridine (1 eq)
p-DMAP (1 eq)
DABCO (1 eq)
DABCO (0.5 eq)
DABCO (0.2 eq)
DABCO (0.5 eq)
None
5
6
trace
trace
16%
57%
99%
7
1
8
configuration in 6a was established by H-NMR spectroscopy.
The observed J value for Hα and Hβ in 6a is 15.7 Hz, which is
9
comparable to those of the α,β-unsaturated ester in
E
10
rt
configuration. Compound 6a was quite sensitive to water under
acidic conditions, as expected, and it readily underwent ring
opening reaction to yield the amino ketone 7.3 However,
treatment of 6a with a base followed by acid workup rendered the
pyrrole product 9a, indicating that the isomerization of 6a under
basic condition could avoid the ring opening hydrolysis.
a A sample of 6a (40 mg, 0.10 mmol) in CDCl3 (0.5 mL) was added with
base. After 1 h, CF3CO2H (0.15 mmol) was added.

3
addition, a benzoyl substituted vinyl aziridine 11 underwent
ACCEPTED MANUSCRIPT
smoothly with phenyacetylene to yield the cycloadduct 12, and
then isomerize to the pyrrole product 13 (Eqn. 2). Notably,
reaction
of
1-[(4-methylphenyl)sulfonyl]-2-[(1E)-2-
phenylethenyl]aziridine, a substrate without an ester functionality,
with phenylacetylene gave a complicated mixture of unidentified
products, indicating the necessity of carbonyl functionality in
aziridine components.
EtO2C
CO2Et
C3H7
C3H7
(1)
[Rh(NBD)2]BF4
N
O
Ts
TsHN
5
10
O
O
O
Ph
Ph
1. DABCO
Figure 1. Partial 1H NMR spectra of 6a (a), 8a (b) and 9a (c) for
2. CF3CO2H
Ph
Ph
(2)
comparison
100%
[Rh(NBD)2]BF4
N
Ph
Ph
Ts
N
N
With the optimal information, a broad range of substituted
phenylacetylenes were explored as substrates leading to the
corresponding pyrroles in a one-pot fashion and the results are
shown in Table 2. Various p-substituted phenylacetylene
participated well in the reaction and furnished the corresponding
pyrroles in good yields except nitro and cyano substituents.
Common functional groups such as alkyl, ester, keto, ether and
halogens were found compatible and the desired products were
Ts
12
Ts
13
11
According to the mechanism of rhodium(I)-catalyzed
cycloaddition of aziridines with alkynes proposed by Zhang,
reaction pathway in this work is presented in Figure 2.3 Oxidative
ring opening of aziridine by Rh(I) gives the π-complex I. Upon
coordination of the alkyne molecule followed by the migratory
insertion renders the metallocycle intermediate III, which then
undergoes the reductive elimination to yield the dihydropyrrole
product IV. This initial product can be either hydrolyzed to
produce the γ-amino ketone V or isomerized under basic
conditions to generate VI. Aromatization of VI provides the
pyrrole product.
obtained
in
good
yields.
Furthermore,
2,4,6-
trimethylphenylacetylene and naphthylacetylene underwent the
cycloaddition followed by isomerization to give 9j (62%) and 9k
(73%), respectively. Notably, 2,4,6-trimethylphenylacetylene
with sterically distinct substituents delivered 9j in good yield.
The use of p-nitrophenylacetylene as the substrate provided a
complicated mixture of products and the desired compound 6h
was determined by NMR in 11% yield. However, reaction of 5
with p-cyanophenylacetylene did not give any desired product,
presumably due to the coordination ability of nitrile group toward
the metal center. The reactivity of diphenylacetylene appeared to
be poor and the reaction only gave 9l in 19% by NMR, but acetyl
phenylacetylene gave 9m in a reasonable yield. Unfortunately,
alkyl substituted alkynes were not applicable to this
methodology. Under the optimal conditions, reaction of 5 with 1-
pentyne afforded γ-aminoketone 10 as the isolated product in
74% (Eqn. 1). However, reaction of 5 with N-ethynyl-N,4-
dimethyl-benzenesulfonamide, a ynamide substrate, did not
provide the pyrrole product under the standard conditions. In
3. Summary
We have developed a synthetic method of preparation of
functionalized pyrroles via rhodium-catalyzed coupling of
vinylaziridines and alkynes followed by double bond migrations in
one-pot fashion. In this work, the double bond migration steps were
investigated in detail, allowing us to understand the nature of
dihydropyrroles. Current research is focused on extending the
rhodium catalyzed coupling of vinylaziridines with other
nucleophiles under various conditions.
Table 2. Reaction of various phenylacetylene with 5 leading to pyrrolesa

4
Tetrahedron
ACCEPTED MANUSCRIPT
a Isolated yields.
b NMR yield, not obtained in a pure form.
Figure 2. Reaction pathway for the cycloaddition and C=C bond migration
4. Experimental section
mL) was added for the extraction the crude product. The organic
extracts were combined, dried over anhydrous MgSO4, filtered
and concentrated to give the crude aldehyde, which was used for
the following step without further purification.
Manipulation was performed by using a standard Schlenk
technique under dry nitrogen atmosphere. Solvents were dried
using standard methods and distilled under nitrogen before use.
The rhodium complex [Rh(NBD)2]BF4,8 methyl 1-[(4-
To a suspension of NaH (60%, 600 mg, 15.0 mmol) in THF
(30 mL) was added triethyl phosphonoacetate (3.0 mL, 15 mmol)
drop-wise at 0 ºC under N2 atmosphere. The resulting mixture
was stirred at ambient temperature until no H2 evolution. The
freshly prepared aldehyde in THF (30 mL) was added to the
above solution with stirring. The reaction was monitored by the
TLC analysis to confirm the completion. The solution was
washed with a saturated aqueous solution of NH4Cl (30 mL) and
extracted with EtOAc (3 x 30 mL). The combined organic layers
were dried over anhydrous MgSO4, filtered and concentrated
under reduced pressure. The residue was chromatographed on
silica gel using EtOAc/hexane = 1/4 as the eluent to give the
desired vinyl aziridine 5 as colorless oil with E/Z > 20/1. (2.245
g, 76% over 2 steps). E/Z > 20/1. E-isomer: 1H-NMR (δ, CDCl3):
methylphenyl)sulfonyl]-2-aziridinecarboxylate9
and
the
ethynylarenes were prepared by following the reported method.
Mass spectra were recorded with a LCQ Advantage (ESI) Mass
Spectrometer. NMR spectra were determined with Bruker
AvanceIII-400 or DMX-500 FT-NMR spectrometers at room
temperature. 1H and 13C-NMR spectra were obtained in CDCl3.
4.1. Preparation of ethyl 1-[(4-methylphenyl)sulfonyl]-2-
aziridineacrylate (5)
To a solution of methyl 1-[(4-methylphenyl)sulfonyl]-2-
aziridinecarboxylate (2.553 g, 10.00 mmol) in CH2Cl2 (30 mL)
was added diisobutylaluminum hydride (1 M, 12.0 mL, 12.0
mmol) drop-wise at -78 ºC under N2 atmosphere. The resulting
mixture was kept at ambient temperature and stirred for 2 h. The
reaction was quenched with 1N HCl (50 mL) and Et2O (3 x 50
3
3
7.82 (d, JHH = 8.1 Hz, 2H, Ts), 7.35 (d, JHH = 8.1 Hz, 2H, Ts),
6.55 (dd, 3JHH = 15.5 Hz, 3JHH = 7.4 Hz, 1H, =CH), 6.10 (dd, 3JHH
= 15.5 Hz, JHH = 0.7 Hz, 1H, =CH), 4.17 (q, 3JHH = 7.1 Hz, 2H,
4

5
3
3
3
Et), 3.37-3.32 (m, 1H, aziridine), 2.87 (d, JHH = 7.1 Hz, 1H,
2.76 (t, JH = 7.4 Hz, 2H, CH2), 2.56 (t, JHH = 7.4 Hz, 2H,
H
3
A
CCEPTED MANUSCRIPT
aziridine), 2.45 (s, 3H, Ts), 2.27 (d, 3JHH = 4.2 Hz, 1H, aziridine),
CH2), 2.36 (s, 3H, Ts), 1.25 (t, JHH = 7.0 Hz, 3H, Et). 13C-NMR
(δ, CDCl3): 172.99 (C=O), 145.21 (C), 135.68 (C), 135.41 (C),
135.23 (C), 131.06 (CH), 130.32 (q, JCF = 32.1 Hz, C), 129.78
(CH), 127.16 (CH), 127.09 (C), 124.62 (q, JCF = 3.6 Hz, CH),
124.44 (q, JCF = 274.3 Hz, CF3), 122.19 (CH), 118.30 (CH),
60.80 (CH2), 34.88 (CH2), 22.33 (CH2), 21.86 (CH3), 14.52
(CH3). 19F-NMR (δ, CDCl3): -62.56 (s, 3F, CF3). ESI-HRMS
(TOF): MH+ found 466.1316. C23H23F3NO4S requires 466.1300.
1.26 (t, JHH = 7.1 Hz, 3H, Et). 13C-NMR (δ, CDCl3): 165.64
3
2
(C=O), 145.32 (C), 141.93 (CH), 135.02 (C), 130.20 (CH),
128.27 (CH), 125.70 (CH), 61.08 (CH2), 38.92 (CH), 34.95
(CH2), 22.00 (CH3), 14.49 (CH3), which are essentially identical
to the literature reported.1c
3
1
4.2. General Procedure for preparation of pyrroles
1
To a solution of 5 (1 equiv.) and [Rh(NBD)2]BF4 (5 mol%) in
1,2-DCE (1 mL) was added the alkyne (1.5 equiv.) in 1,2-DCE (1
mL). The resulting mixture was stirred for 0.5 h. Upon the
addition of 1,4-diazabicyclo[2.2.2]octane (0.5 equiv.), the
mixture was heated to 50 ºC for 1 h. The reaction mixture was
then neutralized with trifluoroacetic acid (1.5 equiv). The solvent
was removed under reduced pressure and the residue was purified
by column chromatography using CH2Cl2/hexane as the eluent to
give the desired pyrrole 9.
9f. Yellow oil. 66 mg, 75%. H-NMR (δ, CDCl3): 7.88 (d,
3JHH = 8.4 Hz, 2H, Ar-H), 7.35 (d, JHH = 8.4 Hz, 2H, Ar-H),
3
7.21-7.19 (m, 3H, Ar-H), 7.09 (d, 3JHH = 8.1 Hz, 2H, Ar-H), 6.09
4
3
(d, JHH = 1.8 Hz, 1H, pyrrole), 4.10 (q, JHH = 7.0 Hz, 2H, Et),
2.73 (t, 3JHH = 7.7 Hz, 2H, CH2), 2.61 (s, 3H, CH3), 2.53 (t, 3JHH
=
3
7.7 Hz, 2H, CH2), 2.33 (s, 3H, Ts), 1.21 (t, JHH = 7.0 Hz, 3H,
Et). 13C-NMR (δ, CDCl3): 197.98 (C=O), 172.89 (C=O), 145.10
(C), 136.57 (C), 136.46 (C), 135.77 (C), 135.62 (C), 130.74
(CH), 129.72 (CH), 127.66 (CH), 127.29 (C), 127.04 (CH),
122.41 (CH), 118.44 (CH), 60.70 (CH2), 34.80 (CH2), 26.90
(CH3), 22.26 (CH2), 21.80 (CH3), 14.46 (CH3). ESI-HRMS
(TOF): MH+ found 440.1532. C24H26NO5S requires 440.1532.
1
9a. Yellow oil. 51 mg, 64%. H-NMR (δ, CDCl3): 7.40-7.26
(m, 8H, Ar-H), 7.15 (d, 3JHH = 8.3 Hz, 2H, Ar-H), 6.09 (d, 4JHH
=
1.8 Hz, 1H, pyrrole), 4.19 (q, 3JHH = 7.1 Hz, 2H, Et), 2.82 (t, 3JHH
= 7.4 Hz, 2H, CH2), 2.62 (t, 3JHH = 7.4 Hz, 2H, CH2), 2.41 (s, 3H,
Ts), 1.31 (t, 3JHH = 7.1 Hz, 3H, Et). 13C-NMR (δ, CDCl3): 173.12
(C=O), 144.81 (C), 136.77 (C), 135.94 (C), 131.77 (C), 131.00
(CH), 129.61 (CH), 128.48 (CH), 127.63 (CH), 127.30 (CH),
126.60 (C), 121.17 (CH), 117.13 (CH), 60.75 (CH2), 34.97
(CH2), 22.44 (CH2), 21.86 (CH3), 14.53 (CH3). ESI-HRMS
(TOF): MH+ found 398.1459. C22H24NO4S requires 398.1426.
1
9g. Yellow oil. 64 mg, 68%. H-NMR (δ, CDCl3): 7.98 (d,
3JHH = 8.5 Hz, 2H, Ar-H), 7.32 (d, JHH = 8.5 Hz, 2H, Ar-H),
3
7.22-7.20 (m, 3H, Ar-H), 7.09 (d, 3JHH = 8.5 Hz, 2H, Ar-H), 6.09
4
3
(d, JHH = 2.1 Hz, 1H, pyrrole), 4.39 (q, JHH = 7.1 Hz, 2H, Et),
4.12 (q, 3JHH = 7.1 Hz, 2H, Et), 2.74 (t, JHH = 7.8 Hz, 2H, CH2),
3
3
3
2.54 (t, JHH = 7.8 Hz, 2H, CH2), 2.34 (s, 3H, Ts), 1.41 (t, JHH
=
7.1 Hz, 3H, Et), 1.23 (t, JHH = 7.1 Hz, 3H, Et). 13C-NMR (δ,
CDCl3): 172.98 (C=O), 166.68 (C=O), 145.08 (C), 136.23 (C),
135.89 (C), 135.71 (C), 130.63 (CH), 130.21 (C), 129.74 (CH),
128.89 (CH), 127.14 (CH), 122.26 (CH), 118.24 (CH), 61.35
(CH2), 60.76 (CH2), 34.89 (CH2), 22.34 (CH2), 21.86 (CH3),
14.64 (CH3), 14.52 (CH3). ESI-HRMS (TOF): MH+ found
470.1638. C25H28NO6S requires 470.1637.
3
1
9b. Yellow oil. 53 mg, 65%. H-NMR (δ, CDCl3): 7.24-7.09
3
(m, 9H, Ar-H), 5.99 (d, 4JHH = 2.1 Hz, 1H, pyrrole), 4.13 (q, JHH
= 7.3 Hz, 2H, Et), 2.74 (t, 3JHH = 7.6 Hz, 2H, CH2), 2.55 (t, 3JHH
=
7.6 Hz, 2H, CH2), 2.39 (s, 3H, CH3), 2.35 (s, 3H, CH3), 1.24 (t,
3JHH = 7.3 Hz, 3H, Et). 13C-NMR (δ, CDCl3): 173.15 (C=O),
144.75 (C), 138.35 (C), 136.91 (C), 135.99 (C), 130.84 (CH),
129.59 (CH), 128.87 (C), 128.36 (CH), 127.29 (CH), 126.67 (C),
120.96 (CH), 116.95 (CH), 60.74 (CH2), 34.95 (CH2), 22.43
(CH2), 21.86 (CH3), 21.62 (CH3), 14.51 (CH3). ESI-HRMS
(TOF): MH+ found 412.1599. C23H26NO4S requires 412.1583.
1
9j. Yellow oil. 55 mg, 62%. H-NMR (δ, CDCl3): 7.30-7.27
(m, 3H, Ts, pyrrole), 7.14 (d, 3JHH = 7.8 Hz, 2H, Ts), 6.80 (s, 2H,
4
3
mesityl), 5.88 (d, JHH3 = 2.1 Hz, 1H, pyrrole), 4.14 (q, JHH = 7.1
Hz, 2H, Et), 2.81 (t, JHH = 7.5 Hz, 2H, CH2), 2.59 (t, JHH = 7.5
3
1
Hz, 2H, CH2), 2.39 (s, 3H, CH3), 2.32 (s, 3H, CH3), 1.66 (s, 6H,
9c. Yellow oil. 57 mg, 67%. H-NMR (δ, CDCl3): 7.31-7.14
CH3), 1.25 (t, JHH = 7.1 Hz, 3H, Et). 13C-NMR (δ, CDCl3):
3
3
(m, 7H, Ar-H), 6.88 (d, JHH = 8.5 Hz, 2H, Ar-H), 6.02 (br, 1H,
3
173.24 (C=O), 144.90 (C), 140.06 (C), 138.76 (C), 136.00 (C),
132.80 (C), 129.67 (CH), 128.17 (CH), 127.84 (CH), 125.34 (C),
118.99 (CH), 115.72 (CH), 60.70 (CH2), 35.28 (CH2), 22.67
(CH2), 21.90 (CH3), 21.53 (CH3), 20.49 (CH3), 14.57 (CH3). ESI-
HRMS (TOF): MH+ found 440.1876. C25H30NO4S requires
440.1896.
pyrrole), 4.18 (q, JHH = 7.1 Hz, 2H, Et), 3.90 (s, 3H, OCH3),
2.80 (t, 3JHH = 7.5 Hz, 2H, CH2), 2.60 (t, 3JHH = 7.5 Hz, 2H, CH2),
3
2.40 (s, 3H, Ts), 1.30 (t, JHH = 7.1 Hz, 3H, Et). 13C-NMR (δ,
CDCl3): 173.16 (C=O), 159.95 (C), 144.74 (C), 136.54 (C),
136.02 (C), 132.32 (CH), 129.61 (CH), 127.33 (CH), 126.52 (C),
124.13 (C), 120.76 (CH), 116.70 (CH), 113.08 (CH), 60.76
(CH2), 55.58 (CH3), 34.99 (CH2), 22.47 (CH2), 21.88 (CH3),
14.55 (CH3). ESI-HRMS (TOF): MH+ found 428.1548.
C23H26NO5S requires 428.1532.
1
9k. Yellow oil. 65 mg, 73%. H-NMR (δ, CDCl3): 7.87-6.82
3
(12H, Ar-H), 6.14 (s, 1H, pyrrole), 4.16 (q, JHH = 7.1 Hz, 2H,
3
3
Et), 2.86 (t, JHH = 7.5 Hz, 2H, CH2), 2.64 (t, JHH = 7.5 Hz, 2H,
CH2), 2.21 (s, 3H, Ts), 1.27 (t, JHH = 7.1 Hz, 3H, Et). 13C-NMR
3
1
9d. Yellow oil. 54 mg, 63%. H-NMR (δ, CDCl3): 7.29-7.11
(m, 9H, Ar-H), 6.03 (d, 4JHH = 1.9 Hz, 1H, pyrrole), 4.13 (q, 3JHH
(δ, CDCl3): 173.18 (C=O), 144.63 (C), 135.46 (C), 133.93 (C),
133.22 (C), 132.60 (C), 130.63 (CH), 129.43 (CH), 129.35 (CH),
128.97 (C), 128.01 (CH), 127.49 (CH), 126.09 (CH), 125.64
(CH), 125.55 (C), 125.48 (CH), 124.69 (CH), 119.96 (CH),
117.73 (CH), 60.74 (CH2), 35.14 (CH2), 22.56 (CH2), 21.67
(CH3), 14.55 (CH3). ESI-HRMS (TOF): MH+ found 448.1610.
C26H26NO4S requires 448.1583.
= 7.1 Hz, 2H, Et), 2.75 (t, 3JHH = 7.5 Hz, 2H, CH2), 2.55 (t, 3JHH
=
3
7.5 Hz, 2H, CH2), 2.36 (s, 3H, Ts), 1.24 (t, JHH = 7.1 Hz, 3H,
Et). 13C-NMR (δ, CDCl3): 173.05 (C=O), 145.05 (C), 135.87 (C),
135.47 (C), 134.64 (C), 132.19 (CH), 130.26 (C), 129.75 (CH),
127.93 (CH), 127.24 (CH), 126.83 (C), 121.60 (CH), 117.58
(CH), 60.80 (CH2), 34.95 (CH2), 22.40 (CH2), 21.90 (CH3), 14.55
(CH3). ESI-HRMS (TOF): MH+ found 432.1052. C22H23ClNO4S
requires 432.1036.
1
9m. Yellow oil. 50 mg, 57%. H-NMR (δ, CDCl3): 7.44 (t,
3JHH = 7.7 Hz, 1H, Ar-H), 7.32-7.28 (m, 3H, Ar-H), 7.16 (d, 3JHH
3
1
= 8.6 Hz, 2H, Ar-H), 7.11 (d, JHH = 8.6 Hz, 2H, Ar-H), 7.05 (d,
9e. Yellow oil. 71 mg, 76%. H-NMR (δ, CDCl3): 7.56 (d,
3JHH = 7.1 Hz, 2H, Ar-H), 4.15 (q, 3JHH = 7.1 Hz, 2H, Et), 3.00 (t,
3
3JHH = 8.1 Hz, 2H, Ar-H), 7.36 (d, JHH = 8.1 Hz, 2H, Ar-H),
3
3JHH = 7.4 Hz, 2H, CH2), 2.62 (t, JHH = 7.4 Hz, 2H, CH2), 2.38
7.23-7.21 (m, 3H, Ar-H), 7.11 (d, 3JHH = 8.1 Hz, 2H, Ar-H), 6.09
(s, 3H, Ts), 1.65 (s, 3H, CH3), 1.27 (t, 3JHH = 7.1 Hz, 3H, Et). 13C-
4
3
(d, JHH = 1.8 Hz, 1H, pyrrole), 4.13 (q, JHH = 7.0 Hz, 2H, Et),

6
Tetrahedron
ACCEPTED MANUSCRIPT
4. C.-Z. Zhu, J.-J. Feng, J. Zhang, Chem. Commun. 53 (2017) 4688-
NMR (δ, CDCl3): 197.06 (C=O), 173.43 (C=O), 145.64 (C),
4691.
138.16 (C), 135.52 (C), 132.22 (CH), 130.46 (C), 129.93 (CH),
129.89 (CH), 128.06 (CH), 127.86 (CH), 125.76 (C), 120.53
(CH), 60.67 (CH2), 34.68 (CH2), 30.78 (CH3), 22.32 (CH2), 21.97
(CH3), 14.62 (CH3). ESI-HRMS (TOF): MH+ found 440.1544.
C24H26NO5S requires 440.1532.
5. F. Jiang, F.-R. Yuan, L.-W. Jin, G.-J. Mei, F. Shi, ACS Catal. 8
(2018) 10234−10240.
6. L, Zhu, X, Qi, Y. Lan, Organometallics 35 (2016) 771−777.
7. F. Antras, S. Laurent, M. Ahmar, H. Chermette, B. Cazes, Eur. J.
Org. Chem. (2010) 3312–3336.
8. R.A. Doohan, J.J. Hannan, N.W.A. Geraghty, Org. Biomol. Chem.
4 (2006) 942-952.
9. P. Marcé, Y. Díaz, M. I. Matheu, S. Castillón, Org. Lett. 10 (2008)
4735-4738.
1
12. Colorless oil. 47 mg, 55%. H-NMR (δ, CDCl3): 7.85 (d,
3JHH = 7.8 Hz, 2H, Ar-H), 7.60-7.39 (m, 10H, Ar-H), 7.21 (d,
3JHH = 7.8 Hz, 2H, Ar-H), 6.58 (d, JHH = 15.2 Hz, 1H, =CH),
3
10. Z. Na, S. Pan, M. Uttamchandani, S. Q. Yao, Angew. Chem. Int.
Ed. 53 (2014) 8421-8426.
6.34 (dd, 3JHH = 15.2 Hz, JHH = 7.1 Hz, 1H, =CH), 5.36 (d, JHH
= 2.8 Hz, 1H, =CH), 4.31 (dd, 2JHH = 13.1 Hz, 3JHH = 9.5 Hz, 1H,
CHH), 3.87 (dd, 2JHH = 13.1 Hz, 3JHH = 6.7 Hz, 1H, CHH), 3.40-
3.34 (m, 1H, CH), 2.27 (s, 3H, Ts). 13C-NMR (δ, CDCl3): 189.79
(C=O), 147.32 (CH), 147.05 (C), 144.75 (C), 137.59 (C), 133.31
(CH), 132.67 (C), 129.93 (CH), 129.51 (CH), 128.91 (CH),
128.77 (CH), 128.35 (CH), 128.30 (CH), 128.21 (CH), 125.88
(CH), 117.42 (CH), 56.52 (CH2), 43.69 (CH), 21.73 (CH3). ESI-
HRMS (TOF): MH+ found 430.1474. C26H24NO3S requires
430.1477.
3
3
Supplementary Material
Procedure for preparation of 5 and 11 and other side products
6a, 7 and 8a. Spectra for all 1H NMR and 13C NMR spectra of
pyrrole compounds. Supplementary data related to this article can
be found at https://doi.org/10.1016/j.tet.xxxxxxxx.
1
3
13. Yellow oil. H-NMR (δ, CDCl3): 7.97 (d, JHH = 7.8 Hz,
3
3
2H, Ar-H), 7.57 (t, JHH = 7.4 Hz, 1H, Ar-H), 7.47 (t, JHH = 7.8
3
Hz, 2H, Ar-H), 7.35-7.20 (m, 8H, Ar-H), 7.07 (d, JHH = 8.1 Hz,
2H, Ar-H), 6.08 (d, 4JHH = 1.8 Hz, 1H, pyrrole), 3.24 (t, 3JHH = 7.4
Hz, 2H, CH2), 2.88 (t, 3JHH = 7.4 Hz, 2H, CH2), 2.34 (s, 3H, Ts).
13C-NMR (δ, CDCl3): 199.01 (C=O), 144.39 (C), 136.77 (C),
136.41 (C), 135.51 (C), 133.03 (CH), 131.40 (C), 130.60 (CH),
129.22 (CH), 128.55 (CH), 128.08 (CH), 127.94 (CH), 127.25
(CH), 126.93 (CH), 126.80 (C), 120.85 (CH), 117.03 (CH), 38.80
(CH2), 21.48 (CH3), 21.08 (CH2). ESI-HRMS (TOF): MH+ found
430.1470. C26H24NO3S requires 430.1477.
Acknowledgments
We thank the Ministry of Science and Technology, Taiwan
(Grant No. MOST106-2113-M-002-018) for the financial support.
We also thank “National Taiwan University Mass Spectrometry-
based Proteomics Core Facility” for the measurement of ESI
mass data.
References and notes
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