Europium(III) triflate-catalyzed Trofimov synthesis of polyfunctionalized pyrroles

Article abstract of DOI:10.1002/adsc.201200036

The synthesis of polyfunctionalized pyrroles by reaction of a ketoxime with dimethyl acetylenedicarboxylate using europium(III) triflate as the catalyst is described. Copyright

Full text of DOI:10.1002/adsc.201200036

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DOI: 10.1002/adsc.201200036
Europium
N
Sridhar Madabhushi,a,* Venkata Sairam Vangipuram,a
Kishore Kumar Reddy Mallu,a Narsaiah Chinthala,a
and China Ramanaiah Beerama
a
Fluoroorganics Division, Indian Institute of Chemical Technology, Hyderabad – 500607, India
Fax : (+91)-40-2716-0387; phone: (+91)-40-2719-1772; e-mail: smiict@gmail.com
Received: January 13, 2012; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200036.
Abstract: The synthesis of polyfunctionalized pyr-
roles by reaction of a ketoxime with dimethyl acety-
inorganic bases, recently, Ngwerume et al.,[13] de-
scribed a modified procedure for the Trofimov reac-
tion using organic bases such as triphenylphosphine,
lenedicarboxylate using europium
the catalyst is described.
ACHTUNGTREN(NGNU III) triflate as
1,4-diazabicyclo
A
E
and
4-
dimethylaminopyridineAHCTNUGTRENNNUG
Keywords: europium
acid catalysis; pyrroles; Trofimov reaction
(III) triflate; ketoximes; Lewis
served an efficient Trofimov reaction also under
Lewis acid catalysis and herein we report, for the first
time, an efficient method for the synthesis of pyrroles
by reaction of a ketoxime and dimethyl acetylenedi-
carboxylate (DMAD) using europium
ACHTUNGTREN(NGNU III) triflate as
a catalyst to obtain polyfunctionalized pyrroles in 60–
Polyfunctionalized pyrroles are ubiquitous in natural 75% yields as shown in Scheme 1.
products,[1] pharmaceuticals[2] and agrochemicals.[3] In
In our preliminary experiments, acetophenone
recent years, they have found applications also in the oxime 1a and DMAD were reacted in the presence of
preparation of organic semiconductors, light-emitting a variety of Lewis acid catalysts such as europium
diodes and solar batteries.[4] The classical methods triflate, zinc(II) triflate, lanthanum
(III) triflate, cop-
available for preparation of pyrroles include Knorr,[5] per(II) triflate, ytterbium
(III) triflate, yttrium(III) tri-
(III) triflate, praseodymium(III) tri-
(III) chloride, indium(III) chloride,
ACHTUNGTRENNUNG(III)
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
Paal–Knorr,[6] Hantzsch reactions,[7] in addition to flate, scandium
E
ACHTUNGTRENNUNG
a variety of cycloadditions,[8] transition metal-cata- flate, antimony
lyzed cyclizations,[9] multicomponent[10] and tandem
reactions.[11]
R
ACHTUNGTRENNUNG
In recent years, the Trofimov[12] method for the
Table 1. Lewis acid-promoted Trofimov reaction of aceto-
phenone oxime and DMAD.
preparation of pyrroles by condensation of a ketoxime
with an acetylene using the super base MOH (M=Li,
Na or K)-dimethyl sulfoxide, as the catalyst has re-
ceived high attention as this method allows the prepa-
ration of a variety of previously inaccesible pyrroles.
Although this reaction was initially carried out using
Entry
Lewis acid[a]
Reaction time [h]
Yield[b] [%] 2a
1
2
3
4
5
6
Eu(OTf)3
T
18
24
24
30
30
30
30
30
30
30
30
30
75
58
65
20
46
15
20
54
35
10
18
30
Zn(OTf)2
La(OTf)3
Cu(OTf)2
Yb(OTf)3
(OTf)3
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
YACHTUNGTRENNUNG
7
8
Sc
Pr
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
9
SbCl3
InCl3
InF3
10
11
12
ZnCl2
[a]
Scheme 1. Europium
roles by the Trofimov reaction.
(III) triflate-catalyzed synthesis of pyr-
10 mol%.
[b]
Yields of isolated prooducts.
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Table 2. EuropiumACTHNUTRGNEUGN(III) triflate-catalyzed Trofimov reaction of a ketoxime and DMAD.
[a]
Yields of isolated products. All compoundss were characterized by 1 H, 13C NMR, IR and
mass spectral data.
indium
(III) fluoride and zinc(II) chloride under reflux
In this study, the formation of pyrrole 2a was ob-
(III)
triflate as the catalyst. When this reaction was studied
conditions using toluene as the solvent as shown in served in maximum yields (75%) with europiumACHTUNGTRENNUNG
Table 1.
2
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EuropiumACHTUNGTRENNUNG(III) Triflate-Catalyzed Trofimov Synthesis of Polyfunctionalized Pyrroles
Scheme 2. A palusible mechanism for the Lewis acid-catalyzed Trofimov reaction.
In conclusion, the present work describes the first
observation of a Lewis acid-catalyzed Trofimov reac-
tion. This work provides an efficient method for the
preparation of polyfunctionalized pyrroles by reaction
of a ketoxime with dimethyl acetylenedicarboxylate
using europiumACHTNUGTRNEUNG(III) triflate as the catalyst.
Experimental Section
Typical Procedure for Europium
Catalyzed Synthesis of Pyrroles
ACHTUNGTREN(NGNU III) Triflate-
Scheme 3. Control study of the europiumACTHNUTRGNEUNG(III) triflate-cata-
lyzed Trofimov reaction.
Acetophenone oxime 1a (0.5 g, 3.69 mmol), dimethyl acety-
lenedicarboxylate (0.52 g, 3.69 mmol), toluene (5 mL) and
europiumACTHNUTRGNE(UNG III) triflate (0.22 g, 0.37 mmol), were charged into
in other solvents such as 1,2-dichloroethane and tetra-
hydrofuran under reflux conditions for 24 h, 2a was
formed in 12 and 20% yields, respectively, and in sol-
vents such as acetonitrile and methanol, no reaction
was observed. The present Lewis acid-catalyzed Trofi-
mov reaction was found to proceed only with DMAD
and this reaction did not proceed with aryl and ali-
phatic acetylenes under similar conditions.
a 25-mL round-bottomed flask fitted with a condenser and
nitrogen balloon. The mixture was refluxed for 18 h and
after completion of the reaction (TLC), the reaction mixture
was concentrated under reduced pressure and purified by
column chromatography (100–200 mesh silica gel, EtOAc-
hexane=1:10) to afford dimethyl 5-phenyl-1H-pyrrole-2,3-
dicarboxylate 2a as a pale yellow solid; yield: 0.72 g (75%);
mp 134–1368C. The product was characterized by the fol-
Next, a variety of ketoximes 1a–n was reacted with
DMAD using europiumACTHUNGTRENNG(U III) triflate as the catalyst
1
lowing spectral data : H NMR (300 MHz, CDCl3): d=9.69
(bs, 1H, exchangeable with D2O), 7.49 (d, 2H, J=7.0 Hz),
7.32 (t, 2H, J=8.0 Hz, 7.0 Hz), 7.23 (t, 1H, J=8.0 Hz,
7.0 Hz), 6.81 (s, 1H), 3.81 (s, 3H), 3.80 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=164.24, 160.72, 134.90, 130.26, 129.08,
128.30, 124.87, 122.65, 121.48, 110.64, 52.22; IR (KBr): n=
3299, 2923, 2853, 1733, 1686, 1513, 1457, 1292, 1257, 1210,
1153, 1068, 927 cmÀ1; ESI-MS: m/z=260 (M+H), 282 (M+
Na); exact mass observed for C14H13O4NNa: 282.0733
(calcd.: 282.0742).
under reflux in toluene to obtain the corresponding
pyrroles 2a–n in 60–75% yields as shown in Table 2.
A plausible pathway for the formation of pyrroles via
the Lewis acid-catalyzed Trofimov reaction is shown
in Scheme 2. It shows that the initial step of the reac-
tion is the formation of ketoxime 1/DMAD adduct
(ketoxime vinyl ether, 3), which subsequently trans-
forms into pyrrole 2 through a 3,3-sigmatropic rear-
rangement under Lewis acid catalysis. In our study,
acetophenone oxime 1a and DMAD gave adduct 3a
in 78% yield under europiumACTHNUTRGENUGN(III) triflate catalysis in
toluene upon heating at 508C for 7 h. When adduct
3a was refluxed in toluene in the absence of
Acknowledgements
VSV is thankful to the Director, IICT for financial support in
the form of Project Assistant; KKRM and CRB are thankful
to CSIR, New Delhi for the financial support in the form of
Senior Research Fellowship. CN is thankful to UGC, New
Delhi for the financial support in the form of Senior Re-
search Fellowship.
europium
ACHTUNGTRENNUNG
after 24 h. In the presence of europiumAHCUTNGTRENNUNG
3a was converted into 2a in 82% yield as shown in
Scheme 3, which confirms the mechanism shown in
Scheme 2.
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Europium
G
5
Polyfunctionalized Pyrroles
Adv. Synth. Catal. 2012, 354, 1 – 5
Sridhar Madabhushi,* Venkata Sairam Vangipuram,
Kishore Kumar Reddy Mallu, Narsaiah Chinthala,
China Ramanaiah Beeram
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