Hypervalent iodine in synthesis. 62: A tandem dimerization-cyclocondensation of enamine-esters with [bis(trifluoroacetoxy)iodo]benzene: A method of synthesis of highly substituted pyrroles

Article abstract of DOI:10.1081/SCC-100103979

A tandem dimerization-cyclocondensation of enamine-esters with [bis(trifluoroacetoxy)iodo]benzene(BTI) provides an effective method for synthesis of highly substituted pyrroles.

Full text of DOI:10.1081/SCC-100103979

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HYPERVALENT IODINE
IN SYNTHESIS. 62: A
TANDEM DIMERIZATION-
CYCLOCONDENSATION OF
ENAMINE-ESTERS WITH
[BIS(TRIFLUOROACETOXY)-
IODO]BENZENE: A METHOD
OF SYNTHESIS OF HIGHLY
SUBSTITUTED PYRROLES
Peng-Fei Zhang a & Zhen-Chu Chen b
a Department of Chemistry , Zhejiang University
(XiXi Campus) , Hangzhou, Zhejiang, 310028, P.R.
China
b Department of Chemistry , Zhejiang University
(XiXi Campus) , Hangzhou, Zhejiang, 310028, P.R.
China
Published online: 09 Nov 2006.
To cite this article: Peng-Fei Zhang & Zhen-Chu Chen (2001) HYPERVALENT IODINE
IN SYNTHESIS. 62: A TANDEM DIMERIZATION-CYCLOCONDENSATION OF ENAMINE-
ESTERS WITH [BIS(TRIFLUOROACETOXY)-IODO]BENZENE: A METHOD OF SYNTHESIS
OF HIGHLY SUBSTITUTED PYRROLES, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 31:11, 1619-1624,
DOI: 10.1081/SCC-100103979

To link to this article: http://dx.doi.org/10.1081/SCC-100103979
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SYNTHETIC COMMUNICATIONS, 31(11), 1619–1624 (2001)
HYPERVALENT IODINE IN SYNTHESIS. 62:
A TANDEM DIMERIZATION-
CYCLOCONDENSATION OF
ENAMINE-ESTERS WITH
[BIS(TRIFLUOROACETOXY)-
IODO]BENZENE: A METHOD OF
SYNTHESIS OF HIGHLY SUBSTITUTED
PYRROLES
Peng-Fei Zhang and Zhen-Chu Chen*
Department of Chemistry, Zhejiang University
(XiXi Campus), Hangzhou, Zhejiang 310028, P.R. China
ABSTRACT
A tandem dimerization-cyclocondensation of enamine-esters
with [bis(trifluoroacetoxy)iodo]benzene(BTI) provides an
effective method for synthesis of highly substituted pyrroles.
The oxidative dimerization is one of the most useful reaction for con-
stituting symmetric molecules in organic synthesis. In recent years, a variety
of hypervalent organoiodine(III) reagents1 have become available and have
been successfully used for oxidative dimerization.2–6 Recently, we also
reported7 the oxidative dimerization of isopropylidene 5-alkylmalonates
* Corresponding author.
1619
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

1620
ZHANGAND CHEN
by using (diacetoxyiodo)benzene(DIB) gives 5,50-bis(isopropylidene alkyl-
malonates). In continuing study of the applications of oxidative dimeriza-
tion by using hypervalent organoiodine(III) reagents in organic synthesis,
we examined the reaction of enamine-esters with (diacyltoxyiodo)benzene
and observed the formation of highly substituted C2-symmetric pyrrole
derivatives via a tandem dimerization-cyclocondensation. Herein we wish
to report our results.
At first, we took the reaction of enamine-esters 1a with (diacetoxy
iodo)benzene(DIB) as the sample into investigation (Scheme 1). The reac-
tion was carried out in methylene chloride at room temperature for 8 hours.
After work-up, 3,4-diethoxycarbonyl-1,2,5-trimethylpyrrole 2a was obtained
in 43% yield.
We found the significant improvement of the yield for the reaction
and relatively short the reaction time were observed when [bis-
(trifluoroacetoxy)iodo]benzene (BTI) was used instead of DIB, as shown
in Table 1.
Scheme 1.
In order to examine the scope of this reaction, a number of enamine-
esters were examined. All the enamine-esters in Table 1 were smoothly
converted to corresponding pyrrole derivatives by treatment with DIB
or BTI. The products were characterized by Mp., 1H NMR, IR and
MS-spectra.
A plausible mechanism of the reaction is analogous to the oxidation of
b-aminocinnamates with lead tetraacetate(LTA)8 and is shown in Scheme 2.
Highly substituted pyrrole derivatives have attracted much interest
in the past few years, since they are the main structural element of many
alkaloids and pharmacologically active compounds.9 The literature methods
of preparing highly substituted C2-symmetric pyrroles include the oxidation
of enamines with LTA,8,10,11,12 or the anodic dimerization of enamines,13 or
the 1,3-dipolar cycloaddition of azalactones to alkynes,14,15 or the reaction
of 2,5-disubstituted pyrroles with dimethyl acetylenedicarboxylate16 or the
Knorr reaction of a-aminoketones with a ketone having a reactive methy-
lene group alpha to the carbonyl group, and the Hantzsch reaction of

HYPERVALENT IODINE IN SYNTHESIS. 62
1621
Table 1. Synthesis of 1,2,3,4,5-Pentasubstituted Pyrroles 2aꢀg
Scheme 2.
a-holoketones with enamines.17 However, these methods have some
disadvantages such as using toxic reagents, uncommon starting material,
harsh reaction conditions and poor yields. Present reaction represent
an effective method for the synthesis of highly substituted C2-symmetric
pyrroles.

1622
ZHANGAND CHEN
In conclusion, A tandem dimerization-cyclocondensation of enamine-
esters with BTI provides an effective method for synthesis of highly substi-
tuted pyrroles. Further study for the reaction of other enamines with BTI is
under way and will be reported in due course.
EXPERIMENTAL
Uncorrected melting points were determined with a micro melting
point apparatus. 1H NMR spectra were measured on a AVANCE
DMX500 spectrometer using TMS as an internal standard. IR spectra
were recorded with a Perkin Elmer 683 spectrometer. Mass spectra were
obtained by electron impact at 70 eV (HP5989B). Preparation of substituted
pyrroles 2aꢀ2g; General procedure:
To a solution of 1a (0.143 g, 1 mmol) in CH2Cl2 (20 ml) was added BTI
(0.430 g, 1 mmol). The mixture was stirred for 2hours at room temperature.
The solvent was removed under reduced pressure and the residue was
chromatographed on silica gel plate by using a mixture of cyclohexane-
ethyl acetate (4:1) as eluent to afford 3,4-diethoxycarbonyl-1,2,5-trimethyl-
pyrrole 2a as a pale yellow solid, 0.11 g, yield: 87%. Mp. 71ꢀ73ꢁC (lit.8
71ꢀ72ꢁC);IR(KBr):1715 cmÀ1(vs),1550 cmÀ1(s),1446 cmÀ1(s),1420 cmÀ1(s);
1H NMR(CDCl3): d 4.24ꢀ4.30 (4H, q, J ¼ 7 Hz), 3.39 (3H, s), 2.35 (6H, s),
1.25ꢀ1.34 (6H, t, J ¼ 7 Hz); Ms: 253 (Mþ, 8.92), 208 (13.65), 180 (14.64),
146 (10.93), 104 (29.27), 43 (100).
1-benzyl-3,4-diethoxycarbonyl-2,5-dimethylpyrrole (2b): Mp. 61ꢀ63ꢁC
(lit.861.5ꢀ63ꢁC);IR(KBr):1750 cmÀ1(vs),1530 cmÀ1(m),1440ꢀ1470 cmÀ1(s),
1390 cmÀ1(s); 1H NMR(CDCl3): d 6.91ꢀ7.36 (5H, m), 5.03 (2H, s),
4.21ꢀ4.34 (4H, q, J ¼ 7 Hz), 2.32 (6H, s), 1.36(6H, t, J ¼7 Hz).
1-(p-chlorophenyl)-3,4-diethoxycarbonyl-2,5-dimethylpyrrole (2c): Mp.
98ꢀ100ꢁC (lit.8 98ꢀ99.5ꢁC); IR(KBr): 1740 cmÀ1(vs), 1565 cmÀ1(s),
1445 cmÀ1(s), 1400 cmÀ1(w); 1H NMR(CDCl3): d 7.31ꢀ7.34 (2H, m),
7.02ꢀ7.04 (2H, m), 4.22ꢀ4.23 (4H, q, J ¼ 7 Hz), 2.10 (6H, s),
1.30ꢀ1.34(6H, t, J ¼ 7 Hz).
1-(p-chlorophenyl)-3,4-diethoxycarbonyl-2,5-diphenylpyrrole (2d): Mp.
174ꢀ176ꢁC (lit.8 175ꢀ177ꢁC); IR(KBr): 1740 cmÀ1(vs), 1560 cmÀ1(s),
1440 cmÀ1(s), 1395 cmÀ1(w); 1H NMR(CCl4, 60 MHz): d 7.13 (10H, s),
6.90ꢀ7.05 (2H, m), 6.65ꢀ6.85 (2H, m), 4.02ꢀ4.18 (4H, q, J ¼ 7 Hz),
1.05ꢀ1.20 (6H, t, J ¼ 7 Hz).
1-benzyl-3,4-diethoxycarbonyl-2,5-diphenylpyrrole(2e):Mp.120ꢀ122ꢁC
(lit.8 120ꢀ121.5ꢁC); IR(KBr): 1745 cmÀ1(vs), 1550 cmÀ1(m), 1450 cmÀ1(s),
1
1415 cmÀ1(s); H NMR(CCl4, 60 MHz): d 6.60ꢀ7.75 (15H, m), 4.87(2H, s),
4.02ꢀ4.20 (4H, q, J ¼ 7 Hz), 1.00ꢀ1.10 (6H, t, J ¼ 7 Hz).

HYPERVALENT IODINE IN SYNTHESIS. 62
1623
3,4-diethoxycarbonyl-2,5-diphenyl-1-methylpyrrole(2f):Mp.125ꢀ127ꢁC
(lit.8 125ꢀ126.5ꢁC); IR(KBr): 1760 cmÀ1(vs), 1560 cmÀ1(s), 1500 cmÀ1(w),
1425 cmÀ1(s); 1H NMR(CCl4, 60 MHz): d7.23ꢀ7.76(10H, m), 4.10ꢀ4.38(4H,
q, J ¼ 7 Hz), 3.36(3H, s), 1.00ꢀ1.30(6H, t, J ¼ 7 Hz).
3,4-diethoxycarbonyl-2,5-diphenyl-1-propylpyrrole (2g): Mp. 89ꢀ91ꢁC
(lit.8 91.5ꢀ93ꢁC);IR(KBr):1765 cmÀ1(vs), 1550 cmÀ1(s), 1450ꢀ1470 cmÀ1(s),
1
1390 cmÀ1(s); H NMR(CCl4, 60 MHz): d 7.16ꢀ7.75 (10H, m), 3.95ꢀ4.20
(4H, q, J ¼ 7 Hz), 3.62ꢀ3.74 (2H, t, J ¼ 6 Hz), 2.20ꢀ2.32 (2H, m), 1.05ꢀ1.25
(6H, t, J ¼ 7 Hz), 0.40ꢀ0.55 (3H, t, J ¼ 6 Hz).
REFERENCES
1. For reviews see: (a) Stang, P.J. Angew. Chem. Int. Ed. Engl. 1992, 31,
274; (b) Prakash, O.; Saini, N.; Sharma, P.K. Heterocycles 1994, 38,
409; (c) Prakash, O.; Saini, N.; Sharma, P.K. Synlett 1994, 221; (d)
Wipf, P.; Venkatraman, S. J. Org. Chem. 1996, 61, 8004; (e) Stang, P.J.;
Zhdankin, V.V. Chem. Rev. 1996, 96, 1123; (f) Stang, P.J.; Zhdankin,
V.V. Tetrahedron 1998, 54, 10927.
2. (a) Zefirov, N.S.; Samsoniya, N.Sh.; Zhdankin, V.V. Zh. Org. Khim.
1991, 27, 220; (b) Kashin, A.N.; Tulchinskii, M.L.; Bumagin, N.A.;
Beleskaya, I.P. Zh. Org. Khim. 1982, 18, 1588.
3. Anderson, D.J.; Gilchrist, T.L.; Rees, C.W. J. Chem. Soc. Chem.
Commun. 1971, 800.
4. Moriarty, R.M.; Prakash, O.; Duncan, M.P. J. Chem. Soc. Perkin
Trans. 1 1987, 559.
5. Moriarty, R.M.; Prakash, O.; Duncan, M. P. J. Chem. Soc. Chem.
Commun. 1985, 420.
6. Moriarty, R.M.; Vaid, R.K.; Ravikunnar, V.T.; Vaid, B.K.; Hopkins,
T.E. Tetrahedron 1988, 44, 1063.
7. Yon, J.; Zhong, L.R.; Chen, Z. C. J. Org. Chem. 1991, 56, 459.
8. Sukari, A.; Vernon, J.M. Tetrahedron 1983, 39, 793.
9. Waldmann, H. Synlett 1995, 133.
10. Richard, M.; Carr Richard, O.C.; Norman, John, M.V. J. Chem. Soc.
Perkin Trans. 1 1980, 156.
11. Khetan, S.K. J. Chem. Soc. Chem. Commun. 1972, 917.
12. Carr, R.M.; Norman, R.O.C.; Vernon, J.M. J. Chem. Soc. Chem.
Commun. 1977, 854.
13. Koch, D.; Schafer, H. Angew. Chem. Int. Ed. 1973, 12, 245.
14. Huisgen, R.; Gottardt, H.; Bayer, H. O. Angew. Chem. 1964, 76, 185.

1624
ZHANGAND CHEN
15. Huisgen, R.; Gotthardt, H.; Bayer, H.O.; Schaefer, F.C. Chem. Ber.
1970, 103, 2611.
16. Gabel, N.W. J. Org. Chem. 1962, 27, 301.
17. Barton, S.D.; Ollis, W.D. Comprehensive Organic Chemistry vol. 4,
p. 275, A. Wheaton & Co. Ltd., Exeter, 1979.
Received in Japan June 7, 2000