Phosphonium ylide-catalyzed cyclotrimerization of ethyl propynoate

Article abstract of DOI:10.1081/SCC-120002015

The cyclotrimerization of ethyl propynoate (2) to yield aromatic triesters is shown to proceed via consecutive [2 + 2] cycloadditions of ethoxycarbonylmethylenetriphenylphosphonium ylide (1) to three moles of (2), followed by cyclization and elimination o

Full text of DOI:10.1081/SCC-120002015

Synthetic Communications
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PHOSPHONIUM YLIDE-CATALYZED
CYCLOTRIMERIZATION OF ETHYL PROPYNOATE
A. Johan H. Labuschagne , Johan S. Malherbe , Cornelius J. Meyer & David F.
Schneider
To cite this article: A. Johan H. Labuschagne , Johan S. Malherbe , Cornelius J. Meyer & David
F. Schneider (2002) PHOSPHONIUM YLIDE-CATALYZED CYCLOTRIMERIZATION OF ETHYL
PROPYNOATE, Synthetic Communications, 32:2, 297-304, DOI: 10.1081/SCC-120002015
To link to this article: http://dx.doi.org/10.1081/SCC-120002015
Published online: 16 Aug 2006.
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Date: 07 August 2017, At: 10:46

SYNTHETIC COMMUNICATIONS, 32(2), 297–304 (2002)
PHOSPHONIUM YLIDE-CATALYZED
CYCLOTRIMERIZATION OF
ETHYL PROPYNOATE
A. Johan H. Labuschagne,* Johan S. Malherbe,
y
Cornelius J. Meyer,and David F. Schneider
Chemistry Department, University of Stellenbosch,
Stellenbosch 7602, South Africa
ABSTRACT
The cyclotrimerization of ethyl propynoate (2) to yield
aromatic triesters is shown to proceed via consecutive [2 þ 2]
cycloadditions of ethoxycarbonylmethylenetriphenylphos-
phonium ylide (1) to three moles of (2), followed by cycliza-
tion and elimination of (1).
During our effects directed at the synthesis of cross-conjugated diesters
we had occasion to synthesize the phosphonium ylide (3). Our synthetic
method comprised the nucleophilic addition of the phosphonium ylide (1)
to ethyl propynoate (2) under very mild conditions, and produced the ylide
(3) in high yield.1–3 In a subsequent paper by Barluenga and co-workers4 it
was pointed out that the formation of the phosphonium ylide (3) should
be regarded as a [2 þ 2] cycloaddition between the ylide (1) and ethyl propy-
noate (2) followed by ring opening, rather than a true Michael addition.5–7
*Deceased.
yCorresponding author.
297
Copyright & 2002 by Marcel Dekker, Inc.
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LABUSCHAGNE ET AL.
However, we found that when the above synthesis was conducted
under slightly more drastic reaction conditions (60ꢀC, 16 h) in the presence
of an excess of ethyl propynoate (2) (3 molar equivalents), the phosphonium
ylide (4) was produced in an isolated yield of 55% at the expense of (3).
When this condensation was performed in a sealed tube (60ꢀC, 120 h) we
noticed that the aromatic triesters (5) and (6) developed in the reaction
mixture as secondary reaction products, while the phosphonium ylide (4)
was isolated in a significantly lower yield (ꢁ5%).
The formation of the aforementioned reaction products under the
respective reaction conditions was interpreted by us as an indication that
an ylide-catalyzed cyclotrimerization of ethyl propynoate (2) was operative
under these circumstances. In order to shed more light on this unusual
reaction mode, the condensation of the ylide (3) with ethyl propynoate (2)
was investigated in more detail.
When the pure phosphonium ylide (3) and three molar equivalents of
ethyl propynoate (2) in chloroform were heated (40ꢀC/117 h) in a sealed tube,
the aromatic triesters (5) (22%) and (6) (6%), the phosphonium ylide (4)
(56%) and the aromatic phosphobetaine (7) (9%) were isolated as pure com-
pounds from the reaction mixture by separation on a chromatotron.
A pure crystalline sample of the phosphonium ylide (4) and one molar
equivalent of ethyl propynoate (2) in deuteriochloroform were heated
(120ꢀC/9 h) in a sealed NMR tube, and the course of the reaction conti-
1
nuously monitored by H NMR analysis. Under these circumstances the
aromatic triester (5) was indeed produced, albeit in modest yield, but no
NMR evidence could be found that the isomeric triester (6) was formed in a
detectable quantity.

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299
Since we have shown that both the phosphonium ylide (4) and the
aromatic phosphobetaine (7) were formed during the condensation of the
ylide (3) with an excess (3 molar equivalents) of ethyl propynoate (2) in a
sealed tube, the formation of the betaine (7) can be rationalized as the result
of intramolecular cyclization of (4).
In order to substantiate the proposed ylide-catalyzed cyclotrimeriza-
tion of ethyl propynoate (2), the pure phosphonium ylide (3) and ten molar
equivalents of the acetylenic ester (2) in deuteriochloroform were heated at
60ꢀC for several days in a sealed NMR tube. H NMR monitoring of the
1
reaction mixture after 72, 144, 216 and 379 h at 60ꢀC revealed that the
aromatic triesters (5) and (6) were present in combined yields of 120%
(63 : 37), 146% (66 : 34), 175% (67 : 33) and 184% (64 : 36), respectively,
calculated on the basis of one molar equivalent of the phosphonium ylide
(3) as starting material. Work-up of the reaction mixture followed by
separation on a chromatotron, yielded the pure aromatic triesters (5)
(127%) and (6) (36%) as the most important reaction products.
This experiment clearly demonstrated that the phosphonium ylide (1),
or the ylide (3) as a primary condensation product, acted as a catalyst which
promoted the cyclotrimerization of ethyl propynoate (2) to yield the aro-
matic triesters (5) and (6). We, therefore, suggest that consecutive [2 þ 2]
cycloadditions of three moles ethyl propynoate (2) led to the formation of
the ylides (3), (4) and (8) of which (3) and (4) were characterized as reaction
intermediates. Intramolecular cyclization of the phosphonium ylide (8),
followed by elimination of the ylide (1) for further utilization in the catalytic
cycle, may lead to the formation of the aromatic triester (5) as the major
condensation product.

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LABUSCHAGNE ET AL.
Formation of the isomeric triester (6) may likewise proceed via the
formation of the phosphonium ylides (4a) and (8a) as reaction inter-
mediates, followed by intramolecular cyclization of (8a).

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301
Ding and co-workers8–12 have extensively investigated the potential of
the reaction of triphenylphosphoranylidenebutenoates with 2-perfluoro-
alkynoates for the synthesis of perfluoroalkyl, polysubstituted benzenoids
and naphthoates via intramolecular Wittig condensations, e.g.
The enhanced electrophilic character of the ester carbonyl group, due
to the activating effect of the perfluoroalkyl substitutent, most probably
facilitated the intramolecular Wittig condensation under these conditions.
The authors mentioned, however, that an unidentified byproduct was
formed with a decrease in the yield of the polysubstituted benzenoid (9)
when an excess of perfluoroalkynoate was used. Similar Wittig-type cycliza-
tions of structurally related arsonium ylides to produce tetrasubstituted
benzenes were recently communicated.13
EXPERIMENTAL
All operations were carried out in an argon atmosphere. Merck silica
gel 60 (particle size 0.063–0.200 mm) and silica gel 60 PF254 with calcium
sulphate were used for column chromatography and separations on the
chromatotron, respectively. NMR spectra were recorded for solutions in
deuteriochloroform on a Varian VXR 300 instrument, and mass spectra
were taken on a Varian Mat 311 A spectrometer. Multiplicities were con-
firmed by APT and SFORD experiments, while HETCOR experiments were
performed to interpret more complex spectra.
1. 1,3,5-Triethoxycarbonylpenta-2,4-dienylidenetriphenylphosphonium
Ylide (4): Ethoxycarbonylmethylenetriphenylphosphonium ylide (1) ( 2 g,
5.74 mmol) and ethyl propynoate (1.69 g, 17.2 mmol) in chloroform
(50 cm3) were stirred for 16 h at 60ꢀC, the solvent evaporated under reduced
pressure at 30ꢀC and the residue chromatographed on silica gel. Elution

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LABUSCHAGNE ET AL.
with ether–petroleum ether (4:1) yielded 1,3,5-triethoxycarbonylpenta-2,4-
dienylidenetriphenylphosphonium ylide (4) (1.71 g, 55%), m.p. 121.5ꢀC (from
ether); dH 0.92 (t, JHH 7.1 Hz, 3H), 1.05 (t, JHH 7.1 Hz, 3H), 1.25 (t, JHH
7.1 Hz, 3H), 3.94 (q, JHH 7.1 Hz, 2H), 3.99 (q, JHH 7.1 Hz, 2H), 4.16
(q, JHH 7.1 Hz, 2H), 6.40 (d, JHH 15.7 Hz, ¼CH), 7.25 (d, JPH 18.8 Hz,
¼CH), 7.71 (d, JHH 15.8 Hz, ¼CH), 7.50–7.91 (m, arom.H, 15H); dC
14.09(CH3), 14.37 (CH3), 14.50(CH3), 59.28(CH2), 59.35(CH2), 59.85(CH2),
63.70 (d, JPC 115.7 Hz, P¼C<), 109.98 (d, JPC 14.4 Hz, ¼C<), 113.0 (¼CH),
124.45 (d, JPC 91.9 Hz, 3 Â arom. C), 129.05 (d, JPC 12.4 Hz, 6 Â m-arom. C),
132.79 (d, JPC 2.7 Hz, 3 Â p-arom. C), 133.87 (d, JPC 9.6 Hz, 6 Â o-arom. C),
142.18 (¼CH), 149.18 (d, JPC 15.5 Hz, ¼CH), 167.51 (>C¼O), 167.66
(>C¼O), 167.71 (>C¼O); Mþ, 544.2023. Calcd. for C32H33O6P : M,
544.2014; Found: C, 70.40; H, 6.10. Required: C, 70.58; H, 6.07.
2. Condensation of 1,3-Diethoxycarbonylallylidenetriphenylphospho-
nium Ylide (3) with Ethyl Propynoate (2) in a Molar Ratio of 1 : 3: The
phosphonium ylide (3) (4.46 g, 10 mmol) and ethyl propynoate (2) ( 3 g,
30 mmol) in chloroform (15 cm3) were heated for 117 h at 40ꢀC in a glass
pressure vessel, the solvent evaporated under reduced pressure at 30ꢀC and
the residue chromatographed on silica gel. Elution with ether–petroleum
ether (2 : 3), ether–petroleum ether (4 : 1) and ethanol–ether (3 : 1), respec-
tively, yielded the following three fractions:
(a) 1,3,5-triethoxycarbonylbenzene (5)3 (0.64 g, 22%), m.p. 135ꢀC
(from ether–petroleum ether)3; Found: C, 61.10; H, 5.80. Calcd. for
C15H18O6: C, 61.22; H, 6.12; 1,2,4-triethoxycarbonylbenzene (6) (0.17 g,
6%), b.p. 150ꢀC (air-bath temp.)/0.05 mm Hg; dH 1.38 (t, J 7.0 Hz, 6H), 1.41
(t, J 7.0 Hz, 3H), 4.40 (q, J 7.1 Hz, 4H), 4.42 (q, J 7.1 Hz, 2H), 7.74 (dd, J 8.0
and 0.6 Hz, H6), 8.20 (dd, J 8.0 and 1.7 Hz, H5), 8.40 (dd, J 1.7 and 0.5 Hz,
H3); dC 14.07 (CH3), 14.12 (CH3), 14.28 (CH3), 61.69 (CH2), 61.94 (CH2),
62.0 (CH2), 128.87 (arom. C), 130.11 (arom. C), 131.99 (arom. C), 132.13
(arom. C), 132.72 (arom. C), 136.29 (arom. C), 164.99 (>C¼O), 166.61
(>C¼O), 167.14 (>C¼O); Mþ, 294.1099. Calcd. for C15H18O6 : M,
294.1103; Found: C, 61.05; H, 6.0. Required: C, 61.22; H, 6.12;
(b) 1,3,5-triethoxycarbonylpenta-2,4-dienylidenetriphenylphosphonium
ylide (4) (3.02 g, 56%); (c) the third fraction was subjected to further
purification by chromatographic separation on a chromatotron with ethanol–
dichloromethane (3 : 7) as eluent to yield 2,4-diethoxycarbonyl-6-triphenyl-
phosphoniumphenoxide (7) (0.42 g, 9%), m.p. 206ꢀC (from ether); dH 1.26 (t,
J 7.1 Hz, 3H), 1.33 (t, J 7.1 Hz, 3H), 4.20 (q, J 7.1 Hz, 2H), 4.32 (q, J 7.1 Hz,
2H), 7.49–7.69 (m, arom. C, 15H), 7.63 ðdd, JPH 15:9 Hz, JH H 2:65 Hz, H5Þ,
5
3
5
8.69 ðdd, JH H 2:5 Hz and JPH 0:6 Hz, H3Þ; dC 14.40 (CH3), 14.52 (CH3),
3
5
3
60.03 (2 Â CH2), 107.02 (d, JPC 101.3 Hz, C6), 110.88 (d, JPC 16.0 Hz, C4),
121.18 (d, JPC 7.1 Hz, C2), 121.94 (d, JPC 92.4 Hz, 3 Â arom.C), 129.39

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303
(d, JPC 12.8 Hz, 6 Â m-arom. C), 133.28 (d, JPC 3.0 Hz, 3 Â p-arom. C), 133.98
(d, JPC 10.2 Hz, 6 Â o-arom. C), 141.45 (d, JPC 1.7 Hz, C3), 143.19 (d, JPC
12.5 Hz, C5), 166.21 (>C¼O), 166.24 (>C¼O), 176.75 (d, JPC 5.8 Hz, C1);
Mþ, 498.1584. Calcd. for C30H27O5P : M, 498.1596; Found: C, 71.75; H, 5.2.
Required: C, 72.29; H, 5.42.
3. Condensation of 1,3,5-Triethoxycarbonylpenta-2,4-dienylidene-
triphenylphosphonium Ylide (4) with one Molar Equivalent of Ethyl
Propynoate (2): The phosphonium ylide (4) (50 mg, 0.1 mmol) and ethyl
propynoate (2) (10 mg, 0.1 mmol) in deuteriochloroform (0.5 cm3) were
heated in a sealed NMR tube at 120ꢀC while the progress of the reaction
was continuously monitored by NMR analysis. After 9 h at 120ꢀC NMR
analysis showed that 1,3,5-triethoxycarbonylbenzene (5)3 (32%) was present
in the reaction mixture while ethyl propynoate (2) was totally consumed at
that stage. No NMR or TLC evidence could be found that 1,2,4-triethoxy-
carbonylbenzene (6) was formed in a detectable quantity under these
circumstances.
4. Phosphonium Ylide-Catalyzed Cyclotrimerization of Ethyl Propy-
noate (2): Ethyl propynoate (2) (0.98 g, 10 mmol) and 1,3-diethoxy-
carbonylallylidenetriphenylphosphonium ylide (3) (0.45 g, 1 mmol) in
deuteriochloroform (1.0 cm3) were heated for several days at 60ꢀC in a
1
sealed NMR tube. H NMR monitoring of the composition of the reaction
mixture after 72, 144, 216 and 379 h at 60ꢀC revealed the presence of mix-
tures of 1,3,5-triethoxycarbonylbenzene (5) and 1,2,4-triethoxycarbonyl-
benzene (6) in combined yields of 120% (63 : 37), 146% (66 : 34), 175%
(67 : 33) and 184% (64 : 36), respectively. The reaction mixture was subjected
to filtration through a silica gel column and the residue from the 5% ether–
dichloromethane eluate was separated on a chromatotron with 10–20%
ether–petroleum ether as eluent to yield the aromatic triesters (5) (376 mg,
127%) and (6) (104 mg, 36%) as pure compounds.
ACKNOWLEDGMENTS
We thank Mr HSC Spies for the NMR spectra and many helpful
discussions and Ms V Truter for the mass spectra. Technical assistance by
Mr MC de Jongh and his staff is gratefully acknowledged.
REFERENCES
1. Labuschagne, A.J.H.; Schneider, D.F. Tetrahedron Lett. 1982, 23, 4235.
2. Labuschagne, A.J.H.; Schneider, D.F. Tetrahedron Lett. 1983, 24, 743.

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LABUSCHAGNE ET AL.
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Received in the UK December 4, 2000

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