A new method for the preparation of 2,3-cycloalkeno-5,6-cycloalkeno-4H-pyran-4-ones

Article abstract of DOI:10.1016/S0040-4039(00)01841-4

Several 2,3-cycloalkeno-5,6-cycloalkeno-4H-pyran-4-ones, such as 2,3,5,6-bicyclopenteno-4H-pyran-4-one and 1,2-dihydronaphtho[3,4-b]cyclopenteno[1,2-e]-4H-pyran-4-one, were synthesized conveniently by the reaction of a cyclic ketone enamine and diacylchloride. This reaction allows a new method for preparation of these compounds, which may be the precursors for the synthesis of some useful heterocycles. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01841-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 10257–10261
A new method for the preparation of
2
,3-cycloalkeno-5,6-cycloalkeno-4H-pyran-4-ones
Fan Xu, Xueqin Cao, Zhengbai Cao* and Lei Zou
Department of Chemistry, Suzhou University, Suzhou 215006, China
Received 17 July 2000; revised 27 September 2000; accepted 19 October 2000
Abstract
Several 2,3-cycloalkeno-5,6-cycloalkeno-4H-pyran-4-ones, such as 2,3,5,6-bicyclopenteno-4H-pyran-4-
one and 1,2-dihydronaphtho[3,4-b]cyclopenteno[1,2-e]-4H-pyran-4-one, were synthesized conveniently by
the reaction of a cyclic ketone enamine and diacylchloride. This reaction allows a new method for
preparation of these compounds, which may be the precursors for the synthesis of some useful
heterocycles. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: cyclic ketone enamine; diacylchloride; 2,3-cycloalkeno-5,6-cycloalkeno-4H-pyran-4-one; preparation.
The Stork reaction, with its generality and wide-ranging applicability, is covered thoroughly
1
,2
in several reviews. The reaction of ketone or aldehyde enamines with alkyl halides furnishes
3
4
alkylated products, while with acid chlorides gives acylated products. Many other different
types of products can also be isolated. For example, application of the Stork reaction to the
5
enamine of N-benzyl-4-piperidone with diketene forms azachromone, while the enamine of
benzocyclopentanone with o-acetoxybenzoyl chloride gives benzopyran-4-one. Furthermore,
6
1
,3,5-triketone and its cyclized derivative 2,3,5,6-bicycloalkeno-4H-pyran-4-one can be obtained
7
by the reaction of two equivalents of cyclic ketone enamine with phosgene. H u¨ nig reported that
bi(1,3-diketone) was formed by the reaction of diacylchloride with cyclopentanone enamine (1:2
mole ratio). Recently, we found that when hexanedioylchloride reacted with 1-piperidino-cyclo-
8
hexene (1:1 mole ratio), 2,3-cyclohexeno-5,6-cyclopenteno-4H-pyran-4-one (3b) was obtained.
This method has not to the best of our knowledge been reported, and the symmetric or
asymmetric 2,3-cycloalkeno-5,6-cycloalkeno-4H-pyran-4-ones can be synthesized easily. In this
paper, this approach was adopted for the preparation of six 2,3-cycloalkeno-5,6-cycloalkeno-
9
1
4
H-pyran-4-ones, which were characterized by conventional IR, H NMR and elemental
analyses. Herein, we wish to report our preliminary results.
*
Corresponding author. Fax: 86-512-5112371; e-mail: orglab@suda.edu.cn
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01841-4

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In a typical experimental procedure, a mixture of cyclic enamine (1.0 equiv.), diacylchloride
1.1 equiv.) and triethylamine (2.0 equiv.) in chloroform was refluxed for several hours. After
(
hydrolysis with 3N hydrochloric acid for 2 h, the organic layer was separated and then the
solvent was removed by distillation. The product was purified by column chromatography on
silica to give the desired product. The results are listed in Table 1.
Using different cyclic enamines or different diacylchlorides, the 4H-pyran-4-ones may be
symmetrical or asymmetrical. Only hexanedioylchloride and heptanedioylchloride were success-
fully used in this method. When pentanedioylchloride or octanedioylchloride were used, the
4
H-pyran-4-one derivative could not be obtained.
From Table 1 we can conclude: (1) the skeleton of the cyclic ketone is preserved in the
product, (2) the self-condensation takes place inside diacylchloride forming a new carbon ring,
and (3) the number of carbon atoms of the new ring is one less than that of diacylchloride. The
Table 1
Formation of 2,3-cycloalkeno-5,6-cycloalkeno-4H-pyran-4-ones

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above conclusions can be explained by a mechanism similar to a Dieckmann reaction. We think
the first step of this reaction, taking the preparation of 3a as an example in Scheme 1, is the
self-condensation of the diacylchloride forming 2-carbonyl cyclopentanoyl chloride (A), which is
an electrophile. Following that, the enamine (B), which is a nucleophile, attacks the exocyclic
carbonyl group giving 1,3,5-triketone (C) after hydrolysis. Then the triketone is enolized and
loses water to form the final product (D). Using this mechanism, the product of reaction of
hexanedioylchloride with 1-piperidino-cyclohexene must be the same as that of heptane-
dioylchloride with 1-piperidino-cyclopentene. The hypothesis was completely confirmed by
experiments (Entries 3b and 3b%). Further reaction of cyclic enamines with pentanedioylchloride
or octanedioylchloride failed, proving the possibility that the self-condensation did not occur
owing to the existence of ring strain. The further study of the mechanism is in progress.
Scheme 1.
The crystal structures of compounds 3a and 3c are presented in Figs. 1 and 2.
Figure 1. Crystal structure of 3a
2
,3-Cycloalkeno-5,6-cycloalkeno-4H-pyran-4-ones can be easily transformed into some useful
derivatives. For example, xanthone (4d) was obtained from compound 3d by catalytic dehydro-
10
genation with Pd–C catalyst at atmospheric pressure in 70% yield.

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Figure 2. Crystal structure of 3c
Acknowledgements
We thank for the National Natural Science Foundation of China (29872030) for financial
support.
References
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. Hickmott, P. W. Tetrahedron 1982, 38, 1975; Hickmott, P. W. Tetrahedron 1982, 38, 3363.
. Hickmott, P. W. Tetrahedron 1984, 40, 2989.
. Whitesell, J. K.; Whitesell, M. A. Synthesis 1983, 517.
. Inukai, T.; Yoshizawa, R. J. Org. Chem. 1967, 32, 404.
. Belsky, I. Tetrahedron Lett. 1970, 4597.
. Gorlitzer, K. Arch. Pharmaz. 1975, 81, 308.
. Belsky, I. Tetrahedron 1972, 28, 771.
. H u¨ nig, S.; Lendle, W. Chem. Ber. 1960, 93, 913.
. Compound 3a: mp 119–120°C; elemental analysis: calcd for C H O : C, 74.97; H, 6.86. Found: C, 74.92; H,
1
1
12
2
1
6
.73. H NMR (400 MHz, CDCl ): l=2.05–2.15 (m, 4H), 2.70–2.78 (m, 4H), 2.81–2.89 (m, 4H). 3b: mp 64–65°C;
elemental analysis: calcd for C H O : C, 75.76; H, 7.42. Found: C, 75.63; H, 7.44. H NMR (400 MHz, CDCl ):
3
1
12
14
2
3
l=1.59–2.10 (m, 6H), 2.40–2.58 (m, 4H), 2.65–2.85 (m, 4H). 3c: mp 109–110°C; elemental analysis: calcd for
1
C H O : C, 80.65; H, 5.92. Found: C, 80.45; H, 5.80. H NMR (400 MHz, CD COCD ): l=2.65–2.78 (m, 4H),
16
14
2
3
3
2
.82–3.08 (m, 4H), 3.20–3.33 (m, 2H), 7.32–7.85 (m, 4H). 3b%: mp 64–65°C; elemental analysis: calcd for

10261
C H O : C, 75.76; H, 7.42. Found: C, 75.83; H, 7.52. 3d: mp 126.5–127°C; elemental analysis: calcd for
1
2
14
2
1
C H O : C, 76.44; H, 7.90. Found: C, 75.94; H, 7.89. H NMR (400 MHz, CDCl ): l=1.66–1.83 (m, 8H),
13
16
2
3
2
.44–2.47 (m, 4H), 2.49–2.53 (m, 4H). 3e: mp 62–63°C; elemental analysis: calcd for C H O : C, 77.03; H, 8.31.
14 18 2
1
Found: C, 77.09; H, 8.44. H NMR (400 MHz, CDCl ): l=1.25 (d, J=6.8, 3H), 1.64–1.78 (m, 8H), 2.41–2.55
3
(
m, 6H), 2.66–2.79 (m, 1H). 3f: mp 117–118°C; elemental analysis: calcd for C H O : C, 80.92; H, 6.39. Found:
17 16 2
1
C, 81.01; H, 6.35. H NMR (400 MHz, CDCl ): l=1.68–1.94 (m, 4H), 2.46–2.72 (m, 4H), 2.79–2.92 (m, 4H),
3
7
.15–7.80 (m, 4H).
1
0. Compound 4d: mp 178–180°C; elemental analysis: calcd for C H O : C, 79.58; H, 4.11. Found: C, 79.75; H,
13
8
2
1
4
.11. H NMR (400 MHz, CDCl ): l=7.37–8.36 (m, 8H).
3
.