A Novel Synthesis of 4H-Chromen-4-ones via Intramolecular Wittig Reaction

Article abstract of DOI:10.1021/ol006518p

formula presented The acylphosphoranes formed in a sequential manner from the reaction of the silyl ester of O-acyl(aroyl)salicylic acids and (trimethylsilyl)-methylenetriphenylphosphorane undergo intramolecular Wittig cyclization on the ester carbonyl to afford the 4H-chromen-4-ones in good to excellent yields.

Full text of DOI:10.1021/ol006518p

ORGANIC
LETTERS
2000
Vol. 2, No. 24
3821-3823
A Novel Synthesis of
4H-Chromen-4-ones via Intramolecular
Wittig Reaction
Pradeep Kumar* and Mandar S. Bodas
DiVision of Organic Chemistry: Technology, National Chemical Laboratory,
Pune 411008, India.
tripathi@dalton.ncl.res.in
Received August 29, 2000
ABSTRACT
The acylphosphoranes formed in a sequential manner from the reaction of the silyl ester of O-acyl(aroyl)salicylic acids and (trimethylsilyl)-
methylenetriphenylphosphorane undergo intramolecular Wittig cyclization on the ester carbonyl to afford the 4H-chromen-4-ones in good to
excellent yields.
Chromones constitute one of the major classes of naturally
occurring compounds, and interest in their chemistry con-
tinues unabated because of their usefulness as biologically
active agents.1 As part of our ongoing program for develop-
ing methodologies using phosphacumulene2 and their sub-
sequent application to biologically useful compounds, the
(trimethylsilyl)methylenetriphenylphosphorane is envisaged
as a versatile reagent offering considerable opportunities for
synthetic manipulations.3 In general, chromones are synthe-
sized by the cyclodehydration of 1-(o-hydroxyaryl)-1,3-
diketone or equivalent intermediates catalyzed by strong
acids or strong bases.4 They have been also prepared on a
large scale by the Allan-Robinson synthesis involving
acylation, rearrangement, and subsequent cyclization.5 In the
Baker-Venkataraman synthesis,6 internal claisen condensa-
tion of 2-aryloxy-1-acetylarenes is employed as a key step.
While a variety of synthetic methodologies for chromones
have been developed,7 the literature describing novel one-
pot cyclization methods based on a consecutive process is
rather scarce. Also, most of these methods suffer either from
harsh reaction conditions, poor substituent tolerance, or low
chemical yields. We now report a new and simple route to
4H-chromen-4-ones via intramolecular ester carbonyl ole-
fination using (trimethylsilyl)methylenetriphenylphosphorane.
Salicylic acid or its substituted derivative 1 was converted
into its O-acyl(aroyl) derivatives 2 by reaction with the
corresponding acid chloride or anhydride. Compound 2 was
(6) (a) Baker, W. J. Chem. Soc. 1933, 1381. (b) Mahal, H. S.;
Venkataraman, K. J. Chem. Soc. 1934, 1767. (c) Dunne, A. T. M.; Gowan,
J. E.; Keane, J.; O’Kelly, B. M.; Sullivan, D. O’.; Roche, M. M.; Ryan, P.
M.; Wheeler, T. S. J. Chem. Soc. 1950, 1252.
(7) (a) Ollis, W. D.; Weight, D. J. Chem. Soc. 1952, 3826. (b) Meyer-
Dayan, M.; Bodo, B.; Deschamps-Vallet, C.; Molho, D. Tetrahedron Lett.
1978, 3359. (c) Banerji, A.; Goomer, N. C. Synthesis 1980, 874. (d) Babin,
P.; Dunoguess, J.; Petraud, M. Tetrahedron 1981, 37, 1131. (e) Hercouet,
A.; Le Corre, M. Synthesis 1982, 597. (f) Bestmann, H. J.; Schade, G. Chem.
Lett. 1983, 997. (g) LeFloch, Y.; Lefeuvre, M. Tetrahedron Lett. 1986, 27,
2751. (h) McGarry, L. W.; Detty, M. R. J. Org. Chem. 1990, 55, 4349. (i)
Nagarathnam, D.; Cushman, M. Tetrahedron 1991, 47, 5071. (j) Nishiraga,
A.; Ando, H.; Marugama, K.; Mushino, T. Synthesis 1992, 9, 839. (k)
Zammattio, F.; Brion, J. D.; Ducrey, P.; LeBaut, G. Synthesis 1992, 4, 375.-
(l) Pinto, D. C. G. A.; Silva, A. M. S.; Cavaleiro, J. A. S. J. Heterocycl.
Chem. 1996, 33, 1887. (m) Riva, C.; Toma, C. D.; Donadel, L.; Boi, C.;
Pennini, R.; Motta, G.; Leonardi, A. Synthesis 1997, 195. (n) Lokshin, V.;
Heynderickx, A.; Samat, A.; Pepe, G.; Guglielmetti, R. Tetrahedron Lett.
1999, 40, 6761. (o) Dekermendjian, K.; Kahnberg, P.; Witt, M.-R.; Sterner,
O.; Nielsen, M.; Liljefors, T. J. Med. Chem. 1999, 42, 4343. (p) Osorio-
Olivares, M.; Cassels, B. K.; Sepulveda-Boza, S.; Rezende, C. Synth.
Commun. 1999, 29, 815.
(1) Miao, H.; Yang, Z. Org. Lett. 2000, 2, 1765 and references therein.
(2) a) Kumar, P.; Rao, A. T.; Pandey, B. J. Chem. Soc., Chem. Commun.
1992, 1580. (b) Kumar, P.; Dinesh, C. U.; Pandey, B. Tetrahedron Lett.
1994, 35, 9228. (c) Kumar, P.; Rao, A. T.; Pandey, B. Synth. Commun.
1994, 24(22), 3297. (d) Kumar, P.; Saravanan, K. Tetrahedron 1998, 54,
2161.
(3) Bestmann, H. J.; Bomhard, A.; Dostalek, R.; Pichl, R.; Riemer, R.;
Zimmermann, R. Synthesis 1992, 787.
(4) Livingstone, R. In Rodd’s Chemistry of Carbon Compounds; Coffey,
S.. Ed.; Elsevier Publishing Co.: Amsterdam, 1977; Vol. IVE, p 139.
(5) Allan, J.; Robinson, R. J. Chem. Soc. 1924, 125, 2192.
10.1021/ol006518p CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/28/2000

then treated with tert-butyldimethylsilyl chloride in the
presence of imidazole to furnish the corresponding silyl ester
3 in excellent yields. When a mixture of compound 3 and
(trimethylsilyl)methylenetriphenylphosphorane3 4 was heated
in refluxing THF, the desired chromones 8 were obtained in
55-80% yields (Table 1). The formation of product 8 could
be explained by a sequence of reaction as depicted in Scheme
1. A possible reaction pathway for the conversion of 3 into
Scheme 1. Syntheses of Chromones 8
Table 1. One-Pot Synthesis of 4H-1-Chromen-4-ones 8 from 3
and 4 via Intramolecular Wittig Cyclization
8
involves acylation of (trimethylsilyl)methylenetri-
phenylphosphorane 4 by 3 to the resulting phosphonium salt
5. There is then migration of the trimethylsilyl group from
C to O, followed by the extrusion of silyl ether 6 and
ultimately leading to the acylphosphorane 7, which subse-
quently undergoes ring closure via the intramolecular Wittig
reaction on the ester carbonyl to afford the desired chromones
8.
To support our suggested mechanism, the intermediacy
of compound 7 has been established by spectroscopic means.
Although the treatment of 3b with 4 in THF at room
temperature did not show any progress of reaction, the
extrusion of silyl ether 6 and formation of acylphosphorane
7 could be observed when the reaction was performed at
higher temperature (50 °C). Interestingly, compound 7b was
found to be stable enough to be isolated and was further
identified by its spectral data. Compound 7b, on heating in
refluxing THF, gave the desired chromone 8b. Even though
we could not isolate the phosphonium salt 5b, presumably
as a result of its fast rearrangement into the acylphosphorane,
the above finding indicates that compound 7b, which results
from 5b after the cleavage of silyl ether 6, is one of the
intermediates that undergoes subsequent intramolecular Wit-
tig cyclization at reflux temperature to furnish the desired
product 8b.
As is apparent from Table 1, the intramolecular Wittig
cyclization involving phosphorus ylide and ester carbonyl
is general for the preparation of a variety of chromone
derivatives. However, steric effect during the Wittig cycliza-
tion resulting from the substitution in aroyl group appears
to be significant. Thus an ortho-substituent such as the chloro
group in 3k and meta-substituent such as the methoxy group
a All products were characterized by their satisfactory IR, 1H NMR, and
mass spectral data and also by comparison with literature data.
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Org. Lett., Vol. 2, No. 24, 2000

in 3l have pronounced steric hindrance due to their close
proximity to the carbonyl group, and hence a longer time is
required to complete the reaction, affording relatively low
yield of the products 8k and 8l, respectively (Table 1, entries
11 and 12). It may be mentioned that for the synthesis of
2-alkyl chromones, the utilization of a large excess of esters
as acylating reagent is reported to be the only acceptable
method.8 Also, the conventional methods employing o-
hydroxy acetophenone as starting material failed to give the
substituted flavones, particularly with methoxy substituents.9
Similarly, few reports employing palladium-catalyzed car-
bonylative coupling of 2-hydroxyaryliodides with ethynyl-
arenes are known to give a mixture of flavones and
aurones.1,10 In this connection, the present methodology for
the synthesis of chromones is noteworthy.
of chromones has been developed. To the best of our
knowledge, this is the first report of chromone synthesis via
intramolecular Wittig ester carbonyl olefination using (tri-
methylsilyl)methylenetriphenylphosphorane. Currently stud-
ies are in progress to extend the synthetic potential of mono-
and bis-silylated phosphorus ylides for the construction of a
variety of carbocyclic and several other heterocyclic com-
pounds.
Acknowledgment. P.K. is thankful to the Department of
Science & Technology, Government of India for generous
funding of the project (grant SP/S1/G-18/98). We are grateful
to Dr. M. K. Gurjar for his support and encouragement. This
is NCL communication 6598.
In summary, an efficient annulation protocol for a variety
Supporting Information Available: Experimental pro-
cedures for 2, 3, 7b, and 8 and the spectroscopic data for
compounds 7b and 8a-l. This material is available free of
charge via the Internet at http://pubs.acs.org.
(8) (a) Heilbron, I. M.; Hey, D. H.; Lowe, A. J. Chem. Soc. 1934, 1311.
(b) Geissman, T. A. J. Am. Chem. Soc. 1951, 73, 3514.
(9) Gupta, V. N.; Seshadri, T. R. J. Sci. Ind. Res. 1957, 16, 116.
(10) Ciattini, P. G.; Morera, E.; Ortar, G.; Rossi, S. S. Tetrahedron 1991,
47, 6449.
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