ORGANIC

LETTERS

A Novel Synthesis of 2000

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

10.1021/ol006518p CCC: $19.00 © 2000 American Chemical Society

Published on Web 10/28/2000
then treated with tert-butyldimethylsilyl chloride in the be explained by a sequence of reaction as depicted in Scheme
presence of imidazole to furnish the corresponding silyl ester 1. A possible reaction pathway for the conversion of 3 into
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
Scheme 1. Syntheses of Chromones 8
55-80% yields (Table 1). The formation of product 8 could

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-
a All products were characterized by their satisfactory IR, 1H NMR, and
tion resulting from the substitution in aroyl group appears
mass spectral data and also by comparison with literature data. to be significant. Thus an ortho-substituent such as the chloro
group in 3k and meta-substituent such as the methoxy group
3822 Org. Lett., Vol. 2, No. 24, 2000
in 3l have pronounced steric hindrance due to their close of chromones has been developed. To the best of our
proximity to the carbonyl group, and hence a longer time is knowledge, this is the first report of chromone synthesis via
required to complete the reaction, affording relatively low intramolecular Wittig ester carbonyl olefination using (tri-
yield of the products 8k and 8l, respectively (Table 1, entries methylsilyl)methylenetriphenylphosphorane. Currently stud-
11 and 12). It may be mentioned that for the synthesis of ies are in progress to extend the synthetic potential of mono-
2-alkyl chromones, the utilization of a large excess of esters and bis-silylated phosphorus ylides for the construction of a
as acylating reagent is reported to be the only acceptable variety of carbocyclic and several other heterocyclic com-
method.8 Also, the conventional methods employing o- pounds.
hydroxy acetophenone as starting material failed to give the
substituted flavones, particularly with methoxy substituents.9 Acknowledgment. P.K. is thankful to the Department of
Similarly, few reports employing palladium-catalyzed car- Science & Technology, Government of India for generous
bonylative coupling of 2-hydroxyaryliodides with ethynyl- funding of the project (grant SP/S1/G-18/98). We are grateful
arenes are known to give a mixture of flavones and to Dr. M. K. Gurjar for his support and encouragement. This
aurones.1,10 In this connection, the present methodology for is NCL communication 6598.
the synthesis of chromones is noteworthy.
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
(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. compounds 7b and 8a-l. This material is available free of
(9) Gupta, V. N.; Seshadri, T. R. J. Sci. Ind. Res. 1957, 16, 116. charge via the Internet at http://pubs.acs.org.
(10) Ciattini, P. G.; Morera, E.; Ortar, G.; Rossi, S. S. Tetrahedron 1991,
47, 6449. OL006518P

Org. Lett., Vol. 2, No. 24, 2000 3823