Vinyltriphenylphosphonium salt mediated synthesis of functionalized coumarins

Article abstract of DOI:10.1016/S0040-4020(01)00703-7

Protonation of the reactive 1:1 intermediate produced in the reaction between triphenylphosphine and dimethyl acetylenedicarboxylate by hydroquinone, resorcinol, catechol or pyrogallol leads to vinylphosphonium salts, which undergo Michael addition with t

Full text of DOI:10.1016/S0040-4020(01)00703-7

TETRAHEDRON
Pergamon
Tetrahedron 57 22001) 7537±7540
Vinyltriphenylphosphonium salt mediated synthesis of
functionalized coumarins
Issa Yavari,p Mehdi Adib and Leila Hojabri
Department of Chemistry, University of Tarbiat Modarres, P.O. Box 14155-4838, Tehran, Iran
Received 5 March 2001; revised 4 June 2001; accepted 28 June 2001
AbstractÐProtonation of the reactive 1:1 intermediate produced in the reaction between triphenylphosphine and dimethyl acetylene-
dicarboxylate by hydroquinone, resorcinol, catechol or pyrogallol leads to vinylphosphonium salts, which undergo Michael addition with
the conjugate base of the hydroxy acid to produce highly functionalized 2-oxo-2H-chromene derivatives in good yields. q 2001 Elsevier
Science Ltd. All rights reserved.
CO2Me
1. Introduction
R'
There has been considerable interest in the 2-oxo-2H-
chromene 2coumarin) ring system, both with regard to
natural product chemistry, and to the pharmacological
activity of several of its derivatives.1,2 In addition, other
2-oxo-2H-chromenes are of interest as a result of their
toxicity,3 carcinogenicity,4 and photodynamic effects.5 The
majority of naturally occurring coumarins are highly
oxygenated.1 There have been many reported studies on
the synthesis of 2-oxo-2H-chromene ring structures.1,2,6±10
We have recently described11 a new and operationally
convenient approach to the synthesis of 4-carboxymethyl-
coumarins 1 based on the aromatic electrophilic substitution
reaction between the conjugate base of substituted phenols
and a vinyltriphenylphosphonium salt. As part of our current
studies on the development of new routes to heterocyclic
and carbocyclic systems, we now report the reaction
between hydroxylated phenols and dimethyl acetylene-
dicarboxylate 2DMAD) in the presence of triphenyl-
phosphine. Thus, reaction of DMAD and tri-
phenylphosphine in the presence of hydroquinone,
resorcinol, catechol, or pyrogallol leads to functionalized
4-carboxymethyl-2-oxo-2H-chromenes. The reactions of
tertiary phosphorus compounds with DMAD and, on
occasion, other acetylenic systems have been discussed
with emphasis upon the synthesis of phosphorus
heterocycles.12
O
O
R
1
2. Results and discussion
2.1. Hydroquinone
The reaction of hydroquinone with two equivalents of
DMAD in the presence of two equivalents of triphenyl-
phosphine was carried outin re¯uxing otluene. The pale
yellow crystals separated from the reaction mixture were
identi®ed as methyl 6-hydroxy-2-oxo-2H-chromene-4-
carboxylate 22) 2Scheme 1). No other compound was
obtained from the tarry residue by column chromatography.
Compound 2 results from the initial addition of triphenyl-
phosphine to the acetylenic ester and a subsequent protona-
tion of the reactive 1:1 adduct, followed by electrophilic
attack of the vinyltriphenylphosphonium cation on the
aromatic ring at the ortho position relative to the strong
O
OH
O
(C H ) P
2
2
6
5 3
MeO2C
DMAD
OH
OH
Keywords: aromatic substitution; ring formation; coumarin derivatives;
vinylation; triphenylphosphine.
Corresponding author. Fax: 198-21-8006544;
e-mail: isayavar@yahoo.com
(50% based on hydroquinone)
2
p
Scheme 1.
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020201)00703-7

7538
I. Yavari et al. / Tetrahedron 57 *2001) 7537±7540
obtained from resorcinol. The products were identi®ed as
H
+
_
O
MeO2C
HO
PPh3
methyl 7-hydroxy-2-oxo-2H-chromene-4-carboxylate 23)
and dimethyl 2,8-dioxo-9-21,1,1-triphenylphosphanyl-
idene)-9,10-dihydro-2H,8H-pyrano[2,3-f]-chromene-4,10-
dicarboxylate 24) 2Scheme 3). Compound 3 is formed by a
mechanism similar to that outlined in Scheme 2 for 2-oxo-
2H-chromene derivative 2. Although, we have not yet
established the mechanism of formation of phosphorane 4
in an experimental manner, a possible explanation is
proposed in Scheme 4.
+
CO2Me
CHCO2Me
CO2Me
(C6H5)3P
Scheme 2.
Scheme 3.
C
H
OH
OH
MeO2C
HO
CO2Me
2
2.3. Catechol
OH
Under the reaction conditions given for resorcinol, two
products were isolated from the reaction mixture of catechol
2Scheme 5). Structures 5 and 7 were assigned to the isolated
O
O
OH
CO2Me
PPh3
O
O
(C H ) P
2
2
6
5 3
+
DMAD
MeO2C
MeO2C
OH
O
O
OH
(35%)
3
(50%)
4
products on the basis of their elemental analyses and IR, 1H-
and 13C NMR spectra. IR spectroscopy was applied to
distinguish the tricyclic ring structure 6 from the phenol
derivative 5. Thus, the IR spectrum of the latter showed a
strong OH stretching band at about 3350 cm21. The 2E)-
con®guration of the carbon±carbon double bond in 5 is
based on the chemical shift of the ole®nic proton.13
O
O
+
CHCO2Me
C
(C6H5)3P
MeO2C
CO2Me
O
O
CO2Me
O
2.4. Pyrogallol
PPh3
MeO2C
4
The reaction of 1,2,3-trihydroxybenzene 2pyrogallol) with
DMAD in the presence of triphenylphosphine proceeded in
boiling toluene, and ®nished in a few hours. Three
compounds were separated from the reaction mixture and
identi®ed as methyl 7,8-dihydroxy-2-oxo-2H-chromene-4-
carboxylate 27), dimethyl 2E)-2-23,4,5-trihydroxyphenyl)-2-
butenedioate 28), and dimethyl 10-hydroxy-2,8-dioxo-
CO2Me
OH
Scheme 4.
activating group. The 2-oxo-2H-chromene derivative 2 is
presumably produced by intramolecular lactonization of
the unsaturated diester 2Scheme 2).
2H,8H-pyrano-[3,2-g]chromene-4,6-dicarboxylate
29)
2Scheme 6). 1H NMR spectroscopy was applied to
distinguish structure 7 from 8 and 9. Thus the NMR
spectrum of 7 displayed an AX pattern for the aromatic
protons, while compounds 8 and 9 exhibited single lines
2.2. Resorcinol
Two compounds were separated from the reaction mixture
O
O
OH
OH
O
O
OH
O
O
2
2
MeO2C
(C6H5)3P
DMAD
MeO2C
+
MeO2C
CO2Me
CO2Me
6(35%)
(40%)
5
Scheme 5.

I. Yavari et al. / Tetrahedron 57 *2001) 7537±7540
7539
OH
OH
OH
HO
OH
O
OH
O
OH
HO
(C H ) P
2
2
6
5 3
+
DMAD
CO2Me
CO2Me
MeO2C
(20%)
(40%)
8
7
OH
O
O
O
O
+
MeO2C
CO2Me
(35%)
9
Scheme 6.
at dˆ6.47 and 8.47, respectively. The assignment of the E
con®guration of 8 is based on the chemical shift of the
vinylic proton.13 Partial assignment of the 13C resonances
in compounds 7±9 are given in Section 4.
toluene 220 mL) was added dropwise a mixture of DMAD
20.57 g, 4 mmol) in toluene 23 mL) at 258C for 10 min. The
reaction mixture was then allowed to warm up to room
temperature and re¯uxed for 8 h. The solvent was removed
under reduced pressure and the residue was puri®ed by
column chromatography using hexane±ethyl acetate 22:1)
as eluent. The solvent was removed under reduced pressure
and the product was recrystallized from hexane±ethyl
acetate 21:2).
3. Conclusions
We anticipate that the reactions described herein represent a
simple entry into the synthesis of polyfunctional coumarin
derivatives of potential interest. The present method carries
the advantage that, not only is the reaction performed under
neutral conditions, but also the substances can be mixed
without any activation or modi®cation. The one-pot nature
of the present procedure makes it an acceptable alternative
to multistep approaches.1,2,9 The presentcoumarin synthesis
complements the older established methods and offers
signi®cant advantages for the synthesis of coumarins having
acid sensitive functional groups. In contrast, the well-known
von Pechmann synthesis14 entails acidic conditions and
frequently affords low and erratic yields.
4.1.1. Methyl 6-hydroxy-2-oxo-2H-chromene-4-carboxyl-
ate -2). Pale yellow crystals, mp 205±2078C 2from 1:2
hexane±ethyl acetate), yield 50%; IR 2KBr) 2nmax/cm21):
3200 2OH), 1722 2CvO ester), 1679 2CvO lactone); MS,
m/z 2%): 220 2M1, 59), 192 218), 161 284), 133 226), 105
233), 77 210), 51 255). Anal. Calcd for C11H8O5 2220.18): C,
60.00; H, 3.66. Found: C, 59.8; H, 3.8%. 1H NMR 2acetone-
d6 solution): d 3.98 23H, s, OCH3), 6.85 21H, s, CH), 7.17
3
4
21H, dd, JHHˆ8.9 and JHHˆ2.8 Hz, CH), 7.26 21H, d,
4
3JHHˆ8.9 Hz, CH), 7.68 21H, d, JHHˆ2.8 Hz, CH), 8.76
21H, s, OH); 13C NMR 2acetone-d6 solution): d 52.58
2OCH3), 111.36 2CH), 116.28 2C), 117.73, 119.31 and
120.39 23CH), 142.20 2CCO2CH3), 147.98 and 153.94
22C±O), 159.38 and 164.24 22CvO).
4. Experimental
DMAD, triphenylphosphine, resorcinol, hydroquinone,
catechol and pyrogallol were obtained from Fluka 2Buchs,
Switzerland) and were used without further puri®cation.
Melting points were measured on an Electrothermal 9100
apparatus. Elemental analyses for C and H were performed
using a Heraeus CHN-O-Rapid analyzer. Mass spectra were
recorded on a FINNIGAN-MATT 8430 mass spectrometer
4.1.2. Methyl 7-hydroxy-2-oxo-2H-chromene-4-carboxyl-
ate -3). Pale yellow crystals, mp 170±1728C 2from 1:2
hexane±ethyl acetate), yield 35%; IR 2KBr) 2nmax/cm21):
3180 2OH), 1719 and 1673 2CvO), 1583 2CvC); MS,
m/z 2%): 220 2M1, 38), 161 272), 133 241), 105 237), 51
262). Anal. Calcd for C11H8O5 2220.18): C, 60.00; H, 3.66.
1
Found: C, 60.2; H, 3.7%. H NMR 2DMSO-d6 solution): d
3.89 23H, s, OCH3), 6.54 21H, s, CH), 6.74 21H, d,
1
operating at an ionization potential of 70 eV. H-, 13C- and
31P NMR spectra were measured with a Brucker DRX-500
AVANCE spectrometer at 500.13, 125.77 and 202.45 MHz,
respectively. IR spectra were recorded on a Shimadzu IR-
460 spectrometer. Chromatography columns were prepared
from Aldrich silica gel 70±230 mesh.
3
4JHHˆ2.3 Hz, CH), 6.81 21H, dd, JHHˆ8.9 and
3
4JHHˆ2.3 Hz, CH), 7.90 21H, d, JHHˆ8.9 Hz, CH), 9.10
21H, s, OH); 13C NMR 2CDCl3 solution): d 53.56 2OCH3),
103.13 2CH), 108.12 2C), 114.01, 114.05 and 128.38 23 CH),
143.43 2CCO2CH3), 156.25 and 160.23 22C±O), 162.21 and
164.83 22CvO).
4.1. General procedure
4.1.3. Dimethyl 2,8-dioxo-9--1,1,1-triphenylphosphanyl-
idene)-9,10-dihydro-2H,8H-pyrano[2,3-f]-chromene-4,10-
dicarboxylate -4). Yellow crystals, mp 196±1988C 2from
To a magnetically stirred solution of triphenylphosphine
21.06 g, 4 mmol) and hydroquinone 20.22 g, 2 mmol) in

7540
I. Yavari et al. / Tetrahedron 57 *2001) 7537±7540
1:1 hexane±ethyl acetate), yield 50%; IR 2KBr) 2nmax
/
4.1.7. Dimethyl -E)-2--3,4,5-trihydroxyphenyl)-2-butene-
dioate -8). Colorless crystals, mp 172±1758C 2from ethyl
acetate), yield 20%; IR 2KBr) 2nmax/cm21): 3445, 3400 and
3280 2OH), 1706 2CvO); MS, m/z 2%): 268 2M1, 55), 236
218), 209 225), 150 232), 121 210), 44 286). Anal. Calcd for
C12H12O7 2268.22): C, 53.73; H, 4.51. Found: C, 53.4; H,
cm21): 1728 2CvO); MS, m/z 2%): 594 2M112, 6), 534
283), 445 234), 330 284), 262 285), 183 263), 108 237).
Anal. Calcd for C34H25O8P 2592.51): C, 68.92; H, 4.25.
1
Found: C, 68.7; H, 4.3%. H NMR 2CDCl33solution): d
3.39 and 3.98 26H, 2s, 2OCH3), 4.24 21H, d, JPHˆ9.6 Hz,
1
P±C±CH), 6.72 21H, s, CH), 7.11 21H, d, Jˆ9.0 Hz, CH),
4.4%. H NMR 2DMSO-d6 solution): d 3.66 and 3.79 26H,
7.5±7.8 215H, m, 3C6H5), 8.14 21H, d, Jˆ9.0 Hz, CH); 13
C
2s, 2OCH3), 6.17 21H, s, CH), 6.47 22H, s, 2CH), 9.05 23H,
br s, 3OH); 13C NMR 2DMSO-d6 solution): d 52.12 and
52.70 22OCH3), 106.52 22CH), 112.57 2C), 122.80 2CH),
137.26 2C), 146.71 22C±OH), 149.56 2C±OH), 165.68 and
168.56 22CvO).
2
NMR 2CDCl3 solution): d 37.80 2d, JPCˆ11.4 Hz, P±C±
1
CH), 38.4 2d, JPCˆ130 Hz, PvC), 52.05 and 53.17
22OCH3), 110.03 and 110.92 22C), 114.43 and 116.15
1
22CH), 123.5 2d, JPCˆ94 Hz, Cipso), 126.71 2CH), 129.2
3
2d, JPCˆ12.4 Hz, Cm), 132.92 2Cp), 133.90 2d,
2JPCˆ9.9 Hz, Co), 142.74 and 151.71 22C±O), 157.08,
159.76, 164.48 and 172.85 24CvO); 31P NMR 2CDCl3 solu-
tion): d 22.70 2Ph3P1±C).
4.1.8. Dimethyl 10-hydroxy-2,8-dioxo-2H,8H-pyrano-
[3,2-g]-chromene-4,6-dicarboxylate -9). Yellow crystals,
mp 262±2648C 2from 1:2 hexane±ethyl acetate), yield
45%; IR 2KBr) 2nmax/cm21): 3365 2OH), 1740 and 1719
2CvO). MS, m/z 2%): 346 2M1, 84), 318 229), 287 249),
259 214), 87 216), 59 224). Anal. Calcd for C16H10O9
4.1.4. Dimethyl -E)-2-[8-hydroxy-4--methoxycarbonyl)-
2-oxo-2H-chromene-6-yl]-2-butenedioate -5). Light
yellow crystals, mp 141±1438C 2from 1:2 hexane±ethyl
acetate), yield 40%; IR 2KBr) 2nmax/cm21): 3385 2OH),
1743 2CvO ester), 1716 2CvO lactone); MS, m/z 2%):
362 2M1, 83), 331 216), 303 233), 271 239), 243 212), 185
211), 101 214), 75 224), 59 240). Anal. Calcd for C17H14O9
1
2346.25): C, 55.50; H, 2.91. Found: C, 55.4; H, 2.8%. H
NMR 2DMSO-d6 solution): d 3.94 26H, s, 2OCH3), 6.94
22H, s, 2CH), 8.47 21H, s, CH), 10.55 21H, br s, OH). 13C
NMR 2DMSO-d6 solution): d 53.79 22OCH3), 113.01 22C),
114.77 22C), 119.25 22CH), 133.09 2CH), 142.38 22C±O),
145.15 2C±O), 159.04 and 164.27 24CvO).
1
2362.29): C, 56.36; H, 3.89. Found: C, 56.4; H, 3.9%. H
NMR 2CDCl3 solution): d 3.80, 3.97 and 4.00 29H, 3s,
3OCH3), 6.32 21H, s, CH), 6.52 21H, br s, OH), 7.00 21H,
References
4
s, CH), 7.31 21H, d, JHHˆ2.0 Hz, CH), 7.98 21H, d,
4JHHˆ2.0 Hz, CH); 13C NMR 2CDCl3 solution): d 52.20,
52.94 and 53.40 23OCH3), 116.47 2C), 116.53, 117.19,
118.43 and 120.25 24CH), 130.35, 142.20 and 143.40
23C), 144.08 and 147.20 22C±O), 158.34, 163.57, 165.12
and 167.84 24CvO).
1. Murray, D. H.; Mendez, J.; Brown, S. A. The Nature of
Coumarins: Occurance, Chemistry and Biochemistry;
Wiley: New York, 1982.
2. Ellis, G. P. Chromenes, Chromanones and Chromones; Wiley:
New York, 1977.
3. Kadis, S.; Ciegler, A.; Ajl, S. Microb. Toxins, Vol. 7; 1972,
Chapter 1.
4.1.5. Dimethyl 2,9-dioxo-2,3,4,9-tetrahydropyrano-[3,2-
h]-chromene-4,7-dicarboxylate -6). Pale yellow crystals,
4. Ellis, G. P.; West, G. B. Prog. Med. Chem. 1974, 10, 109.
5. Wells, P.; Morrison, H. J. Am. Chem. Soc. 1975, 97, 154.
6. Melini, L. Adv. Heterocycl. Chem. 1975, 18, 159.
7. Hepworth, J. D. Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford,
1984; Vol. 3, pp. 573±883.
mp 197±1998C 2from ethanol), yield 35%; IR 2KBr) 2nmax
/
cm21): 1713 2CvO); MS, m/z 2%): 330 2M1, 83), 302 216),
271 285), 243 226), 187 214), 100 210), 59 218). Anal. Calcd
for C16H10O8 2330.25): C, 58.19; H, 3.05. Found: C, 58.4; H,
1
3.2%. H NMR 2CDCl3 solution): d 4.04 26H, s, 2OCH3),
7.13 22H, s, 2CH), 8.25 22H, s, 2CH); 13C NMR 2CDCl3
solution): d 53.50 22OCH3), 118.23 22C), 121.69 22CH),
122.03 22CH), 141.28 22C), 141.62 22C±O), 157.93
22CvO), 163.54 22CvO).
8. Davis, S. G.; Mobbs, B. E.; Goodwin, C. J. J. Chem. Soc.,
Perkin Trans. 1 1987, 2597.
9. Hepworth, J. D.; Gabbutt, C. D.; Heron, B. M. Comprehensive
Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W.,
Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; Vol. 5,
pp. 301±468.
4.1.6. Methyl 7,8-dihydroxy-2-oxo-2H-chromene-4-
carboxylate -7). Yellow crystals, mp 215±2178C 2from
10. Geen, G. R.; Evans, J. M.; Vong, A. K. Comprehensive
Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W.,
Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; Vol. 5,
pp. 469±500.
1:2 hexane±ethyl acetate), yield 15%; IR 2KBr) 2nmax
/
cm21): 3325 and 3200 2OH), 1721 2CvO ester), 1700
2CvO lactone); MS, m/z 2%): 236 2M1, 85), 208 258),
177 257), 150 219), 93 235), 63 236), 39 246). Anal. Calcd
for C11H8O6 2236.18): C, 55.94; H, 3.41. Found: C, 55.6; H,
11. Yavari, I.; Hekmat-Shoar, R.; Zonouzi, A. Tetrahedron Lett.
1998, 39, 2391.
1
3.4%. H NMR 2CDCl3 solution): d 3.97 23H, s, OCH3),
12. Hughes, A. N. Heterocycles 1981, 15, 637 and references
therein.
6.59 21H, s, CH), 6.89 21H, d, Jˆ8.9 Hz, CH), 7.58 21H,
d, Jˆ8.9 Hz, CH), 8.79 22H, br s, 2OH); 13C NMR 2CDCl3
solution): d 57.75 2OCH3), 114.28 2C), 117.66, 119.31 and
123.03 23CH), 137.37 2CCO2CH3), 148.77, 149.16 and
154.69 23C±O), 164.54 and 169.70 22CvO).
13. Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic
Compounds; Wiley: New York, 1994, pp. 569±573.
14. Sethna, S.; Phadke, R. Org. React. *N.Y.) 1953, 7, 1.