Uncatalyzed reaction of silyl ketene acetals with oxalyl chloride: A straightforward preparation of symmetrical pulvinic acids

Article abstract of DOI:10.1021/jo048403v

(Chemical Equation Presented) Several natural pulvinic acids were synthesized. Silyl ketene acetals derived from methyl arylacetates (4 equiv) reacted with oxalyl chloride at -78°C, without the need of adding a catalyst. After treatment of the crude diketones with DBU and acidification with hydrochloric acid, symmetrical pulvinic acids methyl esters were obtained. Saponification of the methyl esters afforded the corresponding pulvinic acids in 60-70% overall yields from oxalyl chloride.

Full text of DOI:10.1021/jo048403v

pulvinic acids have been reported.3 Among these, the
procedure originally described by Vollhardt was espe-
cially suitable for the preparation of symmetrical pulvinic
acids (in which Ar ) Ar′), because it makes use of the
opening of the corresponding pulvinic dilactone. However,
strong conditions are employed during the whole proce-
dure, and we were interested in designing a smoother
way to access to symmetrical pulvinic acids.
The reaction of silyl ketene acetals with acid chlorides
has been shown to afford â-keto esters under a variety
of conditions.4 Thus, Lewis acids, amine, or elevated
temperatures were employed to effect this transforma-
tion. More recently, Langer et al. have shown that 1,3-
bis-silyl enol ethers react with oxalyl chloride to yield
cyclocondensation adducts.5 This method was applied to
the synthesis of pulvinic derivatives.6,7 To the best of our
knowledge, the treatment of 2 equiv of silyl ketene acetals
with oxalyl chloride has not previously been reported.
Such reactions would in principle lead to 3,4-diketo-adipic
diesters, which could serve as precursors to the corre-
sponding pulvinic acids. Herein we thus will present the
results of such a study and the ensuing preparation of
pulvinic acids that was then made possible.
Uncatalyzed Reaction of Silyl Ketene
Acetals with Oxalyl Chloride: A
Straightforward Preparation of
Symmetrical Pulvinic Acids
Benoˆıt Heurtaux,† Claude Lion,‡ Thierry Le Gall,*,† and
Charles Mioskowski*,†,§
1CEA-Saclay, Service de Marquage Mole´culaire et de Chimie
Bioorganique, Baˆt. 547, 91191 Gif-sur-Yvette, France,
2ITODYS, Universite´ de Paris 7, UMR CNRS 7086,
3
1 rue Guy de la Brosse, 75005 Paris, and Laboratoire de
Synthe`se Bio-Organique, UMR CNRS 7514, Faculte´ de
Pharmacie, Universite´ Louis Pasteur, 74 route du Rhin,
B.P. 24, 67401 Illkirch, France
legall@dsvidf.cea.fr; mioskow@aspirine.u-strasbg.fr
Received September 10, 2004
Three silylated ketene acetals 2a-c derived from the
corresponding methyl arylacetates 1a-c were prepared
in quantitative yields, according to the procedure de-
scribed by Ainsworth et al.8 (Scheme 1). They were then
employed without further purification.
A preliminary study of the conditions of the reaction
was carried out using silyl ketene acetal 2b as the
Several natural pulvinic acids were synthesized. Silyl ketene
acetals derived from methyl arylacetates (4 equiv) reacted
with oxalyl chloride at -78 °C, without the need of adding
a catalyst. After treatment of the crude diketones with DBU
and acidification with hydrochloric acid, symmetrical pul-
vinic acids methyl esters were obtained. Saponification of
the methyl esters afforded the corresponding pulvinic acids
in 60-70% overall yields from oxalyl chloride.
(2) (a) Steffan, B.; Steglich, W. Angew. Chem., Int. Ed. Engl. 1984,
23, 445. (b) Gill, M.; Lally, D. A. Phytochemistry 1985, 24, 1351. (c)
Gill, M.; Kiefel, M. J. Aust. J. Chem. 1994, 47, 1967. (d) Winner, M.;
Gime´nez, A.; Schmidt, H.; Sontag, B.; Steffan, B.; Steglich, W. Angew.
Chem., Int. Ed. 2004, 43, 1883.
(3) Selected pulvinic acids syntheses: (a) Vollhardt, J. Liebigs Ann.
Chem. 1894, 282, 1. (b) Asano, M.; Kameda, Y. Ber. Dtsch. Chem. Ges.
1935, 68, 1568. (c) Akermark, B. Acta Chem. Scand. 1961, 15, 1695.
(d) Beaumont, P.; Edwards, R.; Elsworthy, G. J. Chem. Soc., Perkin
Trans. 1 1968, 2968. (e) Wikholm, R. J.; Moore, H. W. J. Am. Chem.
Soc. 1972, 94, 6152. (f) Foden, F.; McCormick, J.; O’Mant, D. J. Med.
Chem. 1975, 18, 199. (g) Knight, D. W.; Pattenden, G. J. Chem. Soc.,
Chem. Commun. 1976, 660. (h) Knight, D.; Pattenden, G. J. Chem.
Soc., Perkin Trans. 1 1979, 62. (i) Knight, D.; Pattenden, G. J. Chem.
Soc., Perkin Trans. 1 1979, 84. (j) Weinstock, J.; Blank, J. E.; Oh, H.-
J.; Sutton, B. M. J. Org. Chem. 1979, 44, 673. (k) Ramage, R.; Griffiths,
G.; Sweeney, J. J. Chem. Soc., Perkin Trans. 1 1984, 1547. (l)
Pattenden, G.; Pegg, N.; Smith, A. Tetrahedron Lett. 1986, 27, 403.
(m) Pattenden, G.; Turvill, M.; Chorlton, A. J. Chem. Soc., Perkin
Trans. 1 1991, 2357. (n) Pattenden, G.; Pegg, N. A.; Kenyon, R. W. J.
Chem. Soc., Perkin Trans. 1 1991, 2363. (o) Gedge, D. R.; Pattenden,
G.; Smith, A. J. Chem. Soc., Perkin Trans. 1 1986, 2127. (p) Frank, R.
L.; Clark, G. R.; Coker, J. N. J. Am. Chem. Soc. 1950, 72, 1824. (q)
Edwards, R. L.; Gill, M. J. Chem. Soc., Perkin Trans. 1 1973, 1529.
(4) (a) Burlachenko, G. S.; Maltsev, V. V.; Baukov, Y. I.; Lutsenko,
I. F. Zh. Obshch. Khim. 1973, 43, 1724. (b) Rathke, M. W.; Sullivan,
D. F. Tetrahedron Lett. 1973, 1297. (c) Wissner A. J. Org. Chem. 1979,
44, 4617. (d) Stefaniak, M. H. Synlett 1979, 677. (e) Rousseau, G.;
Blanco, L. Tetrahedron Lett. 1985, 26, 4195.
Pulvinic acids constitute a group of biologically active
pigments found in mushrooms of the Boletales order and
in lichens.1 The common structural feature of these
compounds is an unsaturated, hydroxylated γ-lactone
substituted by a hydroxycarbonylalkylidene moiety. They
differ by the nature of the aryl groups, which are often
hydroxylated.
Structurally related compounds that bear two pulvinic
chains have also been isolated.2 Several syntheses of
(5) (a) Langer, P.; Stoll, M. Angew. Chem., Int. Ed. 1999, 38, 1803.
(b) Langer, P.; Schneider, T.; Stoll, M. Chem. Eur. J. 2000, 6, 3204. (c)
Langer, P.; Eckardt, T.; Schneider, T.; Go¨bel, C.; Herbst-Irmer, R. J.
Org. Chem. 2001, 66, 2222.
* To whom correspondence should be addressed. Fax: 33 (0) 169
08 79 91.
(6) Ahmed, Z.; Langer,P. J. Org. Chem. 2004, 69, 3753.
† CEA-Saclay.
(7) Desage-El Murr, M.; Nowaczyk, S.; Le Gall, T.; Mioskowski, C.;
Amekraz, B.; Moulin, C. Angew. Chem. 2003, 115, 1327; Angew. Chem.,
Int. Ed. 2003, 42, 1289.
‡ Universite´ de Paris 7.
§ Universite´ Louis Pasteur.
(1) For reviews, see: (a) Gill, M.; Steglich, W. Prog. Chem. Org. Nat.
Prod. 1987, 51, 1. (b) Rao, Y. S. Chem. Rev. 1976, 76, 625.
(8) Ainsworth, C.; Chen, F.; Kuo, Y.-N. J. Org. Met. Chem. 1972,
46, 59.
10.1021/jo048403v CCC: $30.25 © 2005 American Chemical Society
Published on Web 01/22/2005
1474
J. Org. Chem. 2005, 70, 1474-1477

SCHEME 1
SCHEME 2
TABLE 1. Preparation of Methyl Pulvinates 4a-c
It was shown that the quantity of silylated compound
2b employed had a clear effect on the yield of compound
4b based on the quantity of oxalyl chloride employed.
Although only 2 equiv of 2b should be theorically neces-
sary to obtain a quantitative formation of the expected
adduct, the yield was much better using 4 equiv of
substrate (entries 1-4). It could be reasoned that some
of the substrate 2b reacts with the formed â-keto ester,
silylating it, and is converted to methyl arylacetate 1b,
which does not participate in the production of the
pulvinate precursor. Ester 1b was indeed observed in the
1H NMR spectrum of a nonhydrolyzed reaction mixture
conducted in CD2Cl2. Purification of 4b was shown to be
much more efficient using a simple precipitation in acidic
medium rather than a silica gel chromatography (entry
2 versus entry 1). Using this convenient procedure, the
overall yield for the transformation of oxalyl chloride to
pulvinic derivative 4b was 74%. Similar yields were
obtained in the preparation of vulpinic acid (4a), a
natural compound found in lichens, and methyl atro-
mentate (4c). In the latter case, no specific step was
needed for the cleavage of the trimethysilyl aryl ethers.
The relative configuration of the exocyclic double bond
of the compounds synthesized was established by com-
parison of the physical and spectroscopic data reported
for 4a3e,k,n,6,9 and 4b.3e,f,10 The cyclization of the crude
diketone 3 is likely to proceed as described in Scheme 2.
In the methanol solution, the diketone is in equilibrium
with tautomers such as 5, which under the influence of
DBU cyclizes to the corresponding pulvinic derivative.
After acidic treatment, compound 4 having the depicted
configuration is obtained as a single isomer, which
probably is thermodynamically favored.
entry
substrate
x
product
overall yieldc (%)
1
2
3
4
5
6
2b
2b
2b
2b
2a
2c
2
2
3
4
4
4
4ba
4bb
4bb
4bb
4ab
4cb
33
48
48
74
71
60
a In this experiment, compound 4b was purified by chromatog-
raphy. b In these experiments, compounds 4a-c were isolated by
precipitation upon concentrated HCl addition. c Overall yield of
isolated product, based on the quantity of oxalyl chloride employed.
reagent and titanium(IV) tetrachloride as the Lewis acid.
Reactions were performed at -78 °C in methylene
chloride, employing a 2:1 ratio of 2b to oxalyl chloride
and varying amounts of the Lewis acid. However, com-
plex mixtures of compounds were invariably obtained,
apparently resulting from a polymerization. An analo-
gous result was obtained employing trimethylsilyl triflate
as catalyst. We then performed the reaction at -78 °C
in the absence of any catalyst.
This proved to be more satisfactory, since the 1H NMR
spectrum of the crude product was indicative of the
presence of both diastereomers of compound 3b (presence
of two benzylic singlets at δ ) 5.38 and 5.44 ppm);
however, silica gel chromatography did not allow isolation
of these compounds. Rather, products apparently arising
from the cyclization of 3b were obtained, although in
modest yield. A sample of the diketone 3b, obtained as a
single diastereomer, was later isolated by recrystalliza-
tion of the crude reaction product in methanol, albeit with
a low yield (14%).
Finally, the crude product of the reaction of the silyl
ketene acetal with oxalyl chloride was treated directly
with a base (DBU), to favor the cyclization of the diketone
to the corresponding pulvinic derivative. The results
obtained in the preparation of methyl pulvinates 4a-c
are summarized in Table 1.
Several pulvinic methyl esters are natural products.
It was also of interest to prepare carboxylic acids 6a-c,
which are all natural pigments. They were cleanly
obtained in good yields by saponification of the corre-
sponding methyl esters (Scheme 3). Physical and spec-
troscopic data were in agreement with the reported data
for pulvinic acid (6a)3e,k,n and atromentic acid (6c).3f,o
In conclusion, we have shown that silyl ketene acetals
derived from methyl arylacetates react readily at low
temperature with oxalyl chloride without the need of an
activating agent, such as a Lewis acid. This allowed the
straightforward preparation of symmetrical pulvinic
(9) Duncan C. J. G.; Cuendet, M.; Fronczek, F. R.; Pezzuto, J. M.;
Mehta, R. G.; Hamann, M. T.; Ross, S. A. J. Nat. Prod. 2003, 66, 103.
(10) Marumoto, R.; Kilpert, C.; Steglich, W. Z. Naturforsch. 1986,
363.
J. Org. Chem, Vol. 70, No. 4, 2005 1475

1-Methoxy-1-(trimethylsilyloxy)-2-(4-trimethylsilylox-
yphenyl)ethylene (2c). Brownish oil. Mixture of E- and
Z-isomers (ratio 80/20, according to 1H NMR). IR (NaCl, thin
film) νmax ) 2960, 1745, 1657, 1606, 1508, 1451, 1346, 1256,
SCHEME 3
1167, 1070, 968, 916, 846, 757 cm-1 1H NMR (CDCl3, 300
.
MHz): δ (E-isomer) 7.34 (d, J ) 8.5 Hz, 2H), 6.77 (d, J ) 8.5
Hz, 2H), 4.68 (s, 1H), 3.70 (s, 3H), 0.34 (s, 9H), 0.28 (s, 9H). 13
C
NMR (CDCl3, 75 MHz): δ (E-isomer) 156.8, 151.4, 129.8, 127.4
(2C), 119.6 (2C), 85.5, 53.5, 0.0 (3C). Characteristic 1H NMR
signals for Z-isomer: δ 4.58 (s, 1H), 3.66 (s, 3H), 0.31 (s, 9H),
0.29 (s, 9H).
acids. Further developments for the preparation of
unsymmetrical pulvinic acids are in progress.
Preparation of Pulvinic Esters. Typical Procedure. A
solution of silylated compound 2b (504 mg, 2 mmol) in methylene
chloride (10 mL) was cooled under stirring at -78 °C. A solution
of oxalyl chloride (44 µL, 0.5 mmol) in methylene chloride (5 mL)
was added dropwise. The resulting yellow solution was stirred
at -78 °C for 5 h. Saturated aqueous NH4Cl (10 mL) was added
via syringe, and the reaction mixture was allowed to warm to
room temperature. The aqueous phase was extracted with
methylene chloride (3 × 20 mL). The combined organic phases
were dried over MgSO4, and then concentrated under vacuum.
A yellow solid was obtained (374 mg). The yellow solid was then
dissolved in methylene chloride (5 mL) at room temperature
under argon. DBU (151 µL, 1.01 mmol) was added, and the
reaction mixture was stirred at room temperature for 5 h. Acetic
acid (1 mL) was added, and then the reaction mixture was
concentrated in vacuo. A 1:1 mixture of methanol and concen-
trated hydrochloric acid (3 mL) was added to the residue, leading
to the precipitation of a red solid. The solid was filtrated and
washed with acetic acid. Recrystallization (acetic acid) led to
compound 4b (171 mg, 74% yield) as red crystals.
Experimental Section
General. THF was freshly distilled from sodium benzophe-
none ketyl. Methylene chloride was freshly distilled over P2O5.
Moisture-sensitive reactions were performed in a flame-dried
flask, under an argon atmosphere. TLC was performed with
silica gel 60F254 plates, with detection by UV light and with an
ethanol solution of phosphomolybdic acid. Column chromatog-
raphy was on 40-63 µm silica gel. Melting points were uncor-
1
rected. NMR was at 300.13 MHz for H, 75.47 or 100.624 MHz
for 13C. Chemical shifts (δ) are in ppm (s ) singlet, d ) doublet,
t ) triplet, q ) quartet, m ) multiplet, b ) broad); coupling
constants (J) are in Hz.
Methyl 4-(Trimethylsilyloxy)phenylacetate (1c). Triethyl-
amine (3.3 mL, 24 mmol) and chlorotrimethylsilane (3.3 mL, 26
mmol) were successively added to a stirred solution of methyl
4-hydroxyphenylacetate (1.65 g, 10 mmol) in THF (17 mL) at
room temperature. The reaction mixture was stirred for 15 h,
and then pentane (70 mL) was added. The suspension was
filtered through a pad of Celite, under a nitrogen atmosphere.
Concentration of the filtrate under vacuum afforded crude
methyl 4-(trimethylsilyloxy)phenylacetate (2.38 g, quantitative)
as a brown oil that was used in the next reaction without further
purification. 1H NMR (CDCl3, 300 MHz): δ 7.13 (d, J ) 8.5 Hz,
2H), 6.79 (d, J ) 8.5 Hz, 2H), 3.65 (s, 3H), 3.53 (s, 2H), 0.26 (s,
9H); 13C NMR (CDCl3, 75 MHz): δ 171.9, 154.0, 130.0 (2C),
126.6, 119.8 (2C), 51.5, 40.0, 13.8.
Methyl 4,4′-Dimethoxypulvinate (4b). Red solid, mp 170
°C (lit.3e mp 177-178 °C; lit.3f mp 179-181°C). IR (KBr pellet)
1
νmax ) 3439, 2631, 1771, 1677, 1600, 1248, 1063, 823 cm-1. H
NMR (CDCl3, 300 MHz): δ 13.65 (s, 1H), 8.73 (s, 1H), 8.64 (s,
1H), 8.11 (d, J ) 9.1 Hz, 2H), 7.18 (d, J ) 8.6 Hz, 2H), 6.94 (d,
J ) 9.1 Hz, 2H), 6.92 (d, J ) 8.6 Hz, 2H), 3.93 (s, 3H). 13C NMR
(DMSO-d6, 75 MHz): δ 171.7, 165.9 (2C), 159.3 (2C), 158.5,
154.4, 131.2 (3C), 129.1 (3C), 114.8, 113.6 (4C), 105.8, 55.1 (2C),
54.1. Anal. Calcd for C21H18O7: C, 65.96; H, 4.74. Found: C,
65.54; H, 4.71.
Vulpinic Acid (4a). Yellow solid, mp 151 °C (lit.3e mp 146-
147 °C; lit.3k mp 146-148 °C; lit.3n mp 150-151 °C). IR (KBr
pellet) νmax ) 2962, 2513, 1768, 1679, 1609, 1436, 1302, 1070,
952, 689 cm-1. 1H NMR (CDCl3, 300 MHz): δ 13.77 (s, 1H), 8.12
(d, J ) 8.5 Hz, 2H), 7.50-7.25 (m, 8H), 3.88 (s, 3H). 13C NMR
(CDCl3, 75 MHz): δ 171.4, 165.7, 160.1, 154.5, 131.8, 129.7 (2C),
128.8, 128.4 (2C), 128.2, 128.1, 127.9(2C), 127.6 (2C), 115.7,
104.8, 54.3. Anal. Calcd for C19H14O5: C, 70.80; H, 4.38. Found:
C, 70.79; H, 4.42.
Preparation of Silyl Ketene Acetals. Typical Procedure.
A solution of n-butyllithium (2 N in hexanes, 4.5 mL, 9 mmol)
was added dropwise to a solution of diisopropylamine (1.5 mL,
10.8 mmol) in THF (10 mL) cooled at 0 °C. After 10 min at 0°C,
the reaction mixture was cooled at -78 °C, and then methyl
phenylacetate (1.3 mL, 9 mmol) was added dropwise. The
reaction mixture was stirred at -78 °C for 1 h, and then
chlorotrimethylsilane (1.5 mL, 11.25 mmol) was added dropwise.
The reaction mixture was allowed to warm to room temperature
and stirred for 15 h. Pentane (70 mL) was added, and the
resulting suspension was filtered through a short pad of Celite.
Concentration of the filtrate in vacuo afforded silyl ketene acetal
2a (2.05 g, quantitative) as a colorless oil that was used in the
next reaction without further purification.
Methyl Atromentate (4c). Red-brown powder, mp >300 °C
(lit.3f mp 360-362 °C). IR (KBr pellet) νmax ) 3328, 3187, 2565,
1897, 1735, 1679, 1605, 1433, 1312, 1177, 1068, 834 cm-1 1H
.
NMR (acetone-d6, 300 MHz): δ 13.79 (s, 1H), 8.73 (s, 1H), 8.64
(s, 1H), 8.04 (d, J ) 6.7 Hz, 2H), 7.25 (d, J ) 8.6 Hz, 2H), 6.94
(d, J ) 6.7 Hz, 2H), 6.91 (d, J ) 8.6 Hz, 2H), 3.93 (s, 3H). 13C
NMR (DMSO-d6, 75 MHz): δ 173.3, 172.7, 164.4, 162.3, 161.5,
148.5, 135.0 (3C), 134.5 (3C), 119.5 (4C), 109.1, 107.6, 57.4 (2C).
Anal. Calcd for C19H14O7: C, 64.41; H, 3.98. Found: C, 64.08;
H, 4.23.
1-Methoxy-2-(phenyl)-1-(trimethylsilyloxy)ethylene (2a).8
Viscous, colorless oil. Mixture of E- and Z-isomers (ratio 70/30,
1
according to H NMR). IR (NaCl, thin film) νmax ) 2957, 1740,
1706, 1289, 1255, 1128 cm-1. 1H NMR (CDCl3, 300 MHz): δ (E-
isomer) 7.45 (d, J ) 7.9 Hz, 2H), 7.32-7.23 (m, 2H), 7.07 (t, J )
7.3 Hz, 1H), 4.77 (s, 1H), 3.76 (s, 3H), 0.37 (s, 9H). Characteristic
1H NMR signal for Z-isomer: δ 4.64 (s, 1H).
Preparation of Pulvinic Acids. Typical Procedure. A 0.5
N sodium hydroxide solution (2 mL) was added to ester 4a (57.7
mg, 0.179 mmol). The solution was refluxed for 1 h. After cooling
to room temperature, 1 N hydrochloric acid was added until pH
) 1. Filtration of the precipitate and washing with water
afforded pulvinic acid 6a as a yellow solid (52 mg, 95%).
Pulvinic Acid (6a). Yellow solid, mp 210-212 °C (lit.3e mp
216-217 °C; lit.3k mp 202-207 °C). IR (KBr pellet) νmax ) 3195,
2364, 1754, 1674, 1587, 1486, 1441, 1405, 1367, 1215, 1076,
1-Methoxy-2-(4-methoxyphenyl)-1-(trimethylsilyloxy)-
ethylene (2b).11 Viscous, colorless oil. Mixture of E- and
Z-isomers (ratio 93/7, according to 1H NMR). IR (NaCl, thin film)
νmax ) 3057, 2956, 2838, 1740, 1657, 1610, 1510, 1249, 1069,
850 cm-1. 1H NMR (CDCl3, 300 MHz): δ (E-isomer) 7.38 (d, J )
6.7 Hz, 2H), 6.85 (d, J ) 6.7 Hz, 2H), 4.68 (s, 1H), 3.79 (s, 3H),
3.69 (s, 3H), 0.33 (s, 9H). 13C NMR (CDCl3, 75 MHz):
δ
1056, 961, 781, 701 cm-1 1H NMR (CDCl3, 300 MHz): δ 8.14
.
(E-isomer) 156.2, 153.6, 127.4 (3C), 113.4 (2C), 85.5, 55.0, 53.6,
0.0 (3C). Characteristic 1H NMR signal for Z-isomer: δ 4.58 (s,
1H).
(d, J ) 8.5 Hz, 2H), 7.34-7.50 (m, 8H). 13C NMR (CD3OD, 75
MHz): δ 172.2, 165.9, 160.7, 153.0, 132.5, 129.0, 128.6, 127.6,
127.5, 127.2, 126.9, 126.7, 116.7, 102.6. HRMS (ESI-TOF) calcd
for C18H13O5 (M + H)+ 309.0763, found 309.0727.
(11) Emde, H.; Simchen, G. Liebigs Ann. Chem. 1983, 816.
1476 J. Org. Chem., Vol. 70, No. 4, 2005

4,4′-Dimethoxypulvinic Acid (6b). Bright red solid, mp 180
°C. IR (KBr pellet) νmax ) 3478, 2963, 2512, 1766, 1679, 1592,
4b was carried out with the same quantities of reactants. After
the first part of the procedure, the yellow solid obtained after
removal of the solvents under vacuum (380 mg) was recrystal-
lized with methanol (40 mL). Compound 3b was obtained as a
1512, 1473, 1417, 1366, 1305, 1242, 1103, 1058, 962, 830 cm-1
.
1H NMR (CDCl3, 300 MHz): δ 8.11 (d, J ) 9.1 Hz, 2H), 7.25 (d,
J ) 8.5 Hz, 2H), 6.95 (d, J ) 9.1 Hz, 2H), 6.93 (d, J ) 8.5 Hz,
2H). 13C NMR (acetone-d6, 100 MHz): δ 173.2, 165.9, 159.7,
159.5, 159.2, 154.5, 131.5 (2C), 128.9, 128.8, 125.2, 121.9, 115.7,
113.7(2C), 113.1 (2C), 103.6, 54.6 (2C). HRMS (ESI-TOF) calcd
for C20H16O7Na (M + Na)+ 391.0794, found 391.0778.
1
yellow solid (28 mg, 14%). H NMR revealed that it is a single
diastereomer; however, its configuration could not be deter-
mined. This compound was found to be unstable, leading to
cyclization products, and no correct elemental analyses could
be obtained. Yellow powder, mp 136 °C. IR (KBr pellet) νmax
)
Atromentic Acid (6c). Red-brown solid, mp >300 °C (lit.3f
2957, 2839, 1769, 1708, 1676, 1611, 1515, 1444, 1351, 1310,
1287, 1252, 1181, 1159, 1119, 1031, 1010, 954, 837, 798, 759
mp 330-332 °C, lit.3o mp 287-289 °C). IR (KBr pellet) νmax
)
1
cm-1. H NMR (CDCl3, 300 MHz): δ 7.17 (d, J ) 6.7 Hz, 4H),
3306, 2931, 2500, 1757, 1705, 1675, 1599, 1513, 1450, 1428,
1367, 1233, 1055, 964, 837, 752, 702 cm-1 1H NMR (acetone-
.
6.86 (d, J ) 6.7 Hz, 4H), 5.34 (s, 2H), 3.79 (s, 6H), 3.63 (s, 6H).
13C NMR (CDCl3, 75 MHz): δ 190.1 (2C), 168.2 (2C), 159.5 (2C),
130.8 (4C), 122.2 (2C), 114.0 (4C), 56.4 (2C), 55.0 (2C), 52.5 (2C).
d6, 300 MHz): δ 8.04 (d, J ) 9.1 Hz, 2H), 7.30 (d, J ) 8.6 Hz,
2H), 6.93 (d, J ) 9.1 Hz, 2H), 6.90 (d, J ) 8.6 Hz, 2H). 13C NMR
(acetone-d6, 75 MHz): δ 173.8, 166.8, 160.2, 158.0, 157.8, 154.9,
132.3, 131.9, 129.69, 125.1, 121.8, 116.7, 115.7, 115.1, 104.0.
HRMS (ESI-TOF) calcd for C18H12O7Na (M + Na)+ 363.0481,
found 363.0488.
Acknowledgment. This work was supported by a
grant from the De´le´gation Ge´ne´rale pour l’Armement.
Dimethyl 3,4-Diketo-2,5-bis(4methoxyphenyl)adipate
(3b). The procedure employed for the preparation of compound
JO048403V
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