A direct route to isoflavan quinones. The synthesis of colutequinones A and B

Article abstract of DOI:10.1016/j.tet.2003.08.015

The first syntheses of colutequinone A and colutequinone B were achieved. Radical generation via phenyliodoso diacetate was superior to radical generation via ammonium persulfate.

Full text of DOI:10.1016/j.tet.2003.08.015

Tetrahedron 59 (2003) 7935–7937
A direct route to isoflavan quinones.
The synthesis of colutequinones A and B
*
George A. Kraus and Ikyon Kim
Department of Chemistry, Iowa State University, 2759 Gilman Hall, Ames, IA 50011, USA
Received 17 July 2003; revised 12 August 2003; accepted 12 August 2003
Abstract—The first syntheses of colutequinone A and colutequinone B were achieved. Radical generation via phenyliodoso diacetate was
superior to radical generation via ammonium persulfate.
q 2003 Elsevier Ltd. All rights reserved.
Colutequinone A (1),1 colutequinone B (2)2 and clausse-
quinone (3)3 are members of a growing family of isoflavan
quinones. Colutequinone B exhibits antifungal activity in
vitro. Claussequinone exhibits potent activity against
bloodstream forms of Trypanosoma cruzi (Chagas’
disease).4 It also exhibits anti-inflammatory activity, anti-
fertility activity and is a feeding deterrent for the grass grub
Costelytra zealandica.5 – 8 Claussequinone has been
synthesized by Farkas and coworkers using thallium
trinitrate in the key step.9 As part of a program to develop
environmentally benign radical reactions,10,11 we report the
first syntheses of 1 and 2 from quinones 4 and 5 (Scheme 1).
We compared two methods for radical generation from
carboxylic acids: (1) the method using ammonium per-
sulfate in combination with a catalytic amount of a silver
salt and (2) the method using phenyliodoso diacetate. We
evaluated acids 6, 7, and 8. Cyclohexanecarboxylic acid (6)
and 1,2,3,4-tetrahydro-2-naphthoic acid (7) are com-
mercially available. Acid 8 was synthesized from
4-methoxysalicylaldehyde by reaction with tert-butyl
acrylate according to the method of Satoh17 to produce an
unsaturated ester followed by hydrolysis (CF3CO2H) and
reduction (H2, 10% Pd/C).
The reaction of acid 6 with benzoquinone using ammonium
persulfate with a catalytic amount of silver nitrate in
acetonitrile:water at 708C afforded cyclohexylbenzo-
quinone18 in 91% isolated yield (Scheme 2). Similarly, the
reaction of 7 with benzoquinone generated quinone 9 in
55% isolated yield (Scheme 3). The reaction with
phenyliodoso diacetate also produced cyclohexylbenzo-
quinone in 55% yield (at 20% conversion relative to the
quinone) and 9 in 45% yield (at 30% conversion relative to
the quinone).
Scheme 1.
The additions of radicals derived from the decarboxylation
of carboxylic acids to quinones have been reported by
Barton,12 Torssell,13 Schaefer,14 and Theodorakis.15 Using
the persulfate method of radical generation, Torssell13
converted carboxylic acids into alkoxymethyl-, benzyl- and
phenoxymethyl radicals, which reacted with naphtho-
quinones in good to excellent yields. He also generated
alkoxycarbonyl radicals from monoesters of oxalic acid.16
Surprisingly, the reaction of 8 with benzoquinone, 4 or 5
using the standard persulfate conditions did not afford any
desired product, but returned unreacted benzoquinone and
most of the carboxylic acid. Increasing the amount of
persulfate had no effect. Even when we employed a
stoichiometric amount of silver salt, no alkylated quinone
was isolated. The rationale for this unusual result with acids
bearing electron-rich aromatic rings is not clear, particularly
given Torssell’s successful result with phenoxyacetic acid.
Keywords: quinones; persulfate; phenyliodoso diacetate.
*
Corresponding author. Tel.: þ1-515-294-7794; fax: þ1-515-294-0105;
e-mail: gakraus@iastate.edu
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.08.015

7936
G. A. Kraus, I. Kim / Tetrahedron 59 (2003) 7935–7937
Scheme 2.
The reaction of 8 with quinone 12 produced quinone 13, the
major product, in 84% yield (at 9% conversion). Its proton
and carbon NMR are identical to an authentic sample.10
Bieber has shown that radicals add regioselectively to
methoxybenzoquinone.20
In summary, the reaction of chroman carboxylic acids with
benzoquinones provides a direct entry to biologically active
quinones. Using the phenyliodoso diacetate method, the
chemistry is flexible with regard to substitution pattern on
both the quinone and the carboxylic acid.
Scheme 3.
In view of these results, we examined two phenylpropionic
acids. The reaction of 2,4-diacetoxyphenylpropionic acid
(prepared by acetylation of commercially available 2,4-
dihydroxyphenylpropionic acid) with persulfate and a
catalytic amount of silver salt afforded a 28% isolated
yield of quinone 10. In contrast, the reaction of 4-
methoxyphenylpropionic acid (commercially available)
did not produce the desired quinone 11. These results
further show the incompatibility of electric rich aromatic
rings with the persulfate conditions (Scheme 4).
1. Experimental
1.1. General experimental for radical formation using
phenyliodoso diacetate
To a mixture of quinone (1 equiv.) and acid (3 equiv.) in
benzene (5 mL/mmol of quinone) was added phenyliodoso
diacetate (1 equiv.). The reaction mixture was heated to
reflux for 36 h under an argon atmosphere. The mixture was
cooled to rt, diluted with ethyl acetate, and washed with
NaHCO3. The organic layer was dried over MgSO4, filtered,
and evaporated in vacuo. The residue was purified by either
silica gel chromatography or prep tlc (hexanes:ethyl acetate)
to give the product.
1.1.1. Colutequinone A (1). Purified using 4:1 hexanes:
1
ethyl acetate. 300 MHz H NMR (CDCl3) d 6.94 (1H, d,
J¼8.4 Hz), 6.48 (1H, dd, J¼8.7, 2.7 Hz), 6.37 (1H, d,
J¼2.7 Hz), 6.37 (1H, s), 4.25 (1H, dd, J¼10.8, 3.0 Hz), 4.06
(1H, dd, J¼10.8, 6.0 Hz), 4.02 (3H, s), 4.01 (3H, s), 3.76
(3H, s), 3.50–3.40 (1H, m), 3.05 (1H, dd, J¼16.2, 6.0 Hz),
2.71 (1H, dd, J¼15.9, 6.3 Hz); 75 MHz 13C NMR (CDCl3)
d 184.3, 183.7, 159.6, 154.9, 146.8, 145.3, 144.9, 131.2,
130.3, 112.2, 108.3, 101.8, 68.4, 61.6, 61.5, 55.6, 31.0, 29.1;
HRMS m/z for C18H18O6 calcd 330.1103, found 330.1109.
Scheme 4.
The reaction of acid 8 with commercially available 2,6-
dimethoxybenzoquinone 4 and phenyliodoso diacetate19
afforded a 92% isolated yield (at 24% conversion) of
colutequinone B (2). Similarly, the reaction of 5 with 8
produced colutequinone A (1) in 87% yield (at 11%
conversion) (Scheme 5).
TLC (2:1 hexanes:ethyl acetate), Rf¼0.20.
1.1.2. Colutequinone B (2). Purified using 3:1 hexanes:
1
ethyl acetate. 300 MHz H NMR (CDCl3) d 6.92 (1H, d,
J¼8.4 Hz), 6.47 (1H, dd, J¼8.1, 2.4 Hz), 6.41 (1H, d,
J¼2.7 Hz), 5.86 (1H, s), 4.44 (1H, dd, J¼10.8, 10.2 Hz),
4.13 (1H, ddd, J¼10.2, 3.3, 3.0 Hz), 3.97 (3H, s), 3.81 (3H,
s), 3.77 (3H, s), 3.70–3.55 (1H, m), 3.13 (1H, dd, J¼15.0,
12.0 Hz), 2.66 (1H, ddd, J¼15.0, 5.1, 2.1 Hz); 75 MHz 13C
NMR (CDCl3) d 186.9, 178.4, 159.3, 157.4, 155.9, 155.3,
131.6, 130.2, 114.1, 107.7, 107.6, 101.8, 67.9, 61.6, 56.7,
Scheme 5.
The reaction of methoxybenzoquinone 12 with acid 8
presented a question of regiocontrol in the radical addition.

G. A. Kraus, I. Kim / Tetrahedron 59 (2003) 7935–7937
7937
55.6, 31.4, 29.4; HRMS m/z for C18H18O6 calcd 330.1103,
found 330.1109.
116.5, 30.6, 29.0, 21.3, 21.1; HRMS m/z for C18H16O6 calcd
328.0947, found 328.0954.
TLC (2:1 hexanes:ethyl acetate), Rf¼0.30.
TLC (2:1 hexanes:ethyl acetate), Rf¼0.40.
1.1.3. 2-(1,2,3,4-Tetrahydronaphth-2-yl)benzoquinone
1
(9). Purified using 5:1 hexanes:ethyl acetate. 300 MHz H
Acknowledgements
NMR (CDCl3) d 7.20–7.02 (4H, m), 6.80 (1H, d,
J¼9.9 Hz), 6.74 (1H, dd, J¼9.9, 2.1 Hz), 6.58 (1H, dd,
J¼2.4, 1.2 Hz), 3.26–3.13 (1H, m), 3.07–2.84 (3H, m),
2.70 (1H, dd, J¼15.9, 11.1 Hz), 2.10–1.97 (1H, m), 1.82–
1.65 (1H, m); 75 MHz 13C NMR (CDCl3) d 188.1, 187.2,
153.0, 137.3, 136.3, 135.8, 135.3, 131.4, 129.2, 129.16,
126.3, 126.1, 35.1, 33.3, 29.1, 28.3; HRMS m/z for
C16H14O2 calcd 238.0994, found 238.0996.
We thank the Environmental Protection Agency and Iowa
State University for partial support.
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