C
H. Yu, G. A. Kraus
Letter
Synlett
obtained on a 20-gram scale. Tomichaedin methyl ester was
synthesized in three steps from commercially available
compounds.
tored by 1H NMR) then was cooled to ambient temperature.
0.5 M HCl solution was added, and the mixture was extracted
with ethyl acetate three times. The organic phase was washed
with brine and was dried over Na2SO4. Purification by column
chromatography gave the product 9a (45% yield) as a light-
1
brown solid. H NMR (400 MHz, CDCl3): = 8.75 (d, J = 1.6 Hz,
Funding Information
1 H), 8.39 (dd, J = 8.0, 1.5 Hz, 1 H), 8.16 (d, J = 8.1 Hz, 1 H), 6.23
(s, 1 H), 3.98 (s, 3 H), 3.93 (s, 3 H). 13C NMR (101 MHz, CDCl3):
= 184.2, 179.5, 165.6, 160.9, 135.2, 134.9, 134.8, 131.3, 128.2,
126.8, 110.4, 56.8, 53.0. HRMS (ESI-QTOF): m/z [M + H]+ calcd
for C13H10O5: 247.0601; found: 247.0600.
We thank the NSF Engineering Center for Biorenewable Chemicals
(CBiRC) which awarded NSF grant EEC-0813570 for support of this re-
search.
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Synthesis of Tomichaedin Methyl Ester
Methyl 7-Hydroxy-5,8-dioxo-5,8-dihydronaphthalene-2-car-
boxylate (12)
Supporting Information
Supporting information for this article is available online at
Under argon, a suspension of methoxy quinone 9a (180 mg,
0.73 mmol, 1.0 equiv) and AlCl3 (195 mg, 1.46 mmol, 2.0 equiv)
in DCE (5 mL) was stirred under reflux for 1 hour. The reaction
mixture was allowed to cool, 0.5 M HCl was added, and the
mixture was extracted with ethyl acetate three times, and the
organic phase was dried over Na2SO4. Filtration through a thin
silica pad followed by removal of solvent afforded the product
12 as a solid, which was pure enough to use in the next step.
1H NMR (400 MHz, CDCl3): = 8.75 (d, J = 1.7 Hz, 1 H), 8.44 (dd,
J = 8.0, 1.7 Hz, 1 H), 8.20 (d, J = 8.0 Hz, 1 H), 7.39 (s, 1 H), 6.43 (s,
1 H), 4.00 (s, 3 H). 13C NMR (101 MHz, CDCl3): = 184.3, 181.4,
165.4, 156.9, 136.1, 135.7, 134.7, 129.7, 128.0, 127.3, 111.4,
53.1. HRMS (ESI-QTOF): m/z [M]– calcd for C12H8O5: 232.0370;
found: 232.0323.
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References and Notes
(1) Pavel, D.; Shanks, R. Polymer 2005, 46, 6135.
(2) Yaginuma, S.; Asahi, T. Jpn. Kokai Tokkyo Koho JP07285912,
1995.
(3) Kraus, G. A. US Patent No. 9,000,209, 2015.
(4) (a) Andrade, G. S.; Berkner, J. E.; Liotta, C. L.; Eckert, C.; Schiraldi,
D. A.; Andersen, A.; Collard, D. M. Synth. Commun. 2003, 33,
3643. (b) Jones, J. R.; Liotta, C. L.; Collard, D. M.; Schiraldi, D. A.
Macromolecules 1999, 32, 5786. (c) Wu, C. S.; Chiu, W. C.; Wang,
J. P.; Kuo, S. C. Chin. Pharm. J. 2002, 54, 245.
(5) OECD, Meeting report of the Global Forum on Environment:
Plastics in a Circular Economy - Design of Sustainable Plastics
from a Chemicals Perspective 2018.
(6) (a) Jung, M. E.; Brown, R. W. Tetrahedron Lett. 1981, 22, 3355.
(b) Tegmo-Larsson, I. M.; Rozeboom, M. D.; Houk, K. N. Tetrahe-
dron Lett. 1981, 22, 2043. (c) Hendrickson, J. B.; Singh, V.
J. Chem. Soc., Chem. Commun. 1983, 837.
(7) Smith, J.; Thomson, R. H. Tetrahedron 1960, 10, 148.
(8) Diels–Alder Reaction of Methyl Coumalate with Hydroxyqui-
none; Typical Procedure for Methyl 6-Methoxy-5,8-dioxo-
5,8-dihydronaphthalene-2-carboxylate (9a)
Tomichaedin Methyl Ester (13)
To a stainless-steel reactor, hydroxy quinone 12 (68 mg, 0.3
mmol, 1.0 equiv) was dissolved in a mixture of ethanol/water
(1:1 ratio, 2 mL), and paraformaldehyde (40 mg, 1.2 mmol, 4.0
equiv) was added. The reactor was sealed under air, and was
heated to 200 °C for 3 hours. After cooling, the mixture was
diluted with 0.5 M HCl, and extracted with ethyl acetate. Filtra-
tion through a thin silica pad (the compound was found to be
unstable on silica) afforded tomichaedin methyl ester 13 (40%
over two steps) as a light-yellow solid. 1H NMR (400 MHz,
CDCl3): = 8.71 (d, J = 1.7 Hz, 1 H), 8.39 (dd, J = 8.0, 1.8 Hz, 1 H),
8.20 (d, J = 8.0 Hz, 1 H), 3.99 (s, 3 H), 2.13 (s, 3 H). 13C NMR (101
MHz, CDCl3): = 184.5, 180.6, 165.5, 153.7, 135.8, 135.7, 134.5,
129.7, 127.6, 127.3, 121.5, 53.0, 9.0. HRMS (ESI-QTOF): m/z
[M – H]– calcd for C13H9O5: 245.0455; found: 245.0456.
To a solution of methyl coumalate (555 mg, 3.6 mmol, 0.9 equiv)
and hydroxyquinone 8 (552 mg, 4.0 mmol, 1.0 equiv) in aceto-
nitrile (20 mL), triethylamine (405 mg, 4.0 mmol, 1.0 equiv) was
added, and the solution turned dark-red immediately. The
mixture was stirred under argon at 45 °C for 24 hours (moni-
© 2019. Thieme. All rights reserved. — Synlett 2019, 30, A–C