etate. We chose to explore an alternate (and more convergent)
strategy involving the nucleophilic aromatic substitution of
5, where X is a good leaving group, with an R-mercaptoac-
extrapolation of earlier4 findings from these laboratories,
underwent a regiospecific Diels-Alder reaction with diene
95 to give 11 via 10. None of the undesired regioisomer 13
was detected.
Treatment of quinone tosylate 11 with methyl mercap-
toacetate (12) and potassium carbonate in THF resulted in
the desired nucleophilic aromatic substitution to give 6; the
latter was then cyclized in good yield to 1 with methanolic
methoxide. As a result of the paucity (3 mg) of natural 1
originally isolated, direct comparison of synthetic and natural
1 was not possible, but synthetic 1 gave H NMR, IR, and
UV spectra in good agreement with spectra obtained1 for
natural 1.
etate. Concerns existed, however, as to whether the two
acidic phenolic protons in the real substrates (5 and 6) would
interfere with the requisite enolate formation and/or substitu-
tion reaction.
Those worries proved unwarranted, and a short regiospe-
cific route to 1 has been achieved. The synthesis is
summarized in Scheme 1. Tosylate 11 was regioselectively
1
The less than satisfying yield of the Diels-Alder reaction
between 8 and 9 may be due to the known5 tendency of 9 to
exhibit multiple reaction paths with dienophiles. Conse-
quently, a more readily accessible substitute for 11 was
sought. Nitroanthraquinone 14 is a known compound.6 The
preparation of 14 is not regiospecific, but it can nonetheless
be achieved in one step by nitration of 1,8-dihydroxyan-
thraquinone. Nitro groups usually serve as activating sub-
stituents, not leaving groups, in nucleophilic aromatic
substitutions, but the participation of nitrite ion as a leaving
group in such reactions is not unknown.7 In fact, the reaction
of 14 with 12 gives 6 in 51% yield.
Scheme 1
In conclusion, we describe the first synthesis of the
naturally occurring 1. The synthesis is short and regiospecific
and affirms the structure assignment.
Acknowledgment. We thank Dr. A. Sato1 for providing
spectra of natural 1.
Supporting Information Available: Experimental pro-
cedures and characterization data for all compounds. This
material is available free of charge via the Internet at
OL006127A
(4) For a leading reference, see: Kelly, T. R.; Ananthasubramanian, L.;
Borah, K.; Gillard, J. W.; Goerner, R. N., Jr.; King, P. F.; Lyding, J. M.;
Tsang, W.-G.; Vaya, J. Tetrahedron 1984, 40, 4569.
(5) Brassard, P.; Savard, J. Tetrahedron 1984, 40, 3455.
(6) Antonello, C.; Uriarte, E.; Palumbo, M. Arch. Pharm. (Weinheim,
Ger.) 1989, 322, 541.
prepared in two operations from naphthazarin (7). Monoto-
sylation of 7 gave 8, which, as anticipated on the basis of
(3) (a) Krollpfeiffer, V. F.; Schneider, K. L.; Wibner A. Justus Liebigs
Ann. Chem. 1950, 566, 139. (b) Fries, K.; Schurmann, G. Chem. Ber. 1919,
52, 2170.
(7) The removal of isomeric contaminants in the purification of the
explosive TNT provides one example: Fieser, L. F.; Fieser, M. AdVanced
Organic Chemistry Reinhold: New York, 1963; p 682.
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Org. Lett., Vol. 2, No. 15, 2000