4826
J. Cruces et al. / Tetrahedron Letters 42 (2001) 4825–4827
The high and unexpected a-regioselectivity achieved
with classical Heck conditions suggests that the car-
boxymethyl group of aryl halides 1 interacts with the
palladium complex to give a chelate facilitating a-aryla-
tion,11 a mechanism different from the one hypothe-
sized by Cabri et al.8 for arylation of BVE in the
absence of TlOAc. In our work, Cabri coupling condi-
tions facilitated reaction, but were not necessary for
a-selectivity.
and biological interest has previously been restricted to
compounds that can be prepared by Friedel–Crafts
acylations.
Acknowledgements
We thank the Xunta de Galicia and the Spanish Min-
istry of Education and Culture (DGES) for financial
support.
The easy preparation of methyl phenylacetates 3
allowed us to develop a general synthesis of indolon-
aphthoquinones 7 (Z=NH). Nucleophilic attack of the
enolate of acetylphenylacetic acid 3d on o-
References
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gave
2-(2%-nitrophenyl-
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4d, was transformed into indolonaphthoquinone 7b via
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nitrophenylnaphthoquinone
5b,
as
previously
described.12 The final cyclization of this sequence pre-
sumably takes place via the aminophenylnaphtho-
quinone intermediate 6b, the amino group attacking C4.
Similarly, reaction of acetylphenylacetic acid 3c with
o-nitrofluorobenzene gave nitroketoacid 4a, which was
converted to its methyl ester 4c; treatment of 4c with
aq. sodium hydroxide in refluxing methanol for 1 h
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of the latter with NaBH4 in isopropanol at rt gave an
88% yield of unsubstituted indolonaphthoquinone 7a,
presumably through amino attack at C4.
In conclusion, we have established an efficient method
for the preparation of o-acetylphenylacetic acids that
seems to provide unrestricted access to indolonaphtho-
quinones 7 (Z=NH). Work is now in progress to
synthesize a variety of indolonanaphthoquinones for
chemical and biological studies. We are also exploring
additional synthetic applications of ketoacids 3, includ-
ing the general synthesis of 2-phenylacetylphenylacetic
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of carbocyclic and heterocyclic derivatives of chemical
.