amino group was introduced, the yield dropped to 38%
(entry 5). Methyl substituted dibromobenzene reacted with
methyl or methoxy substituted salicylaldehydes smoothly to
give the desired products in better yields (56–63%, entries 6–10).
1H NMR analysis of the crude product mixtures showed the
isomeric ratios to be around 1 : 1 and this indicated that the
meta-methyl only had a marginal effect on the regioselectivity.
It is worthwhile pointing out that 2-hydroxy-1-naphthaldehyde
could also participate in the reaction, even though the
tetracyclic product is only produced in 34% yield (entry 11).
It also seems that the reaction was profoundly influenced by
the electron density on the dibromobenzene. For example,
when two methoxy groups were attached to the aromatic ring,
its reactions with salicylaldehyde and its methyl substituted
analogue only gave the desired xanthones in 36% and 33%
yield, respectively (entries 12 and 13).
Notes and references
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The exact mechanism of this reaction is still not clear at the
present stage. However, on the basis of the results obtained by
Miura8 and others,10 a tentative mechanism is proposed and
shown in Scheme 1. It is thought that the reaction actually
involves two catalytic cycles, both catalyzed by Pd. The first
one, as shown on the left half of Scheme 1, describes the
formation of the biaryl ketone, while the second one, depicted
on the right half of Scheme 1, shows the formation of the ether
linkage. The Pd(0) catalyst first underwent oxidative insertion
into one of the carbon halide bonds to generate the aryl–Pd(II)
intermediate E. This intermediate E, after reacting with the
phenolate to displace the halide, underwent C–H activation of
the C–H bond of the aldehyde to form intermediate F. After
abstraction of the hydrogen atom by the base and reductive
elimination to exclude the Pd(0) catalyst, the biaryl ketone G
was produced. Alternatively, Pd-assisted abstraction of the
aldehyde proton by the base10g,h followed by the intra-
molecular displacement of the halide ion and reductive elimi-
nation also gave the biaryl ketone G. The Pd(0) catalyst
reinserted into the carbon halide bond on the ketone and the
final product was produced after another round of the intra-
molecular displacement of the halide and reductive elimination.
In summary, we have developed a one-step protocol for the
synthesis of xanthones via Pd-catalyzed coupling between
1,2-dibromoarenes and salicylaldehydes. The success of the
reaction heavily relies on the careful selection of proper
Pd-catalyst, solvent and base. Detailed mechanistic investi-
gation on this particular transformation is still ongoing and
the results will be reported in due course.
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Support of this work by the SRF for ROCS, SEM and
a grant from the National Science Foundation of China
(no. 20702012) are gratefully acknowledged.
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Scheme 1 Tentative reaction mechanism.
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 6469–6471 | 6471