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group and the others remained unreacted (3ab, 3ac, 3ad and 3ae).
This result may be attributed to one of the methyl groups on the
toluene derivatives being pre-oxidized to an aldehyde group, and
its electron-withdrawing property was unfavorable to the subse-
quent oxidation. The reaction of p- and m-methyl anisole gave the
moderate yields (3ag and 3ah), and p- and m-methoxybenzoic
acids were detected respectively in the reaction mixtures. These
acids were probably generated by the overoxidation of p- and
m-methyl anisoles. a- and b-methylnaphthalene could also react
with 2-phenylprydine and gave moderate yields (3am and 3an).
To gain more understanding of this reaction, we have
performed some control experiments. When 2-phenylprydine
was treated with toluene in the presence of radical scavengers
(ascorbic acid or 1,4-benzoquinone)17 almost no acylation product
was produced (Scheme 1), which suggested that a radical likely
existed in the catalytic cycle. Moreover, without 2-phenylprydine,
the toluene was oxidized to benzaldehyde with a low yield
regardless of the presence of the palladium catalyst. When
2-phenylprydine treated with benzaldehyde in the absence of
TBHP, we failed to get the desired product. The results showed
that the TBHP may have two different effects, oxidizing toluene
and promoting the formation of radicals.
Scheme 2 Plausible reaction mechanism.
Acknowledgements
The authors thank the national nature science foundation of
China (Project 21272117 and 20972068) and the priority
academic program development of Jiangsu higher education
institutions for the financial support of this work.
On the basis of previous studies and our observations, a
possible mechanism for the reaction is illustrated (Scheme 2). The
palladium catalyst reacted with 2-phenylpyridine to form a
cyclopalladated intermediate (A) by chelation-directed C–H activa-
tion, which was confirmed by many related reports.18 With the
effect of TBHP, the benzaldehyde, which was produced from the
oxidation of toluene, generated an acyl radical (B). Afterward, the
palladacycle (A) reacted with the acyl radical (B) to form either the
reactive Pd(IV)19 or the dimeric Pd(III)20 intermediate (C). Finally,
the reductive elimination of intermediate C afforded coupling
product 3 and regenerated Pd(II) for further catalytic cycles.
In conclusion, we developed the ortho-acylation of 2-arylpyr-
idines by a Pd-catalyzed oxidative coupling without prefunctiona-
lized toluene derivatives to form 2-pyridyldiaryl ketones. It is the
first example of using non prefunctionalized toluene as the
acylation reagent. The mild reaction conditions provide opportu-
nities for future research to apply this methodology in the
synthesis of natural products and other useful compounds.
Further development of other acylations using toluene is under-
way in our laboratories.
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Scheme 1 Control experiments.
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