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could react with benzaldehyde to form intermediate C. Then C was
attacked by the quinoline N-oxide radical which was formed by
TBHP to form species D. Finally, D released the desired product and
CuOTf as well (Scheme 4).
CuOTf þ t-BuOOH ! CuOTfðOBu-tÞ þ HOꢀ
(1)
A
t-BuOOH þ A ! CuOTfðOOBu-tÞ þ t-BuOH
(2)
B
Scheme 3 Control experiments.
In summary, we have developed a direct acetoxylation of quino-
line N-oxides catalyzed by a cheap copper(I) salt. This novel protocol
provided a simple pathway to synthesize pharmaceutically active
quinoline-containing esters. The method features direct dual C–H
bond activation as a key step and uses a minimally toxic and
relatively cheap copper salt as a catalyst. The scope, applications
and mechanism of this reaction are under investigation.
This work was supported by NSF of China (21102133,
21172200) and the NSF of Henan (082300423201).
Notes and references
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Scheme 4 Proposed mechanism for the oxidative esterification.
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gave the corresponding desired products in 36–75% yield (3g–l,
Table 2). 6-Methylquinoline N-oxide reacted smoothly with 2-meth-
oxybenzaldehyde and 3,4-dimethoxybenzaldehyde, affording the
desired products in 94% and 82% yields, respectively (3n and 3r,
Table 2). 6-Methoxyquinoline N-oxide and 7-hydroxyquinoline
N-oxide provided the desired products in 55% and 75% yields,
respectively (3s and 3t, Table 2). Notably, cyclohexylaldehyde could
also be used as a substrate in this catalytic system and gave
2-(cyclohexylcarboxy)quinoline N-oxides in 56%, 59% and 52%
yields, respectively (3e, 3k and 3q, Table 2), which made the present
transformation attractive for future applications. However, this
reaction was limited to the electron-withdrawing aldehydes and
heterocyclic aldehydes. No desired product was detected for the
2-pyridinecarboxylaldehyde. And furfural only gave the desired
product in 10% yield.
To clarify the reaction mechanism and the oxygen source, control
experiments were performed (Scheme 3). When the reaction of
quinoline N-oxide 1a with benzaldehyde 2a was carried out under
an oxygen atmosphere in the absence of TBHP, no desired product
was detected (Scheme 3, eqn (1)). Whereas, the above reaction
proceeded smoothly under a nitrogen atmosphere using 3 equiv.
TBHP as an oxidant and provided the desired product 3a in 82%
yield, which is close to the result obtained under the optimal
reaction conditions (84% yield, 3a, Table 2) (Scheme 3, eqn (2)).
These results indicate that TBHP served as a terminal oxygen source.
The reaction mechanism was proposed according to the litera-
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c
6902 Chem. Commun., 2013, 49, 6900--6902
This journal is The Royal Society of Chemistry 2013