DOI: 10.1002/chem.201503716
Communication
&
Organic Chemistry
Copper-Catalyzed Aerobic Decarboxylation/Ketooxygenation of
Electron-Deficient Alkenes
Qingquan Lu,[a] Pan Peng,[a] Yi Luo,[a] Ying Zhao,[b] Minxian Zhou,[b] and Aiwen Lei*[a, b]
Perkins and Alexanian realized the dioxygenation of elec-
Abstract: A copper-catalyzed ketooxygenation of elec-
tron-netural alkenes with amidoxyl radicals generated from the
tron-deficient alkenes was developed. This approach com-
oxidation of the hydroxamic acid by dioxygen.[4,6] In order to
bines OÀH alkylation, aerobic decarboxylation, and oxy-
gain information on the radical state of hydroxamic acid, we
genation in one transformation. Mechanistic investigation
conducted EPR (electron paramagnetic resonance) experi-
of this reaction showed that the copper salt is responsible
ments. As shown in Figure 1, there was no obvious EPR signal
for both generating the amidoxyl radical and promoting
aerobic decarboxylation.
Dioxygen is the ideal oxygen source/oxidant in synthetic
chemistry due to its abundance and sustainability.[1–2] In this
context, aerobic oxygenation represents one of the most ideal
processes for the incorporation of oxygen into organic frame-
works.[2] Despite great efforts, the development of aerobic oxy-
Figure 1. EPR spectra of A) 2a (0.20 mmol) in DMF (2.0 mL) at 608C under
O2 for 10 min and B) 2a (0.20 mmol) and CuCl2·2H2O (0.02 mmol) in DMF
(2.0 mL) at 608C under O2 for 10 min.
genation reactions remains challenging. For example, the exist-
ing strategies are largely ineffective in the oxidation of inert
chemical bonds and the selective oxygenation of CÀC single
bonds has proven to be difficult.[3]
Hydroxamic acid can be smoothly oxidized into the corre-
sponding amidoxyl radical through a one-electron oxidation
process.[4] These amidoxyl radicals derived from hydroxamic
acid and its derivatives, such as NHPI (N-hydroxyphthalimide),
are effective organocatalysts for CÀH functionalization.[5] Con-
versely, the use of hydroxamic acids as O-centered radical pre-
cursors is less studied.[6–7] Given the importance of CÀO bond
construction in synthetic chemistry, we decided to investigate
the use of hydroxamic acids as nuclephiles in radical oxidative
coupling. In order to successfully achieve a transformation of
this type, we would have to overcome several challenges in-
herent to the use of amidoxyl radicals: the high reactivity of O-
centered radicals, the ability of amidoxyl radicals to act as or-
ganocatalysts and initiate undesirable radical reactions, ad-
dressing the chemical selectivity of amidoxyl radicals,[5] and, fi-
nally, the decomposition of amidoxyl radicals at high tempera-
tures.[5b]
when methyl N-hydroxy-N-phenylcarbamate (2a) was directly
treated with O2. However, a signal corresponding to the ami-
doxyl radical was observed when catalytic amount of copper
salt was added under the same conditions. These results clear-
ly show that copper salt can effectively catalyze the generation
of the amidoxyl radical in the presence of dioxygen.
On the basis of this observation, we wondered whether the
copper-catalyzed generation of amidoxyl radicals could be suc-
cessfully applied in aerobic oxygenation reactions. The use of
O-nucleophiles in transition-metal-catalyzed aerobic oxygena-
tion reactions is relatively sparse.[7b–d] We envisioned that these
highly reactive amidoxyl radicals could prove to be successful
in the oxygenation of CÀC single bonds and electron-deficient
compounds.[8]
With these considerations in mind, a general strategy for the
aerobic ketooxygenation of electron-deficient alkenes was pro-
posed which combined OÀH alkylation, aerobic decarboxyla-
tion, and oxygenation in a single process. As outlined in
Scheme 1, amidoxyl radical I could be formed by copper-cata-
lyzed oxidation of hydroxamic acid (2a). Then, 2-arylacrylic
acid (1a) would act as a radical acceptor to O-centered radical
species I to give rise to carbon-centered radical II. After oxy-
genation of II with dioxygen, followed by radical decarboxyla-
tion,[9] a-oxyketone (3a) could be obtained.[10]
[a] Dr. Q. Lu,+ P. Peng,+ Y. Luo, Prof. A. Lei
College of Chemistry and Molecular Sciences
the Institute for Advanced Studies (IAS)
Wuhan University, Wuhan 430072, Hubei (P. R. China)
E-mail: aiwenlei@whu.edu.cn
[b] Y. Zhao, M. Zhou, Prof. A. Lei
National Research Center for Carbohydrate Synthesis
We initiated our study by examining the ketooxygenation of
2-phenylacrylic acid (1a) with methyl N-hydroxy-N-phenylcar-
bamate (2a) under O2. As shown in Table 1, only a trace
amount of the desired product 3a was detected in the ab-
Jiangxi Normal University, Nanchang 330022, Jiangxi (P. R. China)
[+] Authors contributed equally to this work.
Supporting information for this article is available on the WWW under
Chem. Eur. J. 2015, 21, 18580 – 18583
18580
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