Organic &
Biomolecular Chemistry
COMMUNICATION
CuI-catalyzed and air promoted oxidative cyclization
for one-pot synthesis of polyarylated oxazoles†
Cite this: DOI: 10.1039/c3ob40657a
Received 3rd April 2013,
Accepted 18th May 2013
Ping Hu, Qiang Wang, Yizhe Yan, Shuai Zhang, Baiqun Zhang and Zhiyong Wang*
DOI: 10.1039/c3ob40657a
A facile CuI-catalyzed and air promoted oxidative cyclization was the Li group developed copper-catalyzed cross-dehydrogenative
developed for the synthesis of polyarylated oxazoles. By virtue of coupling (CDC) to construct C–C and C–N bonds.10 Nagasawa
this method, a variety of arylated oxazoles could be easily syn- reported a copper-catalyzed intramolecular oxidative C–O
thesized from readily available starting materials at room temp- coupling.11 The Jiao group also developed CDC for the for-
erature in air.
mation of N–N bonds.12 Since oxidations of aliphatic C–H
bonds are recently considered for being used in organic syn-
thesis,13 oxygen–copper systems in organic synthesis have
been more and more studied, mostly focusing on the oxidation
reactions of C–H bonds.9–12 There is no doubt that dehydro-
genation of aliphatic C–H bonds by atmospheric oxygen (O2)
offers one of the most environmentally benign and ideal oxi-
dation processes in organic synthesis.
We became interested in developing a one-pot, copper cata-
lyzed dehydrogenation domino process for the synthesis of ary-
lated oxazoles. This procedure was attractive due to its
intramolecular C–O bond formation, dehydrogenation by
atmospheric oxygen and rapid experimental procedure at
room temperature.
Initially, benzylamine (1a) and benzil (2a) were chosen as
model substrates to optimize the reaction conditions (Table 1).
Firstly, different copper salts (0.06 mmol) were examined
under the conditions of a typical procedure: 1a (0.2 mmol,
1 equiv.) and 2a (0.6 mmol, 3 equiv.) in 3 mL of DMA for 3 h at
60 °C. When copper(II) salts were used as the catalysts in the
reaction, 3a was detected in less than 5% yields by GC-MS (entries
1–4). Copper(I) salts provided much higher yields than copper(II)
salts (entries 5–7). Obviously, CuI was the most efficient
catalyst. The temperature had little influence on the reaction
and lower temperature favored the reaction (entries 7–9), so we
set the reaction temperature at room temperature. Among the
examined solvents (entries 10–14), DMA was the most effective
solvent for this oxidative cyclization process. Owing to the fact
that the benzylamine tended to be oxidized to phenylaldehyde
in this reaction system, the addition of benzylamine in two
portions was necessary. When 100 mg of 4 Å MS was added,
the yield of the reaction increased to 92% (entry 15). Other
metal salts, such as FeCl3, CoCl2, NiCl2 and ZnCl2, were also
examined. However, no product was detected when they were
examined in the reaction. Thus, the optimized conditions were
The importance of oxazoles in pharmaceuticals1 and func-
tional materials2d continues to inspire the development of new
synthetic approaches to this heterocyclic framework.3–7
Oxazole and its derivatives have attracted more and more inter-
est from both industry and academia over recent decades.2
Recently, arylated oxazoles were obtained through direct cross-
coupling arylation of simple oxazoles and cyclization of acyclic
precursors.3 For instance, Toshiaki Murai developed the
radical trap experiment on C–H bond arylation reaction of
simple oxazoles and obtained di- and triarylated oxazoles.4
The Jiao group reported the synthesis of 2,5-diarylated oxa-
zoles via copper-mediated aerobic oxidative dehydrogenation.5
Taking advantage of TBHP–I2-mediated oxidative cyclization,
our group also developed a series of methods in the synthesis
of oxazoles.6 Besides, the Jiang group also reported an elegant
one-pot protocol involving a TBHP–I2-mediated oxidative cycli-
zation for the synthesis of 2,4-diarylated oxazoles.7 Although
these methods are available for arylated oxazole synthesis,
using extra oxidants and harsh conditions limited their appli-
cations. Therefore, the development of efficient and economic
methods for the synthesis of polyarylated oxazoles is highly
desirable.
Because of its low price, slight toxicity and environmentally
benign features among transition metals, copper is a very
important catalyst in organic synthesis,8 especially in recent
copper-catalyzed oxidative C–H bond activation.9 For example,
Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of
Soft Matter Chemistry and Department of Chemistry, University of Science and
Technology of China, Hefei, Anhui 230026, P. R. China. E-mail: zwang3@ustc.edu.cn;
Fax: (+86) 551-360-3185
†Electronic supplementary information (ESI) available: Experiment procedure
and NMR data. See DOI: 10.1039/c3ob40657a
This journal is © The Royal Society of Chemistry 2013
Org. Biomol. Chem.