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† Electronic Supplementary Information (ESI) available: See
DOI: 10.1039/b000000x/
amide nitrogen and make it more active to undergo the
reaction. Furthermore, the addition of radical inhibitors such
as 1, 1ꢀdiphenylethylene and TEMPO (2, 2, 6, 6ꢀ
45
50
55
60
65
70
75
80
85
90
1
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tetramethylpiperidineꢀNꢀoxyl)
blocked
the
reaction
5
respectively, and no product was detected. To our delight, the
TEMPO adduct 4 was detected instead of the Nꢀacyl urea
during the reaction of Nꢀmethoxybenzamide 1a and DMF 2a
under the optimized conditions (Scheme 2).
2
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10
Scheme 2. Investigations into the reaction mechanism.
From the above results, we believe that the reaction
proceeded via the C−H bond activation of N, Nꢀsubstituted
formamides by
a A hypothesized
radical mechanism.13
6
7
(a) G. Dyker, Angew. Chem. Int. Ed., 1999, 38, 1698; (b) V. Ritleng,
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15 mechanism of this transformation is shown in Scheme 3.
Firstly, the proposed initiated complex 5 generated in situ
under the copperꢀcatalyst and oxidant TBHP. Next, the radical
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intermediate
6 was formed through the abstraction of
hydrogen from the DMF facilitated by CuII and TBHP.14
20 Further the radical intermediate 6 would couple with the
complex 5, and produced the desired Nꢀacyl urea 3a under
reductive elimination.
8
9
O
O
OMe
OMe
Ph
N
H
Ph
N
O
O
CuIILn
5
1a
CuIILn
TBHP
Ph
N
N
OMe
O
O
CuILn
3a
H
N
N
6
TBHP
2a
L= Cl
Scheme 3.The proposed reaction mechanism.
25
In summary, the first efficient and direct synthesis of Nꢀ
acyl ureas catalyzed by copper from two different amides via
C−H/N−H bond activation have been developed under mild
conditions. This novel and distinct protocol provides an
efficient method for the construction of multisubstituted ureas,
10 L. Wang, H. Fu, Y. Y. Jiang and Y. F. Zhao, Chem. Eur. J., 2008, 14,
10722.
11 L. E. Fisher, J. M. Caroon, Jahangir, S. R. Stabler, S. Lundberg, J.
M. Muchowski, J. Org. Chem., 1993, 58, 3643.
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Mehltretter, T. Nsenda, M. Studer and A. F. Indolese, J. Org. Chem.,
2001, 66, 4311; (b) K. Hosoi, K. Nozaki and T. Hiyama, Org. Lett.,
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Org. Lett., 2007, 9, 4615; (d)Y. Jo, J. H. Ju, J. C, K. H. Song and S.
30 which avoids using harsh reaction conditions such as toxic
materials, high temperature and high CO pressure. The two
different amides Nꢀalkoxyaromaticamides and N, Nꢀ
disubstituted formamides are easily available from the
commercial source or laboratory. Further investigations to
35 explore the mechanistic details and the synthetic applications
are currently ongoing.
100
Lee, J. Org. Chem., 2009, 74, 6358; (e) T. Fujihara, Y. Katafuchi, T.
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Wan, Org. Lett., 2011. 13, 6152; For recent work about formamides :
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105
Notes and references
a State Key Laboratory of Coordination Chemistry, School of Chemistry
and Chemical Engineering, Nanjing University, Nanjing 210093,
110 14 The radical intermediate 6 was not trapped in the absence of CuII
catalyst. It indicated that CuII was necessary for the reaction and
promoted the radical formation.
40
People’s Republic of China; E-mail: cjzhu@nju.edu.cn
bState Key Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Shanghai 200032, People’s Republic of China
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