Copper-Catalyzed Intramolecular C-C Bond Cleavage to Construct 2-Substituted Quinazolinones

Article abstract of DOI:10.1002/ejoc.201500473

An efficient method for a copper-catalyzed intramolecular C-C bond cleavage to construct 2-substituted quinazolinones has been developed. The C-C bond at the 2-position of 2,2-disubstituted-1,2,3,4-tetrahydroquinazolinone was selectively cleaved by a Cu/air catalytic system. The trend for the cleavage was dependent on the leaving group in the order of: alkyl > methyl > phenyl > substituted aryl. The process described herein provides an explanation for the mechanism of the reaction between substituted 2-halobenzamides and α-substituted arylmethanamines to construct 2-substituted quinazolinones, which were previously reported and limited to the construction of 2-arylquinazolinones. The C-C bond at the 2-position of 2,2-disubstituted-1,2,3,4-tetrahydroquinazolinones was selectively cleaved by a Cu/air catalytic system to construct 2-substituted quinazolinones. The trend for the cleavage of the C-C bond was dependent on the leaving group in the order of: alkyl > methyl > phenyl > substituted aryl.

Full text of DOI:10.1002/ejoc.201500473

FULL PAPER
DOI: 10.1002/ejoc.201500473
Copper-Catalyzed Intramolecular C–C Bond Cleavage To Construct
2-Substituted Quinazolinones
Ben-Quan Hu,[a,b] Li-Xia Wang,*[a] Luo Yang,*[b] Jun-Feng Xiang,[a] and Ya-Lin Tang*[a]
Keywords: Synthetic methods / Nitrogen heterocycles / Cleavage reactions / Copper / Radicals
An efficient method for a copper-catalyzed intramolecular C–
C bond cleavage to construct 2-substituted quinazolinones
has been developed. The C–C bond at the 2-position of 2,2-
of: alkyl Ͼ methyl Ͼ phenyl Ͼ substituted aryl. The process
described herein provides an explanation for the mechanism
of the reaction between substituted 2-halobenzamides and
disubstituted-1,2,3,4-tetrahydroquinazolinone was selec- α-substituted arylmethanamines to construct 2-substituted
tively cleaved by a Cu/air catalytic system. The trend for the
cleavage was dependent on the leaving group in the order
quinazolinones, which were previously reported and limited
to the construction of 2-arylquinazolinones.
employment of strained carbon skeletons[3] (three- and
four-membered rings) or the use of chelation assistance
Introduction
Carbon–carbon and carbon–hydrogen bonds are the de- strategies,[4] both of which are representative methods to
fining motifs of organic compounds. Selective C–C and C– promote a C–C bond cleavage. The cleavage of unstrained
H bond cleavages have always been an active area of re- inert C–C bonds has traditionally required harsh conditions
search in organic chemistry, but they are mainly dependent with stoichiometric amounts of oxidants such as peroxides
on precious metal complexes.[1,2] C–C bond cleavage is and toxic metal salts. Thus, there is an urgent need for
more challenging than a C–H bond cleavage, in view of chemists to pursue milder and greener processes.
thermodynamic stability and uncontrollable selectivity.[1]
There is a growing interest in the use of inexpensive Cu[5]
Over the years, several approaches have been developed for and Fe[6] metals for the development of new protocols for
the cleavage of a carbon–carbon single bond, including the metal-catalyzed C–C bond cleavages. Molecular oxygen is
Scheme 1. Copper-catalyzed C–C bond cleavage to construct 2-substituted quinazolinones (DMSO = dimethyl sulfoxide).
[a] Beijing National Laboratory for Molecular Sciences (BNLMS),
considered an ideal oxidant because of its atom-economical
Center for Molecular Sciences, State Key Laboratory for
and environmentally benign character.[7] To date, there are
Structural Chemistry of Unstable and Stable Species, Institute
of Chemistry, Chinese Academy of Sciences,
Beijing 100190, P. R. China
few reports of the use of a Cu/O2 catalytic system for a C–C
bond cleavage.[5e,8] Recently, we reported a copper-catalyzed
domino reaction between substituted 2-halobenzamide and
α-substituted arylmethanamine to construct 2-arylquin-
azolinones (Scheme 1).[9] 2,2-Disubstituted-1,2,3,4-tetra-
hydroquinazolinone might serve an important role as a key
intermediate in the intramolecular C–C bond cleavage, but
it could not be detected in the reaction system. Herein, we
prepared 2,2-disubstituted-1,2,3,4-tetrahydroquinazolinone
E-mail: wlx8825@iccas.ac.cn
tangyl@iccas.ac.cn
http://www.iccas.ac.cn
[b] Key Laboratory for Environmentally Friendly Chemistry and
Application, Department of Chemistry, Xiangtan University,
Hunan 411105, P. R. China
E-mail: yangluo@xtu.edu.cn
http://www.xtu.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500473.
4504
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4504–4509

C–C Bond Cleavage To Construct 2-Substituted Quinazolinones
according to literature reports.[10,11] As part of our ongoing C–Caryl bond to give 2a-II did not occur, indicating that the
research, we pursued the copper-catalyzed intramolecular intramolecular C–C bond cleavage at the 2-position of 2-
C–C bond cleavage of 2,2-disubstituted-1,2,3,4-tetrahydro- methyl-2-phenyl-1,2,3,4-tetrahydroquinazolinone (1a) was
quinazolinones to construct 2-substituted quinazolinones selective. In addition to the participation of air, CuBr or
(Scheme 1).
K2CO3 alone did not show any catalytic activity, indicating
that the copper catalyst and base must function concertedly
(Table 1, Entries 13 and 14).
Results and Discussion
To investigate the selectivity of the C–C bond cleavage at
the 2-position, the transformations of various 2,2-disubsti-
tuted-1,2,3,4-tetrahydroquinazolinones were performed un-
der the established conditions (10 mol-% of CuBr as the
catalyst and 2 equiv. of K2CO3 as the base in DMSO under
air at 130 °C for 24 h). As shown in Table 2, the substrates
with R2 as a (substituted) phenyl or heteroaromatic group
and R1 as methyl group provided 2-arylquinazolinone as
the only product in good yields of 46–91% (Table 2, En-
tries 1–6) by proceeding through a C–Calkyl bond cleavage.
Compound 1g, which contained the same alkyl group for
R1 and R2, afforded 2-methylquinazolinone 2g as the major
product (Table 2, Entry 7). Other substrates that contained
different alkyl groups for R1 and R2 afforded products in
low to moderate yields through the cleavage of C–Calkyl
bond of the longer alkyl chain (Table 2, Entries 8 and 9).
Substrates in which R1 and R2 are the same aryl groups
(Table 2, Entries 10–12) or the different aryl groups
(Table 2, Entries 13–15) led to the C–Caryl bond cleavage
products in good yields, with the exception of 2,2-di(2-
pyridyl)-1,2,3,4-tetrahydroquinazolinone (1l), which che-
lated to the copper ion. Mixtures of 2-R1-substituted quin-
azolinone and 2-R2-substituted quinazolinones as the prod-
ucts in varying ratios resulted from substrates 1m–1o
(Table 2, Entries 13–15). In addition, 1,2,3,4-tetrahydro-
quinazolinones with varying electronic properties led to
better yields than those with an unsubstituted phenyl group.
Our initial studies focused on determining the optimal
reaction conditions. 2-Methyl-2-phenyl-1,2,3,4-tetrahydro-
quinazolinone (1a) was chosen as the model substrate,
which was smoothly converted into 2-phenylquinazolinone
2a-I in 90% yield by using 10 mol-% CuBr as the catalyst,
2 equiv. of K2CO3 as the base, and DMSO as the solvent
under air at 130 °C for 24 h (Table 1, Entry 1). Carrying out
the reaction under argon led to a decreased yield of 64%
(Table 1, Entry 2), which indicates that the absence of air
could inhibit the transformation. Thus, we screened other
catalysts as the reaction was performed under air (Table 1,
Entries 3–7) and determined that CuBr provided the highest
yield, whereas both of the examined Fe salts were inefficient
in the process. The base had a significant influence on the
yield. For example, Na2CO3 afforded 2a-I in only 33% yield
(Table 1, Entry 9), whereas Cs2CO3 provided 2a-I in an
equivalent amount as that from K2CO3 (Table 1, compare
Entries 1 and 8). When N,N-dimethylformamide (DMF,
Table 1, Entry 10) was used instead of DMSO, the reaction
gave 2a-I in a lower yield. The effect of temperature was
also investigated, and we found that performing the reac-
tion at 130 °C was optimal (Table 1, compare Entries 1, 11,
and 12). Under these reaction conditions, the cleavage of
Table 1. Optimization of conditions for copper-catalyzed transfor-
mation of 2-methyl-2-phenyl-1,2,3,4-tetrahydroquinazolinone un-
der air.[a,b]
6-Methoxy- and 7-nitro-substituted substrates with R1
=
methyl and R2 = phenyl gave products 2p and 2q in yields
85 and 75%, respectively, by cleavage of C–Calkyl bond
(Table 2, Entries 16 and 17). Cleavage of C–H bond was
shown to be easier than that of the C–Caryl or C–Calkyl
bond (Table 2, Entries 18 and 19), and 2-phenylquinazolin-
one (2a) and 2-(phenylethyl)quinazolinone (2s) were iso-
lated in 100 and 44% yield, respectively. We failed to isolate
the products of spiro compounds 1t and 1u, as neither reac-
tion could provide any clear or distinguishable products by
TLC analysis. The results in Table 2 indicate that the cleav-
age of the C–C bond occurs in the following order: H Ͼ
alkyl Ͼ methyl Ͼ phenyl Ͼ substituted aryl, which may be
explained by the properties of the target C–C bond, such
as the bond energy and steric hindrance.
On the basis of these experimental results, we proposed
a reasonable mechanistic pathway (Scheme 2). The 2,2-di-
substituted-1,2,3,4-tetrahydroquinazolinone is first oxidized
to give radical cation I. A base-assisted deprotonation then
takes place, and radical cation I is converted into II. Finally,
product 2 is produced by a C–C bond cleavage. This radical
process was indirectly confirmed in two ways. In a radical
trapping experiment, the addition of 2,2,6,6-tetramethyl-1-
piperidinyloxy (TEMPO) to the reaction of 1a under the
Entry Catalyst
Base
Solvent
Temp.[°C]
% Yield 2a[c]
1
2
3
4
CuBr
CuBr
CuBr2
CuCl2
CuI
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Na2CO3
K2CO3
K2CO3
K2CO3
K2CO3
–
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
130
130
130
130
130
130
130
130
130
130
150
110
130
130
90
64[d]
63
76
74
21
trace
86
33
69
5
6
7
8
9
10
11
12
13
14
FeCl3
Fe(acac)2
CuBr
CuBr
CuBr
CuBr
CuBr
–
[e]
DMSO
DMSO
DMSO
DMSO
81
31
–
–
CuBr
[a] Reagents and conditions: 1a (0.2 mmol), catalyst (0.02 mmol),
base (0.4 mmol), and solvent (2 mL) under air for 24 h. [b] Product
2a-II was not detected. [c] Isolated yield. [d] Under argon. [e] acac
= acetylacetonate.
Eur. J. Org. Chem. 2015, 4504–4509
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4505

B.-Q. Hu, L.-X. Wang, L. Yang, J.-F. Xiang, Y.-L. Tang
FULL PAPER
Table 2. Substrate scope of CuBr-catalyzed transformations of 2,2-disubstituted-1,2,3,4-tetrahydroquinazolinones.[a]
[a] Reagents and conditions: 1 (0.2 mmol), catalyst (0.02 mmol), base (0.4 mmol), and DMSO (2 mL) under air for 24 h. [b] Isolated yield.
[c] Starting materials 1j and 1n were recovered. [d] A mixture of products were found, and no major products could be isolated.
4506
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4504–4509

C–C Bond Cleavage To Construct 2-Substituted Quinazolinones
24 h under air. Upon completion of the reaction, the mixture was
cooled to room temperature and filtered, and the filtrate was con-
centrated with the aid of a rotary evaporator. The residue was puri-
fied by column chromatography on silica gel (petroleum ether/ethyl
acetate) to provide the desired product 2.
optimized conditions led to a decreased yield of 47%. Then,
in the transformation of 1k, byproducts 4,4Ј-dibromobi-
phenyl and p-bromo(methylthio)benzene were detected by
GC–MS (Figure 1). Multiple pathways may be involved in
this transformation, and a thorough mechanistic study is
needed to unravel the intricacies of this process.
2a:[9] White solid (40 mg, 90%); m.p. 235–236 °C. IR (KBr): ν =
˜
3428, 1672, 1605, 1481, 769 cm–1. 1H NMR (400 MHz, [D6]-
DMSO): δ = 12.53 (br. s, 1 H), 8.20–8.15 (m, 3 H), 7.84 (t, J =
7.2 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1 H), 7.57–7.51 (m, 4 H) ppm.
13C NMR (75 MHz, [D6]DMSO): δ = 162.7, 152.8, 149.2, 135.1,
133.2, 131.9, 129.1, 128.2, 128.0, 127.1, 126.3, 121.4 ppm.
2b:[9] White solid (43 mg, 91%); m.p. 256–257 °C. IR (KBr): ν =
˜
3432, 1668, 1606, 1295, 942 cm–1. 1H NMR (400 MHz, [D6]-
DMSO): δ = 12.46 (br. s, 1 H), 8.15 (d, J = 7.2 Hz, 1 H), 8.10 (d,
J = 8.0 Hz, 2 H), 7.83 (t, J = 7.2 Hz, 1 H), 7.73 (d, J = 8.0 Hz, 1
H), 7.51 (t, J = 7.2 Hz, 1 H), 7.36 (d, J = 8.0 Hz, 2 H), 2.40 (s, 3
H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 162.7, 152.7, 149.3,
141.9, 135.1, 130.4, 129.7, 128.2, 127.9, 126.9, 126.3, 121.4,
21.5 ppm.
Scheme 2. Possible reaction pathway for copper-catalyzed intra-
molecular C–C bond cleavage of 2,2-disubstituted-1,2,3,4-tetra-
hydroquinazolinones.
2c:[9] White solid (33 mg, 65%); m.p. 250–251 °C. IR (KBr): ν =
˜
3437, 1679, 1606, 1258, 1031 cm–1. 1H NMR (400 MHz, [D6]-
DMSO): δ = 12.40 (br. s, 1 H), 8.19 (d, J = 8.8 Hz, 2 H), 8.13 (d,
J = 6.8 Hz, 1 H), 7.82 (t, J = 6.8 Hz, 1 H), 7.70 (d, J = 7.6 Hz, 1
H), 7.49 (t, J = 6.8 Hz, 1 H), 7.09 (d, J = 8.8 Hz, 2 H), 3.85 (s, 3
H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 162.8, 162.3, 152.3,
149.4, 135.1, 129.9, 127.8, 126.6, 126.3, 125.3, 121.1, 114.5,
55.9 ppm.
2d: White solid (44 mg, 86%); m.p. 253–254 °C. IR (KBr): ν =
˜
3430, 1680, 1608, 1310, 1112 cm–1. 1H NMR (300 MHz, [D6]-
DMSO): δ = 8.34 (s, 1 H), 8.26 (d, J = 6.6 Hz, 1 H), 8.04 (d, J =
7.8 Hz, 1 H), 7.64–7.56 (m, 2 H), 7.52–7.45 (m, 2 H), 7.30 (t, J =
7.2 Hz, 1 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 168.2,
157.0, 151.0, 140.4, 133.4, 132.6, 130.4, 129.9, 127.9, 127.1, 126.8,
126.3, 124.7, 122.3 ppm. HRMS: calcd. for C14H10ClN2O [M +
H]+ 257.04762; found 257.04760.
Figure 1. GC–MS analysis of reaction mixture of the transforma-
tion of 1k.
2e:[9] Light yellow solid (21 mg, 46%); m.p. 278–279 °C. IR (KBr):
ν = 3080, 1672, 1607, 1005 cm–1. 1H NMR (400 MHz, [D ]DMSO):
˜
6
δ = 12.77 (br. s, 1 H), 8.79 (d, J = 4.8 Hz, 2 H), 8.19 (d, J = 8.0 Hz,
1 H), 8.12 (d, J = 5.6 Hz, 2 H), 7.89 (t, J = 7.2 Hz, 1 H), 7.80 (d,
J = 8.0 Hz, 1 H), 7.59 (t, J = 7.6 Hz, 1 H) ppm.
Conclusions
In summary, we have demonstrated a copper-catalyzed
approach for the synthesis of 2-substituted quinazolinones 2f:[12] White solid (37 mg, 86%). IR (KBr): ν = 3428, 1682, 1604,
˜
1
1460, 770 cm–1. H NMR (400 MHz, [D6]DMSO): δ = 12.49 (s, 1
through an intramolecular C–C bond cleavage with air as
the oxidant under basic conditions. This reaction not only
provides an efficient method to construct medically impor-
tant quinazolinones but also offers a new strategy for C–C
H), 8.11 (d, J = 7.6 Hz, 1 H), 7.99 (s, 1 H), 7.80 (dt, J = 1.2 Hz, J
= 7.2 Hz, 1 H), 7.68 (d, J = 8 Hz, 1 H), 7.62 (d, J = 3.6 Hz, 1 H),
7.48 (t, J = 8 Hz, 1 H), 6.74 (d, J = 3.6 Hz, 1 H) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ = 162.0, 149.1, 147.1, 146.6, 144.5,
135.1, 127.7, 127.0, 126.4, 121.6, 114.9, 112.9 ppm.
bond cleavage.
2g:[13] White solid (20 mg, 62%); m.p. 234–235 °C. IR (KBr): ν =
˜
3079, 1672, 1606, 1481, 784 cm–1. 1H NMR (300 MHz, [D6]-
DMSO): δ = 12.18 (br. s, 1 H), 8.07 (dd, J = 8.1, 1.5 Hz, 1 H), 7.76
Experimental Section
General Methods: Reactions were monitored by analytical thin-
layer chromatography, and the developed plates were visualized by
ultraviolet light. Purification of products was accomplished by flash
chromatography on silica gel (100–200 mesh), and analytical TLC
showed a single spot for the purified compounds. Chemical shifts
(δ) were reported in ppm downfield from tetramethylsilane, and
either tetramethylsilane or the residual solvent resonance was used
as the internal standard.
(t, J = 8.1 Hz, 1 H), 7.56 (d, J = 8.1 Hz, 1 H), 7.44 (t, J = 7.4 Hz,
1 H), 2.34 (s, 3 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ =
162.2, 154.7, 149.4, 134.7, 127.0, 126.3, 126.1, 121.1, 21.9 ppm.
2k: White solid (50 mg, 80%); m.p. 294–295 °C. IR (KBr): ν =
˜
3343, 1672, 1606, 1481, 1306 cm–1. 1H NMR (300 MHz, [D6]-
DMSO): δ = 12.61 (br. s, 1 H), 8.16–8.10 (m, 3 H), 7.84 (t, J =
8.1 Hz, 1 H), 7.77–7.72 (m, 3 H), 7.53 (t, J = 7.5 Hz, 1 H) ppm.
13C NMR (75 MHz, [D6]DMSO): δ = 162.6, 151.9, 149.1, 135.1,
132.4, 132.1, 130.3, 128.0, 127.3, 126.4, 125.7, 121.5 ppm. HRMS:
calcd. for C14H879BrN2O [M + H]+ 298.98200; found 298.98224;
calcd. for C14H881BrN2O [M + H]+ 300.97995; found 300.98019.
General Procedure: To a vial that contained a stir bar were added
1 (0.2 mmol), K2CO3 (0.4 mmol), and CuBr (0.02 mmol) in DMSO
(2 mL). The resulting mixture was stirred and heated at 130 °C for
Eur. J. Org. Chem. 2015, 4504–4509
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4507

B.-Q. Hu, L.-X. Wang, L. Yang, J.-F. Xiang, Y.-L. Tang
FULL PAPER
2l:[14] Light yellow solid (8 mg, 18%); m.p. 269–270 °C. IR (KBr):
ani, Chem. Soc. Rev. 2008, 37, 300; h) A. Masarwa, I. Marek,
Chem. Eur. J. 2010, 16, 9712; i) M. Murakami, T. Matsuda,
Chem. Commun. 2011, 47, 1100; j) C. Nájera, J. W. Sansano,
Angew. Chem. Int. Ed. 2009, 48, 2452; Angew. Chem. 2009, 121,
2488; k) F. Chen, T. Wang, N. Jiao, Chem. Rev. 2014, 114, 8613;
l) G. B. Dong (Ed.), Topics in Current Chemistry, vol. 346: C–C
Bond Activation, Springer-Verlag, Berlin/Heidelberg, Germany,
2014.
ν = 3081, 1672, 1611, 1012 cm–1. 1H NMR (300 MHz, [D ]DMSO):
˜
6
δ = 10.97 (br. s, 1 H), 8.68 (d, J = 4.2 Hz, 1 H), 8.61 (d, J = 8.1 Hz,
1 H), 8.36 (dd, J = 8.1, 0.9 Hz, 1 H), 7.93 (ddd, J = 7.8, 1.8 Hz, 1
H), 7.86–7.77 (m, 2 H), 7.56–7.47 (m, 2 H) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 161.4, 149.2, 148.9, 148.7, 148.5, 137.5,
134.6, 128.0, 127.3, 126.8, 126.2, 122.5, 122.0 ppm.
[2]
For reviews on C–H bond cleavage, see: a) C.-L. Sun, B.-J. Li,
Z.-J. Shi, Chem. Commun. 2010, 46, 677; b) G. E. Dobereiner,
R. H. Crabtree, Chem. Rev. 2010, 110, 681; c) R. Jazzar, J.
Hitce, A. Renaudat, J. Sofack-Kreutzer, O. Baudoin, Chem.
Eur. J. 2010, 16, 2654; d) D. A. Colby, R. G. Bergman, J. A.
Ellman, Chem. Rev. 2010, 110, 624; e) C. Copéret, Chem. Rev.
2010, 110, 656; f) T. W. Lyons, M. S. Sanford, Chem. Rev. 2010,
110, 1147; g) I. A. I. Mkhalid, J. H. Barnard, T. B. Marder,
J. M. Murphy, J. F. Hartwig, Chem. Rev. 2010, 110, 890; h)
M. P. Doyle, R. Duffy, M. Ratnikov, L. Zhou, Chem. Rev. 2010,
110, 704; i) A. Gunay, K. H. Theopold, Chem. Rev. 2010, 110,
1060; j) D. Balcells, E. Colt, O. Eisenstein, Chem. Rev. 2010,
110, 749; k) F. Bellina, R. Rossi, Chem. Rev. 2010, 110, 1082;
l) C.-L. Sun, B.-J. Li, Z.-J. Shi, Chem. Rev. 2011, 111, 1293; m)
C. S. Yeung, V. M. Dong, Chem. Rev. 2011, 111, 1215; n) J.
Le Bras, J. Muzart, Chem. Rev. 2011, 111, 1170; o) L. Acker-
mann, Chem. Rev. 2011, 111, 1315.
2m: White solid (39 mg, 67%); m.p. Ͼ300 °C. IR (KBr): ν = 3429,
˜
1
1681, 1605, 1311, 772 cm–1. H NMR (300 MHz, [D6]DMSO): δ =
12.74 (br. s, 1 H), 8.33 (d, J = 8.4 Hz, 2 H), 8.17 (d, J = 7.8 Hz, 1
H), 8.02 (d, J = 8.1 Hz, 2 H), 7.86 (t, J = 7.7 Hz, 1 H), 7.77 (d, J
= 8.1 Hz, 1 H), 7.56 (t, J = 7.4 Hz, 1 H) ppm. 13C NMR (75 MHz,
[D6]DMSO): δ = 162.6, 151.4, 148.8, 137.3, 135.2, 132.9, 129.1,
128.2, 127.7, 126.4, 121.7, 118.8, 114.1 ppm. HRMS: calcd. for
C15H8N3O [M + H]+ 246.06729; found 246.06720.
2o: White solid (35 mg, 68%); m.p. 295–296 °C. IR (KBr): ν =
˜
3428, 1678, 1605, 1094, 766 cm–1. 1H NMR (400 MHz, [D6]-
DMSO): δ = 12.73 (br. s, 1 H), 9.30 (s, 1 H), 8.76 (d, J = 3.2 Hz,
1 H), 8.50 (d, J = 7.6 Hz, 1 H), 8.18 (d, J = 7.6 Hz, 1 H), 7.87 (t,
J = 7.6 Hz, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 7.61–7.54 (m, 2 H) ppm.
13C NMR (75 MHz, [D6]DMSO): δ = 162.6, 151.8, 149.1, 136.8,
135.2, 132.0, 130.1, 129.2, 128.0, 127.3, 126.3, 121.5 ppm.
[3]
[4]
a) T. Seiser, T. Saget, D. N. Tran, N. Cramer, Angew. Chem.
Int. Ed. 2011, 50, 7740; Angew. Chem. 2011, 123, 7884; b) T.
Seiser, N. Cramer, J. Am. Chem. Soc. 2010, 132, 5340; c) S. C.
Bart, P. J. Chirik, J. Am. Chem. Soc. 2003, 125, 886; d) P. A.
Wender, A. G. Correa, Y. Sato, R. Sun, J. Am. Chem. Soc.
2000, 122, 7815; e) M. Murakami, H. Amii, K. Shigeto, Y. Ito,
J. Am. Chem. Soc. 1996, 118, 8285.
a) J. W. Suggs, C.-H. Jun, J. Am. Chem. Soc. 1984, 106, 3054;
b) C.-H. Jun, H. Lee, J. Am. Chem. Soc. 1999, 121, 880; c) M.
Gandelman, D. Milstein, Chem. Commun. 2000, 1603; d) C.-
H. Jun, D.-Y. Lee, H. Lee, J.-B. Hong, Angew. Chem. Int. Ed.
2000, 39, 3070; Angew. Chem. 2000, 112, 3214; e) A. M. Dreis,
C. J. Douglas, J. Am. Chem. Soc. 2009, 131, 412; f) N. Chatani,
Y. Ie, F. Kakiuchi, S. Murai, J. Am. Chem. Soc. 1999, 121,
8645; g) J. Wang, W. Chen, S. Zuo, L. Liu, X. Zhang, J. Wang,
Angew. Chem. Int. Ed. 2012, 51, 12334; Angew. Chem. 2012,
124, 12500; h) F. D. Lewis, J. G. Magyar, J. Org. Chem. 1972,
37, 2102; i) N. Zhang, J. Vozzolo, J. Org. Chem. 2002, 67, 1703;
j) Z.-Q. Lei, H. Li, Y. Li, X.-S. Zhang, K. Chen, X. Wang, J.
Sun, Z.-J. Shi, Angew. Chem. Int. Ed. 2012, 51, 2690; Angew.
Chem. 2012, 124, 2744.
2p:[9] White solid (42.6 mg, 85%); m.p. 247–248 °C. IR (KBr): ν =
˜
3428, 1675, 1493, 1262, 1036 cm–1. 1H NMR (300 MHz, [D6]-
DMSO): δ = 12.51 (br. s, 1 H), 8.16 (d, J = 8.1 Hz, 2 H), 7.71 (d,
J = 8.7 Hz, 1 H), 7.56–7.53 (m, 4 H), 7.45 (dd, J = 8.7, 3.0 Hz, 1
H), 3.90 (s, 3 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 162.5,
158.2, 150.6, 143.7, 133.3, 131.5, 129.7, 129.1, 128.0, 124.6, 122.3,
106.3, 56.1 ppm.
2q:[9] Yellow solid (38 mg, 75%); m.p. Ͼ300 °C. IR (KBr): ν = 3080,
˜
1672, 1606, 1451, 1351, 943 cm–1. 1H NMR (300 MHz, [D6]-
DMSO): δ = 12.93 (br. s, 1 H), 8.44 (d, J = 1.8 Hz, 1 H), 8.37 (d,
J = 8.7 Hz, 1 H), 8.22 (d, J = 6.6 Hz, 3 H), 7.67–7.56 (m, 3 H) ppm.
13C NMR (75 MHz, [D6]DMSO): δ = 161.8, 155.0, 151.8, 132.6,
132.5, 130.1, 129.2, 128.7, 128.5, 125.8, 122.9, 120.5 ppm.
2s:[15] White solid (22 mg, 44%); m.p. 208–209 °C. IR (KBr): ν =
˜
3438, 1682, 1618, 1462, 901 cm–1. 1H NMR (300 MHz, [D6]-
DMSO): δ = 12.26 (br. s, 1 H), 8.08 (d, J = 7.8 Hz, 2 H), 7.79 (d,
J = 7.8 Hz, 1 H), 7.81 (d, J = 7.5 Hz, 1 H), 7.69 (d, J = 7.8 Hz, 1
H), 7.48 (t, J = 7.4 Hz, 1 H), 7.08 (d, J = 9.0 Hz, 2 H), 3.84 (s, 3
H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 162.2, 157.1, 149.3,
141.2, 134.8, 128.83, 128.81, 127.3, 126.6, 126.5, 126.2, 121.3, 36.8,
32.9 ppm.
[5]
For a copper-catalyzed cleavage of C–C bonds, see: a) T. Sugii-
shi, A. Kimura, H. Nakamura, J. Am. Chem. Soc. 2010, 132,
5332; b) C. He, S. Guo, L. Huang, A. Lei, J. Am. Chem. Soc.
2010, 132, 8273; c) M. Sai, H. Yorimitsu, K. Oshima, Angew.
Chem. Int. Ed. 2011, 50, 3294; Angew. Chem. 2011, 123, 3352;
d) F. Chen, C. Qin, Y. Cui, N. Jiao, Angew. Chem. Int. Ed.
2011, 50, 11487; Angew. Chem. 2011, 123, 11689; e) C. H. Tang,
N. Jiao, Angew. Chem. Int. Ed. 2014, 53, 6528.
Supporting Information (see footnote on the first page of this arti-
cle): Detailed description of the experimental procedures and ana-
lytical data for all compounds.
[6]
[7]
For an iron-catalyzed cleavage of C–C bonds, see: a) H. Li, W.
Li, W. Liu, Z. He, Z. Li, Angew. Chem. Int. Ed. 2011, 50, 2975;
Angew. Chem. 2011, 123, 3031; b) C. Qin, W. Zhou, F. Chen,
Y. Ou, N. Jiao, Angew. Chem. Int. Ed. 2011, 50, 12595; Angew.
Chem. 2011, 123, 12803; c) C. Qin, T. Shen, C. Tang, N. Jiao,
Angew. Chem. Int. Ed. 2012, 51, 6971; Angew. Chem. 2012, 124,
7077.
For reviews on aerobic oxidative reactions, see: a) S. S. Stahl,
Angew. Chem. Int. Ed. 2004, 43, 3400; Angew. Chem. 2004, 116,
3480; b) B. M. Stoltz, Chem. Lett. 2004, 33, 362; c) T. Punniya-
murthy, S. Velusamy, J. Iqbal, Chem. Rev. 2005, 105, 2329; d)
K. M. Gligorich, M. S. Sigman, Angew. Chem. Int. Ed. 2006,
45, 6612; Angew. Chem. 2006, 118, 6764; e) M. S. Sigman,
D. R. Jensen, Acc. Chem. Res. 2006, 39, 221; f) J. Muzart,
Chem. Asian J. 2006, 1, 508; g) E. M. Beccalli, G. Broggini, M.
Martinelli, S. Sottocornola, Chem. Rev. 2007, 107, 5318; h) J.
Acknowledgments
The authors wish to thank the National Natural Science Foudation
of China (NSFC) (grant numbers 21302188 and 91027033) and the
Chinese Academy of Sciences (grant numbers KJCX2-EW-N06-01
and XDA09030307) for their financial support.
[1] For reviews on C–C bond cleavage, see: a) K. C. Bishop III,
Chem. Rev. 1976, 76, 461; b) R. H. Crabtree, Chem. Rev. 1985,
85, 245; c) B. Rybtchinski, D. Milstein, Angew. Chem. Int. Ed.
1999, 38, 870; Angew. Chem. 1999, 111, 918; d) C.-H. Jun,
Chem. Soc. Rev. 2004, 33, 610; e) C.-H. Jun, J.-W. Park, Top.
Organomet. Chem. 2007, 24, 117; f) Y.-J. Park, J.-W. Park, C.-
H. Jun, Acc. Chem. Res. 2008, 41, 222; g) M. Tobisu, N. Chat-
4508
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4504–4509

C–C Bond Cleavage To Construct 2-Substituted Quinazolinones
Piera, J. E. Bäckvall, Angew. Chem. Int. Ed. 2008, 47, 3506;
Angew. Chem. 2008, 120, 3558; i) S. S. Stahl, Science 2005, 309,
1824; j) M. J. Schultz, M. S. Sigman, Tetrahedron 2006, 62,
8227; k) W. Wu, H. Jiang, Acc. Chem. Res. 2012, 45, 1736; l)
Z. Shi, C. Zhang, C. Tang, N. Jiao, Chem. Soc. Rev. 2012, 41,
3381; m) A. N. Campbell, S. S. Stahl, Acc. Chem. Res. 2012,
45, 851.
[10] T. P. Natin, G. Pediredla, S. Vipender, Eur. J. Org. Chem. 2010,
4719.
[11] R. A. Bunce, B. Nammalwar, J. Heterocycl. Chem. 2011, 48,
991.
[12] J. Zhang, D.-C. Ren, Y.-M. Ma, W.-T. Wang, H. Wu, Tetrahe-
dron 2014, 70, 5274.
[13] B.-Q. Hu, L.-X. Wang, J.-F. Xiang, L. Yang, Y.-L. Tang, Chin.
Chem. Lett. 2015, 26, 369.
[14] A. Ouahrouch, M. Taourirte, J. W. Engels, S. H. Benjelloun, B.
Lazrek, Molecules 2014, 19, 3638.
[8]
a) J. Cossy, D. Belotti, V. Bellosta, D. Brocca, Tetrahedron Lett.
1994, 35, 6089; b) K. M. Steward, J. S. Johnson, Org. Lett.
2011, 13, 2426; c) W. Zhou, Y. Q. Yang, Y. Liu, G. J. Deng,
Green Chem. 2013, 15, 76.
[15] A. Watson, A. C. Maxwell, J. Williams, Org. Biomol. Chem.
2012, 10, 240.
[9] L.-X. Wang, J.-F. Xiang, Y.-L. Tang, Eur. J. Org. Chem. 2014,
Received: April 14, 2015
Published Online: June 9, 2015
2682.
Eur. J. Org. Chem. 2015, 4504–4509
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4509