Copper-catalyzed aerobic oxidative C-C bond cleavage of 1,3-diaryldiketones to synthesize 1,2-diketones

Article abstract of DOI:10.1055/s-0033-1341243

An aerobic oxidative C-C bond cleavage of 1,3-diaryldiketones for the synthesis of 1,2-diketones by using O₂ as the oxidant has been developed. Control experiments illustrate that the copper catalyst not only assist the aerobic oxidative process of 1,3-diketones, but also catalyze the 1,2-Wagner-Meerwein-type rearrangement process. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0033-1341243

1458▌
LETTER
lCettoerpper-Catalyzed Aerobic Oxidative C–C Bond Cleavage of 1,3-Diaryl-
diketones To Synthesize 1,2-Diketones
C–C Bond Cleavage of 1,3-Diaryl Diketones
Chun Zhang,a Xiaoyang Wang,a Ning Jiao*a,b
a
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing
100191, P. R. of China
b
State Key Laboratory of Organometallic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. of China
Fax +86(10)82805297; E-mail: jiaoning@bjmu.edu.cn
Received: 12.02.2014; Accepted after revision: 25.03.2014
O
Abstract: An aerobic oxidative C–C bond cleavage of 1,3-diaryl-
diketones for the synthesis of 1,2-diketones by using O2 as the oxi-
dant has been developed. Control experiments illustrate that the
copper catalyst not only assist the aerobic oxidative process of 1,3-
diketones, but also catalyze the 1,2-Wagner–Meerwein-type rear-
rangement process.
O
O
O
O
O
O
Zhang's work
R2
R2
R2
R1
R1
R1
(a)
(b)
(c)
R1
R1
R1
R2
R2
R2
tert-butyl nitrite (5.0 equiv)
O
O
O
O
O
Yuan's work
Key words: copper, C–C bond cleavage, aerobic oxidative reac-
tion, 1,2-diketones
I2, DMSO, 150 °C
this work
1,2-Diketones are important units in lots of functional
molecules.1 Furthermore, they serve as versatile building
blocks in a variety of chemical transformations.2 In the
past decades, several useful methods, such as Wacker-
type reaction,3 oxidation of benzyl derivative,4 and some
other methods5 have been developed to construct this
structure. However, some drawbacks of the above meth-
ods, such as the requirement of toxic metal catalysts or
special equipment, harsh reaction conditions, and low
chemoselectivity, may limit their applications. Recently,
Zhang and co-workers have developed an iron-promoted
C–C bond cleavage of 1,3-diketones to synthesize 1,2-
diketones which employ five equivalents of tert-butyl ni-
trite as the oxidant (Scheme 1, a).6 Yuan’s group realized
this transformation by using I2/DMSO oxidative condi-
tions at 150 °C (Scheme 1, b).7 In light of the increasing
demand for environmentally benign organic synthesis and
green chemistry, molecular oxygen is probably the ideal
terminal oxidant, because of its remarkable advantages,
such as being inexpensive, having a high atom efficiency,
and in most cases with water as the byproduct.8,9 Herein
O2 (1 atm)
Scheme 1 Oxidative cleavage of 1,3-diaryldiketones to synthesize
1,2-diketones
the above results, we think that the bromide ion may play
an important role in this reaction process. However, when
1.0 equivalent bromine salt was added into the reaction
system, the yield of the desired product decreased (Table
1, entries 7–9). The effects of different solvents were then
surveyed. The reactions proceeded with lower yields in
other solvents (Table 1, entries 10–14). Both increasing
and decreasing the temperature cannot improve the yields
(Table 1, entries 15 and 16). This chemistry did not work
well in the absence of pyridine (Table 1, entry 17,). A 40%
yield of 2a was obtained by using air instead of pure mo-
lecular oxygen as the oxidant (Table 1, entry 18). This
chemistry cannot afford the desired diketone product un-
der argon conditions, which approves that oxidant is nec-
essary in this reaction process (Table 1, entry 19).
we developed a copper-catalyzed C–C bond cleavage of With the optimized conditions in hand, the reaction scope
1,3-diaryldiketones to synthesize 1,2-diketones using mo- of 1,3-diketones were investigated (Table 2). The aromat-
lecular oxygen as oxidant (Scheme 1, c).
ic ring of 1,3-diketones derivatives was found to be toler-
ant of both electron-rich groups, such as methyl (2b and
2d), methoxy (2c), and tert-butyl (2e), and electron-defi-
cient groups, such as fluoride (2f), chloride (2g), and tri-
fluoromethyl (2h). Besides benzene-ring-substituted 1,3-
diketone derivatives, 1,3-di(thiophen-3-yl)propane-1,3-
dione and 1,3-di(naphthalen-2-yl)propane-1,3-dione
could smoothly transform into the corresponding products
2i and 2j. Furthermore, this chemistry could be used to
synthesize unsymmetrical 1,2-diaryldiketones 2k and 2l.
However, aliphatic 1,3-diketones do not work.
Our initial explorations focused on the reaction of 1,3-di-
phenylpropane-1,3-dione (1a) in the presence of copper
salts. Interestingly, benzil (2a) was produced in 51% yield
when CuBr was used as the catalyst (Table 1, entry 1).10
The reaction in the absence of the copper catalyst did not
work (Table 1, entry 2). Except for CuBr2, other catalysts
showed low efficiencies (Table 1, entries 3–6). Based on
SYNLETT 2014, 25, 1458–1460
Advanced online publication: 08.05.2014
DOI: 10.1055/s-0033-1341243; Art ID: st-2014-w0119-l
© Georg Thieme Verlag Stuttgart · New York
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
Based on the previous reports of Zhang and Yuan’s
work,6,7 we hypothesize 1,3-diphenylpropane-1,2,3-trione

LETTER
C–C Bond Cleavage of 1,3-Diaryl Diketones
1459
Table 1 Screening of the Reaction Conditionsa
Table 2 Synthesis of 1,2-Diketones from 1,3-Diketones via Aerobic
Oxidative C–C Bond Cleavage Processa
[Cu] (10 mol%)
pyridine (50 mol%)
O
O
O
O
O2 (1 atm)
CuBr (10 mol%)
O
O
Ph
R2
Ph
Ph
Ph
O2 (1 atm), temp (°C)
solvent (2 mL)
R1
R1
R2
1a
O
2a
toluene (2 mL)
100 °C, 24 h
O
1
2b
Entry Catalyst
Additive Solvent
Temp (°C) Yield (%)b
Entry
R1
R2
Yield of 2 (%)b
1
2
CuBr
none
none
none
none
none
none
none
KBr
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DMF
100
100
100
100
100
100
100
100
100
100
100
100
reflux
reflux
90
51
1
2
Ph
Ph
4-MeC6H4
4-MeOC6H4
2a 51
2b 49
2c 56
2d 46
2e 56
2f 46
2g 45
2h 41
2i 45
2j 42
2k 46
2l 42
0
4-MeC6H4
4-MeOC6H4
3,4-Me2C6H3
4-t-BuC6H4
4-FC6H4
4-ClC6H4
4-F3CC6H4
3-thienyl
2-naphthyl
Ph
3
CuBr2
CuCl
CuI
44
3
4
trace
trace
trace
49
4
3,4-Me2C6H3
4-t-BuC6H4
4-FC6H4
5
5
6
CuOAc
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
6
7
7
4-ClC6H4
8
LiBr
TBAB
none
none
none
none
none
none
none
none
none
none
29
8
4-F3CC6H4
3-thienyl
9
trace
41
9
10
11
12
13
14
15
16
17c
18d
19e
10
11
12
2-naphthyl
4-F3CC6H4
4-MeOC6H4
DMA
40
DMSO
DCE
32
Ph
trace
trace
42
a Reaction conditions: 1 (0.25 mmol), CuBr (0.025 mmol), pyridine
(0.125 mmol), solvent (2 mL), 100 °C under O2 for 24 h.
b Isolated yield.
MeCN
toluene
toluene
toluene
toluene
toluene
110
100
100
100
51
key intermediate 3 was produced from 1a via copper-cat-
alyzed aerobic oxidative process. Subsequently, the key
intermediate 3 coordinated and activated by copper(II)12
underwent a 1,2-Wagner–Meerwein-type rearrangement
to afford the intermediate 4.13 Finally, the C–C bond
cleavage released carbon monoxide and gave 2a as the
terminal product.6,7
trace
40
0
a Reaction conditions: 1a (0.25 mmol), [Cu] (0.025 mmol), pyridine
(0.125 mmol), additive (0.25 mmol), solvent (2 mL), 100 °C under O2
for 24 h.
b Isolated yield.
c Without pyridine.
d Under air.
O
O
O
optimal conditions
e Under Ar.
(1)
(2)
O
O
3
2a: 87%
(3) should be the key intermediate of this reaction process.
Under optimal conditions, 3 could afford 2a in 87% yield,
which could support the reasonability of the above hy-
pothesis (Scheme 2, eq 1). Without copper catalyst, 3 can-
not be converted into 2a (Scheme 2, eq 2). The above
results suggest that copper salt not only improve the aero-
bic oxidative process of 1a, but also catalyze the process
from 3 to 2a. Furthermore, the result of the labeled exper-
iment indicated that both oxygen atoms of the 1,2-dike-
tones originate from 1,3-diketones (Scheme 2, eq 3).
O
O
O
optimal conditions
without [Cu]
O
O
2a: 4%
3
16O 16O
16O
18O2 (1 atm)
CuBr (10 mol%)
(3)
16O
16O-2a: 51%
toluene (2 mL)
100 °C, 24 h
Based on the above results, the proposed mechanism is
shown in Scheme 3. Under molecular oxygen conditions,
copper(I) was initially oxidized to copper(II).11 Then, the
1a
Scheme 2 Control experiments
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1458–1460

1460
C. Zhang et al.
LETTER
Chem. 2007, 46, 1910. (c) Keith, J. A.; Henry, P. M. Angew.
Chem. Int. Ed. 2009, 48, 9038. (d) Ren, W.; Xia, Y.; Ji, S.-
J.; Zhang, Y.; Wan, X.; Zhao, J. Org. Lett. 2009, 11, 1841.
(e) Chen, S.; Liu, Z.; Shi, E.; Chen, L.; Wei, W.; Li, H.;
Cheng, Y.; Wan, X. Org. Lett. 2011, 13, 2274. (f) Ren, W.;
Liu, J.; Chen, L.; Wan, X. Adv. Synth. Catal. 2010, 352,
1424. (g) Mori, S.; Takubo, M.; Yanase, T.; Maegawa, T.;
Monguchi, Y.; Sajiki, H. Adv. Synth. Catal. 2010, 352, 1630.
(4) (a) Okimoto, M.; Takahashi, Y.; Nagata, Y.; Sasaki, G.;
Numata, K. Synthesis 2005, 705. (b) Joo, C.; Kang, S.; Kim,
S. M.; Han, H.; Yang, J. W. Tetrahedron Lett. 2010, 51,
6006. (c) Alamsetti, S. K.; Mannam, S.; Mutupandi, P.;
Sekar, G. Chem. Eur. J. 2009, 15, 1086. (d) Qi, C.; Jiang, H.;
Huang, L.; Chen, Z.; Chen, H. Synthesis 2011, 387.
(5) (a) Tada, N.; Shomura, M.; Nakayama, H.; Miura, T.; Itoh,
A. Synlett 2010, 1979. (b) Karlsson, I.; Hillerstrom, L.;
Stenfeldt, A.-L.; Martensson, J.; Borje, A. Chem. Res.
Toxicol. 2009, 22, 1881. (c) Kim, S. S.; Mah, Y. J.; Kim, A.
R.; Cho, K. W. J. Photosci. 2004, 11, 129. (d) Shimakawa,
Y.; Morikawa, T.; Sakaguchi, S. Tetrahedron Lett. 2010, 51,
1786. (e) Suzuki, Y.; Bakar, A.; Tanoi, T.; Nomura, N.;
Sato, M. Tetrahedron 2011, 67, 4710.
[CuI]Ln
O2
[CuII]Ln
O
O
O
Ph
Ph
CO
+
Ph
Ph
O
1a
2a
H2O
[CuII]Ln
[CuII]Ln
O
O
O
O
Ph
Ph
Ph
Ph
O
3
O
4
Scheme 3 Plausible mechanism of the transformation
In summary, we have developed an aerobic oxidative ap-
proach to 1,2-diaryldiketones. This chemistry employed
O2 as oxidant to realize oxidative C–C bond cleavage of
1,3-diaryldiketones. Control experiments illustrate that
the copper catalyst not only assist the aerobic oxidative
process of 1,3-diketones, but also catalyze the 1,2-Wagner–
Meerwein-type rearrangement process. Further studies on
the reaction mechanism are ongoing in our group.
(6) Huang, L. H.; Cheng, K.; Yao, B. B.; Xie, Y. J.; Zhang, Y.
H. J. Org. Chem. 2011, 76, 5732.
(7) Yuan, Y.; Zhu, H. Eur. J. Org. Chem. 2012, 329.
(8) For some selected reviews about copper-catalyzed aerobic
oxidative dehydrogenative coupling reaction in the last three
years, see: (a) Wendlandt, A. E.; Suess, A. M.; Stahl, S. S.
Angew. Chem. Int. Ed. 2011, 50, 11062. (b) Zhang, C.; Tang,
C.; Jiao, N. Chem. Soc. Rev. 2012, 41, 3464. (c) Campbell,
A. N.; Stahl, S. S. Acc. Chem. Res. 2012, 45, 851.
(9) For some selected examples about copper-catalyzed aerobic
oxidative dehydrogenative coupling reaction in the last three
years, see: (a) Wang, H.; Wang, Y.; Liang, D.; Liu, L.;
Zhang, J.; Zhu, Q. Angew. Chem. Int. Ed. 2011, 50, 5678.
(b) Wang, J.; Wang, J.; Zhu, Y.; Lu, P.; Wang, Y. Chem.
Commun. 2011, 47, 3275. (c) Hausser, A.; Trautmann, M.;
Roduner, E. Chem. Commun. 2011, 47, 6954. (d) Zhang, C.;
Zhang, L.; Jiao, N. Adv. Synth. Catal. 2012, 354, 1293.
(e) Liu, Q.; Wu, P.; Yang, Y.; Zeng, Z.; Liu, J.; Yi, H.; Lei,
A. Angew. Chem. Int. Ed. 2012, 51, 4666. (f) Xu, Z.; Zhang,
C.; Jiao, N. Angew. Chem. Int. Ed. 2012, 51, 11367. (g) Li,
X.; Huang, L.; Chen, H.; Wu, W.; Huang, H.; Jiang, H.
Chem. Sci. 2012, 3, 3463. (h) Du, F.-T.; Ji, J.-X. Chem. Sci.
2012, 3, 460. (i) Zhang, C.; Jiao, N. Angew. Chem. Int. Ed.
2010, 49, 6174. (j) Zhang, C.; Jiao, N. J. Am. Chem. Soc.
2010, 132, 28. (k) Zhang, C.; Xu, Z.; Zhang, L.; Jiao, N.
Angew. Chem. Int. Ed. 2011, 50, 11088. (l) Zhang, C.; Jiao,
N. Org. Chem. Front. 2014, 1, 109.
Acknowledgment
Financial support from National Science Foundation of China (Nos.
21325206, 21172006), National Young Top-notch Talent Support
Program, and the Ph.D. Programs Foundation of the Ministry of
Education of China (No. 20120001110013) are greatly appreciated.
Supporting Information for this article is available online
at
http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000083.SunpfgIpi
o
o
nr
i
References and Notes
(1) (a) Ita, B. I.; Offiong, O. E. Mater. Chem. Phys. 2001, 70,
330. (b) Husar, B.; Commereuc, S.; Lukac, I.; Chmela, S.;
Nedelec, J. M.; Baba, M. J. Phys. Chem. B 2006, 110, 5315.
(c) Corrales, T.; Catalina, F.; Peinado, C.; Allen, N. S.
J. Photochem. Photobiol. A 2003, 159, 103.
(2) (a) Deng, X.; Mani, N. Org. Lett. 2006, 8, 269. (b) Shipe,
W. D.; Yang, F.; Zhao, Z.; Wolkenberg, S. E.; Nolt, M. B.;
Lindsley, C. W. Heterocycles 2006, 70, 655. (c) Held, I.; Xu,
S. J.; Zipse, H. Synthesis 2007, 1185. (d) Boyce, G. R.;
Johnson, J. S. Angew. Chem. Int. Ed. 2010, 49, 8930.
(e) Rong, F.; Chow, S.; Yan, S.; Larson, G.; Hong, Z.; Wu,
J. Bioorg. Med. Chem. Lett. 2007, 17, 1663. (f) McKenna, J.
M.; Halley, F.; Souness, J. E.; McLay, I. M.; Pickett, S. D.;
Collis, A. J.; Page, K.; Ahmed, I. J. Med. Chem. 2002, 45,
2173. (g) Singh, S. K.; Saibaba, V.; Ravikumar, V.;
(10) Typical Procedure
A reaction mixture of CuBr (3.6 mg, 0.025 mmol), pyridine
(10.0 mg, 0.125 mmol), 1,3-diphenylpropane-1,3-dione 1a
(56.1 mg, 0.25 mmol) in toluene (2 mL) under O2 (1 atm)
was stirred at 100 °C for 24 h. After being cooled to r.t. and
concentrated under vacuum, the residue was purified by
flash chromatography on a short silica gel (eluent: PE–
EtOAc, 40:1) to afford 27 mg (51%) of 2a.
(11) Zhang, C.; Feng, P.; Jiao, N. J. Am. Chem. Soc. 2013, 135,
15257.
(12) Barbiero, G.; Kim, W.-G.; Hay, A. S. Tetrahedron Lett.
1994, 35, 5833.
(13) Roberts, J. D.; Smith, D. R.; Lee, C. C. J. Am. Chem. Soc.
1951, 73, 618.
Rudrawar, S. V.; Daga, P.; Rao, C. S.; Akhila, V.; Hegde, P.;
Rao, Y. K. Bioorg. Med. Chem. 2004, 12, 1881.
(3) (a) Cornell, C. N.; Sigman, M. S. Inorg. Chem. 2007, 46,
1903. (b) Kotov, V.; Scarborough, C. C.; Stahl, S. S. Inorg.
Synlett 2014, 25, 1458–1460
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