Tandem coupling reactions of benzynes and 1,3-diones: a novel synthesis of 2,2-diphenyl-1,3-diones

Article abstract of DOI:10.1016/j.tetlet.2007.09.092

A novel, general, and mild method is described to prepare 2,2-diphenyl-1,3-diones with benzyne using CuBr and trichloroacetic acid as the catalyst.

Full text of DOI:10.1016/j.tetlet.2007.09.092

Available online at www.sciencedirect.com
Tetrahedron Letters 48 (2007) 8163–8165
Tandem coupling reactions of benzynes and 1,3-diones:
a novel synthesis of 2,2-diphenyl-1,3-diones
Yun-Yun Yang, Wang-Ge Shou and Yan-Guang Wang*
Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China
Received 2 July 2007; revised 12 September 2007; accepted 14 September 2007
Available online 18 September 2007
Abstract—A novel, general, and mild method is described to prepare 2,2-diphenyl-1,3-diones with benzyne using CuBr and trichlo-
roacetic acid as the catalyst.
Ó 2007 Elsevier Ltd. All rights reserved.
Arynes are highly reactive intermediates, which have
been widely used in organic synthesis.1,2 The recent
reports on formation,3 reactivity,4 and particular appli-
cation5 of arynes illustrate the continued interest in this
area. Nucleophilic addition is a direct approach to the
syntheses of substituted benzenes. The addition of alco-
hols, amines, sulfonamides, carbamates, phenols, and
carboxylic acids to arynes can be considered formally
as the insertion of the arynes into heteroatom-hydrogen
bonds.6 Recently, the insertion of arene into the a,b
single bond of b-ketoesters,2a a-cyanocarbonyl com-
pounds, and 1,3-diones was also reported.7 These reac-
tions led to the acyl-alkylation of arynes to produce
interesting ortho-disubstituted arenes. Herein, we report
a novel tandem reaction of benzyne with 1,3-diones to
furnish 2,2-diphenyl-1,3-diones under mild conditions.
O
O
Ph
+
N2
CuBr
DCE
60 oC
1.5 h
-
CO2
O
1
O
+
O
O
Ph
Ph
2a
3a
Scheme 1.
Benzenediazonium-2-carboxylate (1) is a benzyne pre-
cursor, which is easily prepared from anthranilic
acid.3d,e It can in situ generate benzyne at moderate tem-
perature.8 Initially, we used 1 as the benzyne precursor
to react with one equivalent of 1-phenylpentane-1,3-
dione (2a) in the presence of catalyst CuBr. We surpris-
ingly found that the reaction did not produce the ben-
zyne insertion product, but afforded a,a-diphenyl-
substituted 1,3-dione 3a in 15% yield (Scheme 1). We
then optimized the conditions for this reaction (Table
1). The best yield of 3a was obtained using CuBr
(5 mol %)9 and trichloroacetic acid (5 mol %) as the
co-catalyst system and DCE as the solvent (Table 1,
entry 18).
Encouraged by this result, our next goal was to broaden
the substrate scope to a variety of 1,3-diones using the
optimized conditions. It was found that a wide range
of substrates gave moderate to good yields (Table 2, en-
tries 1–21).10 The ortho-substituted 1-phenyl-1,3-diones
gave moderate yields due to steric hindrance (Table 2,
entries 4–7), while 1-phenyl-1,3-diones bearing a strong
electron-donating group gave relatively low yield (Table
2, entries 17–20). All products were analyzed by IR,
1HNMR, 13CNMR, and MS spectra as well as elemental
analysis.11
Buchwald and co-workers reported a copper-catalyzed
arylation of diethyl malonate.9c However, the method
is only suitable for the synthesis of a-monoarylmalo-
nates. Additionally, Barton et al.12 reported a synthesis
of 2,2-diphenyl-1,3-dicarbonyl compounds via the
*
Corresponding author. Tel./fax: +86 571 87951512; e-mail: orgwyg@
zju.edu.cn
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.09.092

8164
Y.-Y. Yang et al. / Tetrahedron Letters 48 (2007) 8163–8165
Table 1. Optimization of reaction conditions for coupling of benzyne
with 1,3-dione 2aa
Table 2. 2,2-Diphenyl-1,3-diones 3 from benzene-diazonium-2-car-
boxylate (1) and 1,3-diones 3a
O
O
O
O
R2
+
+
5 mol % CuBr,
5 mol% CCl3CO2H
O
O
N2
catalyst
solvent
60 oC, 1.5 h
N2
O
O
R1
Ph
+
2
+
R1
R2
DCE, 60 oC, 1.5 h
-
-
Ph
CO2
CO2
2
2a
1
1
3
3a
Entry
Product
R1
R2
Yieldb (%)
Entry
Catalyst (mmol)
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
3a
3b
3c
3d
3e
3f
Ph
Ph
Ph
2-FC6H4
2-FC6H4
Me
Et
Ph
Me
Et
Me
Et
Me
Et
Et
C3H7
Et
Et
Me
Et
Et
Me
Et
C3H7
Me
Me
90
81
82
75
73
74
72
90
82
84
65
83
85
75
70
72
70
66
60
68
88
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
—
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
THF
MeCN
—
CuCl/0.02
CuCl/0.04
CuBr/0.02
CuBr/0.04
CuBr/0.1
CuI/0.04
CuCl2/0.1
CuBr2/0.1
CuI2/0.1
Trace
Trace
10
15
18
Trace
—
—
—
24
26
30
75
80
81
83
90
90
75c
64d
50
2-ClC6H4
2-ClC6H4
3,5-Br2C6H3
3,5-Br2C6H3
4-ClC6H4
4-ClC6H4
4-BrC6H4
4-CF3C6H4
4-EtC6H4
4-EtC6H4
4-MeC6H4
3-MeOC6H4
3-MeOC6H4
3-MeOC6H4
4-MeOC6H4
Me
3g
3h
3i
3j
3k
3l
CCl3CO2H/0.04
CCl3CO2H/0.1
3m
3n
3o
3p
3q
3r
3s
3t
CuBr/0.1 + CH3COOH/0.1
CuBr/0.04 + CCl3CO2H/0.04
CuBr/0.1 + CCl3CO2H/0.04
CuBr/0.2 + CCl3CO2H/0.04
CuBr/0.04 + CCl3CO2H/0.1
CuBr/0.1 + CCl3CO2H/0.1
CuBr/0.2 + CCl3CO2H/0.2
CuBr/0.1 + CCl3CO2H/0.1
CuBr/0.1 + CCl3CO2H/0.1
CuBr/0.1 + CCl3CO2H/0.1
CuBr/0.1 + CCl3CO2H/0.1
3u
a Reaction conditions: 1 (4 mmol), 2 (2 mmol), CuBr (0.1 mmol) and
trichloroacetic acid (0.1 mmol), DCE (30 mL), 60 °C, 1.5 h.
b Isolated yield.
45
a Reaction conditions: 1 (4 mmol), 2a (2 mmol), solvent (30 mL),
60 °C, 1.5 h.
b Isolated yield by silica gel column chromatography.
c 1 (6 mmol).
d 1 (7 mmol).
Cu
O
O
HO
R1
O
CuBr
H+
O
O
R1
R2
R2
phenylation of enolate anions of 1,3-dicarbonyl com-
pounds using pentavalent organobismuth reagents.
Compared with this method, our procedure is general,
mild, and efficient. Furthermore, the present method
does not require a large amount of metalic reagents
and atmosphere sensitive reagents.
2
R1
R2
+
N2
-
CO2
1
4
CuBr H+
A plausible mechanism is illustrated for the construction
of this class of quarternary stereocenters in Scheme 2.
The tandem process involves two nucleophilic additions
of enol of 1,3-dione to the in situ generated benzyne.
Copper salt and organic acid Cl3CCO2H could promote
the formation of enol and hence catalyze the cascade
reaction. CuX may play a crucial role in the formation,
a six-member ring transition state. For this purpose,
CuBr is a better catalyst than CuBr2.
Cu
O
O
HO
R1
O
R2
R1
R2
3
Scheme 2.
In summary, we have developed a novel and general
method for the 2,2-bisphenylation of 1,3-diones with
benzyne using CuBr and trichloroacetic acid as the
catalysts. This method provides an efficient route to a
wide variety 2,2-diphenyl-1,3-diones from readily avail-
able starting materials under mild conditions. Further
studies on the synthetic applications of this procedure
are underway.
Acknowledgments
This work was financially supported by the National
Natural Science Foundation of China (No. 20672093)
and the Natural Science Foundation of Zhejiang Prov-
ince (No. R404109) as well as the Specialized Research

Y.-Y. Yang et al. / Tetrahedron Letters 48 (2007) 8163–8165
8165
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Supplementary data
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References and notes
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10. General procedure for the synthesis of 2,2-diphenylpentane-
1,3-diones 3. To a solution of 1,3-dione 2 (2 mmol),
trichloroacetic acid (0.10 mmol) and CuBr (0.10 mmol) in
DCE (5 mL) was added a suspension of benzenediazoni-
um-2-carbolylate (4 mmol) in DCE (30 mL) at 60 °C over
a period of 1.5 h, the color changed from light yellow to
deep brown. After completion of the reaction as indicated
by TLC, the solvent was evaporated in vacuum and the
residual oil was purified by silica gel column chromato-
graphy using hexane–EtOAc (20:1, v/v) as the eluant to
afford 3. The product was recrystallized from hexane–
EtOAc.
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;
7.77 (d, J = 7.0 Hz, 2H), 7.40–7.32 (m, 11H), 7.24 (t,
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128.7, 128.3, 128.1, 79.3, 29.7 ppm; MS (ESI): m/z 337
([M + Na]+); Anal. Calcd for C22H18O2: C, 84.05; H, 5.77.
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mp 97–98 °C; IR (KBr): 1725, 1663, 1594, 1447,
1232 cmÀ1 1H NMR (500 MHz, CDCl3): d 7.74 (d,
;
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C
NMR (125 MHz, CDCl3): d 207.0, 198.3, 137.0, 136.3,
132.9, 130.9, 130.8, 128.6, 128.3, 128.0, 79.3, 35.6,
10.0 ppm; MS (ESI): m/z 351 ([M+Na]+); Anal. Calcd
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1
1717, 1664, 1580, 1485, 1264 cmÀ1; H NMR (500 MHz,
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6.92 (t, J = 6.2 Hz, 1H), 3.65 (s, 3H), 2.29 (t, J = 7.5 Hz,
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