Phosphotungstic acid catalyzed direct benzylation of β-dicarbonyl compounds

Article abstract of DOI:10.1002/ejoc.200800624

12-Phosphotungstic acid was used as an efficient, ecofriendly, and air- and moisture-stable catalyst to promote the direct substitution of the hydroxy group of benzylic and allylic alcohols with various β-dicarbonyl compounds. This powerful protocol for c

Full text of DOI:10.1002/ejoc.200800624

FULL PAPER
DOI: 10.1002/ejoc.200800624
Phosphotungstic Acid Catalyzed Direct Benzylation of β-Dicarbonyl
Compounds
Guan-Wu Wang,*[a] Ye-Bing Shen,[a] and Xue-Liang Wu[a]
Keywords: Phosphotungstic acid / Benzylation / Alcohols / β-Dicarbonyl compounds / Atom-economical reactions
12-Phosphotungstic acid was used as an efficient, ecofri-
endly, and air- and moisture-stable catalyst to promote the
direct substitution of the hydroxy group of benzylic and al-
lylic alcohols with various β-dicarbonyl compounds. This
powerful protocol for carbon–carbon bond-forming reactions
provides monoalkylated dicarbonyl compounds in high
yields with great efficiency.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
triflic acid,[16c] and dodecylbenzenesulfonic acid[17] have
been demonstrated to facilitate the dehydrative substitution
of allylic and benzylic alcohols with β-dicarbonyl com-
pounds. Furthermore, molecular iodine has also been found
to be effective in this transformation.[18]
The heteropoly acids (HPAs) such as 12-phosphotungstic
acid (PWA) and 12-phosphomolybdic acid (PMA) are often
employed as efficient and green catalysts in many organic
processes.[19] Recently, we reported the PWA-catalyzed am-
idation of alcohols[20a] and hydroalkylation of olefins with
1,3-diketones.[20b] Herein we describe a direct carbon–car-
bon bond forming reaction of benzylic alcohols with vari-
ous β-dicarbonyl compounds catalyzed by PWA.
Introduction
The construction of carbon–carbon bonds is a funda-
mental task in organic synthesis.[1] One important protocol
to accomplish this goal is the alkylation of active methylene
compounds such as β-diketones, β-keto esters, and malonic
esters.[2] Typically, this transformation is performed with
alkyl halides in the presence of at least an equimolar
amount of base, which results in the generation of large
quantities of waste salts.[3] This is the significant drawback
of this protocol. As green chemistry becomes a crucial con-
cern in contemporary chemistry, a synthetic approach with
environmental benignity, simple manipulation, and high
atom economy is extremely desirable.[4] The catalytic direct
alkylation of β-dicarbonyl compounds with unmodified
electrophiles such as alcohols, providing water as the only
byproduct, would be a suitable alternative. However, be-
cause of the poor leaving ability of the hydroxy group, ex-
cess amount of Brønsted or Lewis acids is required for this
kind of transformation.[5]
Recent examples have shown that the direct alkylation of
β-dicarbonyl compounds with allylic alcohols catalyzed by
Pd,[6] Co,[7] and Cu[8] in the presence of various additives
has been well developed. Very recently, many chemists have
focused their attention on the acid-catalyzed alkylation pro-
cesses that are considered to be the most promising ap-
proaches in this field. In this context, various Lewis acids
such as InCl3,[9] InBr3,[10] FeCl3,[11] Bi(OTf)3,[12] Ln(OTf)3
(Ln = La, Yb, Sc, Hf),[13] a Lewis acidic ruthenium com-
plex,[14] as well as Brønsted acids including proton-ex-
changed montmorillonite,[15] p-toluenesulfonic acid,[16]
Results and Discussion
As a starting point for reaction conditions optimizations,
the reaction of acetylacetone (1a) and benzhydryl alcohol
(2a) was chosen as the prototype reaction and various con-
ditions were screened. The results are listed in Table 1.
When the two reactants were mixed with PWA in toluene
at 20 °C, only a trace amount of product was observed after
20 h (Table 1, entry 1). Elevating the reaction temperature
proved helpful, and the yield of desired product 3aa in-
creased considerably (Table 1, entries 2 and 3). We were ple-
ased to find that the reaction proceeded with the highest
efficiency at 80 °C, affording 3aa in 92% yield with shorter
reaction time (Table 1, entry 4). Further increasing the reac-
tion temperature was unnecessary as a slight decrease in
yield was observed (Table 1, entry 5). Then other protic and
aprotic solvents of different polarities were examined. n-
Heptane was also employed as the reaction medium in this
transformation; however, in our protocol only a moderate
yield was obtained (Table 1, entry 6). A similar result was
found in cyclohexane (Table 1, entry 7), whereas the reac-
tion in the halogenated solvent 1,2-dichloroethane (DCE)
[a] Hefei National Laboratory for Physical Sciences at Microscale,
Joint Laboratory of Green Synthetic Chemistry, and Depart-
ment of Chemistry, University of Science and Technology of
China,
Hefei, Anhui 230026, P. R. China
Fax: +86-551-360-7864
E-mail: gwang@ustc.edu.cn
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G.-W. Wang, Y.-B. Shen, X.-L. Wu
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proceeded with higher efficiency (86% yield; Table 1, en- Table 2. PWA-catalyzed direct alkylation of β-dicarbonyl com-
pounds with benzylic alcohols.[a]
try 8). A high yield (85%) was also achieved with acetoni-
trile as the solvent (Table 1, entry 9). Surprisingly, the reac-
tion proceeded smoothly and efficiently in ethyl acetate, af-
fording the alkylated diketone in 90% yield (Table 1, en-
try 10). No expected reaction was observed with ethanol
and PEG-400 as the reaction media (Table 1, entries 11 and
12). An attempt to perform the reaction in water was also
unsuccessful (Table 1, entry 13).
Table 1. Optimizing the reaction conditions for the direct alkylation
of acetylacetone (1a) with benzhydryl alcohol (2a) catalyzed by
PWA.[a]
Entry
Solvent
T [°C]
Time [h]
Yield [%][b]
1
2
3
4
5
6
7
8
toluene
toluene
toluene
toluene
toluene
n-heptane
cyclohexane
DCE
20
40
60
80
90
80
reflux
80
20
16
16
10
8
12
14
8
trace
24
68
92
89
75
79
86
9
CH3CN
EtOAc
EtOH
PEG-400
H2O
reflux
reflux
reflux
80
10
9
12
12
12
85
90
10
11
12
13
NR[c]
NR[c]
NR[c]
80
[a] All reactions were performed with acetylacetone (1a;
0.25 mmol), benzhydryl alcohol (2a; 0.25 mmol), and PWA (5 mg)
in the indicated solvent. [b] Isolated yield after flash column
chromatography. [c] No expected reaction was observed.
After optimizing the reaction conditions, we commenced
to test the substrate generality of this protocol with regard
to both coupling partners. These results are summarized in
Table 2. At 80 °C in toluene, the reaction of acetylacetone
with benzhydrylic alcohols proceeded in excellent yields
(90–96%), and the electron-withdrawing group on the
phenyl ring of alcohols improved the yield slightly (Table 2,
entries 1–3). High yields (83–94%) of the corresponding
products were also obtained when benzoylacetone was em-
ployed (Table 2, entries 4–6). The unsymmetric benzhy-
drylic alcohols gave the final products as mixtures of two
inseparable diastereomers (Table 2, entries 5 and 6). To our
delight, ethyl acetoacetate was also tolerable under the pres-
ent conditions, giving the alkylated β-keto esters in high
yields (85–89%; Table 2, entries 7 and 8). Similarly, the re-
actions of ethyl benzoylacetate with the benzhydrylic
alcohols proceeded smoothly and efficiently (Table 2, en-
tries 9–11). Diastereomers were also observed when unsym-
metric benzhydrylic alcohols were employed. Unfortunately,
when 1-phenylethanol was utilized as the alkylating agent
in the reaction with acetylacetone, desired product 3ad was
isolated in poor yield even when the reaction time was pro-
longed (Table 2, entry 12).
[a] All reactions were performed with β-dicarbonyl compound 1
(0.25 mmol), benzylic alcohol 2 (0.25 mmol), and PWA (5 mg) in
toluene (1 mL) at 80 °C. [b] Isolated yield after flash column
chromatography. [c] Ratio of the two diastereomers determined by
1H NMR spectroscopic analysis.
5000
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Phosphotungstic Acid Catalyzed Direct Benzylation of β-Dicarbonyls
Accordingly, the above reaction system was not suitable methane at 20 °C, delivering the corresponding alkylated
for 1-phenylethanol, and further improvement was required products in excellent yields. The dehydration agent MgSO4
urgently. Delightfully, after screening various solvents and played a crucial role in the high conversion of the reaction.
additives, we finally discovered that the reactions of β-dike- The results are shown in Table 3. Obviously, the reaction
tones with 1-phenyethanol were highly efficient in nitro- of β-diketones including acetylacetone, benzoylacetone, and
dibenzoylmethanes with 1-phenylethanol gave the corre-
sponding products in high yields, ranging from 84 to 95%
Table 3. PWA-catalyzed direct alkylation of β-dicarbonyl com-
within 2 h (Table 3, entries 1–6). The allylic alcohol derived
from chalcone was also tolerable under the current reaction
conditions, affording the allylated diketones in excellent
yields (91–97%) within 30 min (Table 3, entries 7 and 8).
Because PWA is soluble in nitromethane, the homogeneous
reaction system might increase the reaction rate. In con-
trast, the reaction of acetylacetone with benzhydryl alcohol
in nitromethane was disadvantageous, and product 3aa was
isolated in low yield along with a large quantity of benzo-
phenone derived from the alcohol (Table 3, entry 9). As a
result, the reactions in toluene and in nitromethane were
complementary to each other, offering the alkylation reac-
tions of β-dicarbonyl compounds with both benzylic and
allylic alcohols in high yields.
pounds with alcohols in nitromethane.[a]
It should be mentioned that in the above reactions the
catalyst loading of PWA (H3PW12O40·nH2O) was very low,
that is, only 5 mg (≈0.6 mol-%), reflecting the high effi-
ciency of PWA.
To further highlight the advantage of our protocol,
the gram-scale synthesis of the monoalkylated dicarbonyl
compounds under different conditions was performed
(Scheme 1). After optimizing the reaction conditions, we
were pleased to find that the reaction of acetylacetone (1a)
with benzhydryl alcohol (2a) in toluene was able to proceed
on a 20-mmol scale, giving final product 3aa in 90% yield.
The reaction of dibenzoylmethane (1e) with 1-phenyl-
ethanol (2d) in nitromethane was also examined, and alkyl-
ated product 3ed was obtained in 92% yield. It is important
to emphasize that these reactions should be performed in
higher concentrations relative to those performed on small
scale. The yield decreased obviously when the reaction was
carried out in a more dilute solution. Noteworthy is that
the catalyst loading of PWA could be further reduced in the
multigram synthesis.
[a] Unless otherwise specified, all reactions were performed with β-
dicarbonyl compound
1
(0.25 mmol), benzylic alcohol
2
Scheme 1. Gram-scale synthesis of 3aa and 3ed.
(0.25 mmol), MgSO4 (50 mg), and PWA (5 mg) in CH3NO2 (1 mL)
at 20 °C. [b] Isolated yield after flash column chromatography. [c] A
larger amount of alcohol (0.4 mmol) was employed, and the reac-
tion was performed at 80 °C. [d] Ratio of the two diastereomers
According to our previous work on the PWA-catalyzed
direct amidation of benzylic alcohols,[20a] we hypothesized
that an SN1 pathway would be reasonable for this alkylation
1
determined by H NMR spectroscopic analysis.
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G.-W. Wang, Y.-B. Shen, X.-L. Wu
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completion, the solvent was removed under reduced pressure, and
the residue was purified by column chromatography (silica gel; pe-
troleum ether/ethyl acetate, 4:1) to obtain desired product 3. 3ad
(42.4 mg, 84%); 3bd (63.2 mg, 95%); 3ed (75.0 mg, 92%); 3fd
(78.3 mg, 88%); 3gd (94.1 mg, 95%); 3hd (84.2 mg, 93%); 3ee
(100.9 mg, 97%); 3ae (66.4 mg, 91%); 3aa (26.6 mg, 40%).
reaction. By action of PWA, the alcohol was protonated
to generate a stable benzyl cation after dehydration. This
carbocation could quickly combine with the employed β-
dicarbonyl compound to produce, after the release of H+,
the final alkylated product (Scheme 2).
Procedure for the Gram-Scale Synthesis of Alkylated Product 3aa in
Toluene: To a 50-mL round-bottom flask was added acetylacetone
(2.01 g, 20 mmol), benzhydryl alcohol (3.68 g, 20 mmol), 12-phos-
photungstic acid (0.30 g), and toluene (10 mL). The mixture stirred
at 80 °C for 12 h (monitored by TLC). Upon completion, the sol-
vent was removed under reduced pressure, and the residue was was
purified by column chromatography (silica gel; petroleum ether/
ethyl acetate, 4:1) to obtain desired product 3aa (4.79 g, 90%).
Procedure for the Gram-scale Synthesis of Alkylated Product 3ed in
Nitromethane: To a 100-mL round-bottom flask was added diben-
zoylmethane (4.46 g, 20 mmol), 1-phenylethanol (2.44 g, 20 mmol),
MgSO4 (1.00 g), 12-phosphotungstic acid (0.30 g), and nitrometh-
ane (60 mL). The mixture was allowed to stir at 20 °C for 4 h (mon-
itored by TLC). Upon completion, the solvent was removed under
reduced pressure, and the residue was purified by column
chromatography (silica gel; petroleum ether/ethyl acetate, 4:1) to
obtain desired product 3ed (6.01 g, 92%).
Scheme 2. Proposed mechanism for the catalytic addition of β-di-
carbonyl compounds to alcohols.
Conclusions
Compounds 3aa,[9a,16c] 3ab,[16c] 3ba,[21] 3ca,[5b,16c] 3da,[22]
3ad,[9a,12,16c] 3bd,[12,16c] 3ed,[12,16c] 3ee,[23] and 3ae[9a] were previously
reported and their structures were confirmed by comparison of
their spectroscopic data with the reported data. Characterization
data for new compounds 3ac, 3bb, 3bc, 3cc, 3 db, 3dc, 3fd, 3gd and
3hd are given below.
In summary, we have demonstrated a highly efficient
methodology for the direct alkylation of β-dicarbonyl com-
pounds with various benzylic and allylic alcohols as alkylat-
ing agents catalyzed by cheap 12-phosphotungstic acid.
This protocol provides a clean, efficient, synthetically com-
petitive, and cheap alternative to the existing catalytic sys-
tems.
3-[Phenyl(p-tolyl)methyl]pentane-2,4-dione
(3ac):
1H
NMR
(300 MHz, CDCl3): δ = 7.25–7.23 (m, 4 H, ArH), 7.17–7.12 (m, 3
H, ArH), 7.06 (d, J = 7.5 Hz, 2 H, ArH), 4.76 (d, J = 12.3 Hz, 1
H, CH), 4.69 (d, J = 12.3 Hz, 1 H, CH), 2.25 (s, 3 H, ArCH3), 1.99
(s, 3 H, COCH3), 1.98 (s, 3 H, COCH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 203.09, 141.66, 138.40, 136.70, 129.69, 128.98, 127.77,
Experimental Section
General: Reagents and solvents were obtained from commercial
sources and were not further purified before use. All melting points
are uncorrected. Infrared spectra were recorded in KBr pellets and
reported in cm–1. 1H NMR spectra were recorded at 300 MHz and
are reported in parts per million (ppm) relative to tetramethylsilane
(δ = 0.00 ppm). 13C NMR spectra were recorded at 75 MHz and
are reported in parts per million (ppm) relative to CDCl3 (δ =
77.16 ppm). High-resolution mass spectra (HRMS) were recorded
in the EI mode.
127.68, 127.01, 74.69, 51.00, 29.79, 29.69, 21.01 ppm. IR (KBr): ν
˜
= 3024, 2924, 1730, 1704, 1513, 1494, 1452, 1417, 1358, 1283, 1238,
1187, 1167, 1143, 956, 831, 796, 777, 738, 697, 618, 583, 535,
489 cm–1. HRMS (EI–TOF): calcd. for C19H20O2 [M]+ 280.1463;
found 280.1461.
2-[(4-Chlorophenyl)(phenyl)methyl]-1-phenylbutane-1,3-dione (3bb):
Characterized as
a
1:1 diastereomeric mixture. 1H NMR
(300 MHz, CDCl3): δ = 7.90–7.85 (m, 2 H, ArH), 7.53–7.45 (m, 1
H, ArH), 7.39–7.33 (m, 2 H, ArH), 7.26–7.00 (m, 9 H, ArH), 5.48
(d, J = 12.0 Hz, 1 H, CH), 5.02 (d, J = 12.0 Hz, 1 H, CH), 1.98 (s,
1.5 H, COCH3), 1.95 (s, 1.5 H, COCH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 202.63, 202.56, 194.07, 141.31, 140.85, 140.48, 139.99,
136.97, 136.89, 133.97, 133.86, 133.11, 132.64, 129.59, 129.26,
129.22, 128.99, 128.96, 128.92, 128.89, 128.82, 128.18, 127.79,
General Procedure for the Direct Alkylation of β-Dicarbonyl Com-
pounds with Benzylic Alcohols in Toluene: To a small vial was added
β-dicarbonyl compound 1 (0.25 mmol), alcohol 2 (0.25 mmol), and
12-phosphotungstic acid (5 mg) in toluene (1 mL). The mixture was
stirred at 80 °C for the indicated time (monitored by TLC). Upon
completion, the solvent was removed under reduced pressure, and
the residue was purified by column chromatography (silica gel; pe-
troleum ether/ethyl acetate, 4:1) to obtain desired product 3. 3aa
(61.2 mg, 92%); 3ab (72.1 mg, 96%); 3ac (63.0 mg, 90%); 3ba
(75.5 mg, 92%); 3bb (85.5 mg, 94%); 3bc (71.2 mg, 83%); 3ca
(66.4 mg, 89%); 3cc (66.3 mg, 85%); 3da (82.4 mg, 92%); 3db
(85.2 mg, 87%); 3dc (78.2 mg, 84%); 3ad (16.1 mg, 32%).
127.45, 127.03, 68.94, 50.93, 50.88, 28.03, 27.94 ppm. IR (KBr): ν
˜
= 2922, 1721, 1668, 1596, 1491, 1449, 1358, 1263, 1207, 1154, 1091,
1014, 769, 755, 697, 546 cm–1. HRMS (EI–TOF): calcd. for
C23H19O235Cl [M]+ 362.1074; found 362.1080.
1-Phenyl-2-[phenyl(p-tolyl)methyl]butane-1,3-dione (3bc): Charac-
terized as a 1:1 diastereomeric mixture. 1H NMR (300 MHz,
CDCl3): δ = 7.95–7.90 (m, 2 H, ArH), 7.52–7.48 (m, 1 H, ArH),
7.42–6.98 (m, 10 H, ArH), 6.92 (d, J = 7.8 Hz, 1 H, ArH), 5.57 (d,
J = 12.0 Hz, 0.5 H, CH), 5.56 (d, J = 12.0 Hz, 0.5 H, CH), 5.04
(d, J = 12.0 Hz, 1 H, CH), 2.26 (s, 1.5 H, ArCH3), 2.14 (s, 1.5 H,
General Procedure for the Direct Alkylation of β-Dicarbonyl Com-
pounds with Benzylic Alcohols in Nitromethane: To a small vial was
added β-dicarbonyl compound
1
(0.25 mmol), alcohol
2
(0.25 mmol), MgSO4 (50 mg), 12-phosphotungstic acid (5 mg), and
CH3NO2 (1 mL). The vial was sealed, and the reaction mixture was
stirred at 20 °C for the indicated time (monitored by TLC). Upon
ArCH3), 2.02 (s, 1.5 H, COCH3), 2.00 (s, 1.5 H, COCH3) ppm. 13
NMR (75 MHz, CDCl3): δ = 203.15, 203.12, 194.52, 194.36,
C
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Phosphotungstic Acid Catalyzed Direct Benzylation of β-Dicarbonyls
142.10, 141.64, 138.91, 138.36, 137.16, 137.04, 136.82, 136.32,
133.70, 129.78, 129.47, 129.06, 128.88, 128.83, 128.74, 128.22,
128.11, 127.80, 127.66, 127.12, 126.71, 69.19, 69.15, 51.28, 51.24,
1,3-Bis(4-chlorophenyl)-2-(1-phenylethyl)propane-1,3-dione
(3gd):
1H NMR (300 MHz, CDCl3): δ = 7.95 (d, J = 8.4 Hz, 2 H, ArH),
7.66 (d, J = 8.4 Hz, 2 H, ArH), 7.42 (d, J = 8.4 Hz, 2 H, ArH),
7.26 (d, J = 8.4 Hz, 2 H, ArH), 7.20–7.09 (m, 5 H, ArH), 5.42 (d,
J = 10.2 Hz, 1 H, CH), 4.04 (dq, J = 10.2, 6.9 Hz, 1 H, CHCH3),
1.33 (d, J = 6.9 Hz, 3 H, CHCH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 193.74, 193.61, 143.46, 140.52, 139.93, 135.40, 135.24,
130.38, 130.05, 129.40, 129.01, 128.68, 127.83, 127.00, 65.91, 41.28,
27.88, 21.12, 20.98 ppm. IR (KBr): ν = 3058, 3027, 2921, 1722,
˜
1671, 1596, 1449, 1357, 1265, 1153, 974, 770, 697, 538 cm–1. HRMS
(EI–TOF): calcd. for C24H22O2 [M]+ 342.1620; found 342.1626.
Ethyl 3-Oxo-2-[phenyl(p-tolyl)methyl]butanoate (3cc): Charac-
terized as a 2:1 diastereomeric mixture. 1H NMR (300 MHz,
CDCl3): δ = 7.24–6.99 (m, 9 H, ArH), 4.67 (d, J = 12.2 Hz, 1 H,
CH), 4.44 (d, J = 12.2 Hz, 1 H, CH), 3.97–3.88 (m, 2 H,
OCH2CH3), 2.21 (s, 3 H, ArCH3), 2.05 (s, 1 H, COCH3), 2.03 (s,
2 H, COCH3), 0.98 (t, J = 7.1 Hz, 2 H, OCH2CH3), 0.94 (t, J =
7.1 Hz, 1 H, OCH2CH3) ppm. 13C NMR (75 MHz, CDCl3): δ =
201.90, 167.86, 167.82, 141.95, 141.65, 138.73, 138.39, 136.63,
136.46, 129.63, 129.39, 128.91, 128.68, 127.88, 127.77, 127.65,
126.96, 126.84, 65.44, 65.40, 61.53, 50.69, 50.65, 30.03, 29.98,
20.33 ppm. IR (KBr): ν = 2964, 1695, 1660, 1587, 1489, 1399, 1273,
˜
1219, 1200, 1094, 982, 910, 847, 831, 756, 696, 615, 530 cm–1.
HRMS (EI–TOF): calcd. for C23H18O235Cl2 [M]+ 396.0684; found
396.0678.
1-(4-Chlorophenyl)-3-phenyl-2-(1-phenylethyl)propane-1,3-dione (3hd):
Characterized as
a
3:2 diastereomeric mixture. 1H NMR
(300 MHz, CDCl3): δ = 8.02 (d, J = 8.1 Hz, 1.2 H, ArH), 7.96 (d,
J = 8.1 Hz, 0.8 H, ArH), 7.72 (d, J = 8.1 Hz, 0.8 H, ArH), 7.67 (d,
J = 8.1 Hz, 1.2 H, ArH), 7.59–7.09 (m, 10 H, ArH), 5.53–5.48 (m,
1 H, CH), 4.09–4.03 (m, 1 H, CHCH3), 1.34 (d, J = 6.9 Hz, 3 H,
CHCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 194.86, 194.66,
193.95, 193.68, 143.71, 140.29, 139.70, 137.20, 136.96, 135.53,
135.37, 133.82, 133.31, 130.37, 130.03, 129.29, 129.05, 128.93,
128.62, 127.84, 126.87, 65.51, 65.42, 41.35, 41.21, 20.41, 20.23 ppm.
21.05, 13.90, 13.86 ppm. IR (KBr): ν = 2981, 2921, 1738, 1710,
˜
1513, 1495, 1453, 1362, 1299, 1276, 1215, 1163, 1019, 802, 701,
538 cm–1. HRMS (EI–TOF): calcd. for C20H22O3 [M]+ 310.1569;
found 310.1574.
Ethyl 2-Benzoyl-3-(4-chlorophenyl)-3-phenylpropanoate (3db): Char-
acterized as a 2:1 diastereomeric mixture. 1H NMR (300 MHz,
CDCl3): δ = 7.99–7.94 (m, 2 H, ArH), 7.53–7.49 (m, 1 H, ArH),
7.43–7.37 (m, 2 H, ArH), 7.29–7.02 (m, 9 H, ArH), 5.33–5.28 (m,
1 H, CH), 5.02 (d, J = 11.7 Hz, 1 H, CH), 3.94–3.83 (m, 2 H,
OCH2CH3), 0.93 (t, J = 7.1 Hz, 2 H, OCH2CH3), 0.88 (t, J =
7.1 Hz, 1 H, OCH2CH3) ppm. 13C NMR (75 MHz, CDCl3): δ =
192.70, 192.65, 167.71, 167.61, 141.35, 140.52, 136.68, 136.61,
133.88, 133.77, 132.83, 132.51, 129.74, 129.22, 128.83, 128.76,
128.29, 127.77, 127.21, 126.92, 61.83, 61.79, 59.59, 59.41, 50.38,
IR (KBr): ν = 2964, 1695, 1659, 1588, 1491, 1448, 1399, 1270,
˜
1220, 1199, 1094, 981, 907, 846, 760, 695, 615, 531 cm–1. HRMS
(EI–TOF): calcd. for C23H19O235Cl [M]+ 362.1074; found 362.1070.
Acknowledgments
The authors are grateful for the financial support from the
National Natural Science Foundation of China (Nos. 20621061 and
20772117).
13.89, 13.81 ppm. IR (KBr): ν = 2925, 1720, 1675, 1492, 1450,
˜
1368, 1299, 1248, 1211, 1095, 1023, 984, 806, 697, 595 cm–1. HRMS
(EI–TOF): calcd. for C24H21O335Cl [M]+ 392.1179; found 392.1175.
[1] a) J. March, Advanced Organic Chemistry, 4th ed., Wiley, New
York, 1992; b) C. Scolastico, F. Nicotra, Current Trends in Or-
ganic Synthesis, Plenum, New York, 1999.
[2] a) H. O. House, Modern Synthetic Research, 2nd ed., Benjamin,
Menlopark, CA, 1972, p. 492; b) F. S. Prout, E. P.-Y. Huang,
R. J. Hartman, C. J. Korpies, J. Am. Chem. Soc. 1954, 76,
1911–1913.
[3] B. M. Trost, I. Fleming (Eds.), Comprehensive Organic Synthe-
sis, Pergamon, Oxford, 1991, vol. 3.
[4] a) B. M. Trost, Science 1991, 254, 1471–1477; b) B. M. Trost,
Angew. Chem. Int. Ed. Engl. 1995, 34, 259–281; c) B. M. Trost,
Acc. Chem. Res. 2002, 35, 695–705.
[5] For examples, see: a) G. C. Gullickson, D. E. Lewis, Aust. J.
Chem. 2003, 56, 385–388; b) F. Bisaro, G. Prestat, M. Vitale,
G. Poli, Synlett 2002, 1823–1826; c) J. T. Adams, B. Abramov-
itch, C. R. Hauser, J. Am. Chem. Soc. 1943, 65, 552–554.
[6] For a recent review, see: J. Muzart, Tetrahedron 2005, 61, 4179–
4212.
Ethyl 2-Benzoyl-3-phenyl-3-p-tolylpropanoate (3dc): Characterized
1
as a 1:1 diastereomeric mixture. H NMR (300 MHz, CDCl3): δ =
8.03–7.98 (m, 2 H, ArH), 7.52–7.47 (m, 1 H, ArH), 7.46–7.38 (m,
2 H, ArH), 7.36 (d, J = 7.2 Hz, 1 H, ArH), 7.29–7.01 (m, 7 H,
ArH), 6.94 (d, J = 8.1 Hz, 1 H, ArH), 5.38 (d, J = 11.7 Hz, 1 H,
CH), 5.03 (d, J = 11.7 Hz, 1 H, CH), 3.94–3.89 (m, 2 H,
OCH2CH3), 2.27 (s, 1.5 H, ArCH3), 2.17 (s, 1.5 H, ArCH3), 0.95
(t, J = 7.2 Hz, 1.5 H, OCH2CH3), 0.92 (t, J = 7.2 Hz, 1.5 H,
OCH2CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 193.09, 192.93,
167.92, 142.13, 138.93, 138.90, 136.87, 136.83, 136.47, 136.16,
133.61, 129.40, 129.36, 128.83, 128.79, 128.76, 128.65, 128.34,
128.15, 127.80, 127.65, 126.88, 126.58, 61.62, 59.67, 50.67, 21.11,
20.99, 13.85, 13.81 ppm. IR (KBr): ν = 2980, 2923, 1739, 1674,
˜
1449, 1294, 1264, 1249, 1211, 1153, 1026, 986, 802, 741, 698, 599,
569 cm–1. HRMS (EI–TOF): calcd. for C25H24O3 [M]+ 372.1725;
found 372.1732.
[7] M. Mukhopadhyay, J. Iqbal, Tetrahedron Lett. 1995, 36, 6761–
6764.
1,3-Bis(4-methylphenyl)-2-(1-phenylethyl)propane-1,3-dione
(3fd):
[8] J. B. Baruah, A. G. Samuelson, J. Organomet. Chem. 1989, 361,
57–60.
1H NMR (300 MHz, CDCl3): δ = 7.95 (d, J = 8.1 Hz, 2 H, ArH),
7.66 (d, J = 8.1 Hz, 2 H, ArH), 7.28–7.06 (m, 9 H, ArH), 5.54 (d,
J = 10.2 Hz, 1 H, CH), 4.07 (dq, J = 10.2, 6.9 Hz, 1 H, CHCH3),
2.38 (s, 3 H, ArCH3), 2.29 (s, 3 H, ArCH3), 1.32 (d, J = 6.9 Hz, 3
H, CHCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 194.78, 194.29,
144.59, 144.32, 143.99, 134.92, 134.66, 129.66, 129.28, 129.17,
128.84, 128.51, 127.87, 126.64, 65.00, 41.21, 21.77, 21.68,
[9] a) M. Yasuda, T. Somyo, A. Baba, Angew. Chem. Int. Ed. 2006,
45, 793–796. For reactions of alcohols with other nucleophiles,
see: b) M. Yasuda, T. Saito, M. Ueba, A. Baba, Angew. Chem.
Int. Ed. 2004, 43, 1414–1416; c) M. Yasuda, S. Yamasaki, Y.
Onishi, A. Baba, J. Am. Chem. Soc. 2004, 126, 7186–7187; d)
T. Saito, Y. Nishimoto, M. Yasuda, A. Baba, J. Org. Chem.
2006, 71, 8516–8522.
[10] P. Vicennati, P. G. Cozzi, Eur. J. Org. Chem. 2007, 2248–2253.
[11] a) J. Kischel, K. Mertins, D. Michalik, A. Zapf, M. Beller, Adv.
Synth. Catal. 2007, 349, 865–870; b) Y. Yuan, Z. Shi, X. Feng,
X. Liu, Appl. Organomet. Chem. 2007, 21, 958–964; c) U. Jana,
20.44 ppm. IR (KBr): ν = 2962, 1689, 1654, 1606, 1450, 1408, 1317,
˜
1273, 1224, 1179, 1119, 1024, 977, 908, 815, 699, 614, 594, 562,
533 cm–1. HRMS (EI–TOF): calcd. for C25H24O2 [M]+ 356.1776;
found 356.1774.
Eur. J. Org. Chem. 2008, 4999–5004
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5003

G.-W. Wang, Y.-B. Shen, X.-L. Wu
FULL PAPER
S. Biswas, S. Maiti, Tetrahedron Lett. 2007, 48, 4065–4069; for
other nucleophiles, see: d) I. Iovel, K. Mertins, J. Kischel, A.
Zapf, M. Beller, Angew. Chem. Int. Ed. 2005, 44, 3913–3917; e)
P. Salehi, N. lranpoor, F. K. Behbahani, Tetrahedron 1998, 54,
943–948.
A. Martínez, J. M. Álvarez-Gutiérrez, F. Rodríguez, Org. Lett.
2007, 9, 2027–2030.
S. Shirakawa, S. Kobayashi, Org. Lett. 2007, 9, 311–314.
W. Rao, A. H. L. Tay, P. J. Goh, J. M. L. Choy, J. K. Ke,
P. W. H. Chan, Tetrahedron Lett. 2008, 49, 122–126.
a) I. V. Kozhevnikov, Chem. Rev. 1998, 98, 171–198; b) M. Mis-
ono, I. Ono, G. Koyano, A. Aoshima, Pure Appl. Chem. 2000,
72, 1305–1311; c) Y. Izumi, K. Urabe, M. Onaka, Zeolite, Clay
and Heteropoly Acid in Organic Reactions, Kodansha/VCH, To-
kyo, 1992.
a) G.-W. Wang, Y.-B. Shen, X.-L. Wu, Eur. J. Org. Chem. 2008,
4367–4371; b) G.-W. Wang, Y.-B. Shen, X.-L. Wu, Tetrahedron
Lett. 2008, 49, 5090–5093.
[17]
[18]
[12] M. Rueping, B. J. Nachtsheim, A. Kuenkel, Org. Lett. 2007, 9,
[19]
825–828.
[13] a) M. Noji, Y. Konno, K. Ishii, J. Org. Chem. 2007, 72, 5161–
5167; b) W. Huang, J. Wang, Q. Shen, X. Zhou, Tetrahedron
Lett. 2007, 48, 3969–3973.
[14] P. N. Liu, Z. Y. Zhou, C. P. Lau, Chem. Eur. J. 2007, 13, 8610–
[20]
[21]
8619.
[15] a) K. Motokura, N. Fujita, K. Mori, T. Mizugaki, K. Ebitani,
K. Kaneda, Angew. Chem. Int. Ed. 2006, 45, 2605–2609; b) K.
Motokura, N. Nakagiri, T. Mizugaki, K. Ebitani, K. Kaneda,
J. Org. Chem. 2007, 72, 6006–6015.
[16] a) R. Sanz, A. Martínez, D. Miguel, J. M. Álvarez-Gutiérrez,
F. Rodríguez, Adv. Synth. Catal. 2006, 348, 1841–1845; b) R.
Sanz, D. Miguel, A. Martínez, J. M. Álvarez-Gutiérrez, F.
Rodríguez, Org. Lett. 2007, 9, 727–730; c) R. Sanz, D. Miguel,
P. Yates, G. D. Abrams, M. J. Belts, S. Goldstein, Can. J. Chem.
1971, 49, 2850–2860.
K. Yamamura, J. Org. Chem. 1978, 43, 724–727.
K. Manabe, S. Kobayashi, Org. Lett. 2003, 5, 3241–3244.
Received: June 24, 2008
[22]
[23]
Published Online: September 2, 2008
5004
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 4999–5004