DBU catalyzed cyanoacylation of ketones with acyl cyanides

Article abstract of DOI:10.1039/b602197b

The reaction of cyclohexanone with benzoyl cyanide by amines provides the corresponding O-benzoyl cyanohedrin adducts in moderate to good yields under mild conditions. DBU was found to be the most effective promoter among the catalyst, allowing the reacti

Full text of DOI:10.1039/b602197b

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
DBU catalyzed cyanoacylation of ketones with acyl cyanides
Wen Zhang and Min Shi*
Received 14th February 2006, Accepted 2nd March 2006
First published as an Advance Article on the web 29th March 2006
DOI: 10.1039/b602197b
The reaction of cyclohexanone with benzoyl cyanide catalyzed by amines provides the corresponding
O-benzoyl cyanohydrin adducts in moderate to good yields under mild conditions. Among the catalysts,
DBU was found to be the most effective promoter allowing the reaction to proceed smoothly at room
temperature and to give the corresponding O-acyl cyanohydrin adducts in higher yields for a variety of
substituted cyclohexanones, cyclopentanone, acetone or pentan-3-one and various acyl cyanides.
Quaternary stereocenters are useful structures in pharmaceu-
tical, medicinal and natural products.1 Cyanohydrins are of
synthetic interest as they can be transformed into a num-
ber of relevant functional groups such as b-amino alcohols,
a-hydroxyacids and a-hydroxyesters, a-sulfonyloxynitriles, a-
aminonitriles, a-fluoronitriles, 3-amino-2-alkenoates and sub-
stituted azacycloalkenes.2 The synthesis of cyanohydrins and
their O-protected derivatives can be accomplished by enzymes,3
organocatalysts1,4 and metal complexes.5–8 Among various cyanide
ion sources, trimethylsilyl cyanide is a safer and more easily
handled reagent compared to hydrogen cyanide, and various
cyanosilylations of aldehydes catalyzed by Lewis acids have
already been developed.9 On the other hand, acyl cyanides are also
safer and commercially available reagents.10 It has already been
reported that base catalysts such as potassium carbonate11 and
1,4-diazabicyclo[2.2.2]octane (DABCO)12 are required to promote
the cyanoacylation of aldehydes. Recently, the direct preparation
of cyanohydrin esters by the reaction of aldehydes with acyl
cyanides in DMSO using no catalyst has also been reported.13 Al-
though these reactions are very efficient methods for synthesizing
cyanohydrin derivatives of aldehydes, only one example of a Et3N
catalyzed reaction of 4-tert-butylcyclohexanone with cyanides has
been reported.14 Herein, we report the cyanoacylation of ketones
catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to give the
corresponding cyanohydrin esters in moderate to high yields at
room temperature in toluene within 2 h (Scheme 1).
in DMF or using DBN as a catalyst in THF at room temperature
within 4 h (Table 1, entries 1 to 8). In our next investigation, we
examined various solvents such as toluene, THF, DMSO, MeOH,
MeCN, and CH2Cl2 with DBU as a Lewis base catalyst. We found
that 3a was obtained in 96% yield in toluene in the presence of
DBU (30 mol%) within 2 h (Table 1, entries 1, and 9 to 14). These
are the best reaction conditions for the preparation of 3a.
Under these optimized conditions, various substituted acyl
cyanides were examined in this reaction. The results are sum-
marized in Table 2. In most cases, cyanoacylation proceeded
smoothly to give the corresponding 3 in moderate to excellent
yields. Electron-donating substituents on the benzene ring of 1
produced the corresponding 3 in higher yields at room temperature
under identical conditions (Table 2, entries 2 to 4). Electron-
withdrawing substituents such as the nitro group on the benzene
Table 1 Cyanobenzoylation of cyclohexanone with benzoyl cyanide in
the presence of various solvents and basesa,b
Entry
Lewis base
Solvent
Time/h
3ac (%)
1
2
3
4
5
6
7
8
DBU
DMF
DMF
DMF
DMF
PhMe
DMF
PhMe
THF
4
9
9
63
25
30
31
DMAP
DABCO
iPr2NEt
Et3N
Pyridine
DBN
9
19
24
2
51
NRd
50
DBN
2
63
9
DBU
DBU
DBU
DBU
DBU
DBU
DMSO
MeOH
MeCN
THF
CH2Cl2
PhMe
4
24
4
4
2
30
10
11
12
13
14
NRd
94
Scheme 1 Cyanoacylation of ketones with acyl cyanides.
96
90
96
Optimization of the reaction conditions was performed with
benzoyl cyanide 1a and cyclohexenone 2a. Initially, we examined
the effect of the various amino base catalysts such as DBU, DMAP,
DABCO, Pr2NEt, Et3N, pyridine and DBN (30 mol%) in this
reaction. The best yield of 3a was 63% by using DBU as a catalyst
2
a All reactions were carried out using benzoyl cyanide 1a (0.5 mmol),
cyclohexanone 2a (1.0 mmol), and Lewis base (0.15 mmol)
in solvent (0.5 mL, 1.0 M) at room temperature. b DBU:
1,8-diazabicyclo[5.4.0]undec-7-ene, DMAP: 4-dimethylaminopyridine,
DABCO: 1,4-diazabicyclo[2.2.2]octane, DBN: 1,5-diazabicyclo[4.3.0]-5-
nonene, DMF: N,N-dimethyl formamide, DMSO: dimethyl sulfone, THF:
tetrahydrofuran. c Isolated yields. d No reaction took place.
i
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai
200032, China. E-mail: mshi@pub.sioc.ac.cn
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Table 2 Cyanoacylation of cyclohexanone with acyl cyanidesa
cyclohexanones 2c and 2d, the corresponding products 4b and
4c were formed in high yields under the standard conditions
(Table 3, entries 2 and 3). Additionally, cyclopentanone 2e, acetone
2f and pentan-3-one 2g were also examined in this reaction to give
the corresponding products 4d–4f in moderate yields, respectively
(Table 3, entries 4 to 6).
A plausible mechanism, similar to that proposed by Deng
and Tian4 for the asymmetric cyanation of ethyl cyanoformate
to ketones, is shown in Scheme 2. We suppose that benzoyl
cyanide is activated by a nucleophilic attack by DBU to form
the corresponding intermediate A, which reacts with the ketone
to give the cyanoalkoxide intermediate B. Then, intramolecular
nucleophilic attack of the cyanoalkoxide on the carbonyl group in
intermediate B produces the final O-acyl cyanohydrin ester 3 or 4
and regenerates the DBU catalyst.
Entry
R1(1)
Time/h
3 (%)b
1
2
3
4
5
6
7
8
C6H5 (1a)
2
2
2
2
2
2
2
2
3a, 96
3b, 70
3c, 89
3d, 97
3e, 31
3f, 52
3g, 89
3h, 51
4-ClC6H4 (1b)
3,5-Me2C6H3 (1c)
3,4,5-(MeO)3C6H2 (1d)
4-NO2C6H4 (1e)
2-BrC6H4 (1f)
Furan (1g)
=
Furan–CH CH (1h)
a All reactions were carried out using acyl cyanides (0.5 mmol), cyclo-
hexanone (1.0 mmol), DBU (0.15 mmol) in PhMe (0.5 mL) at room
temperature for 2 h. b Isolated yields.
ring of 1e retarded the reaction to give the corresponding 3e in
a lower yield (31%) under identical conditions (Table 2, entry 5).
For ortho-substituted acyl cyanide (1f), the corresponding 3f was
obtained in a lower yield (52%) as well, presumably due to the
steric effect (Table 2, entry 6). The reaction of furan-2-carbonyl
cyanide (1g) with 2a produced the corresponding 3g in 89% yield
under the standard conditions (Table 2, entry 7). Alkyl substrates
such as 3-furan-2-ylacryloyl cyanide (1h) also reacted smoothly
with 2a to give the corresponding 3h in 51% yield under identical
conditions (Table 2, entry 8).
Next, in order to compare the reactivity of ketones in this
reaction, we attempted the reaction of benzoyl cyanide with
various ketones under the standard conditions. The results
are summarized in Table 3. 1-Benzyl-4-piperidone (2b) reacted
smoothly with benzoyl cyanide 1a to give the corresponding
product 4a in 84% yield (Table 3, entry 1). By using substituted
Scheme 2 Proposed DBU catalyzed cyanoacylation of ketones with acyl
cyanides.
As a conclusion, in this paper, we disclosed an efficient catalytic
system for the cyanoacylation of ketones with acyl cyanides
catalyzed by the organocatalyst DBU. These reactions take place
smoothly at room temperature in toluene to give the corresponding
O-acyl cyanohydrin esters 3 or 4 in moderate to high yields within
2 h. Efforts are under way to elucidate the catalytic asymmetric
version of this reaction.
Table 3 Cyanobenzoylation of ketones with benzoyl cyanidea
Entry
1
Ketone (2)
Time/h
2
4 (%)b
4a, 84
Experimental
General remarks
2
3
2
2
4b, 92
4c, 92
MPs were obtained with a Yanagimoto micro melting point appa-
ratus and are uncorrected. 1H NMR and 13C NMR spectra were
recorded for a solution in CDCl3 with tetramethylsilane (TMS)
as an internal standard. J values are in Hz. Mass spectra were
recorded with a HP-5989 instrument and HRMS was measured
on a Finnigan MA+ mass spectrometer. The solid compounds
reported in this paper gave satisfactory CHN microanalyses with a
Carlo-Erba 1106 analyzer. Commercially obtained reagents were
used without further purification. All reactions were monitored
by TLC with Huanghai GF254 silica gel coated plates. Flash
column chromatography was carried out using 200–300 mesh silica
gel at increased pressure. Reaction experiments were performed
under ambient atmosphere. The starting materials 1b–1h15 were
synthesized according to the previous literature.
4
5
6
2
2
2
4d, 57
4e, 68
4f, 44
a All reactions were carried out using benzoyl cyanide (0.5 mmol), ketone
(1.0 mmol), DBU (0.15 mmol) in PhMe (0.5 mL) at room temperature for
2 h. b Isolated yields.
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General reaction procedure
2-Bromobenzoic acid 1-cyanocyclohexyl ester (3f). A colorless
oil: 80 mg, 52% yield. IR (CH2Cl2) m 2941, 2864, 1743, 1433, 1292,
1244, 1028 cm−1. 1H NMR (CDCl3, 300 MHz, TMS): d 1.41–1.88
(m, 6H, 3CH2), 2.00–2.09 (m, 2H, CH2), 2.41–2.45 (m, 2H, CH2),
7.36–7.40 (m, 2H, Ar), 7.66–7.69 (m, 1H, Ar), 7.79–7.82 (m, 1H,
Ar). 13C NMR (CDCl3, 75 MHz): d 22.0, 24.4, 35.0, 73.9, 118.2,
121.7, 127.2, 131.0, 131.5, 133.1, 134.4, 163.8. MS (EI) m/e: 308
(M+, 1.38), 200 (56.77), 185 (100), 183 (78.29), 107 (48.23). HRMS
(MALDI) for C14H14NO2BrNa+: 330.0104; found: 330.0100.
A mixture of benzoyl cyanide (65.5 mg, 0.5 mmol), cyclohexanone
(104 lL, 1.0 mmol), base (0.15 mmol) and solvent (0.5 mL) was
stirred under ambient atmosphere at room temperature for the
required time indicated in the Tables 1–3. After the reaction the
solution was concentrated under reduced pressure and the residue
was purified by flash chromatography on silica gel (eluent: EtOAc–
petroleum ether = 1 : 20) to afford the pure products 3 or 4.
Benzoic acid 1-cyanocyclohexyl ester (3a) (a known com-
Furan-3-carboxylic acid 1-cyanocyclohexyl ester (3g). A white
solid: 97 mg, 89% yield. Mp: 75–77 ◦C. IR (CH2Cl2) m 2942, 2865,
1737, 1471, 1302, 1015 cm−1. 1H NMR (CDCl3, 300 MHz, TMS):
d 1.20–1.78 (m, 6H, 3CH2), 1.92–2.01 (m, 2H, CH2), 2.29–2.37 (m,
2H, CH2), 6.50 (dd, J = 1.8, 3.6 Hz, 1H, Fu), 7.19 (d, J = 3.6 Hz,
1H, Fu), 7.58 (d, J = 2.4 Hz, 1H, Fu). 13C NMR (CDCl3, 75 MHz):
d 21.8, 24.2, 35.0, 73.1, 112.0, 118.1, 119.1, 143.2, 147.0, 156.0. MS
(EI) m/e: 219 (M+, 0.54), 112 (66.92), 107 (100), 95 (65.98). Anal.
calcd for C12H13NO3: C, 65.74%; H, 5.98%; N, 6.39%; found: C,
65.93%; H, 6.23%; N, 6.16%.
1
pound)16. A white solid: 110 mg, 96% yield. H NMR (CDCl3,
300 MHz, TMS): d 1.40–1.83 (m, 6H, 3CH2), 2.01–2.10 (m, 2H,
CH2), 2.35–2.43 (m, 2H, CH2), 7.50 (dd, J = 7.2, 8.4 Hz, 2H, Ar),
7.60 (t, J = 7.5 Hz, 1H, Ar), 8.03 (d, J = 8.1 Hz, 2H, Ar). 13C
NMR (CDCl3, 75 MHz): d 21.8, 24.3, 34.9, 72.7, 118.5, 128.4,
129.0, 129.5, 133.5, 164.0. MS (EI) m/e: 230 (M+ + 1, 6.13), 105
(100), 77 (31.39), 51 (18.85). Anal. calcd for C14H15NO2: C, 73.34%;
H, 6.59%; N, 6.11%; found: C, 73.57%; H, 6.59%; N, 5.95%.
4-Chlorobenzoic acid 1-cyanocyclohexyl ester (3b). A white
solid: 92 mg, 70% yield. Mp: 78–80 ◦C. IR (CH2Cl2) m 2942, 2864,
1730, 1594, 1402, 1274, 1253 cm−1. 1H NMR (CDCl3, 300 MHz,
TMS): d 1.37–1.83 (m, 6H, 3CH2), 1.99–2.08 (m, 2H, CH2), 2.38–
2.42 (m, 2H, CH2), 7.44 (d, J = 8.7 Hz, 2H, Ar), 7.96 (d, J =
8.7 Hz, 2H, Ar). 13C NMR (CDCl3, 75 MHz): d 21.9, 24.4, 35.0,
73.1, 118.3, 127.5, 128.8, 131.0, 140.1, 163.3. MS (EI) m/e: 263
(M+, 0.24), 156 (57.65), 139 (100), 107 (49.76). Anal. calcd for
C14H14ClNO2: C, 63.76%; H, 5.35%; N, 5.31%; found: C, 63.90%;
H, 5.34%; N, 5.17%.
3-Furan-2-ylacrylic acid 1-cyanocyclohexyl ester (3h). A white
solid: 62 mg, 51% yield. Mp: 125–127 ◦C. IR (CH2Cl2) m 2944,
1722, 1637, 1482, 1139 cm−1. 1H NMR (CDCl3, 300 MHz, TMS):
d 1.36–1.80 (m, 6H, 3CH2), 1.89–1.98 (m, 2H, CH2), 2.31–2.36 (m,
2H, CH2), 6.28 (d, J = 15.6 Hz, 1H, CH), 6.49 (d, J = 3.3 Hz,
1H, Fu), 6.66 (d, J = 3.3 Hz, 1H, Fu), 7.46 (d, J = 15.9 Hz, 1H,
CH), 7.50 (s, 1H, Fu). 13C NMR (CDCl3, 75 MHz): d 21.9, 24.4,
35.0, 72.4, 112.4, 114.2, 115.8, 118.6, 132.4, 145.2, 150.4, 164.6.
MS (EI) m/e: 245 (M+, 15.84), 138 (62.67), 121 (100), 65 (48.86).
Anal. calcd for C14H15NO3: C, 68.56%; H, 6.16%; N, 5.71%; found:
C, 68.54%; H, 6.10%; N, 5.52%.
3,5-Dimethylbenzoic acid 1-cyanocyclohexyl ester (3c). A white
solid: 114 mg, 89% yield. Mp: 83–85 ◦C. IR (CH2Cl2) m 2941, 1728,
1312, 1112 cm−1. 1H NMR (CDCl3, 300 MHz, TMS): d 1.40–1.83
(m, 6H, 3CH2), 2.00–2.09 (m, 2H, CH2), 2.37–2.43 (m, 2H, CH2),
2.39 (s, 6H, 2CH3), 7.23 (s, 1H, Ar), 7.63 (s, 2H, Ar). 13C NMR
(CDCl3, 75 MHz): d 20.9, 21.8, 24.3, 34.9, 72.5, 118.5, 127.2, 128.8,
135.1, 138.0, 164.3. MS (EI) m/e: 257 (M+, 5.00), 150 (66.05),
133 (100), 105 (44.90). Anal. calcd for C16H19NO2: C, 74.68%; H,
7.44%; N, 5.44%; found: C, 74.47%; H, 7.29%; N, 5.20%.
Benzoic acid 1-benzyl-4-cyanopiperidin-4-yl ester (4a). A light
yellow oil: 135 mg, 84% yield. IR (CH2Cl2) m 2948, 2812, 2771,
1723, 1601, 1452, 1253, 1177 cm−1. 1H NMR (CDCl3, 300 MHz,
TMS): d 2.46 (t, J = 5.7 Hz, 4H, 2CH2), 2.76 (t, J = 6.0 Hz, 4H,
2CH2), 3.56 (s, 2H, CH2), 7.27–7.36 (m, 5H, Ar), 7.48 (dd, J =
7.8, 7.5 Hz, 2H, Ar), 7.62 (t, J = 7.5 Hz, 1H, Ar), 8.02 (d, J =
8.1 Hz, 2H, Ar). 13C NMR (CDCl3, 75 MHz): d 34.5, 41.0, 62.2,
70.9, 118.0, 127.1, 128.1, 128.4, 128.7, 128.8, 129.6, 133.6, 137.6,
164.0. MS (EI) m/e: 320 (M+, 3.02), 198 (10.23), 107 (36.08), 91
3,4,5-Trimethoxybenzoic acid 1-cyanocyclohexyl ester (3d).
A
white solid: 154 mg, 97% yield. Mp: 82–84 ◦C. IR (CH2Cl2) m 2941,
1725, 1416, 1336, 1218, 1128 cm−1. 1H NMR (CDCl3, 300 MHz,
TMS): d 1.40–1.83 (m, 6H, 3CH2), 2.00–2.09 (m, 2H, CH2), 2.37–
2.43 (m, 2H, CH2), 3.91 (s, 6H, 2CH3), 3.92 (s, 3H, CH3), 7.23 (s,
2H, Ar). 13C NMR (CDCl3, 75 MHz): d 21.8, 24.1, 34.8, 55.9, 60.5,
72.7, 106.6, 118.2, 123.7, 142.5, 152.6, 163.6. MS (EI) m/e: 319
(M+, 64.34), 212 (100), 197 (70.93), 93 (20.07), 81 (17.66). Anal.
calcd for C17H21NO5: C, 63.94%; H, 6.63%; N, 4.39%; found: C,
63.76%; H, 6.52%; N, 4.16%.
+
(100), 77 (12.42). HRMS (MALDI) for C20H21N2O2 : 321.1602;
found: 321.1598.
Benzoic acid 1-cyano-4-phenylcyclohexyl ester (4b). A white
◦
solid: 141 mg, 92% yield. Mp: 146–148 C. IR (CH2Cl2) m 2949,
1728, 1451, 1278, 719 cm−1. 1H NMR (CDCl3, 300 MHz, TMS):
d 1.90–2.12 (m, 6H, 3CH2), 2.50–2.55 (m, 1H, CH), 2.80–2.84 (m,
2H, CH2), 7.21–7.37 (m, 5H, Ar), 7.48 (dd, J = 7.8, 8.1 Hz, 2H,
Ar), 7.62 (t, J = 7.8 Hz, 1H, Ar), 8.05 (d, J = 8.4 Hz, 2H, Ar).
13C NMR (CDCl3, 75 MHz): d 30.1, 33.7, 35.2, 73.4, 117.8, 126.4,
126.5, 126.6, 128.3, 128.4, 129.6, 133.5, 144.4, 164.1. MS (EI) m/e:
305 (M+, 0.24), 183 (37.42), 117 (21.07), 104 (100), 77 (36.35). Anal.
calcd for C20H19NO2: C, 78.66%; H, 6.27%; N, 4.59%; found: C,
78.83%; H, 6.25%; N, 4.33%.
4-Nitrobenzoic acid 1-cyanocyclohexyl ester (3e). A white
solid: 42 mg, 31% yield. Mp: 104–106 ◦C. IR (CH2Cl2) m 2946,
1
1730, 1527, 1350, 1290, 718 cm−1. H NMR (CDCl3, 300 MHz,
TMS): d 1.66–1.86 (m, 6H, 3CH2), 2.00–2.09 (m, 2H, CH2), 2.41–
2.48 (m, 2H, CH2), 8.19 (d, J = 8.7 Hz, 2H, Ar), 8.31 (d, J =
9.3 Hz, 2H, Ar). 13C NMR (CDCl3, 75 MHz): d 22.1, 24.4, 35.0,
74.1, 118.0, 123.7, 130.9, 134.5, 150.8, 162.4. MS (EI) m/e: 275
(M+ + 1, 1.07), 150 (71.63), 107 (100), 81 (39.75), 56 (51.53). Anal.
calcd for C14H14N2O4: C, 61.31%; H, 5.14%; N, 10.21%; found: C,
61.40%; H, 5.12%; N, 10.16%.
1-Cyano-2-methylcyclohexyl benzoate (4c). A white solid:
112 mg, 92% yield. Mp: 84–86 ◦C. IR (CH2Cl2) m 2937, 1731,
1453, 1278, 1068 cm−1. 1H NMR (CDCl3, 300 MHz, TMS): d 1.24
(d, J = 6.9 Hz, 3H, CH3), 1.29–1.86 (m, 7H, 4CH2), 2.08–2.15 (m,
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1H, CH2), 2.91–2.96 (m, 1H, CH), 7.45 (dd, J = 7.8, 7.8 Hz, 2H,
Ar), 7.59 (t, J = 8.1 Hz, 1H, Ar), 8.01 (d, J = 7.2 Hz, 2H, Ar).
13C NMR (CDCl3, 75 MHz): d 16.3, 22.9, 24.4, 31.0, 34.3, 40.2,
78.5, 116.5, 128.4, 129.2, 129.6, 133.5, 164.2. MS (EI) m/e: 244
(M+ + 1, 11.22), 105 (100), 77 (15.23). Anal. calcd for C15H17NO2:
C, 74.05%; H, 7.04%; N, 5.76%; found: C, 73.90%; H, 7.03%; N,
5.55%.
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Benzoic acid 1-cyanocyclopentyl ester (4d) (a known com-
pound)17. A light yellow solid: 61 mg, 57% yield. 1H NMR
(CDCl3, 300 MHz, TMS): d 1.87–1.96 (m, 4H, 2CH2), 2.38–2.50
(m, 4H, 2CH2), 7.46 (dd, J = 7.8, 7.8 Hz, 2H, Ar), 7.61 (t, J =
8.1 Hz, 1H, Ar), 8.01 (d, J = 7.8 Hz, 2H, Ar). 13C NMR (CDCl3,
75 MHz): d 23.3, 39.0, 76.7, 119.3, 128.5, 128.8, 129.6, 133.6, 164.6.
MS (EI) m/e: 215 (M+, 0.61), 105 (100), 77 (18.48), 51 (12.85).
Anal. calcd for C13H13NO2: C, 72.54%; H, 6.09%; N, 6.51%; found:
C, 72.56%; H, 5.95%; N, 6.58%.
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Benzoic acid cyanodimethylmethyl ester (4e) (a known com-
1
pound)18. A yellow solid, 64 mg, 68% yield. H NMR (CDCl3,
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300 MHz, TMS): d 1.89 (s, 6H, 2CH3), 7.47 (dd, J = 7.5, 8.1 Hz,
2H, Ar), 7.61 (t, J = 7.5 Hz, 1H, Ar), 8.02 (d, J = 8.4 Hz, 2H,
Ar). 13C NMR (CDCl3, 75 MHz): d 26.8, 68.7, 119.3, 128.4, 128.9,
129.6, 133.6, 164.3. MS (EI) m/e: 189 (M+, 2.53), 122 (47.55), 105
(100), 77 (35.31), 51 (25.48).
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Benzoic acid 1-cyano-1-ethylpropyl ester (4f) (a known
1
compound)19. A light yellow oil: 47 mg, 44% yield. H NMR
(CDCl3, 300 MHz, TMS): d 1.14 (t, J = 7.5 Hz, 6H, 2CH3), 2.12–
2.29 (m, 4H, 2CH2), 7.47 (dd, J = 8.4, 6.9 Hz, 2H, Ar), 7.61 (t, J =
7.5 Hz, 1H, Ar), 8.02 (d, J = 7.8 Hz, 2H, Ar). 13C NMR (CDCl3,
75 MHz): d 8.0, 29.5, 77.1, 118.1, 128.5, 129.1, 129.6, 133.6, 164.3.
MS (ESI) m/e: 218 (M+ + 1).
Acknowledgements
We thank the State Key Project of Basic Research (Project 973)
(No. G2000048007), Shanghai Municipal Committee of Science
and Technology (04JC14083), Chinese Academy of Sciences
(KGCX2-210-01), and the National Natural Science Founda-
tion of China for financial support (20025206, 203900502 and
20272069).
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1674 | Org. Biomol. Chem., 2006, 4, 1671–1674
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