Highly efficient syntheses of β-cyanoketones via conjugate addition of Me3SiCN to aromatic enones

Article abstract of DOI:10.1002/cjoc.201090182

An efficient 1,4-addition of Me₃SiCN to aromatic enones has been achieved with excellent yields (91%-99%) using CsF (1 mol%) as the catalyst and H₂O (4 equiv.) as the additive in refluxing dioxane within 7 h. The perfect regioselecti

Full text of DOI:10.1002/cjoc.201090182

FULL PAPER
Highly Efficient Syntheses of β-Cyanoketones via Conjugate
Addition of Me3SiCN to Aromatic Enones
Yang, Jingyaa,b(杨靖亚)
Chen, Fuxue*,a(陈甫雪)
a Department of Applied Chemistry, School of Chemical Engineering & Environment,
Beijing Institute of Technology, Beijing 100081, China
b College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu 730070, China
An efficient 1,4-addition of Me3SiCN to aromatic enones has been achieved with excellent yields (91%— 99%)
using CsF (1 mol%) as the catalyst and H2O (4 equiv.) as the additive in refluxing dioxane within 7 h. The perfect
regioselectivity is proposed accounting from H2O-facilitated reversion of the 1,2-adduct in the presence of CsF and
subsequent irreversible 1,4-addition reaction.
Keywords 1,4-addition, regioselectivity, enones, cyanides, CsF
Introduction
oselective version of conjugate addition of cyanide to
enones is also described by Shibasaki.14 Despite these
convincing achievements, practical regioselective
1,4-additon of Me3SiCN to enones is still demanding.15
Due to special property and low nucleophilicity of
fluoride ion, cesium fluoride is extensively used in or-
ganic synthesis.16-18 Though CsF-catalyzed silylcyana-
tion of ketones17 and Michael reaction18 have been pre-
sented, to the best our knowledge, CsF is scarcely ap-
plied to the 1,4-addition of cyanide to α,β-unsaturated
carbonyl compounds. Herein, we report in full length an
efficient CsF-catalyzed 1,4-addition of Me3SiCN to
aromatic enones in the presence of water as well as the
insight of the role of water.19
Among the most widely used methods for the con-
struction of carbon-carbon bonds are conjugate addition
reactions of carbon nucleophiles to α,β-unsaturated car-
bonyl compounds.1 While transition metal-catalyzed
1,4-addition of aryl2 and alkyl reagents is well docu-
mented,3 the regioselective 1,4-addition rather than
1,2-addition of weak nucleophiles such as cyanide to
α,β-unsaturated carbonyl compounds remains challeng-
ing (Scheme 1).
Scheme 1
Results and discussion
Model reaction is conducted with chalcone (1a) and
Me3SiCN under argon. Initially, various catalysts are
screened in dioxane at reflux temperature (Table 1).
Without any catalyst added, just trace of product 2a can
be detected by TLC (thin layer chromatography) (Entry
1). Considering high affinity of silicon for fluoride an-
ion,20 we presume that fluorides could be used to acti-
vate Me3SiCN in this transformation.16 Then, various
fluorides are examined (Entries 2— 4). Thus, 41% yield
is obtained with hydrated KF (20 mol%, Entry 2) while
Bu4NF gives moderate 75% yield (Entry 3). Exhilarat-
ingly, the reaction proceeds smoothly in the presence of
CsF to afford the product 2a in 92% yield (Entry 4).
Comparing the results of KF and CsF, a possible ‘ce-
sium effect’ cannot be ruled out.21 Nevertheless, a con-
trol experiment using CsCl yields the product in only
16% yield (Entry 5). More basic monohydrated CsOH
In the literature, 1,4-addition of cyanide to enones
has been widely employed in syntheses of biologically
active molecules4 and complex natural products.5 In this
framework, mild cyanide source such as Me3SiCN6 and
Et2AlCN7 are frequently involved with catalysts such as
Et3Al,6,9a Pd(OAc)2,8 and Lewis acids.9 Ionic liquid and
microwave have also been applied to this reaction in line
of the concept of green chemistry.10,11 Recently,
Shibasaki and co-workers developed an entirely distinct
Ni(0)-cyclooctdiene (COD) complex in the elegant syn-
thesis of Tamiflu,12 an anti-influenza drug, and subse-
quent Ni(0) and Gd(OTf)3 as the cooperative catalyst in
the 1,4-addition of Me3SiCN to aliphatic enones with
good substrate generality.13 The first catalytic enanti-
*
E-mail: fuxue.chen@bit.edu.cn; Fax: 0086-010-68918296
Received November 17, 2009; revised February 3, 2010; accepted March 10, 2010.
Project supported by the National Natural Science Foundation of China (No. 20972016) and Beijing Institute of Technology.
Chin. J. Chem. 2010, 28, 981— 987
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
981

Yang & Chen
FULL PAPER
gives an inferior result (Entry 6).
2—3 vs. Entry 1). Subsequent increasing the concentra-
－
1
tion of chalcone to 0.15 and 0.3 mol•L , the model re-
action produces lower yield even with a longer reaction
time (Entries 4—6 vs. Entries 1—3). Considering pro-
ton might be needed to complete the reaction sequence,
water as protonic additive is added (Entries 7—9). Dra-
matically, the reaction proceeds much fast and cleanly
affording almost quantitative yields with 4 equiv. of
water within 4 h even catalyst loading down to 1 mol%
at concentrated conditions (Entries 7—9). Additionally,
comparable result is obtained when the reaction is con-
ducted under open-to-air conditions (Entry 9).
Table 1 Screening in the model reaction
Entrya
Catalyst
Yieldb/%
1
2
3
4
5
6
none
KF•2H2O
Bu4NF
CsF
trace
41
75
92
CsCl
16
Table 3 Effects of catalyst loading and concentration of chal-
cone on the CsF-catalyzed 1,4-addition of Me3SiCN to chalcone
(1a)
CsOH•H2O
86
a
Reaction conditions: chalcone 1a (0.15 mmol), Me3SiCN (0.33
mmol, 2.2 equiv.), CsF (20 mol%), dioxane (1.5 mL), reflux, 5.5
h. b Isolated yield.
With CsF as the catalyst, the effects of solvent and
reaction temperature on the model reaction are investi-
gated (Table 2). First, various solvents are evaluated at
reflux temperature (Entries 1—4). When CH2Cl2 is used
as the solvent, no reaction happens (Entry 1). 30% yield
is obtained in THF (Entry 3) while trace product in
toluene (Entry 2). Although having similar boiling point
to toluene, dioxane gives the excellent yield of 92%
(Entry 4). Second, the effect of reaction temperature is
examined in dioxane. Decrease of reaction temperature
from 102 to 0 ℃ leads to sharp drop in yield (Entries
4—6). High temperature is required for high yield in
dioxane.
Concn.c/ Additiveb/
Entrya CsFb/mol%
Time/h Yieldd/%
－
1
(mol•L )
equiv.
1
2
3
4
5
6
7
8
9e
20
10
5
0.1
5.5
7
92
91
84
89
76
63
99
99
99
0.1
0.1
7
20
10
5
0.15
0.15
0.3
9.5
9.5
9.5
4
20
5
0.1
H2O (4)
H2O (4)
H2O (4)
0.3
4
1
0.3
4
a
Table 2 Effects of solvent and reaction temperature on the
CsF-catalyzed 1,4-addition of Me3SiCN to chalcone (1a)
Unless otherwise noted, all reactions are conducted with chal-
cone (1a) and Me3SiCN (2.2 equiv.) in refluxing dioxane under
b
c
d
argon. Relative to 1a. Concentration of chalcone. Isolated
yield. e Performed open to air.
To insight the role of additive, other proton resources
are introduced into the reaction mixture with results
listed in Table 4. Without any proton additive, the yield
is 52% (Entry 1). Increasing the amount of H2O from
0.3 to 1 equiv., the yield of 2a increases gradually from
59% to 70% (Entries 2 and 3). Other proton sources
such as alcohol and phenol (2,6-dimethylphenol) give
inferior yields (Entries 4 and 5). It implies that H2O is
not only used to provide proton.22 The optimum yield is
obtained with 4 equiv. of water (Entry 6). However,
using excessive amount of H2O reduces the yield (Entry
7).
Entrya
Solvent
CH2Cl2
toluene
THF
Temp./℃
Yieldb/%
1
2
3
4
5
6
40
110
66
0
trace
30
92
7
dioxane
dioxane
dioxane
102
40
0
0
a
Reaction conditions: chalcone 1a (0.15 mmol), Me3SiCN (0.33
mmol, 2.2 equiv.), catalyst (20 mol%), solvent (1.5 mL), 5.5 h.
b Isolated yield.
With optimal reaction conditions in hands: enone (0.3
mmol), Me3SiCN (2.2 equiv.), CsF (1 mol%), H2O (4
equiv.), dioxane (1 mL), substrate concentration (0.3
mol•L ), at reflux reaction temperature, the substrate
generality is evaluated (Table 5). In general, chalcone
derivatives give excellent yields (91%—99%) at varying
reaction rate (Entries 1—9). With electron-donating sub-
stituent, the reactions proceed slowly than chalcone
To obtain the optimum reaction conditions further
optimization focusing on catalyst loading and concen-
tration of chalcone is performed (Table 3). Reasonably,
as reducing catalyst loading from 20 mol% to 5 mol%
－
1
without any additive at 0.1 mol•L－ concentration of
1
chalcone, the yield of product 2a decreases gradually
from 92% to 84% with a longer reaction time (Entries
982
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Chin. J. Chem. 2010, 28, 981— 987

Highly Efficient Syntheses of β-Cyanoketones
Table 4 Effect of protonic additive on the CsF-catalyzed
1,4-addition of Me3SiCN to chalcone (1a)
is based on the thermodynamic stability,7 cyanide rear-
rangement14 and kinetic control.13 Although CsF has
been used to catalyze the 1,2-addition of Me3SiCN to
α,β-unsaturated ketones,17b no 1,2-adduct is produced by
TLC analysis during the course of the reaction under the
present reaction conditions. It is supposed that 1,2-
adducts should be rapidly converted into 1,4-adducts via
certain way14 if they are formed in this protocol.
To the mechanistic insight, O-trimethylsilyl cyano-
hydrin 3a, the 1,2-addition product,23 is prepared and
tested under the reaction conditions (Table 6). Those
results indicate that H2O presumably partly facilitates
reversion of in situ formed 1,2-adduct (3a) back to 1a in
the presence of CsF, which is followed by the subsequent
irreversible formation of 1,4-addition product 2a in 65%
yield (Entry 1 vs. Entry 2). Side evidence comes from
that the reversion is restrained by additional 2.2 equiv. of
Me3SiCN which would drive the equilibrium to left side
(Entry 3). However, no reaction occurs in the absence of
CsF (Entries 4 and 5). Referring to Entry 1 in Table 4, it
is concluded that water assists the catalyst CsF to convert
enone into 1,4-adduct completely (Scheme 2). So, the
key factors to the perfect 1,4-selectivity are: (1) CsF
rapidly catalyzing irreversible 1,4-addition at high tem-
perature, and (2) H2O facilitating reversion of the possi-
ble 1,2-addition in the presence of CsF.
Entrya
Additiveb
None
Yieldc/%
1d
2d
3
4d
5d
6
52
59
70
55
64
99
77
H2O (0.3 equiv.)
H2O (1 equiv.)
i-PrOH (1 equiv.)
DMP (1 equiv.)
H2O (4 equiv.)
H2O (0.2 mL)
7
a Conditions: 1a (62.5 mg, 0.3 mmol), CsF (0.5 mg, 0.003 mmol, 1
mol%), Me3SiCN (84 µL, 0.66 mmol, 2.2 equiv.), dioxane (1.0
mL), under argon, 4 h. b Relative to 1a. c Isolated yield. d Quenched
with 1 mol•L－ 1 HCl. DMP＝2,6-dimethylphenol.
(Entries 2—5 vs. Entry 1). On the other hand, electron-
deficient α,β-unsaturated enones are converted into
β-cyanoketones much faster (Entries 6—9). β-Alkyl
substituted enone 1j also gives excellent yield under the
optimal reaction conditions (Entry 10). However, ali-
phatic enones can not be converted to the product under
these conditions.
Table 6 Control experiments
Table 5 Scope of substrate
H2O
(x equiv.)b
Me3SiCN
(y equiv.)b
Entrya
1ac/% 2ac/% 4ad/%
Entrya
Product
Time/h Yieldb/%
1c,d
2a R1＝Ph, R2＝H
4
7
99
99
99
99
99
99
99
91
93
97
1
2
0
4
4
4
4
0
0
trace
trace
trace
0
0
65
10
0
0
0
0
0
0
2
2b R1＝o-MeOC6H4, R2＝H
2c R1＝m-MeOC6H4, R2＝H
2d R1＝p-MeOC6H4, R2＝H
2e R1＝p-MeC6H4, R2＝H
2f R1＝o-ClC6H4, R2＝H
2g R1＝o,p-Cl2C6H3, R2＝H
2h R1＝m-O2NC6H4, R2＝H
2i R1＝o-ClC6H4, R2＝NO2
2j R1＝Me, R2＝H
3
2.2
2.2
0
3
5
4e
5e
4
7
0
0
5
6
a
Reaction conditions: 3a (30.7 mg, 0.1 mmol), dioxane (1 mL),
6
1.5
1.5
1.5
1
under argon, 4 h. b Relative to 3a. c Isolated yield. d Monitored by
7
TLC. e Without CsF.
8
9
Scheme 2 Role of water
10
1.5
a
Conditions: enone (0.3 mmol), CsF (0.5 mg, 0.003 mmol, 1
mol%), Me3SiCN (84 µL, 0.66 mmol, 2.2 equiv.), H2O (22 µL,
b
1.2 mmol, 4 equiv.), dioxane (1.0 mL), under argon. Isolated
c
yield. Comparable results are obtained under open-to-air condi-
d
tion.
Comparable results are obtained with 1.5 equiv. of
Me3SiCN.
In the literature, 1,4-regioselectivity of this reaction
Chin. J. Chem. 2010, 28, 981— 987
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983

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FULL PAPER
General procedure for the 1,4-addition of Me3SiCN
On the basis of experimental results, CsF is proposed
to act as a bifunctional catalyst,24 in which Me3SiCN is
activated by fluoride ion in a manner of hypervalent
silicon intermediate and enone by cesium ion.25 A plau-
sible catalytic cycle is shown in Scheme 3. By taking
advantage of the intensive studies on hypervalent silicon
intermediates,25 transition state 5 is formed. In this
manner, the fluoride ion as a Lewis base might favor the
formation of a pentacoordinate silicon intermediate with
Me3SiCN, meanwhile, the cesium ion as a Lewis acid
might serve to activate the carbonyl substrate in the
manner of dual activation.24 The activated nucleophile
and electrophile make the 1,4-addition easily to give the
silyl enol ether 4 with high regioselectivity, which is
also promoted by the subsequent protonation of 4 fur-
nishing the corresponding product 2 and regenerating
catalyst CsF.
to enones 1a— 1j
After CsF (0.5 mg, 0.003 mmol, 1 mol%), enone (1,
0.3 mmol), and 1 mL dioxane were placed in a dry
Schlenk tube equipped with cold finger under argon,
Me3SiCN (84 µL, 0.66 mmol, 2.2 equiv.) and H2O (22
µL, 1.2 mmol, 4 equiv.) were added. The reaction mix-
ture was stirred at reflux until the reaction was com-
pleted (monitored by TLC). 2 mL H2O was added, and
the resulting mixture was extracted with EtOAc (5 mL)
(Caution! HCN generated in the reaction mixture is
highly toxic. Those operations should be conducted in a
well-ventilated hood). The extract was washed with wa-
ter, brine, dried over anhydrous Na2SO4, and concen-
trated. The crude products were purified by flash chro-
matography on silica gel (PE-EtOAc, 20∶1, V∶V,
unless otherwise noted) to afford pure products 2.
4-Oxo-2,4-diphenylbutanenitrile (2a)11
White
solid, yield 99%, m.p. 120—122 ℃ (Lit.11 122—125
Scheme 3 Proposed catalytic cycle
1
℃); H NMR (CDCl3, 400 MHz) δ: 3.52 (dd, J＝6.0,
18.0 Hz, 1H, NCCHCHAHBCO), 3.74 (dd, J＝8.0, 18.0
Hz, 1H, NCCHCHAHBCO), 4.57 (dd, J＝6.0, 8.0 Hz,
1H, NCCHCHAHBCO), 7.34—7.49 (m, 7H, ArH), 7.58
—7.62 (m, 1H, ArH), 7.92—7.94 (m, 2H, ArH); 13C
NMR (CDCl3, 100 MHz) δ: 31.9, 44.5, 120.6, 127.5,
128.1, 128.4, 128.8, 129.3, 133.9, 135.3, 135.8, 194.6;
－
1
IR (KBr) ν: 1681, 2236 cm .
2-(2-Methoxyphenyl)-4-oxo-4-phenylbutanenitrile
1
(2b)7 White solid, yield 99%, m.p. 84—86 ℃; H
NMR (CDCl3, 400 MHz) δ: 3.50 (dd, J＝4.8, 18.0 Hz,
1H, NCCHCHAHBCO), 3.65 (dd, J＝8.8, 18.0 Hz, 1H,
NCCHCHAHBCO), 3.87 (s, 3H, OCH3), 4.78 (dd, J＝
4.8, 8.8 Hz, 1H, NCCHCHAHBCO), 6.91—7.02 (m, 2H,
ArH), 7.31—7.35 (m, 1H, ArH), 7.45—7.51 (m, 3H,
ArH), 7.56—7.61 (m, 1H, ArH), 7.93—7.95 (m, 2H,
ArH); 13C NMR (CDCl3, 100 MHz) δ: 27.5, 42.2, 55.6,
111.0, 120.5, 121.1, 123.2, 128.1, 128.7, 129.0, 129.8,
Experimental
－
1
1H NMR spectra are recorded on a Bruker AVIII 400
133.6, 136.0, 156.3, 195.3; IR (KBr) ν: 1685, 2245 cm .
2-(3-Methoxyphenyl)-4-oxo-4-phenylbutanenitrile
(2c)7 White solid, yield 99%, m.p. 106—108 ℃;
1H NMR (CDCl3, 400 MHz) δ: 3.50 (dd, J＝6.0, 18.0
Hz, 1H, NCCHCHAHBCO), 3.72 (dd, J＝8.0, 18.0 Hz,
1H, NCCHCHAHBCO), 3.82 (s, 3H, OCH3), 4.55 (dd,
J＝6.0, 8.0 Hz, 1H, NCCHCHAHBCO), 6.86—6.88 (m,
1H, ArH), 6.96—7.02 (m, 2H, ArH), 7.28—7.32 (m, 1H,
ArH), 7.45—7.49 (m, 2H, ArH), 7.58—7.62 (m, 1H,
ArH), 7.92—7.94 (m, 2H, ArH); 13C NMR (CDCl3, 100
MHz) δ: 31.9, 44.5, 55.4, 113.3, 113.8, 119.6, 120.5,
128.1, 128.8, 130.4, 133.9, 135.8, 136.7, 160.2, 194.6;
1
spectrometer, operating at 400 MHz for H NMR, and
100 MHz for 13C NMR. Chemical shifts for H NMR
1
and 13C NMR spectra are reported as δ downfield from
Me4Si and relative to the signal of CDCl3. The IR spec-
tra are recorded on a PerkinElmer Spectrum One with
KBr pellets. The elemental analyses are performed on an
Elementar Vario MICRO CUBE instrument. All melting
points are determined on a XT4A melting point appara-
tus without correction. Analytical thin layer chromatog-
raphy (TLC) is performed using F254 pre-coated silica
gel plate. Column chromatography is performed with
silica gel (200—300 mesh). Petroleum ether (PE) used
has a boiling point range of 60—90 ℃.
－
1
IR (KBr) ν: 1678, 2236 cm .
2-(4-Methoxyphenyl)-4-oxo-4-phenylbutanenitrile
(2d)7 White solid, yield 99%, m.p. 111—113 ℃ (Lit.11
All reactions are carried out under argon atmosphere
using typical vacuum-line techniques unless otherwise
noted. Me3SiCN and CsF are purchased from Alfa Ae-
sar and used directly. All dry solvents are distilled under
argon prior to use. Enones 1a—1j are synthesized
according to reported procedure.26
1
113—114 ℃); H NMR (CDCl3, 400 MHz) δ: 3.49 (dd,
J＝6.4, 18.0 Hz, 1H, NCCHCHAHBCO), 3.73 (dd, J＝7.6,
18.0 Hz, 1H, NCCHCHAHBCO), 3.80 (s, 3H, OCH3),
4.53 (dd, J＝6.4, 7.6 Hz, 1H, NCCHCHAHBCO), 6.89—
6.92 (m, 2H, ArH), 7.33—7.36 (m, 2H, ArH), 7.45—
7.49 (m, 2H, ArH), 7.57—7.61 (m, 1H, ArH), 7.91—
984
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Chin. J. Chem. 2010, 28, 981— 987

Highly Efficient Syntheses of β-Cyanoketones
1
7.93 (m, 2H, ArH); 13C NMR (CDCl3, 100 MHz) δ: 31.2,
44.6, 55.4, 114.6, 120.9, 127.2, 128.1, 128.7, 128.8,
133.8, 135.8, 159.6, 194.7; IR (KBr) ν: 1677, 2234
℃; H NMR (CDCl3, 400 MHz) δ: 3.57 (dd, J＝4.4,
18.0 Hz, 1H, NCCHCHAHBCO), 3.71 (dd, J＝9.6, 18.0
Hz, 1H, NCCHCHAHBCO), 4.93 (dd, J＝4.4, 9.6 Hz,
1H, NCCHCHAHBCO), 7.33 — 7.40 (m, 2H, ArH),
7.44—7.46 (m, 1H, ArH), 7.69—7.71 (m, 1H, ArH),
8.10—8.13 (m, 2H, ArH), 8.32—8.35 (m, 2H, ArH);
13C NMR (CDCl3, 100 MHz) δ: 30.0, 42.9, 119.2, 124.1,
127.9, 129.2, 129.5, 130.2, 130.4, 132.1, 132.6, 139.9,
150.8, 193.1; IR (KBr) ν: 1691, 2252 cm . Anal. calcd
for C16H11ClN2O3: C 61.06, H 3.52, N 8.90; found C
61.88, H 3.84, N 8.87.
－
1
cm .
4-Oxo-4-phenyl-2-p-tolylbutanenitrile
(2e)11,27
White solid, yield 99%, 129—131 ℃ (Lit.11 135—137
1
℃); H NMR (CDCl3, 400 MHz) δ: 2.35 (s, 3H, CH3),
3.49 (dd, J＝6.4, 18.0 Hz, 1H, NCCHCHAHBCO), 3.70
(dd, J＝8.0, 18.0 Hz, 1H, NCCHCHAHBCO), 4.53 (dd,
J＝6.4, 8.0 Hz, 1H, NCCHCHAHBCO), 7.19 (d, J＝8.0
Hz, 2H, ArH), 7.31 (d, J＝8.0 Hz, 2H, ArH), 7.45—
7.48 (m, 2H, ArH), 7.57—7.61 (m, 1H, ArH), 7.91—
7.93 (m, 2H, ArH); 13C NMR (CDCl3, 100 MHz) δ: 21.0,
31.5, 44.6, 120.8, 127.4, 128.1, 128.8, 129.9, 132.3,
133.8, 135.8, 138.3, 194.7; IR (KBr) ν: 1674, 2239
－
1
2-Methyl-4-oxo-4-phenylbutanenitrile
(2j)14
Colorless oil, yield 97%; 1H NMR (CDCl3, 400 MHz) δ:
1.35 (d, J＝6.8 Hz, 3H, CH3), 3.14 (dd, J＝6.4, 17.2 Hz,
1H, NCCHCHAHBCO), 3.27 (dd, J＝6.4, 13.2 Hz, 1H,
NCCHCHAHBCO), 3.34 (m, 1H, NCCHCHAHBCO),
7.40—7.44 (m, 2H, ArH), 7.52—7.55 (m, 1H, ArH),
7.87—7.89 (m, 2H, ArH); 13C NMR (CDCl3, 100 MHz)
δ: 17.9, 20.5, 42.2, 122.6, 128.0, 128.8, 133.8, 135.9,
－
1
cm .
2-(2-Chlorophenyl)-4-oxo-4-phenylbutanenitrile
(2f)7,28 White solid, yield 99%, m.p. 100—102 ℃
1
(Lit.28 106—108 ℃); H NMR (CDCl3, 400 MHz) δ:
－
1
3.53 (dd, J＝4.8, 18.0 Hz, 1H, NCCHCHAHBCO), 3.68
(dd, J＝9.2, 18.0 Hz, 1H, NCCHCHAHBCO), 4.93 (dd,
J＝4.8, 9.2 Hz, 1H, NCCHCHAHBCO), 7.29—7.38 (m,
2H, ArH), 7.42—7.50 (m, 3H, ArH), 7.58—7.62 (m, 1H,
ArH), 7.67—7.69 (m, 1H, ArH), 7.94—7.96 (m, 2H,
ArH); 13C NMR (CDCl3, 100 MHz) δ: 30.1, 42.4, 119.7,
127.8, 128.1, 128.8, 129.5, 129.9, 130.3, 132.7, 133.9,
195.1; IR (film) ν: 1686, 2236 cm .
Conclusion
In conclusion, the highly regioselective 1,4-addition
of Me3SiCN to aromatic enones has been achieved with
good substrate generality. The 1,4-adducts are obtained
in excellent yields with 1 mol% of CsF as the catalyst
and 4 equiv. of H2O as the additive. Further mechanism
elucidation and extension to asymmetric version of this
protocol are under way in our group.
－
1
135.6, 194.4; IR (KBr) ν: 1686, 2247 cm .
2-(2,4-Dichlorophenyl)-4-oxo-4-phenylbutanenitri-
1
le (2g) White solid, yield 99%, m.p. 90—91 ℃; H
NMR (CDCl3, 400 MHz) δ: 3.52 (dd, J＝4.8, 18.0 Hz,
1H, NCCHCHAHBCO), 3.67 (dd, J＝9.2, 18.0 Hz, 1H,
NCCHCHAHBCO), 4.88 (dd, J ＝ 4.8, 9.2 Hz, 1H,
NCCHCHAHBCO), 7.33—7.36 (m, 1H, ArH), 7.45—
7.50 (m, 3H, ArH), 7.59—7.63 (m, 2H, ArH), 7.93—
7.95 (m, 2H, ArH); 13C NMR (CDCl3, 100 MHz) δ: 29.7,
42.2, 119.3, 128.08, 128.11, 128.9, 130.1, 130.5, 131.3,
133.5, 134.0, 135.3, 135.5, 194.1; IR (KBr) ν: 1682,
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2247 cm . Anal. calcd for C16H11Cl2NO: C 63.18, H
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