Synthesis of β-ketonitriles, α,β-alkynones and biscabinols from esters using tert-butoxide-assisted C(=O)-C (i.e., acyl-C) coupling under ambient conditions

Article abstract of DOI:10.1016/j.tet.2013.10.007

We demonstrated the synthesis of β-ketonitriles, α,β- alkynones, and biscarbinols using tert-butoxide-assisted C(CO)-C (i.e., acyl-C) coupling of esters under ambient conditions. tert-Butoxide-assisted C(CO)-C (i.e., acyl-C) coupling of esters with cyanomethylenes and acetylenes under transition metal-free ambient conditions gives β-ketonitriles, α,β-alkynones and/or aryl bis(phenylethynyl)carbinols in moderate-to-good yields. It is noteworthy that this is a rapid, facile, and efficient process under ambient conditions, and use of cheap and stable starting materials.

Full text of DOI:10.1016/j.tet.2013.10.007

Accepted Manuscript
Synthesis of β-Ketonitriles, α,β-Alkynones and Biscabinols from Esters Using tert-
Butoxide-assisted C(=O)-C (i.e., acyl-C) Coupling under Ambient Conditions
Bo Ram Kim, Hyung-Geun Lee, Seung-Beom Kang, Kwang-Ju Jung, Gi Hyeon Sung,
Jeum-Jong Kim, Sang-Gyeong Lee, Yong-Jin Yoon
PII:
S0040-4020(13)01541-X
10.1016/j.tet.2013.10.007
TET 24882
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 17 July 2013
Revised Date: 2 October 2013
Accepted Date: 4 October 2013
Please cite this article as: Kim BR, Lee H-G, Kang S-B, Jung K-J, Sung GH, Kim J-J, Lee S-G, Yoon
Y-J, Synthesis of β-Ketonitriles, α,β-Alkynones and Biscabinols from Esters Using tert-Butoxide-
assisted C(=O)-C (i.e., acyl-C) Coupling under Ambient Conditions, Tetrahedron (2013), doi: 10.1016/
j.tet.2013.10.007.
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Synthesis of β-Ketonitriles, α,β-Alkynones
and Biscabinols from Esters Using tert-
Butoxide-assisted C(=O)-C (i.e., acyl-C)
Coupling under Ambient Conditions
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Bo Ram Kim,a Hyung-Geun Lee,a Seung-Beom Kang,a Kwang-Ju Jung,a Gi Hyeon Sung,a Jeum-Jong
Kim,b Sang-Gyeong Lee,a Yong-Jin Yoon*a
aDepartment of Chemistry, Research Institute of Natural Sciences, Gyeongsang National University, Jinju 660-
701, Korea. Fax; 082-55-772-1489; E-mail: yjyoon@gnu.ac.kr
bAdvanced Solar Technology Research Department, Electronics and Telecommunications Research Institute,
Daejeon 305-700, Korea

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1
Tetrahedron
journal homepage: www.elsevier.com
Synthesis of β-Ketonitriles, α,β-Alkynones and Biscabinols from Esters Using tert-
Butoxide-assisted C(=O)-C (i.e., acyl-C) Coupling under Ambient Conditions
Bo Ram Kim,a Hyung-Geun Lee,a Seung-Beom Kang,a Kwang-Ju Jung,a Gi Hyeon Sung,a Jeum-Jong
Kim,b Sang-Gyeong Lee,a Yong-Jin Yoon*a
aDepartment of Chemistry, Research Institute of Natural Sciences, Gyeongsang National University, Jinju 660-701, Korea. Fax; 082-55-772-1489; E-mail:
yjyoon@gnu.ac.kr
bAdvanced Solar Technology Research Department, Electronics and Telecommunications Research Institute, Daejeon 305-700, Korea
ARTICLE INFO
ABSTRACT
Article history:
Received
We demonstrated the synthesis of β−ketonitriles, α,β-alkynones and biscarbinolsusing tert-
butoxide-assisted C(C=O)-C (i.e., acyl-C) coupling of esters under ambient conditions. tert-
Received in revised form
Accepted
Butoxide-assisted C(C=O)-C (i.e., acyl-C) coupling of esters with cyanomethylenes and
acetylenes under transition metal-free ambient conditions gives
β-ketonitriles, α,β-alkynones
Available online
and/or aryl bis(phenylethynyl)carbinols in moderate-to-good yields. It is noteworthy that this is a
rapid, facile and efficient process under ambient conditions, and use of cheap and stable starting
materials.
Keywords:
α,β-Alkynylketone
Aryl bis(phenylethynyl)carbinols
tert-Butoxide-assisted reaction
C(=O)-C Coupling
2009 Elsevier Ltd. All rights reserved
.
β
-Ketonitriles
intermediate,25 we attempted to develop the synthetic methods
using -ketonitriles and -alkynones from esters under ambient
conditions.
1. Introduction
-Ketonitriles1-3 and
β
α,β
β
α,β
-alkynones4-10 are useful synthetic
intermediate. They have also been used as key materials for the
synthesis of various heterocycles.1-4, 9-14 Several methods for the
2. Results and discussion
synthesis of
β-ketonitriles and α,β-alkynones have been
reported.5-24 However, these methods suffer from one or more
disadvantages such as the requirement of harsh reaction
conditions and metal catalysts and/or expensive additional
reagents. Therefore, significant academic efforts are underway to
develop more efficient and facile method using the low-priced
starting materials.
In order to evaluate the acyl sources under the literature
conditions,25 we first carried out the C(=O)-C coupling reactions
of seven carboxylic acid derivatives, namely, ethyl benzoate (1a),
methyl benzoate (2), phenyl benzoate (3), benzoic acid (4),
benzoyl chloride (5), benzoic anhydride (6) and benzamide (7)
with benzyl cyanide (8a). Fortunately, we found that the ethyl
ester provided the corresponding 3-oxo-2,3-diphenylpropanoate
(9a) at the best yield among the seven (Scheme 1). Whereas, the
benzamide (7) did not convert to 9a. Thus, we selected the ethyl
esters for the tert-butoxide-assisted C(=O)-C coupling reactions.
Esters are a very stable and inexpensive chemical species.
They are used for a variety of purposes in synthesis. Although the
ester function is an acyl source, the esters are not used generally
as the acylating agents due to their low reactivity. Therefore,
significant effort is ongoing in order to find more convenient and
effective methods for the preparation of the corresponding acyl
radicals or ions. Our research goal is the development of a
convenient and efficient method for the synthesis of
ketonitriles and -alkynones using C(=O)-C (i.e., acyl-C)
coupling of the esters under metal-free ambient conditions.
Herein we firstly describe a synthesis of -ketonitriles and α,β-
O
i) 2 KOtBu
O
ii) PhCH2CN(8a)
Y
CN
THF(tech.),a.t. in air
1a-7
9a
β-
α,β
1a
2
3
4
5
6
7
NH2
-
O2CPh
OEt OMe OPh OH Cl
Y =
9a(%)a
97
63
28 11
21
17
β
a Isolated yields. Average of two runs.
alkynones by tert-butoxide-assisted C(=O)-C coupling of esters
with benzyl (or alkyl) cyanides and acetylenes under transition
metal-free ambient condition. Inspired by recent our report of the
tert-butoxide-assisted amidation of esters via acyl radical
Scheme 1. tert-Butoxide-assisted C(=O)-C coupling of
carboxylic acid derivatives 1-7 with benzyl cyanide (8a).

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2
Tetrahedron
In addition, we attempted to evaluate the effect of the
In order to compare the yields of our reaction with the
Dieckmann-type reaction,26 we also performed two C(=O)-C
couplings under the different conditions (Scheme 2).
solvent for the reaction of ester with benzyl cyanide and phenyl
acetylene. Tetrahydrofuran showed the best results in both
reactions (Entry 5, Table 1; Entry 6, Table 2). Based on the
literature description25 and the results of solvent screening (Table
1 and 2), we selected the followings as an optimized conditions:
ester (1 equiv.) / KOtBu (2 equiv.) / cyanide or acetylene (1
equiv.) / air / THF(tech.) / ambient temperature system.
First, C(=O)-C coupling of 1a with 8a under our conditions
via benzoyl radical intermediate25 afforded 3-oxo-2,3-
diphenylpropionitrile (9a) at 97% yield, whereas the Dieckmann-
type reaction via cyanophenyl methanide gave 9a at 10% yield
(Scheme 2). On the other hand, the reaction of 1a with 8a using
KOtAmyl instead of KOtBu according to the literature14 under
same conditions gave 9a in 51% yield. In the coupling of ethyl
acetate (1b) with phenyl acetylene (10a) to give 4-phenylbut-3-
yn-2-one (11a), the yield of our process was also higher than that
of the Dieckmann-type process. In the C(=O)-C coupling of the
ester under our conditions, the radical path may be more
favorable than the anion path.
Table 1. Screening of solvents for the coupling of ethyl
benzoate with benzyl cyanide and KOtBu in air at ambient
temperaturea
O
O
CN
KOtBu
solvent
OEt
CN
9a
8a
1a
Time
(minute)
Entry Solvent
9a (%)b
1
2
3
4
5
6
7
8
n-hexane
40
20
26
23
39
97
10
7
cyclohexane
benzene
40
40
40
30
40
40
40
diethyl ether
tetrahydrofuran
dimethylformamide
dimethylsulfoxide
1,4-dioxane
Scheme 2. Reaction of ethyl benzoate (1a) or ethyl acetate (1b)
with benzyl cyanide (8a) or phenyl acetylene (10a) under our
conditions and the Dieckmann-type reaction conditions
8
To illustrate the versatility of the tert-butoxide-assisted
C(=O)-C coupling of esters, the C(=O)-C coupling of aliphatic
and aromatic esters with aryl (or alkyl) cyanides or acetylenes
was examined (Tables 3 and 4). The coupling of aromatic esters
1 and aliphatic esters with acetonitrile or butyronitrile under the
a KOtBu (2 equiv., 95%), Solvent (tech. involving about 0.2%
H2O), 1a (1 equiv.) and 8a (1 equiv.) in air at ambient
temperature. b All yields were isolated, pure material. Average of
two runs.
above conditions afforded the corresponding β-ketonitriles 9b-9f
at 79 – 91% yields (Entries 1-5, Table 3). Aliphatic and aromatic
esters were treated with benzyl cyanide (8a) under the same
Table 2. Screening of solvents for the coupling of ethyl
acetate with phenyl acetylene and KOtBu in air at ambient
temperature a
conditions to afford the corresponding
β-ketonitriles 9h-9j in
good yields except for ethyl acetate (Entries 7 – 9, Table 3).
Ethyl acetate (1b) was allowed to react with 8a under the same
conditions to afford the corresponding
β-ketonitriles 9g (26%)
and ethyl 3-oxobutanoate (21%) as the by-product (Entry 6,
Table 3).
In addition, the aliphatic esters such as ethyl acetate, ethyl 2-
methylpropanoate, and ethyl 3-phenylpropanoate were allowed to
react with phenyl acetylene (10a) or 1-ethynylcyclohex-1-ene
(10b) to afford the corresponding α,β-alkynones 11a-c and 11d
in 60 - 76% yields (Entries 1 – 3, and 5, Table 4). In contrast
C(=O)-C coupling of the aromatic esters such as ethyl benzoate,
ethyl 4-pyrydinecarboxylate, and ethyl 4-cyanobenzoate with 2
equiv. of phenyl acetylene (10a) under the same condition gave
the corresponding aryl bis(phenylethynyl)carbinols 12a-12d as
over addition product instead of α,β-alkynones at 23 - 86%
yields (Entries 6 – 9, Table 4). On the other hand, when ethyl 2-
methylpropanoate was allowed to react with 2 equiv. of phenyl
acetylene (10a) under the same conditions, the corresponding
alkynone (36%), the carbinol (3%) and unknown products (Entry
4, Table 4) were formed. These give evidence that the carbinol
was produced via the alkynone intermediate. When ethyl
benzoates and ethyl 4-pyridinecarboxlate were made to react with
1 equiv. of phenyl acetylene (10a), we did not detect the
corresponding α,β−alkynones. Under our conditions, the
aliphatic esters underwent the substitution, whereas the aromatic
esters undergo the addition of acyl radical after initial
substitution. These results may be due to the different reactivity
Time
(minute)
10
Entry Solvent
9a (%)b
1
2
n-hexane
2
toluene
10
10
10
10
5
5
3
benzene
no reaction
4
diethyl ether
methylene chloride
tetrahydrofuran
chloroform
4
5
6
6
76
7
10
10
no reaction
8
ethyl acetate
6
9
dimethyl formamide 10
50
10
1,4-dioxane
10
no reaction
a KOtBu (2 equiv., 95%), Solvent (tech. involving about 0.2%
H2O), 1b (1 equiv.) and 10a (1 equiv.) in air at ambient
temperature. b All yields were isolated, pure material. Average of
two runs.

ACCEPTED MANUSCRIPT
3
of carbonyls in the two α,β-alkynones. On the other hand, we
Table 3. Synthesis of β-ketonitriles by tert-butoxide-assisted
C(=O)-C coupling of esters with nitriles and KOtBu in
THF(tech.) in air at ambient temperaturea.
determined the structure of 12b according to the IR and NMR
spectral data, and X-ray crystallographic data (Figure 1).
9 (%)b
Entry
R
Ph
R1
Time
30min
30min
30min
2h
1
2
3
4
5
6
7
8
9
H
CH3CH2
H
9b (90)
9c (82)
9d (91)
9e (79)
9f (92)
9g (26)c
9h (75)
9i (81)
9j (90)
Ph
p-ClPh
p-ClPh
i-Pr
CH3CH2
H
30min
7h
CH3
Ph
i-Pr
Ph
8h
Ph(CH2)2
4-pyridyl
Ph
1h
Figure 1. ORTEP diagram of 12b (CCDC 949963)
Ph
1h
a KOtBu (2 equiv., 95%), THF (tech. involving about 0.2% H2O),
ester (1 equiv.) and cyanide (1 equiv.) in air at ambient
temperature. b All yields were isolated, pure material. Average of
two runs. cEthyl 3-oxobutanoate as by-product was formed in 21%
yield.
We first carried out the tert-butoxide-assisted C(=O)-C coupling
of the esters with benzyl (or alkyl) cyanides or acetylenes to
afford the corresponding β-ketonitriles, α,β-alkynones and aryl
bis(phenylethynyl)carbinols. Although metal-catalyzed C(=O)-C
coupling of thioesters have been reported,27-31 transition metal-
free C(=O)-C coupling of the esters with benzyl cyanide and
phenyl acetylene had not been yet achieved. The reactions in the
present study are the first example (to our knowledge) of tert-
butoxide-assisted C(=O)-C coupling of esters with alkynes and
cyanomethylenes via the radical intermediate. The structures of
all synthetic compounds were established by IR, NMR and X-ray
for 12b, also m/z of the molecular ion were obtained by HRMS.
Table 4. Synthesis of α,β-alkynones or
bis(phenylethnyl)carbinols by the tert-butoxide-assisted C(=O)-C
couplings of esters with acetylenesa
3. Conclusion
En
try
Isolated Yield (%)b
R
R1
Time
(min)
In conclusion, we developed a metal-free C(=O)-C coupling
reaction of esters with benzyl (or alkyl) cyanides or acetylenes
under ambient conditions to give the corresponding
11
12
β-
__
ketonitriles, -alkynones, and aryl bis(phenylethynyl)carbinols.
α,β
1
CH3
Ph
5
6
11a (76)
These are novel C(=O)-C coupling reaction via the acyl radical
intermediate derived from ester under a tert-butoxide-assisted
processes and ambient conditions. Interestingly, the
decarbonylation reaction, which generates a new carbon-centered
radical and carbon monoxide, was not observed under our
reaction conditions. This synthetic method is rapid, convenient,
and effective for a broad range of C(=O)-C coupling reactions of
esters. More importantly, this process can be achieved under
metal-free conditions in air using technical grade solvent. We
believe that the assisted C(=O)-C coupling would be applicable
in synthetic, medicinal, and industrial chemistry. Further work on
the theoretical study and the exploration of the tremendous
potential of esters and internal alkynes is under way in our
laboratory.
__
__
c
2
3
4
5
6
CH3
c-C6H9
Ph
11b (73)
11c (60)
11c (36)
11d (66)
__
i-Pr
5
i-Pr
Ph
30
5
3d
__
Ph(CH2)2
Ph
12a (86)
12b (73)
12c (40)
12d (23)
Ph
Ph
Ph
3
3
__
7
8
9
4-pyridyl
__
__
4-NCPh
Ph
Ph
3
PhCH=CH
10
4. Experimental section
aAcetylene (1 equiv. for aliphatic esters, 2 equiv. for aromatic
b
esters) in air at ambient temperature. All yields were isolated,
4.1. General
c
d
pure material. Average of two runs. 1-Cyclohexenyl. 2 equiv.
of phenyl acetylene was used. We also detected unknown
products.
NMR spectra were run in CDCl3 or DMSO-d6 on a 300MHz
instrument and recorded at the following frequencies: proton (1H,

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Tetrahedron
300MHz), carbon (13C, 75MHz). Chemical shifts are expressed
column (3 × 10 cm, n-hexane : ethyl acetate = 3 : 1, v/v) to give
pure 11a in 67% (0.94 g) yields.
in parts per million related to internal TMS and coupling constant
(J) are in hertz. Infrared specta were recorded on a Fourier
transform spectrometer. Mass spectra were recorded under
electron ionization (EI). Melting points were determined in open
4.5. Typical procedure for reaction of esters with cyanides to β-
ketonitilres 9 under the optimized conditions
glass
capillaries
and
are
uncorrected.
Thin-Layer
Ethyl ester 1 (6.65 mmol, 1 equiv.) was dissolved in THF (30
mL, technical grade involving 0.2% water) with stirring (about
230 rpm) at ambient temperature for 5 minutes. Potassium tert-
butoxide (1.57 g, 14.0 mmol, 95%, 2 equiv.) was added
immediately to the above THF solution. After stirring enough the
flask, the corresponding cyanide 8 (6.65 mmol, 1 equiv) was then
added. The resulting mixture was stirred at ambient temperature.
The reaction mixture was quenched by addition of water (50 mL)
and then stirred for 5 minutes. After adding ethyl acetate (40 mL)
and then HCl solution (1 mL, 12 M), the organic layer was
separated and dried over anhydrous magnesium sulfate. The
solvent was evaporated under reduced pressure, and the resulting
residue was applied to the top of an open-bed silica gel column
(for 9a - 9e, 9g - 9j : 3 × 15 cm, n-hexane : ethyl acetate (3:1,
Chromatography (TLC) analyses were performed using
precoated silica gel plates. Column chromatography was
performed with silica gel 60 as the stationary phase.
Crystallographic data for compounds 12b (CCDC 949963) can
be obtained free of charge from Cambridge Crystallographic
Data Centre. X-ray diffraction data were obtained using a
diffractometer equipped with a graphite monochromated MoK
α (λ = 0.71073 Å) radiation source and a scintilation counter
detector.
4.2. Reaction of benzoic acid derivatives with benzyl cyanide
Benzoic acid derivative (1-7, 6.65 mmol) was dissolved in
THF (30 mL, technical grade involving 0.2% water) with stirring
about 230 rpm) at room temperature for 5 minutes. Potassium
tert-butoxide (1.57 g, 14.0 mmol, 95%) was added immediately
to the above THF solution. After stirring enough the flask, benzyl
cyanide (8a, 0.78 g, 6.65 mmol) was then added. The resulting
mixture was stirred for 30 minute at room temperature. The
reaction mixture was quenched by addition of water (50 mL) and
then stirred for 5 minutes. After adding ethyl acetate (40 mL) and
then HCl solution (1 mL, 12 M), the organic layer was separated
and dried over anhydrous magnesium sulfate. The solvent was
evaporated under reduced pressure, and the resulting residue was
applied to the top of an open-bed silica gel column (3 × 15 cm).
The column was eluted with n-hexane : ethyl acetate (3:1, v/v).
Fractions containing the product were combined and evaporated
under reduced pressure to give 9a.
v/v); for 9f : 3.5 × 8 cm, CH2Cl2). Fractions containing the
product were combined and evaporated under reduced pressure to
give the corresponding β-ketonitriles.
4.5.1. 3-Oxo-2,3-diphenylpropanenitrile (9a)
Yield 97% (1.43 g), Yellow solid, mp 93-94 oC. (lit.38 mp 93-
94.5 oC), TLC (n-hexane : EtOAc, 3:1 (v/v)), RF = 0.33, IR
(KBr): 3062, 3030, 2924, 2250, 1689, 1595, 1580, 1448, 1228,
1
939, 763, 750 cm-1, H NMR (300 MHz, CDCl3): δ 5.66 (s, 1H),
7.34–7.58 (m, 8H), 7.93 (d, 2H, J = 7.7 Hz), 13C NMR (75 MHz,
CDCl3): δ 46.6, 116.8, 128.3, 129.1, 129.2, 129.3, 129.7, 130.4,
133.6, 134.5, 189.1, HRMS(EI) m/z: [M]+ calcd for C15H11NO
221.0841; found, 221.0843.
4.5.2. 3-Oxo-3-phenylpropanenitrile (9b)
o
Yield 90% (0.87 g), Yellow solid, mp 78-79 C. (lit.39 79-81
oC), TLC (CH2Cl2): RF = 0.51, IR (KBr): 3362, 3076, 2953, 2922,
2262, 2254, 1691, 1651, 1596, 1582, 1450, 1393, 1311, 1219,
756 cm-1, 1H NMR (300 MHz, CDCl3): δ 4.13 (s, 2H), 7.44 (t, 2H,
J = 7.8 Hz), 7.56–7.61 (m, 1H), 7.84 (d, 2H, J = 8.0 Hz), 13C
NMR (75 MHz, CDCl3): δ 29.7, 114.5, 128.5, 129.1, 134.2,
134.7, 188.0, HRMS(EI) m/z: [M]+ calcd for C9H7NO 145.0528;
found, 145.0529.
4.3. Dieckmann-type reaction of ethyl benzoate with benzyl
cyanide
A mixture of benzyl cyanide (8a, 0.985 mL, 8.536 mmol),
KOtBu (1.915g, 17.07mmol) and dry THF (30 mL) was stirred
for 30 minutes at room temperature in argon atmosphere. After
adding compound 1a (1.225 mL, 8.536 mmol), the mixture was
stirred for 2 hours at room temperature. Water (50 mL) and ethyl
acetate (30 mL) were added into the reaction mixture with
stirring. The organic layer was separated using separating funnel
and dried over anhydrous magnesium sulfate. The solvent was
evaporated under reduced pressure, and the resulting residue was
applied to the top of an open-bed silica gel column (3 × 15 cm, n-
hexane/ethyl acetate (3:1, v/v)). Fractions containing the product
were combined and evaporated under reduced pressure to give 9a
in 10% (0.15 g) yields.
4.5.3. 2-Ethyl-3-oxo-3-phenylpropanenitrile (9c)
Yield 82% (0.94 g), Clear liquid, TLC (n-hexane: ethyl
acetate = 3:1(v/v)): RF = 0.51, IR (KBr): 3070, 2973, 2942, 2682,
2553, 2086, 1689, 1600, 1454, 1421, 1326, 1290, 1274, 1180,
1126, 933, 806, 707 cm-1, 1H NMR (300 MHz, CDCl3): δ 1.38 (t,
3H, J = 7.44 Hz), 1.93- 2.12 (m, 2H), 4.43-4.47 (m, 1H), 7.47-
7.52 (m, 2H), 7.60-7.65 (m, 1H), 7.93-7.96 (m, 2H), 13C NMR
(75 MHz, CDCl3): δ 11.37, 23.68, 41.56, 117.4, 128.7, 129.1,
133.9, 134.4, 191.2, HRMS(EI) m/z: [M]+ calcd for C11H11NO
173.0841; found, 173.0842.
4.4. Dieckmann-type reaction of ethyl acetate with phenyl
acetylene
4.5.4. 3-Oxo-3-(p-chlorophenyl)propanenitrile (9d)
o
Yield 91% (0.96 g), Light yellow solid, mp 124-126 C. (lit.39
A mixture of phenyl acetylene (10a, 1.24 mL, 11.34 mmol),
KOtBu (1.34 g, 11.34 mmol) and dry THF (30 mL) was stirred
for 20 minutes at room temperature under argon atmosphere.
After adding compound 1b (1 g, 11.34 mmol), the mixture was
stirred for 20 minutes at room temperature. The reaction was
quenched by addition of cold water (20 mL). The mixture was
poured into mixture of ethyl acetate (80 mL). The organic layer
was separated and dried over anhydrous magnesium sulfate. The
solvent was evaporated under reduced pressure at 80oC below to
give crude 11a. The crude product was purified by silica gel
126-128 oC), TLC (CH2Cl2): RF = 0.75, IR (KBr): 3088, 2951,
2920, 1686, 1589, 1401, 1327, 1219, 1095, 1004, 821 cm-1, H
1
NMR (300 MHz, CDCl3): δ 4.08 (s, 2H), 7.51 – 7.54 (m, 2H),
7.87 – 7.90 (m, 2H), 13C NMR (75 MHz, CDCl3): δ 29.41, 113.5,
129.6, 129.9, 132.6, 141.5, 186.0, HRMS(EI) m/z: [M]+ calcd for
C9H6ClNO 179.0138; found, 179.0135.
4.5.5. 2-Ethyl-3-oxo-3-(p-chlorophenyl)propanenitrile (9e)
Yield 79% (0.95 g), Clear liquid, TLC (CH2Cl2): RF = 0.51, IR
(KBr): 3093, 2981, 2940, 2883, 1689, 1589, 1488, 1420, 1272,

ACCEPTED MANUSCRIPT
5
1
1241, 1093, 1012, 850, 759 cm-1, H NMR (300MHz, CDCl3): δ
1.15 (t, 3H, J1 = 7.36 Hz, J2 = 7.44 Hz), 1.94 – 2.14 (m, 2H), 4.51
– 4.49 (m, 2H), 7.46 – 7.49 (m, 2H), 7.91 (d, 2H, J = 8.48 Hz),
13C NMR (75 MHz, CDCl3): δ 11.32, 23.59, 41.60, 117.3, 129.4,
130.2, 132.3, 140.9, 190.2, HRMS(EI) m/z: [M]+ calcd for
C11H10ClNO 207.0451; found, 207.0458.
quenched by addition of water (20 mL). The mixture was
poured into mixture of ethyl acetate (60 mL) and ice powder (25-
30 g). The organic layer was separated and dried over anhydrous
magnesium sulfate. The solvent was evaporated under reduced
pressure at 80oC (for 11a, 11b) or 40oC (for 11c, 11d) below and
the resulting residue was applied to the top of an open-bed silica
gel column (for 11a-11c: 3 × 8 cm, n-hexane : ethyl acetate (3:1,
v/v); 11d : 3 × 5 cm, n-hexane : ethyl acetate (10:1, v/v).
Fractions containing the product were combined and evaporated
4.5.6. 4-Methyl-3-oxopentanenitrile (9f)
Yield 92% (0.88 g), Clear liquid, TLC (CH2Cl2): RF = 0.42, IR
(KBr): 2975, 2931, 2881, 2260, 1724, 1625, 1465, 1390, 1305,
1045, 939, 889 cm-1, 1H NMR (300M Hz, CDCl3): δ 1.11 – 1.21
(m, 6H), 2.77 – 2.82 (m, 1H), 3.68 – 3.71 (m, 2H), 13C NMR (75
MHz, CDCl3): δ 17.70, 30.18, 40.47, 114.3, 201.9, HRMS(EI)
m/z: [M]+ calcd for C6H9NO 111.0684; found, 111.0677.
under reduced pressure to give the corresponding α,β-Alkynones.
4.6.1. 4-Phenylbut-3-yn-2-one (11a)
Yield 76% (1.24 g), Yellow liquid, TLC (n-hexane : EtOAc,
3:1 (v/v)): RF = 0.62, IR (KBr): 3060, 2978, 2201, 1673, 1488,
1442, 1358, 1280, 1156, 976, 757 cm-1, 1H-NMR (300 MHz,
DMSO-d6): δ 2.41 (s, 3H), 7.41–7.61 (m, 5H), 13C-NMR (75
MHz, DMSO-d6): δ 33.0, 88.6, 89.6, 119.6, 129.3, 131.4, 133.2,
184.3, HRMS(EI) m/z: [M]+ calcd for C10H8O 144.0575; found,
144.0577.
4.5.7. 3-Oxo-2-phenylbutanenitrile (9g)
Yield 26% (0.47g), Light yellow solid, mp 75-77 oC. (lit.40 78-
o
79 C) , TLC (CH2Cl2): RF = 0.46, IR (KBr): 3133, 3069, 2962,
2921, 2215, 1636, 1593, 1496, 1388, 1363, 1334, 1303, 1279,
1237, 1115, 1069, 1021, 916, 907, 761 cm-1, 1H NMR (300 MHz,
CDCl3): δ 2.27 (s, 3H), 4.70 (s, 1H), 7.40 – 7.49 (m, 5H), 13C
NMR (75 MHz, CDCl3): δ 26.94, 51.51, 116.2, 127.9, 129.3,
129.6, 129.7, 196.4, HRMS(EI) m/z: [M]+ calcd for C10H9NO
159.0684; found, 159.0684.
4.6.2. 4-Cyclohexenylbut-3-yn-2-one (11b).
Yield 73% (0.62 g), Liquid, TLC (n-hexane : EtOAc, 3:1
(v/v)): RF = 0.74, IR (KBr): 3008, 2990, 2941, 2913, 2867, 2185,
1759, 1727, 1700, 1677, 1662, 1645, 1568, 1541, 1358, 1275,
1260, 1175, 1133, 1047, 1018, 981, 961, 922, 845, 763, 749 cm-1,
1H NMR (300 MHz, CDCl3), δ 1.58-1.71 (m, 4H), 2.14-2.19 (m,
4H), 2.36 (s, 3H), 6.44-6.47 (m, 1H), 13C NMR (75 MHz,
CDCl3): δ 21.1, 21.9, 26.1, 28.3, 32.7, 86.6, 92.9, 118.9, 142.4,
184.8, HRMS(EI) m/z: [M]+ calcd for C10H12O 148.0888; found,
148.0874.
4.5.8. 4-Methyl-3-oxo-2-phenylpentanenitrile (9h)
Yield 75% (0.47 g), Liquid, TLC (CH2Cl2): RF = 0.76, IR
(KBr): 3064, 3033, 2975, 2935, 2876, 2250, 2204, 1725, 1702,
1599, 1495, 1385, 1348, 1275, 1203, 1096, 1078, 1050, 1029,
957, 754, 716 cm-1, 1H NMR (300 MHz, CDCl3): δ 0.89 (d, 3H, J
= 6.6 Hz), 1.04 (d, 3H, J = 6.9 Hz ), 2.77–2.84 (m, 1H), 5.00 (s,
1H), 7.28–7.39 (m, 5H), 13C-NMR (75 MHz, CDCl3): δ 18.3,
18.7, 19.3, 38.6, 49.0, 116.8, 128.3, 128.5, 128.9, 129.1, 129.5,
130.2, 203.2, HRMS(EI) m/z: [M]+ calcd for C12H13NO
187.0997; found, 187.0998.
4.6.3. 1-Phenyl-4-methylpent-1-yn-3-one (11c)
Yield: 60% (0.89 g), Liquid, TLC (n-hexane : EtOAc, 3:1
(v/v)): RF = 0.58, IR (KBr): 3320, 3058, 2972, 2933, 2872, 2199,
1667, 1597, 1573, 1488, 1465, 1444, 1384, 1337, 1280, 1257,
1179, 1158, 1124, 1054, 996, 961, 920, 891, 814, 757, 728 cm-1.
1H NMR (300 MHz, CDCl3): δ 1.24–1.34 (m, 6H), 2.70-2.79 (m,
1H), 7.34–7.43 (m, 3H), 7.54–7.57 (m, 2H), 13C NMR (75 MHz,
CDCl3): δ 18.0, 43.1, 86.8, 91.6, 120.1, 128.6, 130.6, 132.5,
132.9, 192.0, HRMS(EI) m/z: [M]+ calcd for C12H12O 172.0888;
found, 172.0885.
4.5.9. 3-Oxo-2,5-diphenylpentanenitrile (9i)
Yield 81% (0.81 g), Light yellow solid, mp 73-74 oC (lit.41 73-
74oC) TLC (n-hexane : EtOAc = 3:1 (v/v): RF = 0.42, IR (KBr):
3086, 3062, 3029, 2934, 2251, 1729, 1716, 1603, 1496, 1454,
1266, 1077, 749 cm-1, H NMR (300 MHz, CDCl3): δ 2.81–2.97
1
(m, 4H), 4.62 (s, 1H), 7.07 (t, 2H, J = 6.6 Hz), 7.19–7.25 (m, 3H),
7.31–7.33 (m, 2H), 7.38–7.40 (m, 3H), 13C NMR (75 MHz,
CDCl3): δ 29.6, 41.2, 51.1, 116.1, 126.4, 128.0, 128.2, 128.6,
129.3, 129.5, 129.6, 139.7, 197.9, HRMS(EI) m/z: [M]+ calcd for
C17H15NO 249.1154; found, 249.1157.
4.6.4. 1,5-Diphenylpent-1-yn-3-one (11d)
Yield 66% (0.86g),Colorless liquid, TLC (n-hexane : EtOAc,
10:1 (v/v)): RF = 0.39, IR (KBr): 3060, 3027, 3005, 2988, 2925,
2202, 1699, 1670, 1490, 1454, 1362, 1276, 1262, 1092, 1071,
912, 747, 700 cm-1, 1H NMR (300 MHz, CDCl3): δ 3.01–3.10 (m,
4H), 7.20–7.25 (m, 2H), 7.26–7.48 (m, 6H), 7.56–7.60 (m, 2H),
13C NMR (75 MHz, CDCl3): δ 30.0, 47.0, 87.8, 91.2, 120.0,
126.3, 128.3, 128.5, 128.6, 130.7, 133.0, 140.2, 186.8,
HRMS(EI) m/z: [M]+ calcd for C17H14O 234.1045; found,
234.1044.
4.5.10. 3-Oxo-2-phenyl-3-(pyridine-4-yl)propanenitrile (9j)
o
Yield 90% (1.32 g), Light yellow solid, mp 113-115 C, TLC
(EtOAc): RF = 0.13, IR (KBr): 3092, 3053, 2200, 1605, 1593,
1305, 1017, 759 cm-1, H NMR (300 MHz, DMSO-d6): δ 7.20-
1
7.31 (m, 2H), 7.40-7.46 (m, 2H), 7.68 (d, 2H, J = 4.5 Hz), 7.79 (t,
2H, J = 7.9 Hz), 8.77-8.79 (m, 2H), 13C NMR (75 MHz, DMSO-
d6): δ 89.2, 120.9, 123.5, 127.5, 127.7, 128.9, 129.1, 133.0, 150.1,
166.2, HRMS(EI) m/z: [M]+ calcd for C14H10N2O 222.0793;
found, 222.0795.
4.7. General procedure for reaction of esters and acetylenes to
biscarbinols 12.
Ethyl ester (1, 6.65 mmol) was dissolved in cold THF (30 mL,
technical grade involving 0.2% water, cooling in ice bath for 5
minute). Potassium tert-butoxide (1.57 g, 14.0 mmol, 95%) and
acetylene (10, 13.3 mmol) were added immediately. After the
reaction was quenched by addition of water (20 mL) was then
added. The reaction mixture was poured into the mixture of ethyl
acetate (60 mL)/ice powder (25-30 g). The organic layer was
separated and dried over anhydrous magnesium sulfate. After
4.6. General procedure for reaction of esters and acetylenes to
α,β-alkynones 11.
Potassium tert-butoxide (2.68 g, 23.89 mmol, 95%, 2 equiv)
was dissolved in THF (30mL, technical grade involving 0.2%
water) and the THF solution of ethyl ester 1 and acetylene 10,
which was dissolved ester 1 (11.34 mmol, 1 equiv) and acetylene
10 (11.34 mmol, 1 equiv) in THF (10 mL), was dropped
o
evaporating the solvent under reduced pressure at 60 C below,
immediately for
1 minute in above solution at ambient
the residue was applied to the top of an open-bed silica gel
column (for 12a,12c, 12d: 4.5 × 15 cm, n-hexane : ethyl acetate
(3:1, v/v)) or washed with n-hexane (50 mL, for 12b) to give 12
temperature (for 11a-11c) or -15oC icebath (for 11d). After
stirring at ambient temperature, the reaction mixture was

ACCEPTED MANUSCRIPT
6
Tetrahedron
12. Beech. W. F.; Piggott, H. A. J. Chem. Soc. 1955, 423.
4.7.1. 1,3,5-Triphenylpenta-1,4-diyn-3-ol (12a)
13. Fleming, F. F.; Iyer, P. S. Synthesis, 2006, 893.
14. Ji, Y.; Trenkle, W. C.; Viwles, J. V. Org. Lett. 2006, 8, 1161.
15. Katritzky, A. R.; Abdel-Fatth, A. A. A.; Wang, M. J. Org. Chem.
2003, 68, 4932.
Yield 86% (1.72 g) ,Orange liquid, TLC (n-hexane : EtOAc,
3:1 (v/v)): RF = 0.51, IR (KBr): 3534, 3401, 3080, 3060, 3032,
2925, 2852, 2228, 1954, 1884, 1809, 1689, 1597, 1489, 1449,
1265, 1176, 1051, 1029, 940, 917, 775 cm-1, 1H NMR (300 MHz,
DMSO-d6): δ 7.32 (bs, OH, D2O exchangeable), 7.37–7.52 (m,
13H), 7.82–7.85 (m, 2H), 13C NMR (75 MHz, DMSO-d6): δ 64.7,
83.8, 91.3, 121.9, 126.0, 128.6, 128.8, 129.2, 129.5, 131.9, 143.6,
HRMS(EI) m/z: [M-H]+ calcd. for C23H15O 307.1123; found,
307.1124
16. Cahiez, G.; Gager, O.; Moyeux, A.; Laboue-Bertrand, B. Synthesis
2010, 4213.
17. Aijou, A. N.; Ferguson, G. Tetrahedron Lett. 2006, 47, 3719.
18. Maeda, Y.; Kakiuchi, N.; Matsumura, S.; Nishimura, T.;
Kawamura, T.; Uemura, S. J. Org. Chem. 2002, 67, 6718.
19. Dieter, R. K. Tetrahedron 1999, 55, 4177.
20. Oh, C. H.; Reddy, V. R. Tetrahedron Lett. 2004, 45, 8545.
21. Marko, I. E.; Southern, J. M. J. Org. Chem. 1990, 55, 3368.
22. Auge, J.; Lubin-Germain, N.; Seghrouchni, L. Tetrahedron Lett.
2003, 44, 819.
4.7.2. 1,5-Diphenyl-3-(pyridine-4-yl)penta-1,4-
diyn-3-ol (12b)
o
23. Liu, J.; Xie, X.; Ma, S. Synthesis 2012, 44, 1569.
24. Ajjou, A. N.; Ferguson, G. Tetrahedron Lett. 2006, 47, 3719.
25. Kim, B. R.; Lee, H. G.; Kang, S. B.; Sung, G. H.; Kim, J. J.; Park,
J. K.; Lee, S. G.; Yoon, Y. J. Synthesis 2012, 44, 42.
26. Kurti, L.; Czako, B. “Strategic Applications of Named Reactions
in Organic Synthesis”, Elsevier Academic Press, Amsterdam,
2005, pp138-139.
Yield 73% (1.48 g), White solid, mp 195-196 C, TLC (n-
hexane : EtOAc, 3:1 (v/v)): RF = 0.38, IR (KBr): 3092, 3054,
2786, 2655, 2437, 2226, 1603, 1566, 1487, 1441, 1414, 1321,
1263, 1220, 1190, 1098, 1058, 1008, 998, 963, 921, 821, 767,
750 cm-1, 1H NMR (300 MHz, DMSO-d6): δ 7.39–7.43 (m, 6H),
7.50–7.53 (m, 4H), 7.65 (bs, OH, D2O exchangeable), 7.78–7.80
(m, 2H), 8.67–8.69 (m, 2H), 13C NMR (75 MHz, DMSO-d6): δ
64.0, 84.5, 90.0, 120.8, 121.5, 129.2, 129.8, 132.0, 150.5, 151.9,
HRMS(EI) m/z: [M-H]+ calcd for C22H14NO 308.1075; found,
308.1070.
27. Liebeskind, L. S.; Srogl, J. J. Am. Chem. Soc. 2000, 122(45),
11260.
28. Procopcova, H.; Kappe, C. O. Angew. Chem.Int. Ed. 2008, 47,
3674.
29. Ngai, M. –Y.; Kong, J. –R.; Krische, M. J. J. Org. Chem. 2007,
72(4), 1063.
30. Yang, H.; Li, H.; Wittenberg, R.; Egi, M.; Huang, W.; Liebeskind,
L. S. J. Am. Chem. Soc. 2007, 129(5), 1132.
31. Villalobos, J. M.; Srogl, J.; Liebeskind, L. S. J. Am. Chem. Soc.
2007, 129(51), 15734.
4.7.3. 1-Cyanophenyl-3,5-diphenylpenta-1,4-diyn-3-
ol (12c)
Yield 40% (0.78 g), Light ivory solid, mp 132– 134 oC. TLC
32. Hanson, S. K.; Wu, R.; “Pete” Silks, L. A. Org. Lett. 2011, 13,
(n-hexane : EtOAc, 3:1 (v/v)): RF = 0.51, IR (KBr): 3411, 3097,
3079, 3057, 3022, 2990, 2816, 2229, 1598, 1573, 1489, 1443,
1402, 1265, 1186, 1167, 1069, 1035, 1019, 997, 942, 843, 755
cm-1, 1H NMR (300 MHz, DMSO-d6): δ 7.37–7.44 (m, 6H),
7.46–7.53(m, 4H), 7.65 (bs, OH, D2O exchangeable), 7.92–8.02
(m, 4H), 13C NMR (75 MHz, DMSO-d6): δ 64.4, 84.6, 90.2,
111.6, 119.0, 121.5, 127.0, 129.2, 129.8, 131.9, 133.1, 148.6,
HRMS(EI) m/z: [M]+ for C24H15NO 333.1154; found, 333.1153.
1908.
33. Caldwell, S. E; Porter, N. A.; J. Am. Chem. Soc. 1995, 117, 8676.
34. Nakanishi, W.; Ikeda, Y.; Iwamura, H. J. Org. Chem. 1982, 47,
2275.
35. Staab, H. A.; Rohr, W.; Graf, F. Chem. Ber. 1965, 98, 1122.
36. Hamada, Y.; Mizuno, A.; Ohno, T.; Shiori, T. Chem. Pharm. Bull.
1984, 32, 3683.
37. Stepanov, F. N.; Vul’fson, N. S. Org. Poluprod. i Krasiteli,
Nauch.-Issledovatel. Inst. Org. Poluprod. i Krasitelei im. K. E.
Voroshilova, Sbornik Statei. 1959, 1, 222.
38. Takahashi, K; Yamada, K; Iida, H. Bull. Chem. Soc. Jpn. 1978,
51(11), 3389.
4.7.4. 1,5-Diphenyl-3-(phenylethynyl)pent-1-en-4-
yn-3-ol (12d)
39. Al-Qalaf, F.; Mandani, F.; Abdelkhalik, M. M.; Bassam, A. A.
Molecules, 2009, 14(1),78.
40. Kamila, S.; Koh, B.; Biehl, E. R. Synth. Commun. 2005, 36(23),
3493.
Yield 23% (0.43 g), Liquid, TLC (n-hexane : EtOAc, 3:1
(v/v)): RF = 0.44, IR (KBr, CH2Cl2): 3418, 2226, 1642, 1601,
1489, 1444, 1366, 1272, 1099, 1031, 991, 963, 755 cm-1, 1H
NMR (300 MHz, CDCl3): δ 3.08 (bs, 1H, D2O exchangeable),
6.53 (d, 1H, J = 15.6 Hz), 7.15 (d, 2H, J = 15.6 Hz), 7.26 – 7.34
(m, 9H), 7.44-7.47 (m, 2H), 7.50-7.53(m, 4H), 13C NMR (75
MHz, CDCl3): δ 64.27, 85.22, 87.87, 122.0, 127.2, 128.4, 128.7,
128.9, 129.6, 131.0, 132.0, 135.8, HRMS (EI) m/z: [M-H]+ for
C25H17O 333.1279; found, 333.1281.
41. Ruggli, P.; Weis, P.; Rupe, H. Helv. Chim. Acta. 1946, 29, 1788.
References
1. Elnagdi, M. H.; Elmoghayar, M. R. H.; Elgemeie, G. E. H.
Synthesis, 1984, 1.
2. Laufer, S. A.; Zimmermann, W.; Ruff, K. J. J. Med. Chem. 2004,
47, 6311.
3. Hauser, C. R.; Eby, C. J. J. Am. Chem. Soc. 1957, 79, 728.
4. Cao, H.; Jiang, H.; Mai, R.; Zhu, S.; Qi, C. Adv. Synth. Catal.
2010, 143.
5. Lakshmi, B. V.; Kazmaier, U. Synlett 2010, 407.
6. Yoshikawa, T.; Mori, S.; Shindo, M. J. Am. Chem. Soc. 2009, 131,
2092.
7. Baxendale, I. R.; Schou, S. C.; Sedelmeier, J. Ley, S. V. Chem.
Eur. J. 2010, 16, 89.
8. Sheng, H.; Lin, S.; Huang, Y. Tetrahedron Lett. 1986, 27(40),
4893.
9. Sydnes, L. K.; Holmelid, B.; Sengee, M.; Hanstein, M. J. Org.
Chem. 2009,74, 3430.
10. Payette, J. N.; Yamamoto, H. Angew. Chem. Int. Ed. 2009, 48,
8060.
11. Sheng, H.; Lin, S.; Huang, Y. Synthesis 1987, 1022.

ACCEPTED MANUSCRIPT
Supporting Information
Synthesis of β-Ketonitriles, α,β-Alkynones and Biscabinols from
Esters Using tert-Butoxide-assisted C(=O)-C (i.e., acyl-C) Coupling
under Ambient Conditions
Bo Ram Kim,a Hyung-Geun Lee,a Seung-Beom Kang,a Kwang-Ju Jung,a Gi Hyeon Sung,a
Jeum-Jong Kim,b Sang-Gyeong Lee,a Yong-Jin Yoon*a
aDepartment of Chemistry, Research Institute of Natural Sciences, Gyeongsang National
University, Jinju 660-701, Korea. Fax; 082-55-772-1489; E-mail: yjyoon@gnu.ac.kr
bAdvanced Solar Technology Research Department, Electronics and Telecommunications R
esearch Institute, Daejeon 305-700, Korea
Contents
1. Spectral data for compounds 9, 11 and 12
Section
S1-S18

ACCEPTED MANUSCRIPT
1. Spectral data for compounds 9, 11 and 12
Figure 1. 1H(top) and 13C NMR(bottom) spectra in CDCl3 of compound 9a.
S1

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Figure 2. 1H(top) and 13C NMR(bottom) spectra in CDCl3 of compound 9b.
S2

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Figure 3. 1H(top) and 13C NMR(bottom) spectra in CDCl3 of compound 9c.
S3

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O
CN
Cl
9d
O
CN
Cl
9d
Figure 4. 1H(top) and 13C NMR(bottom) spectra in CDCl3 of compound 9d
S4

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Figure 5. 1H(top) and 13C NMR(bottom) spectra in CDCl3 of compound 9e.
S5

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Figure 6. 1H(top) and 13C NMR(bottom) spectra in CDCl3 of compound 9f.
S6

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Figure 7. 1H(top) and 13C NMR(bottom) spectra in CDCl3 of compound 9g.
S7

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Figure 8. 1H(top) and 13C NMR(bottom) spectra in CDCl3 of compound 9h.
S8

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O
CN
9i
O
CN
9i
Figure 9. 1H(top) and 13C NMR(bottom) spectra in CDCl3 of compound 9i.
S9

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Figure 10. 1H(top) and 13C NMR(bottom) spectra in CDCl3 of compound 9j.
S10

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Figure 11. 1H(top) and 13C NMR(bottom) spectra in DMSO-d6 of compound 11a.
S11

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Figure 12. 1H(top) and 13C NMR(bottom) spectra in CDCl3 of compound 11b.
S12

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O
11c
Figure 13. 1H(top) and 13C NMR(bottom) spectra in CDCl3 of compound 11c.
S13

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Figure 14. 1H(top) and 13C NMR(bottom) spectra in CDCl3 of compound 11d.
S14

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Figure 15. 1H(top) and 13C NMR(bottom) spectra in DMSO-d6 of compound 12a.
S15

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Figure 16. 1H(top) and 13C NMR(bottom) spectra in DMSO-d6 of compound 12b.
S16

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Figure 17. 1H(top) and 13C NMR(bottom) spectra in DMSO-d6 of compound 12c.
S17

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Figure 18. 1H(top) and 13C NMR(bottom) spectra in DMSO-d6 of compound 12d.
S18