Silver acetate catalyzed hydroamination of 1-(2-(sulfonylamino)phenyl)prop- 2-yn-1-ols to (Z)-2-methylene-1-sulfonylindolin-3-ols

Article abstract of DOI:10.1021/jo301198z

A method to prepare (Z)-2-methylene-1-sulfonylindolin-3-ols efficiently that relies on silver acetate catalyzed hydroamination of 1-(2-(sulfonylamino) phenyl)prop-2-yn-1-ols is reported. The reactions proceed rapidly at room temperature with catalyst loadings as low as 1 mol % under conditions that did not require the exclusion of air or moisture. The utility of this N-heterocyclic ring-forming strategy as a synthetic tool that makes use of unsaturated alcohols was exemplified by the conversion of the (Z)-2-methylene-1- sulfonylindolin-3-ol to examples of other members of the indole family of compounds.

Full text of DOI:10.1021/jo301198z

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pubs.acs.org/joc
Silver Acetate Catalyzed Hydroamination of 1‑(2-
(Sulfonylamino)phenyl)prop-2-yn-1-ols to (Z)-2‑Methylene-1-
sulfonylindolin-3-ols
Dewi Susanti, Fujiet Koh, Jeffrey Antonius Kusuma, Prasath Kothandaraman, and Philip Wai Hong Chan*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 637371, Singapore
S
* Supporting Information
ABSTRACT: A method to prepare (Z)-2-methylene-1-sulfony-
lindolin-3-ols efficiently that relies on silver acetate catalyzed
hydroamination of 1-(2-(sulfonylamino)phenyl)prop-2-yn-1-ols
is reported. The reactions proceed rapidly at room temperature
with catalyst loadings as low as 1 mol % under conditions that
did not require the exclusion of air or moisture. The utility of this
N-heterocyclic ring-forming strategy as a synthetic tool that
makes use of unsaturated alcohols was exemplified by the
conversion of the (Z)-2-methylene-1-sulfonylindolin-3-ol to examples of other members of the indole family of compounds.
(Scheme 1, eq 2).8,9 This process provides a convenient and
operationally straightforward synthetic method that provides
(Z)-2-methylene-1-sulfonylindolin-3-ols in excellent yields for a
INTRODUCTION
■
The indole ring system is a common structural motif found in a
myriad of bioactive natural compounds and pharmaceutical
products as well as optoelectronic functional materials.1−4
variety of substrates under mild conditions that did not require
the exclusion of air or moisture at room temperature. The
Added to this is their utility as substrates in strategies to various
application of this catalytic nitrogen ring formation process to
synthetically valuable products. While this has led to a number
the synthesis of other members of the indole family of
of impressive works to this class of compounds being developed
compounds is also presented.
over the years, those that focus on the synthesis of (Z)-2-
methylene-1-sulfonylindolin-3-ols have been less well ex-
plored.3 This is surprising given the potential of this member
of the indole family of compounds to serve as a versatile
building block in organic synthesis and their presence in a
number of bioactive natural products.4 For this reason, it is
desirable to establish new synthetic methods to prepare (Z)-2-
methylene-1-sulfonylindolin-3-ols in an efficient manner and
with selective control of substitution patterns under mild
conditions from acyclic substrates and a catalyst system that are
readily accessible, atom-economical, and low cost.
RESULTS AND DISCUSSION
■
Our studies began by examining the silver(I) catalyzed
hydroamination of 1a to establish the reaction conditions
(Table 1). This initially revealed that treating a MeCN solution
of 1a contained in an open round-bottom flask with 10 mol %
of AgOAc at room temperature for 15 min furnished 2a in near
quantitative yield (entry 1). Our studies subsequently showed
that a gradual decrease in the catalyst loading of AgOAc from
10 to 5 to 1 mol % also provided the N-heterocycle in near
quantitative yield albeit with the need for longer reaction times
of 1 and 18 h, respectively (entries 2 and 3). A similar outcome
was found on changing the solvent from MeCN to PhMe and
CH2Cl2 or performing the reaction with other inexpensive and
readily available silver(I) salts in place of AgOAc as the catalyst
(entries 5−6 and 8−13). On the other hand, the analogous
reactions with THF as the solvent or AgSbF6 as the catalyst
were found to give a markedly lower product yield of 17 and
27%, respectively (entries 4 and 7). Low product yields were
also obtained in control experiments with the Brønsted acid
catalysts TfOH and Tf2NH, whereas AcOH was found to result
in the recovery of the substrate in near quantitative yield
Lewis acid catalyzed reactions of unsaturated alcohols with
amine nucleophiles have come under increasing scrutiny in
recent years as efficient and convenient strategies for N-
heterocyclic synthesis.5−7 For example, we described one
method to prepare a variety of benzo-fused and 2,3-
disubstituted indoles that relied on gold(I) catalyzed cyclo-
isomerization of 1-(2-(tosylamino)phenyl)prop-2-yn-1-ols.2d In
the course of this work, we noticed in one control experiment
that when 1,3-diphenyl-1-(2-(tosylamino)phenyl)prop-2-yn-1-
ol (1a, R1 = R2 = Ph) was treated with AgOTf as the catalyst,
(Z)-benzylidene-3-phenyl-1-tosylindolin-3-ol 2a was obtained
as the product instead of the anticipated indenyl-fused indole
3a.2d In a continuation of this study, a significant expansion of
this chemistry with the discovery that under the appropriate
conditions, simple silver(I) salts can efficiently effect the
hydroamination of propargylic alcohols 1 is reported herein
Received: June 14, 2012
Published: August 16, 2012
© 2012 American Chemical Society
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Scheme 1. Silver-Catalyzed Cycloisomerization of 1-(2-(Tosylamino)phenyl)prop-2-yn-1-ols (1)
a
shown to be well tolerated and afford the corresponding
products 2b−2d in excellent yields of 87−97%. Similarly,
starting alcohols with an embedded naphthalene ring moiety
(1e) or a pendant of electron-withdrawing and electron-
donating containing phenyl ring on the carbinol carbon center
(1f-1h) were found to proceed well, furnishing 2e-2h in
excellent yields of 92−99%. Likewise, the present procedure
was found to work well for substrates 1i-1n where the
propargylic carbon center contained a thiophene, alkyl or
cycloalkane moiety or a phenyl group with an electron-
withdrawing or electron-donating substituent at the para
position. In these reactions, the corresponding (Z)-2-
methylene-1-sulfonylindolin-3-ol adducts 2i-2n were obtained
in 88−99% yield. The presence of a methyl and n-butyl group
on the respective carbinol and propargylic carbon centers was
found to have no influence on the outcome of the reaction with
2o afforded in 98% yield. Additionally, substrates with either a
pendant terminal alkyne moiety or where the carbinol carbon
center is a secondary alcohol, as in 1p−1u, were found to
proceed well and provide 2p-2u in 68−96% yield. Substrates
containing an Ns (1v), Ms (1w), Ac (1x) or Boc (1y) instead
of a Ts protecting group on the nitrogen center were also
examined under the standard conditions. In these experiments,
the corresponding N-sulfonyl protected products 2v and 2w
were both obtained in near quantitative yield. In contrast, those
with the Ac or Boc protecting group on the nitrogen center
were found to be unreactive and resulted in recovery of starting
materials in near quantitative yields.
A tentative mechanism for the present Ag(I) catalyzed (Z)-2-
methylene-1-sulfonylindolin-3-ol forming reaction is illustrated
in Scheme 2. This could initially involve activation of 1 through
coordination of the metal catalyst with the alkyne moiety of the
substrate to provide the silver(I) coordinated intermediate A.
This is the active species that undergoes the intramolecular
amination process involving anti addition of the sulfonamide
moiety to the alkyne bond to afford the vinyl silver complex
B.10 Protodemetalation of this putative organosilver complex
would then provide 2. The role of the silver(I) catalyst in
triggering the hydroamination process by coordinating to the
alkyne moiety of the substrate was supported by repeating the
Ag(I) catalyzed reaction of 1a in the presence of D2O under the
conditions described in Scheme 3. This test led to the
formation of d1-2a in 99% yield with 55% deuterium
incorporation.
Table 1. Optimization of the Reaction Conditions
b
entry
solvent
catalyst
AgOAc
yield (%)
c
1
MeCN
MeCN
MeCN
THF
99
d
e
2
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgSbF6
AgBF4
99 (99)
f
3
99
17
99
99
27
94
99
99
99
99
99
i
4
5
6
7
8
PhMe
CH2Cl2
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
g
9
Ag2CO3
AgNO3
AgOTf
Ag2O
10
11
h
12
13
14
15
16
AgNTf2
CH3CO2H
TfOH
11
11
Tf2NH
a
All reactions were performed with 0.2 mmol of 1a and 5 mol % of
b
catalyst at room temperature for 18 h. 1H NMR yield with CH2Br2 as
c
the internal standard. Reaction performed with 10 mol % catalyst
loading for 15 min. Reaction performed with 5 mol % catalyst loading
for 1 h. Value in parentheses denotes isolated product yield. Reaction
performed with 1 mol % catalyst loading. Reaction performed with
2.5 mol % catalyst loading. Reaction performed with 2.5 mol %
catalyst loading for 4.5 h. Recovery of starting material in near-
d
e
f
g
h
i
quantitative yield.
(entries 14−16). On the basis of the above results, reaction of
1a in the presence of 5 mol % of AgOAc in MeCN at room
temperature for 1 h contained in an open round-bottom flask
was deemed to provide the optimum conditions.
To define the generality of the present procedure, we next
turn our attentions to the reactions of a variety of 1-(2-
(sulfonylamino)phenyl)prop-2-yn-1-ols and the results are
summarized in Table 2. In general, these experiments
demonstrated that by using AgOAc as the catalyst, the reaction
conditions proved to be broad and a wide variety of substituted
(Z)-2-methylene-1-sulfonylindolin-3-ols could be furnished in
good to excellent yields. In our hands, no other side products
arising from 6-endo-trig cyclization of the substrate was
Next, the synthetic utility of the (Z)-2-methylene-1-
sulfonylindolin-3-ols obtained via the Ag(I) catalyzed hydro-
amination reaction was examined (Scheme 4). First, we
demonstrated that Brønsted acid catalyzed 1,3-allylic alcohol
isomerization (1,3-AAI) of 2a to the (1H-indol-2-yl)methanol
1
detected by TLC and H NMR analysis of the crude reaction
mixtures. Reactions of 1b-1d with an electron-donating or
electron-withdrawing substituent on the aniline ring were
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a
Table 2. Cycloisomerization of 1b−y Catalyzed by AgOAc
a
Unless otherwise stated, all reactions were performed in MeCN at room temperature for 1 h with 0.2 mmol of 1a in the presence of 5 mol % of
b
c
d
e
AgOAc. Values in parentheses denote isolated product yields. Reaction time = 1.5 h. Reaction time = 2.5 h. Reaction time = 3 h. Reaction time =
2 h. Recovery of starting material in near-quantitative yield.
f
Scheme 2. Proposed Mechanism
Scheme 4. Selective Transformations of (Z)-2-Methylene-1-
sulfonylindolin-3-ols 2a, 2p, and 2r
Scheme 3. Hydroamination of 1a in the Presence of D2O
Catalyzed by AgOAc
exposing the secondary alcohol 2r to the same conditions of 2
equiv of NIS in MeCN at reflux for 1 h (Scheme 4, eq 4).
4a could be achieved in 90% yield in the presence of 5 mol % of
p-TsOH·H2O under the conditions depicted in Scheme 4, eq
1.11 On the other hand, subjecting 2p to 5 equiv of DAST in
dichloromethane from −78 °C to room temperature over 4 h
provided the 2-fluoromethylindole 5p in 56% yield (Scheme 4,
eq 2).12 Treating the same starting material to 2 equiv of NIS
(N-iodosuccinimide) in MeCN at reflux for 1 h gave the 3-
iodomethyloxindole 6p in 87% yield (Scheme 4, eq 3).13,14
Finally, the indolin-3-one 7r could be furnished in 71% yield on
CONCLUSION
■
In summary, an efficient silver(I) catalyzed synthetic route to
(Z)-2-methylene-1-sulfonylindolin-3-ols based on intramolecu-
lar hydroamination of 1-(2-(sulfonylamino)phenyl)prop-2-yn-
1-ols has been reported. Achieved under mild conditions at
room temperature and without the need to exclude air or
moisture, the reaction was shown to be applicable to a wide
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pressure. Purification by flash column chromatography on silica gel
(10% EtOAc/n-hexane) gave the title compound.
range of alcohol substrates containing electron-withdrawing,
electron-donating and sterically demanding functional groups.
The synthetic utility of the present method to this partially
hydrogenated member of this indole family was also
demonstrated in 1,3-AAI, nucleophilic substitution, oxidation,
and rearrangement reactions.
General Experimental Procedure for the Preparation of 1v−
x. To a mixture of 2-aminobenzophenone (0.493 g, 2.5 mmol) and
pyridine (1.21 mL, 15 mmol) in dichloromethane (10 mL) was added
the corresponding sulfonyl chloride (3 mmol, for 1v and 1w) or acyl
chloride (3 mmol, for 1x) at 0 °C for 15 min. The reaction mixture
was then brought up to room temperature and stirred for 4 h. Upon
completion, the reaction mixture was quenched with 10% aqueous
HCl (10 mL) and extracted with dichloromethane (2 × 10 mL). The
combined organic layers were washed with brine (15 mL), dried over
MgSO4, concentrated under reduced pressure, and dried under
vacuum to afford the ketone as solid which was used directly for the
next step. To a stirred solution of diisopropylamine (0.21 mL, 1.5
mmol) in anhydrous THF at −20 °C was added n-butyllithium (2.0 M
in cyclohexane solution, 0.75 mL, 1.5 mmol) dropwise, and the
resulting solution was allowed to stirred at the same temperature for
10 min. On lowering the reaction temperature to −78 °C, the
appropriate alkyne (1 mmol) was added in a dropwise manner. The
resulting mixture was stirred at the same temperature for 1 h. The
ketone (0.5 mmol) obtained from the previous step was dissolved in
THF (2 mL), added to the reaction mixture dropwise, and allowed to
stir for 1 h at the same temperature. The reaction mixture was slowly
warmed up to room temperature and stirred for a further 1 h. Upon
completion, the reaction mixture was quenched by adding saturated
NH4Cl (10 mL) and extracted with EtOAc (2 × 10 mL). The
combined organic layers were washed with brine (20 mL), dried over
MgSO4, and concentrated under reduced pressure. Purification by
flash column chromatography on silica gel (15% EtOAc/n-hexane)
gave the title compound.
Experimental Procedure for the Preparation of 1y. To a
mixture of 2-aminobenzophenone (0.986 g, 5 mmol) and DMAP
(0.061 g, 0.5 mmol) in CH2Cl2 (10 mL) at 0 °C was added Boc2O
(1.378 mL, 6 mmol) and Et3N (0.766 mL, 5.5 mmol). The reaction
mixture was allowed to warm to room temperature and stirred for 15
h. Upon completion, H2O (10 mL) was added to the reaction mixture
and extracted with CH2Cl2 (2 × 10 mL). The combined organic layers
were washed with brine, dried over MgSO4 and concentrated under
reduced pressure to give the ketone as yellow liquid which was used
directly to the next step. To a stirred solution of diisopropylamine
(0.21 mL, 1.5 mmol) in anhydrous THF at −20 °C was added n-
butyllithium (2.0 M in cyclohexane solution, 0.75 mL, 1.5 mmol)
dropwise and the resulting solution was allowed to stirred at the same
temperature for 10 min. On lowering the reaction temperature to −78
°C, the appropriate alkyne (1 mmol) was added in a dropwise manner.
The resulting mixture was stirred at the same temperature for 1 h. The
ketone (0.5 mmol) obtained from the previous step was dissolved in
THF (2 mL) and added to the reaction mixture dropwise and allowed
to stir for 1 h at the same temperature. The reaction mixture was
slowly warmed up to room temperature and stirred for a further 1 h.
Upon completion, the reaction mixture was quenched by adding
saturated NH4Cl (10 mL) and extracted with EtOAc (2 × 10 mL).
The combined organic layers were washed with brine (20 mL), dried
over MgSO4, and concentrated under reduced pressure. Purification by
flash column chromatography on silica gel (12% EtOAc/n-hexane)
gave the title compound.
EXPERIMENTAL SECTION
■
General Considerations. All reactions were performed under
atmospheric conditions unless otherwise stated. Unless specified, all
reagents and starting materials were purchased from commercial
sources and used as received. Solvents were purified following standard
literature procedures. Analytical thin-layer chromatography (TLC) was
performed using precoated silica gel plates. Visualization was achieved
by UV light (254 nm). Flash chromatography was performed using
silica gel and gradient solvent system (EtOAc/n-hexane as eluent). 1H
and 13C NMR spectra were measured on 300 and 400 MHz NMR
spectrometers. Chemical shifts (ppm) were recorded with tetrame-
thylsilane (TMS) as the internal reference standard. Multiplicities are
given as: s (singlet), d (doublet), t (triplet), q (quartet), dd (doublet of
doublets), dt (doublet of triplets), tq (triplet of quartets) or m
(multiplet). The number of protons (n) for a given resonance is
indicated by nH, and coupling constants are reported as a J value in
Hz. Infrared spectra were recorded on an FTIR spectrometer. All
samples were examined as a thin film between NaCl salt plates. Solid
samples were examined as a thin film between NaCl salt plates using
chloroform as the solvent. Low-resolution mass spectra were
determined on a mass spectrometer and are reported in units of
mass to charge (m/z). High resolution mass spectra (HRMS) were
obtained using a TOF spectrometer using simultaneous electrospray
(ESI).
General Experimental Procedure for the Preparation of 1a−
o,r−u. To a solution of the appropriate 1-(2-aminophenyl)ketone or
aldehyde (1 mmol) in pyridine (0.5 mL) was added p-TsCl (0.23 g,
1.2 mmol) at room temperature under an nitrogen atmosphere. The
resulting solution was stirred for 4 h at room temperature. On
completion, the reaction mixture was quenched by adding H2O (5
mL), filtered, dried, and used directly for the next step. To a stirred
solution of diisopropylamine (0.21 mL 1.5 mmol) in anhydrous THF
at −20 °C was added n-butyllithium (2.0 M in cyclohexane solution,
0.75 mL, 1.5 mmol) dropwise, and the resulting solution was allowed
to stirred at the same temperature for 10 min. On lowering the
reaction temperature to −78 °C, the appropriate alkyne (1 mmol) was
added in a dropwise manner. The resulting mixture was stirred at the
same temperature for 1 h. The ketone (0.5 mmol) obtained from the
previous step was dissolved in THF (2 mL) and added to the reaction
mixture dropwise and allowed to stir for 1 h at the same temperature.
The reaction mixture was slowly warmed up to room temperature and
stirred for a further 1 h. Upon completion, the reaction mixture was
quenched by adding saturated NH4Cl (10 mL) and extracted with
EtOAc (2 × 10 mL). The combined organic layers were washed with
brine (20 mL), dried over MgSO4, and concentrated under reduced
pressure. Purification by flash column chromatography on silica gel
(10% EtOAc/n-hexane) gave the title compound.
General Experimental Procedure for the Preparation of
1p,q. To a solution of the appropriate 1-(2-aminophenyl)ketone (1
mmol) in pyridine (0.5 mL) was added p-TsCl (0.23 g, 1.2 mmol) at
room temperature under nitrogen atmosphere. The resulting solution
was stirred for 4 h at room temperature. On completion, the reaction
mixture was quenched by adding H2O (5 mL), filtered, dried, and used
directly for the next step. The solid (0.5 mmol) was dissolved in THF
(5 mL), and a solution of ethynylmagnesium bromide (0.5 M in THF
solution, 3 mL, 1.5 mmol) was added at room temperature, brought
up to reflux, and allowed to stir at this temperature for 3 h. Upon
completion, the reaction mixture was cooled to room temperature and
quenched by addition of saturated NH4Cl (10 mL). The reaction
mixture was extracted with EtOAc (2 × 10 mL), washed with brine
(20 mL), dried over MgSO4, and concentrated under reduced
General Experimental Procedure for Optimizing the Hydro-
amination of 1a. To a solution of 1a (0.2 mmol) in the appropriate
solvent (2 mL) was added the appropriate catalyst (0.01 mmol). The
reaction was stirred at room temperature and monitored by TLC
analysis. Upon completion, the reaction mixture was filtered through
Celite, washed with CH2Cl2 (10 mL) and concentrated under reduced
pressure. Purification by flash column chromatography on silica gel
(10% EtOAc/n-hexane) gave 2a.
General Experimental Procedure for AgOAc Catalyzed
Hydroamination of 1. To a solution of 1 (0.2 mmol) in acetonitrile
(2 mL) was added AgOAc (0.01 mmol). The reaction was stirred at
room temperature and monitored by TLC analysis. Upon completion,
the reaction mixture was filtered through Celite, washed with CH2Cl2
(10 mL), and concentrated under reduced pressure. Purification by
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flash column chromatography on silica gel (10% EtOAc/n-hexane)
gave 2.
136.3, 136.0, 134.1, 131.8, 130.3, 129.8, 129.4, 129.2, 128.9, 128.6,
128.4, 127.2, 127.0, 123.0, 121.6, 119.3, 89.7, 89.3, 75.1, 21.5.
N-(2-(1-(4-Bromophenyl)-1-hydroxy-3-phenylprop-2-yn-1-
yl)phenyl)-4-methylbenzenesulfonamide (1h):2d yield 64%;
Experimental Procedure for AgOAc Catalyzed Hydroamina-
tion of 1a in the Presence of D2O. To a solution of 1a (90.7 mg,
0.2 mmol) and D2O (18 μL, 1 mmol) in anhydrous acetonitrile (2
mL) was added AgOAc (0.01 mmol). The reaction was stirred at room
temperature under nitrogen atmosphere and monitored by by TLC
analysis. Upon completion, the reaction mixture was filtered through
Celite, washed with CH2Cl2 (10 mL) and concentrated under reduced
pressure. Purification by flash column chromatography on silica gel
(10% EtOAc/n-hexane) gave (d1-2a).
1
0.171 g; white solid; H NMR (CDCl3, 400 MHz) δ 8.57 (1H, brs),
7.71 (2H, t, J = 7.8 Hz), 7.43 (2H, d, J = 6.72 Hz), 7.21−7.34 (10H,
m), 7.03−7.07 (3H, m), 3.45 (1H, brs), 2.35 (3H, s); 13C NMR
(CDCl3, 100 MHz) δ 143.5, 142.0, 136.3, 136.0, 131.8, 131.6, 130.2,
129.9, 129.4, 129.2, 128.9, 128.4, 127.5, 127.0, 123.0, 122.4, 121.5,
119.2, 89.8, 89.2, 75.2, 21.6.
N-(2-(3-(4-Fluorophenyl)-1-hydroxy-1-phenylprop-2-yn-1-
yl)phenyl)-4-methylbenzenesulfonamide (1i):2d yield 94%; 0.222
N-(2-(1-Hydroxy-1,3-diphenylprop-2-yn-1-yl)phenyl)-4-
methylbenzenesulfonamide (1a):2d yield 90%; 0.204 g; white
solid; 1H NMR (CDCl3, 400 MHz) δ 8.89 (1H, brs), 7.58 (1H, d, J =
7.8 Hz), 7.52 (1H, d, J = 8.16 Hz), 7.40−7.46 (4H, m), 7.31 (2H, d, J
= 8.16 Hz), 7.23−7.28 (6H, m), 7.14−7.20 (1H, m), 6.93−6.97 (3H,
m), 4.24 (1H, brs), 2.23 (3H, s); 13C NMR (CDCl3, 100 MHz) δ
143.4, 143.1, 136.3, 136.0, 131.8, 130.9, 129.5, 129.4, 129.0, 128.7,
128.4, 128.1, 127.4, 126.1, 122.8, 122.0, 118.7, 90.0, 89.1, 75.5, 21.5.
N-(2-(1-Hydroxy-1,3-diphenylprop-2-yn-1-yl)-4-methyl-
phenyl)-4-methylbenzenesulfonamide (1b): yield 80%; 0.187 g;
1
g; white solid; H NMR (CDCl3, 400 MHz) δ 8.61 (1H, brs), 7.53
(2H, t, J = 7.32 Hz), 7.44−7.47 (4H, m), 7.39 (2H, d, J = 8.16 Hz),
7.32−7.35 (3H, m), 7.22 (2H, t, J = 7.8 Hz), 6.98−7.05 (5H, m), 3.23
(1H, brs), 2.32 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 161.7 (1C, d,
JC−F = 249 Hz), 142.7 (1C, d, JC−F = 74.5 Hz), 136.5, 136.0, 133.9,
133.8, 130.6, 129.6, 129.4, 128.7 (1C, d, JC−F = 11 Hz), 128.3, 127.4,
126.0, 122.8, 118.9, 115.6 (1C, d, JC−F = 22 Hz), 89.4, 88.3, 75.5, 21.5.
N-(2-(1-Hydroxy-1-phenyl-3-(4-(trifluoromethyl)phenyl)-
prop-2-yn-1-yl)phenyl)-4-methylbenzenesulfonamide (1j):
1
1
yield 70%; 0.183 g; yellow solid; mp 70−73 °C; H NMR (CDCl3,
white solid; mp 140−142 °C; H NMR (CDCl3, 400 MHz) δ 8.67
400 MHz) δ 8.67 (1H, brs), 7.56 (4H, s), 7.46−7.54 (4H, m), 7.33−
7.39 (5H, m), 7.22 (1H, t, J = 7.84 Hz), 6.98−7.04 (3H, m), 3.67 (1H,
brs), 2.31 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 143.5, 142.4,
136.5, 136.1, 132.1, 130.5, 129.7, 129.5, 128.8, 128.8, 128.4, 127.3,
126.1, 125.6, 125.3 (1C, q, JC−F = 3.6 Hz), 122.9, 119.0, 92.0, 87.7,
75.5, 21.5; IR (NaCl, neat) ν 3423, 3019, 2399, 1603, 1493, 1323,
1159, 1092 cm−1; HRMS (ESI) calcd for C29H23F3 NO3S (M+ + H)
522.1351, found 522.1360.
(1H, brs), 7.59 (2H, t, J = 8.8 Hz), 7.44−7.46 (2H, m), 7.38 (2H, d, J
= 8.24 Hz), 7.28−7.34 (5H, m), 7.19−7.24 (1H, m), 7.10 (2H, d, J =
8.04 Hz), 6.97−7.01 (3H, m), 3.32 (1H, brs), 2.38 (3H, s), 2.30 (3H,
s); 13C NMR (CDCl3, 100 MHz) δ 143.3, 139.9, 138.0, 136.5, 136.0,
131.8, 130.8, 129.4, 129.3, 129.0, 128.8, 128.4, 127.4, 126.0, 122.8,
121.9, 118.8, 89.9, 89.1, 75.4, 21.5, 21.2; IR (NaCl, neat) ν 3445, 3019,
2399, 1491, 1159 cm−1; HRMS (ESI) calcd for C29H26NO3S (M+ +
H) 468.1655, found 468.1633.
N-(2-(1-Hydroxy-1-phenyl-3-p-tolylprop-2-yn-1-yl)phenyl)-
4-methylbenzenesulfonamide (1k):2d yield 88%; 0.206 g; white
solid; 1H NMR (CDCl3, 400 MHz) δ 8.73 (1H, brs), 7.56 (2H, dd, J =
7.84, 16.4 Hz), 7.44−7.46 (2H, m), 7.29−7.36 (7H, m), 7.19 (1H, t, J
= 7.52 Hz), 7.10 (2H, d, J = 7.88 Hz), 6.96−7.00 (3H, m), 3.53 (1H,
brs), 2.33 (3H, s), 2.28 (3H, s); 13C NMR (CDCl3, 100 MHz) δ
143.4, 143.0, 139.3, 136.4, 136.0, 131.7, 130.8, 129.4, 129.1, 128.9,
128.6, 128.2, 127.4, 126.1, 122.8, 118.8, 89.5, 89.2, 75.5, 21.6, 21.5.
N-(2-(1-Hydroxy-1-phenyl-3-(thiophene-3-yl)prop-2-yn-1-
yl)phenyl)-4-methylbenzenesulfonamide (1l): yield 88%; 0.202
N-(4-Bromo-2-(1-hydroxy-1,3-diphenylprop-2-yn-1-yl)-
phenyl)-4-methylbenzenesulfonamide (1c):2d yield 96%; 0.256
1
g; white solid; H NMR (CDCl3, 300 MHz) δ 8.54 (1H, brs), 7.68
(2H, td, J = 7.71, 1.47 Hz), 7.42−7.45 (2H, m), 7.30−7.36 (8H, m),
7.21 −7.26 (2H, m), 7.03−7.08 (3H, m), 3.35 (1H, brs), 2.35 (3H, s);
13C NMR (CDCl3, 75 MHz) δ 143.6, 142.3, 136.2, 135.9, 131.8, 131.5,
130.4, 129.8, 129.5, 129.1, 129.1, 128.4, 127.6, 127.0, 123.1, 122.3,
121.7, 119.2, 89.7, 89.4, 75.1, 21.6.
N-(4-Chloro-2-(1-hydroxy-1,3-diphenylprop-2-yn-1-yl)-
phenyl)-4-methylbenzenesulfonamide (1d):2d yield 94%; 0.229
1
g; white solid; mp 126−127 °C; H NMR (CDCl3, 400 MHz) δ 8.64
1
g; yellow solid; H NMR (CDCl3, 300 MHz) δ 8.70 (1H, brs), 7.57
(1H, brs), 7.51−7.55 (3H, m), 7.45−7.47 (2H, m), 7.38 (2H, d, J =
8.24 Hz), 7.31−7.34 (3H, m). 7.27−7.30 (2H, m), 7.22 (1H, td, J =
1.28, 7.12 Hz), 7.13 (1H, d, J = 4.96 Hz), 6.97−7.04 (3H, m), 3.31
(1H, brs), 2.32 (3H, s); 13C NMR (CDCl3, 75 MHz) δ 162.3, 143.4,
142.8, 136.4, 136.0, 130.7, 129.9, 129.8, 129.4, 128.9, 128.7, 128.2,
127.4, 126.1, 125.6, 122.8, 120.8, 118.8, 89.4, 84.6, 75.6, 21.5; IR
(NaCl, neat) ν 3447, 3019, 2243, 1601, 1493, 1335, 1159, 1092 cm−1;
HRMS (ESI) calcd for C26H22NO3S2 (M+ + H) 460.1041, found
460.1049.
(1H, s), 7.42−7.50 (5H, m), 7.23−7.31 (8H, m), 7.14 (1H, dd, J =
2.22, 8.73 Hz), 6.97 (2H, d, J = 8.01 Hz), 3.88 (1H, brs), 2.28 (3H, s);
13C NMR (CDCl3, 75 MHz) δ 143.7, 142.3, 135.9, 134.5, 132.6, 131.8,
129.5, 129.3, 129.2, 128.8, 128.4, 128.2, 127.4, 126.0, 121.6, 120.0,
89.7, 89.1, 75.0, 21.5.
N-(3-(1-Hydroxy-1,3-diphenylprop-2-yn-1-yl)naphthalen-2-
yl)-4-methylbenzenesulfonamide (1e):2d yield 75%; 0.189 g; pale
yellow solid; 1H NMR ((CD3)2CO, 400 MHz) δ 9.31 (1H, brs), 8.35
(1H, s), 7.96 (1H, s), 7.87 (1H, d, J = 8.08, Hz), 7.79 (1H, d, J = 8.16
Hz), 7.46−7.53 (5H, m), 7.36−7.42 (9H, m), 7.23 (1H, s), 7.09 (2H,
d, J = 8 Hz), 2.88 (1H, brs), 2.26 (3H, s); 13C NMR ((CD3)2CO, 100
MHz) δ 143.6, 136.3, 134.1, 133.6, 131.5, 131.4, 129.4, 129.0, 128.9,
128.6, 128.5, 128.2, 128.0, 127.4, 127.2, 126.7, 125.8, 125.1, 122.2,
114.1, 90.6, 88.5, 75.1, 20.4.
N-(2-(3-Cyclopropyl-1-hydroxy-1-phenylprop-2-yn-1-yl)-
phenyl)-4-methylbenzenesulfonamide (1m):2d Yield 80%; 0.167
1
g; white solid; H NMR (CDCl3, 300 MHz) δ 8.58 (1H, brs), 7.50
(2H, d, J = 8.1 Hz), 7.25−7.38 (7H, m), 7.18 (1H, td, J = 1.44, 7.02
Hz), 7.05 (2H, d, J = 8.1 Hz), 6.97 (1H, td, J = 1.11, 7.68 Hz), 3.09
(1H, brs), 2.32 (3H, s), 1.28−1.36 (1H, m), 0.75−0.83 (4H, m); 13C
NMR (CDCl3, 75 MHz) δ 143.3, 143.2, 136.5, 135.8, 131.1, 129.4,
129.3, 128.7, 128.5, 128.0, 127.4, 125.9, 122.7, 118.6, 93.7, 76.4, 75.0,
21.5, 8.5, −0.4.
N-(2-(1-Hydroxy-3-phenyl-1-(p-tolyl)prop-2-yn-1-yl)phenyl)-
4-methylbenzenesulfonamide (1f):2d yield 82%; 0.192 g; pale
1
yellow solid; H NMR (CDCl3, 400 MHz) δ 7.55−7.60 (2H, m),
7.46−7.47 (2H, m), 7.40 (2H, d, J = 8.28 Hz), 7.29−7.35 (5H, m),
7.22 (2H, td, J = 8.32, 1.4 Hz), 7.11 (2H, d, J = 8.08 Hz), 6.97−7.03
(3H, m), 2.38 (3H, s), 2.31 (3H, s); 13C NMR (CDCl3, 100 MHz) δ
143.3, 140.0, 138.0, 136.4, 136.0, 131.8, 130.9, 129.4, 129.3, 129.3,
128.9, 128.9, 128.4, 127.4, 126.0, 122.8, 121.9, 118.8, 90.0, 89.0, 75.4,
21.5, 21.2.
N-(2-(1-Hydroxy-1-phenylhept-2-yn-1-yl)phenyl)-4-methyl-
benzenesulfonamide (1n):2d yield 80%; 0.173 g; white solid; H
1
NMR (CDCl3, 300 MHz) δ 8.67 (1H, brs), 7.58 (1H, dd, J = 1.41,
7.83 Hz), 7.51 (1H, d, J = 7.41 Hz), 7.24−7.38 (6H, m), 7.17 (1H, td,
J = 1.47, 8.25 Hz), 6.94−7.03 (3H, m), 3.38 (1H, brs), 2.30 (3H, s),
2.27 (2H, t, J = 7.17 Hz), 1.47−1.54 (2H, m), 1.34−1.42 (2H, m),
0.88 (3H, t, J = 7.26 Hz), 13C NMR (CDCl3, 75 MHz) δ 143.5, 143.3,
136.4, 135.8, 131.2, 129.4, 129.3, 128.8, 128.5, 127.9, 127.4, 125.9,
122.7, 118.6, 90.9, 81.4, 75.1, 30.4, 22.1, 21.5, 18.6, 13.6.
N-(2-(1-(4-Chlorophenyl)-1-hydroxy-3-phenylprop-2-yn-1-
yl)phenyl)-4-methylbenzenesulfonamide (1g):2d yield 93%;
1
0.227 g; white solid; H NMR (CDCl3, 400 MHz) δ 8.56 (1H, brs),
7.70 (2H, td, J = 7.92, 1.28 Hz), 7.44 (2H, dd, J = 7.84, 1.6 Hz), 7.26−
7.36 (8H, m), 7.18 (2H, d, J = 8.48 Hz), 7.04−7.07 (3H, m), 3.42
(1H, brs), 2.34 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 143.5, 141.5,
N-(2-(2-Hydroxyoct-3-yn-2-yl)phenyl)-4-methylbenzenesul-
1
fonamide (1o): yield 70%; 0.130 g; colorless oil; H NMR (CDCl3,
400 MHz) δ 9.19 (1H, brs), 7.76 (2H, d, J = 8.24 Hz), 7.57 (1H, dd, J
7170
dx.doi.org/10.1021/jo301198z | J. Org. Chem. 2012, 77, 7166−7175

The Journal of Organic Chemistry
Featured Article
= 1.2, 7.88 Hz), 7.53 (1H, d, J = 8.2 Hz), 7.16−7.26 (3H, m), 6.99
(1H, t, J = 7.44 Hz), 3.00 (1H, brs), 2.36 (3H, s), 2.26 (2H, t, J = 7
Hz), 1.60 (3H, s), 1.49−1.56 (2H, m), 1.38−1.46 (2H, m), 0.91 (3H,
t, J = 7.32 Hz); 13C NMR (CDCl3, 75 MHz) δ 143.7, 137.2, 135.6,
131.9, 129.6, 128.8, 127.4, 127.2, 123.3, 119.7, 87.8, 82.4, 71.9, 31.6,
30.5, 22.0, 21.5, 18.4, 13.6; IR (NaCl, neat) ν 3453, 3225, 2957, 2932,
2243, 1584, 1495, 1333, 1159, 1092 cm−1; HRMS (ESI) calcd for
C21H26NO3S (M+ + H) 372.1633, found 372.1652.
d, J = 8.48 Hz), 7.68 (1H, d, J = 8.12 Hz), 7.60 (1H, d, J = 7.6 Hz),
7.52 (2H, d, J = 8.56 Hz), 7.37 (4H, d, J = 7.24 Hz), 7.22−7.33 (7H,
m), 7.07 (1H, t, J = 7.52 Hz), 3.91 (1H, brs); 13C NMR (CDCl3, 100
MHz) δ 149.7, 144.8, 142.8, 135.1, 131.7, 131.4, 129.8, 129.4, 129.2,
128.7, 128.5, 128.3, 128.2, 125.9, 124.0, 123.9, 121.5, 119.3, 89.5, 75.6;
IR (NaCl, neat) ν 3453, 3264, 3019, 1605, 1531, 1491, 1348, 1261,
1043 cm−1; HRMS (ESI) calcd for C27H20N2O5SNa (M+ + Na)
507.0991, found 507.0997.
N-(2-(1-Hydroxy-1,3-diphenylprop-2-yn-1-yl)phenyl)-
methanesulfonamide (1w): yield 83%; 0.157 g; pale yellow solid;
mp 141−143 °C; 1H NMR (CDCl3, 400 MHz) δ 8.31 (1H, brs), 7.83
(1H, d, J = 7.8 Hz), 7.71 (1H, d, J = 8.08 Hz), 7.57 (2H, d, J = 7.28
Hz), 7.47 (2H, dd, J = 1.48, 7.52 Hz), 7.31−7.40 (7H, m), 7.17 (1H,
td, J = 0.8, 7.72 Hz), 3.74 (1H, brs), 2.09 (3H, s); 13C NMR (CDCl3,
100 MHz) δ 143.4, 135.9, 132.7, 131.8, 130.0, 129.2, 128.8, 128.5,
128.3, 126.0, 124.0, 121.6, 120.9, 89.6, 89.5, 75.1, 38.0; IR (NaCl,
neat) ν 3447, 3019, 2376, 1395, 1335, 1215, 1043 cm−1; HRMS (ESI)
calcd for C22H20NO3S (M+ + H) 378.1164, found 378.1156.
N-(2-(1-Hydroxy-1,3-diphenylprop-2-yn-1-yl)phenyl)-
acetamide (1x): yield 76%; 0.130 g; pale yellow solid; mp 72−75 °C;
1H NMR (CDCl3, 400 MHz) δ 8.68 (1H, brs), 7.96 (1H, d, J = 8 Hz),
N-(2-(1-Hydroxy-1-phenylprop-2-yn-1-yl)phenyl)-4-methyl-
benzenesulfonamide (1p):.2b,d yield 88%; 0.166 g; white solid; H
1
NMR (CDCl3, 400 MHz) δ 8.63 (1H, brs), 7.55 (2H, d, J = 6.4 Hz),
7.25−7.40 (7H, m), 7.21 (1H, t, J = 8.24 Hz), 7.04 (2H, d, J = 7.76
Hz), 6.99 (1H, t, J = 7.8 Hz), 3.81 (1H, brs), 2.88 (1H, s), 2.31 (3H,
s); 13C NMR (CDCl3, 100 MHz) δ 143.6, 142.4, 136.3, 135.9, 130.3,
129.7, 129.5, 129.0, 128.8, 128.4, 127.4, 126.0, 123.0, 119.0, 84.6, 77.9,
75.0, 21.6.
N-(2-(2-Hydroxybut-3-yn-2-yl)phenyl)-4-methylbenzenesul-
fonamide (1q): yield 71%; 0.112 g; white solid; mp 109−110 °C; 1H
NMR (CDCl3, 300 MHz) δ 9.13 (1H, brs), 7.75 (2H, d, J = 8.25 Hz),
7.55 (2H, d, J = 8.07 Hz), 7.17−7.25 (3H, m), 7.00 (1H, t, J = 7.77
Hz), 3.40 (1H, brs), 2.70 (1H, s), 2.35 (3H, s), 1.67 (3H, s); 13C
NMR (CDCl3, 75 MHz) δ 143.8, 137.1, 135.6, 130.8, 129.7, 129.1,
127.3, 127.3, 123.5, 119.9, 85.7, 74.8, 71.6, 31.2, 21.5; IR (NaCl, neat)
ν 3444, 3302, 3021, 2132, 1599, 1584, 1334, 1161, 1092 cm−1; HRMS
(ESI) calcd for C17H17NO3SNa (M+ + Na) 338.0827, found 338.0810.
N-(2-(1-Hydroxy-3-phenylprop-2-yn-1-yl)phenyl)-4-methyl-
benzenesulfonamide (1r): yield 85%; 0.160 g; pale yellow solid; mp
7.72 (1H, d, J = 7.48 Hz), 7.51 (2H, d, J = 7.12 Hz), 7.42 (2H, d, J =
6.68 Hz), 7.26−7.34 (7H, m), 7.11 (1H, t, J = 7.48 Hz), 4.44 (1H,
brs), 1.77 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 168.3, 143.3,
136.2, 132.8, 131.7, 129.2, 128.9, 128.5, 128.4, 128.1, 128.0, 125.9,
124.2, 123.8, 122.1, 90.1, 88.8, 75.0, 24.3; IR (NaCl, neat) ν: 3564,
3364, 3017, 2359, 1678, 1491, 1215, 1042 cm−1; HRMS (ESI) calcd
for C23H19NO2Na (M+ + Na): 364.1313, found 364.1313.
1
139−141 °C; H NMR (CDCl3, 400 MHz) δ 7.69 (2H, d, J = 7.72
Hz), 7.56 (1H, d, J = 7.36 Hz), 7.42−7.46 (3H, m), 7.26−7.34 (4H,
m), 7.11−7.17 (3H, m), 5.52 (1H, s), 2.87 (1H, brs), 2.34 (3H, s); 13C
NMR (CDCl3, 100 MHz) δ 143.9, 136.7, 135.5, 131.8, 130.9, 129.7,
129.0, 128.4, 127.2, 125.2, 122.8, 121.9, 88.5, 86.4, 63.4, 21.6; IR
(NaCl, neat) ν 3448, 3019, 2230, 1587, 1491, 1331, 1159, 1092 cm−1;
HRMS (ESI) calcd for C22H19NO3SNa (M+ + Na) 400.0983, found
400.0992.
N-(2-(1-Hydroxybut-2-yn-1-yl)phenyl)-4-methylbenzenesul-
fonamide (1s): yield 97%; 0.153 g; white solid; mp 128−130 °C; 1H
NMR (CDCl3, 400 MHz) δ 7.68 (2H, d, J = 8.2 Hz), 7.42−7.47 (2H,
m), 7.21−7.26 (3H, m), 7.10 (1H, t, J = 7.56 Hz), 5.21 (1H, d, J =
1.92 Hz), 2.38 (3H, s), 1.90 (3H, s); 13C NMR (CDCl3, 100 MHz) δ
143.9, 136.9, 135.5, 131.2, 129.7, 129.5, 128.2, 127.2, 125.0, 122.7,
85.3, 76.9, 63.2, 21.6, 3.8; IR (NaCl, neat) ν 3442, 3026, 2399, 1491,
1215, 1159, 1092 cm−1; HRMS (ESI) calcd for C17H18NO3S (M+ +
H) 316.1007, found 316.1005.
tert-Butyl (2-(1-hydroxy-1,3-diphenylprop-2-yn-1-yl)-
phenyl)carbamate (1y): yield 25%; 0.1 g; pale yellow solid; mp
1
67−69 °C; H NMR (CDCl3, 400 MHz) δ 7.73−7.77 (2H, m), 7.59
(1H, d, J = 7.68 Hz), 7.46 (2H, d, J = 7.56 Hz), 7.38 (2H, d, J = 5.76
Hz), 7.20−7.27 (7H, m), 6.97 (1H, t, J = 7.56 Hz), 3.39 (1H, brs),
1.24 (9H, s); 13C NMR (CDCl3, 100 MHz) δ 153.0, 143.2, 136.8,
131.8, 129.3, 128.9, 128.4, 128.3, 128.0, 127.7, 126.0, 122.8, 122.1,
90.2, 88.8, 79.8, 75.0, 28.2; IR (NaCl, neat) ν 3402, 2978, 1719, 1587,
1491, 1159, 1026 cm−1; HRMS (ESI) calcd for C26H25NO3Na (M+ +
Na) 422.1732, found 422.1732.
(Z)-2-Benzylidene-3-phenyl-1-tosylindolin-3-ol (2a):2d 0.089
1
g; pale yellow solid; H NMR (CDCl3, 400 MHz) δ 7.90 (1H, d, J =
8.08 Hz), 7.66 (2H, d, J = 7.2 Hz), 7.42 (1H, t, J = 7.8 Hz), 7.30−7.37
(4H, m), 7.14−7.23 (7H, m), 6.96−7.02 (3H, m), 6.26 (1H, s), 2.28
(3H, s); 13C NMR (CDCl3, 100 MHz) δ 145.4, 144.8, 142.5, 141.9,
138.2, 135.6, 133.0, 130.0, 129.6, 129.4, 128.3, 127.9, 127.9, 127.8,
127.3, 126.9, 126.7, 125.4, 124.8, 119.5, 81.8, 21.6.
N-(2-(1-Hydroxyhept-2-yn-1-yl)phenyl)-4-methylbenzene-
sulfonamide (1t): yield 71%; 0.127 g; yellow solid; mp 92−94 °C;
1H NMR (CDCl3, 300 MHz) δ 8.00 (1H, brs), 7.67 (2H, d, J = 8.22
(Z)-2-Benzylidene-5-methyl-3-phenyl-1-tosylindolin-3-ol
1
(2b): 0.091 g; white solid; mp 147−148 °C; H NMR (CDCl3, 400
Hz), 7.48 (1H, d, J = 7.44 Hz), 7.39 (1H, d, J = 7.92 Hz), 7.19−7.26
(3H, m), 7.09 (1H, t, J = 7.29 Hz), 5.24 (1H, s), 2.89 (1H, brs), 2.36
(3H, s), 2.24 (2H, t, J = 7.08 Hz), 1.46−1.54 (2H, m), 1.34−1.44 (2H,
m), 0.90 (3H, t, J = 7.2 Hz); 13C NMR (CDCl3, 75 MHz) δ 143.8,
136.8, 135.4, 131.5, 129.7, 129.4, 128.2, 127.2, 125.1, 122.7, 89.7, 77.8,
62.9, 30.5, 22.0, 21.5, 18.5, 13.6; IR (NaCl, neat) ν 3566, 3472, 3462,
3312, 3019, 2959, 2934, 1587, 1493, 1458, 1333, 1161, 1092 cm−1;
HRMS (ESI) calcd for C20H24NO3S (M+ + H) 358.1477, found
358.1467.
MHz) δ 7.90 (1H, d, J = 8.08 Hz), 7.66 (2H, d, J = 7.72 Hz), 7.42
(1H, td, J = 1.12, 8.2 Hz), 7.31−7.36 (4H, m), 7.20−7.24 (1H, m),
7.16 (1H, t, J = 7.44 Hz), 7.08 (2H, d, J = 8.04 Hz), 6.97−7.02 (5H,
m), 6.27 (1H, s), 2.29 (3H, s), 2.29 (3H, s); 13C NMR (CDCl3, 100
MHz) δ 145.4, 144.8, 141.9, 139.5, 138.3, 137.0, 135.7, 133.1, 129.9,
129.6, 129.3, 128.6, 128.3, 127.9, 127.7, 126.8, 126.6, 125.3, 124.6,
119.5, 81.8, 21.6, 21.1; IR (NaCl, neat) ν 3566, 3026, 2872, 1616,
1599, 1449, 1366, 1169, 1086 cm−1; HRMS (ESI) calcd for
C29H25NO3SNa (M+ + Na) 490.1453, found 490.1465.
N-(2-(3-Cyclopropyl-1-hydroxyprop-2-yn-1-yl)phenyl)-4-
methylbenzenesulfonamide (1u): yield 74%; 0.126 g; white solid;
mp 116−118 °C; 1H NMR (CDCl3, 300 MHz) δ 7.96 (1H, brs), 7.68
(2H, d, J = 8.25 Hz), 7.38−7.44 (2H, m), 7.20−7.26 (3H, m), 7.08
(1H, td, J = 0.87, 7.56 Hz), 5.20 (1H, s), 2.71 (1H, brs), 2.37 (3H, s),
1.25−1.32 (1H, m), 0.78−0.83 (2H, m), 0.73−0.76 (2H, m); 13C
NMR (CDCl3, 75 MHz) δ 143.9, 136.8, 135.5, 131.2, 129.7, 129.4,
128.2, 127.2, 125.0, 122.6, 92.8, 72.9, 63.1, 21.5, 8.4, −0.5; IR (NaCl,
neat) ν 3429, 3019, 2236, 1587, 1491, 1458, 1331, 1277, 1159, 1092
cm−1; HRMS (ESI) calcd for C19H20NO3S (M+ + H) 342.1164, found
342.1177.
(Z)-2-Benzylidene-5-bromo-3-phenyl-1-tosylindolin-3-ol
1
(2c): 0.093 g; white solid; mp 149−151 °C; H NMR (CDCl3, 400
MHz) δ 7.92 (1H, d, J = 8.12 Hz), 7.66 (2H, d, J = 7.52 Hz), 7.46
(1H, t, J = 7.4 Hz), 7.19−7.36 (8H, m), 7.06 (4H, t, J = 8.52 Hz), 6.99
(1H, d, J = 7.56 Hz), 6.27 (1H, s), 2.34 (3H, s); 13C NMR (CDCl3, 75
MHz) δ 145.0, 145.0, 141.9, 141.7, 135.3, 133.1, 131.0, 130.2, 129.6,
129.4, 128.5, 128.3, 127.9, 126.9, 125.2, 124.8, 121.6, 119.6, 81.6, 21.6;
IR (NaCl, neat) ν 3566, 3026, 2872, 1616, 1599, 1445, 1371, 1171,
1038 cm−1; HRMS (ESI) calcd for C28H22BrNO3SNa (M+ + Na)
554.0401, found 554.0394.
(Z)-2-Benzylidene-5-chloro-3-phenyl-1-tosylindolin-3-ol
1
(2d): 0.094 g; yellow solid; mp 102−107 °C; H NMR (CDCl3, 400
N-(2-(1-Hydroxy-1,3-diphenylprop-2-yn-1-yl)phenyl)-4-ni-
trobenzenesulfonamide (1v): yield 90%; 0.218 g; yellow solid; mp
83−85 °C; 1H NMR (CDCl3, 400 MHz) δ 9.08 (1H, brs); 7.90 (2H,
MHz) δ 7.85 (1H, d, J = 8.64 Hz), 7.63 (2H, d, J = 7.48 Hz), 7.32−
7.42 (4H, m), 7.22−7.26 (7H, m), 7.09 (2H, d, J = 8.2 Hz), 6.95 (1H,
7171
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The Journal of Organic Chemistry
Featured Article
d, J = 2.12 Hz), 6.24 (1H, s), 2.35 (3H, s); 13C NMR (CDCl3, 75
MHz) δ 145.1, 144.9, 141.9, 140.4, 140.1, 135.3, 132.8, 132.2, 130.1,
129.6, 128.4, 128.1, 127.9, 127.6, 126.6, 125.5, 125.3, 120.7, 81.7, 21.6;
IR (NaCl, neat) ν 3570, 3026, 2872, 1616, 1599, 1462, 1445, 1371,
1171, 1038 cm−1; HRMS (ESI) calcd for C28H22ClNO3SNa (M+ +
Na) 510.0907, found 510.0893.
1597, 1462, 1369, 1323, 1171, 1088, 1019 cm−1; HRMS (ESI) calcd
for C29H22F3NO3SNa (M+ + Na) 544.1170, found 544.1183.
(Z)-2-(4-Methylbenzylidene)-3-phenyl-1-tosylindolin-3-ol
1
(2k): 0.093 g; yellow solid; mp 137−139 °C; H NMR (CDCl3, 400
MHz) δ 7.92 (1H, d, J = 8.08 Hz), 7.57 (2H, d, J = 7.64 Hz), 7.43
(1H, t, J = 7.76 Hz), 7.37 (2H, d, J = 7.76 Hz), 7.13−7.24 (8H, m),
7.04 (2H, d, J = 7.96 Hz), 6.97 (1H, d, J = 7.52 Hz), 6.22 (1H, s), 2.34
(3H, s), 2.31 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 144.8, 144.5,
142.6, 142.0, 138.4, 137.8, 133.1, 132.6, 129.9, 129.6, 129.4, 128.6,
128.4, 127.9, 127.3, 126.8, 126.7, 125.3, 125.1, 119.6, 81.8, 21.6, 21.5;
IR (NaCl, neat) ν 3441, 3019, 2924, 1659, 1628, 1512, 1462, 1369,
1171, 1088, 1015 cm−1; HRMS (ESI) calcd for C29H25NO3SNa (M+ +
Na) 490.1453, found 490.1458.
(Z)-3-Phenyl-2-(thiophene-3-ylmethylene)-1-tosylindolin-3-
ol (2l): 0.091 g; yellow oil; 1H NMR (CDCl3, 300 MHz) δ 7.91 (1H,
d, J = 8.07 Hz), 7.71 (1H, d, J = 4.83 Hz), 7.36−7.45 (4H, m), 7.27−
7.28 (1H, m), 7.19 (6H, s), 6.96−7.04 (3H, m), 6.32 (1H, s), 2.31
(3H, s); 13C NMR (CDCl3, 75 MHz) δ 162.3, 144.8, 144.0, 142.0,
138.4, 136.4, 133.0, 129.9, 129.3, 128.7, 128.4, 127.9, 127.3, 126.9,
126.7, 126.5, 125.4, 124.4, 119.8, 119.5, 81.8, 21.6; IR (NaCl, neat) ν
3564, 3019, 2870, 1670, 1521, 1464, 1362, 1169, 1087, 1056, 1030
cm−1; HRMS (ESI) calcd for C26H21NO3S2Na (M+ + Na) 482.0861,
found 482.0869.
(Z)-2-Benzylidene-3-phenyl-1-tosyl-2,3-dihydro-1H-benzo-
1
[f ]indol-3-ol (2e): 0.1 g; yellow solid; mp 123−125 °C; H NMR
(CDCl3, 400 MHz) δ 8.31 (1H, s), 7.96 (1H, d, J = 8.24 Hz), 7.70
(3H, d, J = 7.76 Hz), 7.54 (1H, t, J = 7.2 Hz), 7.34−7.47 (6H, m),
7.18−7.27 (6H, m), 6.94 (2H, d, 8.04 Hz), 6.33 (1H, s), 2.25 (3H, s);
13C NMR (CDCl3, 100 MHz) δ 145.3, 144.6, 142.2, 139.4, 137.8,
135.7, 134.4, 133.6, 132.1, 129.5, 129.3, 128.4, 128.3, 128.0, 127.8,
127.5, 127.2, 126.9, 125.9, 125.0, 124.0, 116.3, 81.7, 21.5; IR (NaCl,
neat) ν 3570, 3026, 2872, 1616, 1599, 1506, 1445, 1371, 1038 cm−1;
HRMS (ESI) calcd for C32H25NO3SNa (M+ + Na) 526.1453, found
526.1454.
(Z)-2-Benzylidene-3-p-tolyl-1-tosylindolin-3-ol (2f): 0.086 g;
1
white solid; mp 145−147 °C; H NMR (CDCl3, 400 MHz) δ 7.91
(1H, d, J = 8.12 Hz), 7.66 (2H, d, J = 7.64 Hz), 7.43 (1H, t, J = 7.96
Hz), 7.32−7.38 (4H, m), 7.16−7.24 (2H, m), 7.10 (2H, d, J = 7.96
Hz), 7.04 (2H, d, J = 8 Hz), 7.00 (3H, d, J = 8.44 Hz), 6.27 (1H, s),
2.32 (3H, s), 2.30 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 145.4,
144.8, 141.9, 139.5, 138.4, 137.0, 135.7, 133.1, 129.9, 129.6, 129.3,
128.6, 128.3, 127.9, 127.7, 126.8, 126.6, 125.3, 124.6, 119.5, 81.8, 21.6,
21.1; IR (NaCl, neat) ν 3566, 3016, 2924, 1628, 1597, 1462, 1445,
1368, 1088 cm−1; HRMS (ESI) calcd for C29H25NO3SNa (M+ + Na)
490.1453, found 490.1457.
(Z)-2-(Cyclopropylmethylene)-3-phenyl-1-tosylindolin-3-ol
1
(2m): 0.082 g; yellow solid; mp 174−176 °C; H NMR (CDCl3, 400
MHz) δ 7.87 (1H, d, J = 8.12 Hz), 7.42 (2H, d, J = 8.16 Hz), 7.38
(1H, t, J = 7.64 Hz), 7.06−7.17 (8H, m), 6.90 (1H, d, J = 7.48 Hz),
4.75 (1H, d, J = 10.44 Hz), 2.40−2.48 (1H, m), 2.32 (3H, s), 0.94−
1.00 (1H, m), 0.81−0.88 (1H, m), 0.42−0.48 (1H, m), 0.24−0.30
(1H, m); 13C NMR (CDCl3, 100 MHz) δ 144.6, 143.9, 142.8, 142.1,
138.5, 133.3, 133.2, 129.7, 129.4, 128.2, 127.7, 127.0, 126.7, 126.5,
125.2, 119.6, 80.9, 21.6, 12.0, 8.3, 7.7; IR (NaCl, neat) ν 3568, 3019,
1670, 1636, 1597, 1449, 1364, 1169, 1090, 1018 cm−1; HRMS (ESI)
calcd for C25H23NO3SNa (M+ + Na) 440.1296, found 440.1303.
(Z)-2-Pentylidene-3-phenyl-1-tosylindolin-3-ol (2n): 0.085 g;
yellow oil; 1H NMR (CDCl3, 400 MHz) δ 7.85 (1H, d, J = 8.12 Hz),
7.36−7.40 (3H, m), 7.10−7.18 (6H, m), 7.05 (2H, d, J = 8.4 Hz), 6.92
(1H, d, J = 7.6 Hz), 5.41 (1H, t, J = 8 Hz), 2.58−2.65 (1H, m), 2.50−
2.55 (1H, m), 2.32 (3H, s), 1.23−1.35 (4H, m), 0.87 (3H, t, J = 6.8
Hz); 13C NMR (CDCl3, 100 MHz) δ 145.3, 144.6, 142.8, 142.1, 138.4,
133.5, 129.7, 129.4, 129.1, 128.1, 127.7, 127.1, 126.7, 126.5, 125.2,
119.4, 81.0, 31.4, 29.0, 22.4, 21.6, 13.9; IR (NaCl, neat) ν 3547, 3028,
2957, 1670, 1636, 1597, 1449, 1366, 1173, 1090, 1016 cm−1; HRMS
(ESI) calcd for C26H27NO3SNa (M+ + Na) 456.1609, found 456.1619.
(Z)-3-Methyl-2-pentylidene-1-tosylindolin-3-ol (2o): 0.073 g;
yellow oil; 1H NMR (CDCl3, 400 MHz) δ 7.80 (1H, d, J = 8.08 Hz),
7.34−7.39 (3H, m), 7.17−7.24 (2H, m), 7.12 (2H, d, J = 8.12 Hz),
5.75 (1H, t, J = 7.2 Hz), 2.59−2.61 (2H, m), 2.32 (3H, s), 1.36−1.47
(4H, m), 1.07 (3H, s), 0.93 (3H, t, J = 7.08 Hz); 13C NMR (CDCl3,
100 MHz) δ 144.7, 144.1, 141.2, 138.2, 133.6, 129.5, 129.4, 128.0,
126.4, 124.7, 123.1, 119.6, 76.4, 31.7, 28.9, 26.6, 22.5, 21.5, 14.0; IR
(NaCl, neat) ν 3523, 3019, 2871, 1670, 1521, 1464, 1362, 1171, 1088,
1056, 1030 cm−1; HRMS (ESI) calcd for C21H25NO3SNa (M+ + Na)
394.1453, found 394.1458.
(Z)-2-Benzylidene-3-(4-chlorophenyl)-1-tosylindolin-3-ol
1
(2g): 0.095 g; white solid; mp 94−95 °C; H NMR (CDCl3, 400
MHz) δ 7.92 (1H, d, J = 8.12 Hz), 7.66 (2H, d, J = 7.64 Hz), 7.46
(1H, t, J = 7.84 Hz), 7.34 (4H, t, J = 7.2 Hz), 7.19−7.27 (3H, m),
7.12−7.17 (4H, m), 7.05 (2H, d, J = 8.04 Hz), 6.99 (1H, d, J = 7.52
Hz), 6.26 (1H, s), 2.33 (3H, s); 13C NMR (CDCl3, 100 MHz) δ
145.0, 141.9, 141.1, 137.7, 135.3, 133.3, 133.1, 130.2, 129.6, 129.4,
128.3, 128.1, 128.1, 127.9, 126.9, 125.2, 124.8, 119.6, 81.6, 21.6; IR
(NaCl, neat) ν 3445, 3024, 2924, 1628, 1597, 1489, 1462, 1368, 1071
cm−1; HRMS (ESI) calcd for C28H22ClNO3SNa (M+ + Na) 510.0907,
found 510.0889.
(Z)-2-Benzylidene-3-(4-bromophenyl)-1-tosylindolin-3-ol
1
(2h): 0.105 g; yellow solid; mp 105−107 °C; H NMR (CDCl3, 400
MHz) δ 7.91 (1H, d, J = 8.12 Hz), 7.66 (2H, d, J = 7.64 Hz), 7.45
(1H, t, J = 7.96 Hz), 7.18−7.35 (8H, m), 6.98−7.06 (5H, m), 6.28
(1H, s), 2.32 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 145.0, 145.0,
141.9, 141.7, 137.6, 135.3, 133.1, 131.0, 130.2, 129.6, 129.4, 128.5,
128.3, 127.9, 127.0, 125.2, 124.8, 121.6, 119.6, 81.6, 21.6; IR (NaCl,
neat) ν 3445, 3019, 2924, 1628, 1597, 1489, 1462, 1370, 1171, 1088,
1011 cm−1; HRMS (ESI) calcd for C28H22BrNO3SNa (M+ + Na)
554.0401, found 554.0407.
(Z)-2-(4-Fluorobenzylidene)-3-phenyl-1-tosylindolin-3-ol
1
(2i): 0.083 g; white solid; mp 162−163 °C; H NMR (CDCl3, 400
MHz) δ 7.90 (1H, d, J = 8.08 Hz), 7.65 (2H, t, J = 7.56 Hz), 7.43 (1H,
t, J = 7.8 Hz), 7.36 (2H, d, J = 7.92 Hz), 7.16−7.24 (6H, m), 6.97−
7.05 (5H, m), 6.22 (1H, s), 2.31 (3H, s); 13C NMR (CDCl3, 100
MHz) δ 160.8 (1C, d, JC−F = 247 Hz), 145.2, 144.9, 141.8 (1C, d, JC−F
= 62 Hz), 138.2, 133.0, 131.6, 131.4, 131.3, 130.0, 129.4, 128.3, 128.0,
127.4, 126.9, 126.7, 125.4, 123.7, 119.5, 114.8 (1C, d, JC−F = 21 Hz),
81.8, 21.6; IR (NaCl, neat) ν 3445, 3019, 2924, 1636, 1603, 1509,
1462, 1171, 1088 cm−1; HRMS (ESI) calcd for C28H22FNO3SNa (M+
+ Na) 494.1202, found 494.1208.
2-Methylene-3-phenyl-1-tosylindolin-3-ol (2p): 0.066 g; white
solid; mp 160−161 °C; 1H NMR (CDCl3, 400 MHz) δ 7.97 (1H, d, J
= 8.28 Hz), 7.59 (2H, d, J = 8.04 Hz), 7.37 (1H, t, J = 7.84 Hz), 7.01−
7.16 (7H, m), 6.92 (2H, d, J = 7.68 Hz), 5.88 (1H, s), 4.91 (1H, s),
2.37 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 153.4, 144.8, 143.6,
140.9, 135.4, 134.0, 130.3, 129.6, 127.9, 127.4, 127.2, 125.6, 125.5,
125.2, 116.4, 101.6, 80.7, 21.6; IR (NaCl, neat) ν 3441, 3019, 2924,
1638, 1628, 1601, 1462, 1362, 1171, 1088, 1011 cm−1; HRMS (ESI)
calcd for C22H19NO3SNa (M+ + Na) 400.0983, found 400.0997.
3-Methyl-2-methylene-1-tosylindolin-3-ol (2q): 0.061 g; color-
less oil; 1H NMR (CDCl3, 400 MHz) δ 7.87 (1H, d, J = 8.24 Hz), 7.57
(2H, d, J = 8.12 Hz), 7.26−7.37 (2H, m), 7.13−7.18 (3H, m), 5.78
(1H, s), 5.14 (1H, s), 2.34 (3H, s), 1.17 (3H, s); 13C NMR (CDCl3,
75 MHz) δ 152.8, 144.7, 140.0, 135.4, 134.0, 129.9, 129.4, 127.3,
125.3, 123.3, 116.6, 98.6, 28.9, 21.5; IR (NaCl, neat) ν 3581, 3019,
(Z)-3-Phenyl-1-tosyl-2-(4-(trifluoromethyl)benzylidene)-
indolin-3-ol (2j): 0.1 g; white solid; mp 178−179 °C; 1H NMR
(CDCl3, 400 MHz) δ 7.91 (1H, d, J = 8.12 Hz), 7.74 (2H, d, J = 8.08
Hz), 7.56 (2H, d, J = 8.12 Hz), 7.45 (1H, t, J = 7.8 Hz), 7.35 (2H, d, J
= 8.04 Hz), 7.18−7.24 (6H, m), 6.99−7.04 (3H, m), 6.27 (1H, s),
2.31 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 147.6, 145.1, 142.2,
141.7, 139.4, 137.8, 132.9, 130.2, 129.7, 129.4, 129.4, 128.3, 128.0,
127.5, 127.0, 126.6, 125.4, 124.8(1C, q, J = 3.71 Hz), 122.8, 119.4,
81.9, 21.6; IR (NaCl, neat) ν 3564, 3019, 2924, 1659, 1628, 1616,
7172
dx.doi.org/10.1021/jo301198z | J. Org. Chem. 2012, 77, 7166−7175

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Featured Article
2976, 2924, 1659, 1603, 1462, 1360, 1173, 1090 cm−1; HRMS (ESI)
calcd for C17H17NO3SNa (M+ + Na) 338.0827, found 338.0839.
(Z)-2-Benzylidene-1-tosylindolin-3-ol (2r): 0.065 g; yellow
Phenyl(3-phenyl-1-tosyl-1H-indol-2-yl)methanol (4a).2d To a
stirred solution of 2a (90.7 mg, 0.2 mmol) in acetonitrile (2 mL) was
added p-TsOH.H2O (1.9 mg, 0.01 mmol) at atmospheric condition.
The reaction mixture was allowed to stir for 3 h at room temperature.
Upon completion, the reaction mixture was added H2O (5 mL),
extracted with EtOAc (2 × 10 mL), washed with brine (20 mL), dried
over MgSO4, and concentrated under reduced pressure. Purification by
flash column chromatography on silica gel (15% EtOAc/n-hexane)
gave title compound as a yellow oil (81.6 mg, 90%): 1H NMR (CDCl3,
400 MHz) δ 8.05 (1H, d, J = 8.4 Hz), 7.49 (2H, d, J = 7.12 Hz), 7.44
(3H, t, J = 7.76 Hz), 7.32−7.38 (4H, m), 7.20−7.26 (7H, m), 7.06
(2H, d, J = 8.2 Hz), 6.30 (1H, d, J = 11.84 Hz), 4.72 (1H, d, J = 11.8
Hz), 2.29 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 144.9, 142.5, 137.2,
136.4, 135.3, 132.3, 130.2, 129.7, 128.9, 128.2, 128.2, 127.2, 126.9,
125.7, 125.6, 123.9, 120.7, 114.7, 68.6, 21.6.
2-(Fluoromethyl)-3-phenyl-1-tosyl-1H-indole (5p). To a sol-
ution of 2p (37.7 mg, 0.1 mmol) in dry CH2Cl2 (1 mL) at −78 °C was
added N,N-diethylaminosulfur trifluoride (66 μL, 0.5 mmol). After
stirring for 1 h at this temperature, the reaction mixture was warmed
up to room temperature. After stirring for 3 h at this temperature, the
reaction mixture was quenched with saturated aqueous NaHCO3 (5
mL) dropwise at 0 °C. The reaction mixture was allowed to stir for 5
min at room temperature, extracted with CH2Cl2 (3 × 10 mL), and
washed with brine (20 mL). The combined organic layers were dried
over MgSO4 and concentrated under reduced pressure. Purification by
flash column chromatography on silica gel (5% EtOAc/n-hexane) gave
the title compound as a white solid (21.2 mg, 56%): mp 111−113 °C ;
1H NMR (CDCl3, 400 MHz) δ 9.25 (1H, d, J = 8.44 Hz), 8.92 (2H, d,
J = 8.16 Hz), 8.55 (1H, d, J = 7.8 Hz), 8.41−8.48 (6H, m), 8.21−8.28
(3H, m), 6.72 (2H, d, JH−F = 48.4 Hz), 3.34 (3H, s); 13C NMR
(CDCl3, 100 MHz) δ 145.0, 136.4, 135.5, 130.2, 130.1, 129.7, 128.8,
1
solid; mp 122−123 °C; H NMR (CDCl3, 400 MHz) δ 7.77−7.81
(3H, m), 7.33−7.42 (4H, m), 7.19−7.29 (4H, m), 7.08 (2H, d, J =
8.12 Hz), 6.59 (1H, s), 4.84 (1H, s), 2.32 (3H, s); 13C NMR (CDCl3,
100 MHz) δ 144.8, 142.5, 141.3, 134.9, 134.8, 133.0, 129.8, 129.7,
129.3, 128.1, 128.0, 126.8, 124.6, 123.6, 120.3, 73.7, 21.6; IR (NaCl,
neat) ν 3447, 3019, 1670, 1636, 1521, 1464, 1368, 1171, 1088, 1056,
1030 cm−1; HRMS (ESI) calcd for C22H19NO3SNa (M+ + Na)
400.0983, found 400.0981.
(Z)-2-Ethylidene-1-tosylindolin-3-ol (2s): 0.043 g; yellow oil;
1H NMR (CDCl3, 400 MHz) δ 7.73 (1H, d, J = 8.08 Hz), 7.34−7.38
(3H, m), 7.15−7.22 (2H, m), 7.11 (2H, d, J = 8.08 Hz), 5.89 (1H, qd,
J = 1.48, 7.16 Hz), 4.66 (1H, s), 2.33 (3H, s), 2.08 (3H, dd, J = 1.4,
7.16 Hz); 13C NMR (CDCl3, 100 MHz) δ 144.6, 142.6, 142.3, 135.0,
133.2, 129.6, 129.3, 127.9, 126.5, 124.6, 122.4, 120.2, 72.7, 21.6, 15.0;
IR (NaCl, neat) ν 3422, 3028, 1670, 1636, 1522, 1462, 1358, 1169,
1088, 1055, 1030 cm−1; HRMS (ESI) calcd for C17H17NO3SNa (M+ +
Na) 338.0827, found 338.0820.
(Z)-2-Pentylidene-1-tosylindolin-3-ol (2t). 0.051 g; white solid;
mp 117−120 °C; 1H NMR (CDCl3, 400 MHz) δ 7.74 (1H, d, J = 8.08
Hz), 7.33−7.39 (3H, m), 7.16−7.23 (2H, m), 7.10 (2H, d, J = 8.12
Hz), 5.77 (1H, td, J = 1.16, 7.24 Hz), 4.66 (1H, d, J = 9.84 Hz), 2.58−
2.63 (2H, m), 2.33 (3H, s), 1.39−1.47 (4H, m), 0.93 (3H, t, J = 7.08
Hz); 13C NMR (CDCl3, 100 MHz) δ 144.6, 142.6, 141.0, 135.0, 133.2,
129.6, 129.3, 128.0, 127.9, 126.5, 124.6, 120.2, 72.7, 31.5, 28.6, 22.5,
21.6, 14.0; IR (NaCl, neat) ν 3419, 3019, 2871, 1670, 1636, 1522,
1464, 1358, 1169, 1088, 1055, 1030 cm−1; HRMS (ESI) calcd for
C20H23NO3SNa (M+ + Na) 380.1296, found 380.1300.
(Z)-2-(Cyclopropylmethylene)-1-tosylindolin-3-ol (2u): 0.053
1
128.4, 127.3, 127.2, 126.5, 123.9, 120.9, 114.9, 73.9 (1C, d, JC−F
=
g; white solid; mp 97−99 °C; H NMR (CDCl3, 400 MHz) δ 7.75
163.2 Hz), 21.6; IR (NaCl, neat) ν 3019, 1599, 1497, 1454, 1375,
1279, 1175, 1090, 1053, 1026 cm−1; HRMS (ESI) calcd for
C22H19FNO2S (M+ + H) 380.1121, found 380.1128.
(1H, d, J = 8.08 Hz), 7.34−7.39 (3H, m), 7.15−7.22 (2H, m), 7.11
(2H, d, J = 8.08 Hz), 5.12 (1H, d, J = 10.4 Hz), 4.64 (1H, s), 2.35−
2.42 (1H, m), 2.33 (3H, s), 0.95−0.99 (2H, m), 0.51−0.53 (2H, m);
13C NMR (CDCl3, 100 MHz) δ 144.6, 142.7, 139.5, 135.0, 133.1,
3-(Iodomethyl)-3-phenyl-1-tosylindolin-2-one (6p). To a
solution of 2p (37.7 mg, 0.1 mmol) in anhydrous MeCN (1 mL)
was added NIS (45 mg, 0.2 mmol). The reaction mixture was stirred
for 1 h at reflux and monitored by TLC analysis. Upon completion, the
reaction mixture was cooled to room temperature, quenched by
addition of 10% Na2S2O3·5H2O (5 mL) and extracted with EtOAc (2
× 10 mL). The combined organic layers were washed with brine, dried
over MgSO4, and concentrated under reduced pressure. Purification by
flash column chromatography on silica gel (5% EtOAc/n-hexane) gave
the title compound as white solid (43.7 mg, 87%): mp 148−151 °C;
1H NMR (CDCl3, 400 MHz) δ 8.05 (1H, d, J = 8.24 Hz), 7.98 (2H, d,
J = 8.24 Hz), 7.48 (1H, t, J = 8.2 Hz), 7.24−7.32 (9H, m), 3.99 (1H, d,
J = 9.92 Hz), 3.53 (1H, d, J = 9.88 Hz), 2.39 (3H, s); 13C NMR
(CDCl3, 100 MHz) δ 174.8, 145.8, 139.7, 136.6, 134.9, 129.9, 129.8,
129.7, 129.1, 128.6, 128.3, 127.0, 125.1, 114.1, 57.2, 21.7, 9.2; IR
(NaCl, neat) ν 3059, 2962, 1597, 1381, 1176, 575, 544 cm−1; HRMS
(ESI) calcd for C22H19INO3S (M+ + H) 504.0130, found 504.0130.
(Z)-2-Benzylidene-1-tosylindolin-3-one (7r). To a solution of
2r (37.7 mg, 0.1 mmol) in MeCN (1 mL) was added NIS (45 mg, 0.2
mmol). The reaction mixture was stirred at reflux for 1 h and
monitored by TLC analysis. Upon completion, the reaction mixture
was cooled to room temperature, quenched by addition of 10%
Na2S2O3·5H2O (5 mL), and extracted with EtOAc (2 × 10 mL). The
combined organic layers were washed with brine (20 mL), dried over
MgSO4, and concentrated under reduced pressure. Purification by
flash column chromatography on silica gel (5% EtOAc/n-hexane) gave
the title compound as a yellow solid (26.7 mg, 71%): mp 110−112 °C;
1H NMR (CDCl3, 400 MHz) δ 8.14 (1H, d, J = 8.28 Hz), 8.0 (1H, s),
7.87−7.89 (2H, m), 7.61−7.69 (2H, m), 7.42−7.45 (5H, m), 7.25
(1H, t, J = 7.52 Hz), 7.12 (2H, d, J = 8 Hz), 2.32 (3H, s); 13C NMR
(CDCl3, 100 MHz) δ 183.1, 148.5, 145.2, 136.0, 133.6, 133.1, 133.0,
132.3, 131.3, 130.6, 129.7, 128.1, 127.4, 126.7, 125.6, 124.3, 118.9,
21.6; IR (NaCl, neat) ν 3019, 1701, 1616, 1474, 1460, 1364, 1119,
1090 cm−1; HRMS (ESI) calcd for C22H18NO3S (M+ + H) 376.1007,
found 376.1012.
132.2, 129.6, 129.3, 128.0, 126.5, 124.6, 120.3, 72.7, 21.6, 11.6, 8.0, 8.0;
IR (NaCl, neat) ν 3565, 3019, 2870, 1670, 1521, 1464, 1362, 1169,
1088, 1056, 1030 cm−1; HRMS (ESI) calcd for C19H19NO3SNa (M+ +
Na) 364.0983, found 364.0986.
(Z)-2-Benzylidene-1-((4-nitrophenyl)sulfonyl)-3-phenylindo-
lin-3-ol (2v): 0.096 g; yellow solid; mp 108−110 °C; 1H NMR
(CDCl3, 400 MHz) δ 7.94 (1H, d, J = 8.12 Hz), 7.87 (2H, d, J = 8.6
Hz), 7.68 (2H, d, J =7.48 Hz), 7.54 (2H, d, J = 8.64 Hz), 7.49 (1H, t, J
= 8.08 Hz), 7.36 (2H, t, J = 7.76 Hz), 7.19−7.29 (4H, m), 7.08−7.15
(5H, m), 6.55 (1H, s), 2.12 (1H, brs); 13C NMR (CDCl3, 100 MHz) δ
144.9, 141.8, 141.1, 137.4, 135.2, 130.4, 129.6, 129.4, 128.3, 128.2,
128.0, 127.2, 126.6, 125.6, 124.0, 123.5, 119.1, 82.2; IR (NaCl, neat) ν
3443, 3022, 1667, 1604, 1530, 1348, 1172, 1063 cm−1; HRMS (ESI)
calcd for C27H20N2O5SNa (M+ + Na) 507.0991, found 507.0976.
(Z)-2-Benzylidene-1-(methylsulfonyl)-3-phenylindolin-3-ol
(2w): 0.075 g; pale yellow solid; mp 79−81 °C; 1H NMR (CDCl3, 400
MHz) δ 7.71 (1H, d, J = 8 Hz), 7.61 (2H, d, J = 7.36 Hz), 7.51 (2H, d,
J = 6.68 Hz), 7.43 (1H, t, J = 7.52 Hz), 7.30−7.38 (5H, m), 7.17−7.26
(3H, m), 6.24 (1H, s), 2.88 (1H, brs), 2.72 (3H, s); 13C NMR
(CDCl3, 100 MHz) δ 145.4, 142.2, 141.7, 138.1, 135.3, 130.4, 129.4,
128.3, 128.1, 128.0, 127.0, 126.8, 125.1, 123.9, 118.4, 82.8, 37.8; IR
(NaCl, neat) ν 3462, 3021, 1602, 1462, 1321, 1215, 1161, 1082 cm−1;
HRMS (ESI) calcd for C22H19NO3SNa (M+ + Na) 400.0983, found
400.0984.
(Z)-2-Benzylidene-3-phenyl-1-tosylindolin-3-ol (d1-2a): 0.09
g; white solid; mp 163−165 °C; 1H NMR (CDCl3, 300 MHz) δ 7.91
(1H, d, J = 8.07 Hz), 7.66 (2H, d, J = 7.53 Hz), 7.30−7.45 (5H, m),
7.14−7.24 (8H, m), 6.96−7.03 (3H, m), 6.26 (0.45H, s), 2.29 (3H, s);
13C NMR (CDCl3, 75 MHz) δ 145.4, 144.8, 142.5, 141.9, 138.3, 135.6,
133.1, 130.0, 129.6, 129.4, 128.4, 127.9, 127.9, 127.8, 127.3, 126.9,
126.7, 125.4, 124.8, 119.5, 81.8, 21.6; IR (NaCl, neat) ν 3526, 3078,
2956, 2860, 1718, 1660, 1598, 1450, 1367, 1186, 1172 cm−1; HRMS
(ESI) calcd for C28H22DNO3SNa (M+ + Na) 477.1359, found
477.1361.
7173
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The Journal of Organic Chemistry
Featured Article
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for all starting materials and products,
LC−MS spectrum of d1-2a, and X-ray data for 5p and 6p
(CIF). This material is available free of charge via the Internet
at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: waihong@ntu.edu.sg.
Notes
■
The authors declare no competing financial interest.
(6) For selected recent examples by us, refer to refs 2a, b, d, and:
(a) Kothandaraman, P.; Huang, C.; Susanti, D.; Rao, W.; Chan, P. W.
H. Chem.Eur. J. 2011, 17, 10081. (b) Zhang, X.; Teo, W. T.; Chan,
P. W. H. J. Organomet. Chem. 2011, 696, 331. (c) Rao, W.;
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ACKNOWLEDGMENTS
■
This work is supported by a University Research Committee
Grant (RG55/06) from Nanyang Technological University and
a Science and Engineering Research Council Grant (092 101
0053) from A*STAR, Singapore. We thank Dr. Yongxin Li of
this Division for providing the X-ray crystallographic data
reported in this work.
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