Gold-catalyzed cycloisomerizations of 1-(2-(Tosylamino)phenyl)prop-2-yn-1- ols to 1H-Indole-2-carbaldehydes and (E)-2-(Iodomethylene)Indolin-3-ols

Article abstract of DOI:10.1021/jo201208e

A method to prepare lH-indole-2-carbaldehydes and (E)-2-(iodomethylene) indolin-3-ols by gold(I)-catalyzed cycloisomerization of l-(2-(tosylamino) phenyl)prop-2-yn-1-ols with N-iodosuccinimide (NIS) is reported. The reactions were shown to be operationally simplistic and proceed efficiently for a wide variety of substrates, affording the corresponding products in good to excellent yields (70-99%). The mechanism is suggested to involve activation of the alkyne moiety of the substrate by the gold(I) catalyst. This triggers intramolecular addition of the tethered aniline moiety to give a vinyl gold intermediate, which undergoes iododeauration with NIS to give the (E)-2-(iodomethylene)indolin-3-ol adduct. Subsequent 1,3-allylic alcohol isomerization (1,3-AAI) followed by formylation of this vinyl iodide intermediate then gives the 1H-indole-2-carbaldehyde.

Full text of DOI:10.1021/jo201208e

FEATURED ARTICLE
pubs.acs.org/joc
Gold-Catalyzed Cycloisomerizations of
1-(2-(Tosylamino)phenyl)prop-2-yn-1-ols to 1H-Indole-
2-carbaldehydes and (E)-2-(Iodomethylene)indolin-3-ols
Prasath Kothandaraman, Srinivasa Reddy Mothe, Sharon Si Min Toh, 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
b
ABSTRACT: A method to prepare 1H-indole-2-carbaldehydes
and (E)-2-(iodomethylene)indolin-3-ols by gold(I)-catalyzed
cycloisomerization of 1-(2-(tosylamino)phenyl)prop-2-yn-1-
ols with N-iodosuccinimide (NIS) is reported. The reactions
were shown to be operationally simplistic and proceed effi-
ciently for a wide variety of substrates, affording the correspond-
ing products in good to excellent yields (70À99%). The
mechanism is suggested to involve activation of the alkyne
moiety of the substrate by the gold(I) catalyst. This triggers
intramolecular addition of the tethered aniline moiety to give a
vinyl gold intermediate, which undergoes iododeauration with NIS to give the (E)-2-(iodomethylene)indolin-3-ol adduct.
Subsequent 1,3-allylic alcohol isomerization (1,3-AAI) followed by formylation of this vinyl iodide intermediate then gives the
1H-indole-2-carbaldehyde.
’ INTRODUCTION
for the involvement of this transient organometallic species was first
reported by the groups of Hammond and Hashmi by isolating and
characterizing the vinyl gold complex by X-ray crystallography in the
respective Au(I)-catalyzed cycloisomerizations of allenoates6c to
γ-lactones and N-propargylcarboxamides to aromatic oxazoles.6a At
about the same time, F€urstner and co-workers showed that
rearrangement of 3,3-disubstituted cyclopropenes with Au(I) salts
1H-Indole-2-carbaldehydes are immensely important targets
in organic synthesis because of their frequent use as building
blocks in numerous strategies to natural products and bioactive
compounds of current therapeutic interest.1 The presence of the
vinyl iodide moiety in (E)-2-(iodomethylene)indolin-3-ols also
makes this class of compounds a potentially valuable coupling
partner in the field of transition metal-catalyzed cross-coupling
reactions.2 Generally, synthetic methods to the former have
relied on oxidation or formylation of a prefunctionalized indole
substrate, while there are no known examples to the latter. In the
case of 1H-indole-2-carbaldehyde synthesis, this is far from ideal
as each step in such stepwise transformations often require their
own set of stoichiometric or excess amounts of various reagents
that can lead to equimolar or more amounts of waste products. In
this regard, it is therefore surprising to find that single step or
one-pot intramolecular strategies to these synthetically useful
compounds have not been widely investigated. This is all the
more so given the myriad of works to other members of
the indole family using this more atom economical synthetic
approach.3,4 Hence, synthetic methods to 1H-indole-2-carbalde-
hydes and (E)-2-(iodomethylene)indolin-3-ols that can con-
struct both the indole ring and aldehyde or vinyl iodide moiety
in one step or in a one-pot manner from readily available, low
cost, and simple acyclic substrates are desirable.
gave the corresponding vinyl gold complexes based on 1H and 31
P
NMR measurements.6b Following these seminal works, an increas-
ing number of reports have provided further experimental evidence
for the involvement of such a reactive species in a variety of gold-
mediated reactions.7,8 This has hitherto included trapping the vinyl
gold species with an iodide source such as NIS to give the vinyl
iodide derivative8 and its further functionalization by using Pd-
catalyzed cross-coupling chemistry.7 Examples of iododeaurations
followed by in situ formylation, by contrast, have not been widely
investigated. As part of an ongoing program exploring the scope of
gold catalysis in heterocyclic synthesis,9 we report herein that the
Au(I) complex A can mediate cascade cycloisomerization/1,3-AAI/
formylation of propargylic alcohols of the type 1 with NIS
(Scheme 1, route 1). This process provides a convenient synthetic
route to 1H-indole-2-carbaldehydes in 70À98% yield for a wide
variety of substrates under mild conditions. By lowering the reaction
temperature, the transformation could also be halted at the
Within the emerging field of gold catalysis, the in situ formation
of a putative vinyl gold species is often put forward as a key
intermediate in reactions involving alkyne substrates.5À8 Evidence
Received: June 10, 2011
Published: July 11, 2011
r
2011 American Chemical Society
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Scheme 1. Gold(I)-Catalyzed Cycloisomerization Reactions
of 2-Tosylaminophenylprop-1-yn-3-ols with NIS (Cy =
Cyclohexane)
forming process (entry 9). Likewise, molecular iodine, reported
to promote the intramolecular cyclization of substituted 2-al-
kynylanilines to 2-acyl-1H-indoles and quinolines, was found to
be ineffective (entry 10).10 On the basis of the above results,
reaction of 1a in the presence of 2 equiv of NIS in acetone at
reflux for 2 h was deemed to provide the optimal conditions.
Having established the reaction conditions, we next sought
to define the scope of the present procedure to a variety of
terminal propargylic alcohols, and the results are summarized in
Table 2. In general, these experiments showed the reaction
conditions to be broad, providing a variety of substituted
indole-2-carbaldehydes in good to excellent yields. Substrates
containing an electron-donating group on the aniline ring were
found to be well tolerated and afforded the corresponding
products 2b and 2c in good yields of 75 and 70%, respectively.
Similarly, reaction of starting alcohols with an embedded
naphthalene ring moiety as in 1g and 1l were found to proceed
well, furnishing 2g and 2l in 78 and 90% yield, respectively.
Indole-2-carbaldehydes 2hÀk with a pendant electron-donat-
ing or electron-withdrawing group at the C-3 position were also
obtained in excellent yields of 82À88% from the corresponding
propargylic alcohols 1hÀk. In contrast, no product formation
was observed for reactions of substrates 1d and 1e containing
an electron-withdrawing group on the aniline ring, even when
the reaction time was extended to 18 h. In these reactions, only
the trans-iodomethylene adducts 3d and 3e were obtained in 98
and 96% yields, respectively. The o,p-dimethylaniline alcohol 1f
was also found to proceed less well under the standard reaction
conditions, giving a mixture of decomposition products based
iododeauration step to afford the (E)-2-(iodomethylene)indolin-
3-ol adduct (Scheme 1, route 2).
’ RESULTS AND DISCUSSION
To test the feasibility of our hypothesis, the propargylic
alcohol 1a was prepared and treated with a variety of gold
catalysts and NIS to establish the reaction conditions (Table 1).
This initially revealed treatment of 1a with 5 mol % of the Au(I)
complex A and 2 equiv of NIS in toluene at reflux for 3 h
afforded 2a in 90% yield (entry 1). Our studies subsequently
showed that a further increase of 8% in product yield could be
achieved when the reaction was repeated in acetone in place of
toluene (entry 2). On the other hand, lower product yields
(62À85%) were obtained on employing chlorinated solvents
such as CH2Cl2 and 1,2-dichloroethane or decreasing the
amount of NIS employed from 2 to 1.3 equiv (entries 3À5).
Similarly, a survey of other Lewis acidic gold catalysts was found
to give 2a in lower yields of 72À85% (entries 6À8). More
notably, the near-quantitative recovery of the starting alcohol
when the reaction was carried out in the absence of the gold
catalyst demonstrated that NIS alone could not effect the indole
1
on TLC and H NMR analysis of the crude mixture. On the
other hand, reactions of alcohols 1mÀp with a pendent alkyl or
thiophene group on the carbinol carbon were found to rapidly
give the corresponding products 2mÀp in yields of 78À84% at
room temperature. Reaction of the secondary alcohol 1q was
also shown to work well to produce 2q in 72% yield at room
temperature and with 1.3 equiv of NIS. The more reactive
nature of these latter substrates was further underlined by
repeating the reactions under the optimal conditions and
finding only a variety of byproducts that could not be identified
based on TLC and 1H NMR analysis of the crude mixtures.
With the reaction conditions to indole-2-carbaldehydes
established, we then proceeded to examine the scope of
this new methodology for (E)-2-(iodomethylene)indolin-3-ol
synthesis (Table 3). Based on the rationale illustrated in
Scheme 1, we anticipated such control in product chemoselec-
tivity could be achieved by simply conducting the cycloisome-
rization process at a lower temperature. With this in mind, we
first tested the reaction of 1a with 5 mol % of A under the standard
conditions at room temperature and found that (E)-3a could be
obtained as the sole product in near quantitative yield. Under
similar conditions, repeating the reaction with 1d,e,j,g,h,o,q as
representative examples gave the corresponding (E)-indolin-3-
ol products 3d,e,j,g,h,o,q in excellent yields of 80À99% yield. In
these latter reactions, the trans stereochemistry and structure of
the indolin-3-ol products were determined on the basis of X-ray
crystal structure analysis of 3e (see Figure S40 in the Supporting
Information).11 Additionally, no other side products were detected
by TLC and 1H NMR analysis of the crude mixtures.
Table 1. Optimization of the Reaction Conditionsa
entry
catalyst
solvent
yield (%)
1b
2c
3d
4
A
A
A
A
A
B
toluene
acetone
acetone
CH2Cl2
(CH2Cl)2
acetone
acetone
acetone
acetone
acetone
90
98
85
62
72
85
82
72
g
5
6
7e
Ph3PAuNTf2
8
AuCl/AgOTf
9
f
10
I2
g
a Unless otherwise stated, all reactions were performed at reflux for 16 h
with catalyst/1a/NIS ratio = 1:20:40. b Reaction time = 3 h. c Reaction
time = 2 h. d Reaction performed with 1.3 equiv of NIS for 18 h.
A tentative mechanism for the present Au(I)-catalyzed indole
forming reaction is outlined in Scheme 2. This could involve
activation of the alkyne moiety of 1 by the gold catalyst that
results in cyclization of the pendant aniline group to the alkyne
f
e Reaction time = 6 h. Reaction conducted in the absence of a gold
catalyst at room temperature. g Recovery of 1a in near quantitative yield.
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Table 2. Tandem Cycloisomerization/Formylation of 2-To-
Table 3. Synthesis of (E)-2-(Iodomethylene)indolin-3-ols
3a,dÀe,j,gÀh,o,qa
sylaminophenylprop-1-yn-3-ols 1bÀq Catalyzed by Aa
a Unless otherwise stated, all reactions were performed at room tem-
perature for 0.25 h with A/1/NIS ratio = 1:20:40. Values in parentheses
denote product yields. b Reaction performed at À40 °C. c Reaction
performed with 1.3 equiv of NIS.
Scheme 2. Proposed Mechanism
Table 4. Gold(I)-Catalyzed Reactions of 1a with NIS in the
Presence of H218Oa
a Unless otherwise stated, all reactions were performed at reflux for 2 h
with A/1/NIS ratio = 1:20:40. Values in parentheses denote product
yields. b Mixture of unknown side products based on 1H NMR analysis of
thecrude reaction mixture.c Reactiontime= 18 h. d Reactionperformedat
room temperature for 0.5 h. e Reaction performed with 1.3 equiv of NIS.
H218O (equiv)
yield (%)
18O incorporation (%)
1
3
96
93
0
11
a All reactions were performed at reflux for 16 h with A/1/NIS ratio =
moiety and formation of the putative vinyl gold species I.
Iododeauration of this newly formed organogold intermediate
with NIS then delivers 3, which can rapidly undergo Au(I)-
mediated 1,3-AAI when the reaction is carried out at reflux. This
gives the iodomethanol intermediate II that subsequently elim-
inates HI to provide 2.
To demonstrate that 3 is the actual intermediate that leads to
the formation of 2, we first examined the reaction of 3a to 5 mol
% of A in acetone at reflux for 2 h. This afforded 2a in 98% yield,
which is the same as that directly furnished from 1a as described
in entry 2 in Table 1. The role of the gold catalyst in facilitating
the 1,3-AAI step could also be shown by repeating the reaction in
the absence of the catalyst, which gave only recovery of the
starting iodide in near quantitative yield. The premise that the
isomerization occurs in an intramolecular manner was supported
by our findings for the reactions of 1a in the presence of 5 mol %
1:20:40 and 1À3 equiv of H218O in acetone.
of A and 1 or 3 equiv of H218O (Table 4). These latter experi-
ments showed that there was either no or only 11% 18O
incorporation in the respective aldehydes obtained on the basis
of LCMS analysis of the crude reaction mixtures. Our previous
finding showing 3d and 3e could only be obtained additionally
hints to the possibility that the rearrangement could be cationic
in nature since such a process may not be expected to be
favorable in substrates with an electron-withdrawing group.
’ CONCLUSION
In summary, we have described a mild method for the prepartion
of 1H-indole-2-carbaldehydes and (E)-2-(iodomethylene)indolin-
3-ols. The attractiveness of the synthetic approach lies in the fact
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that both the indole ring and aldehyde or vinyl iodide moiety are
sequentially formed from cycloisomerization of a common alcoholic
substrate. The reactions are also operationally simplistic and rapid
and can make use of a wide variety of starting alcohols and a catalytic
system that are readily available and ecologically benign.
Na2SO4, and concentrated under reduced pressure. Purification by flash
column chromatography on silica gel (eluent: n-hexane/EtOAc = 10:1)
gave the title compound.
General Procedure for Optimizing the Lewis Acid Catalyzed
Cycloisomerization of 1-Phenyl-1-(2-(tosylamino)phenyl)prop-
2-yn-1-ol (1a). For reactions with a gold/silver catalyst combination, the
gold (13.2 μmol) and silver (13.2 μmol) catalysts were first stirred in the
respective solvent (1 mL) at room temperature for 10 min. In all other cases,
the catalyst was added to a respective solvent prior to adding the starting
materials. A solution of NIS (0.52 mmol) in acetone (0.5 mL) was then
added and stirred for another 10 min at room temperature followed by slow
dropwise addition of a solution of 1a (0.26 mmol) in acetone (1 mL). The
resultant reaction mixture was stirred at reflux and monitored to
completion by TLC analysis. On cooling to room temperature, the
solvent was removed under reduced pressure, and the residue obtained
was purified by flash column chromatography on silica gel (eluent:
n-hexane/EtOAc = 24:1) to give 2a.
General Procedure for Gold(I)-Catalyzed Cycloisomeriza-
tion of 1-(2-(Tosylamino)phenyl)prop-2-yn-1-ol (1). To a
solution of the gold(I) complex A (13.2 μmol) in acetone (1 mL)
was added a solution of NIS (0.52 mmol) in acetone (0.5 mL) and
stirred for 10 min at room temperature. A solution of 1 (0.26 mmol) in
acetone (1 mL) was then added slowly dropwise, and the reaction mixture
was stirred atrefluxand monitored byTLC analysis(note: for compounds
2nÀq the reaction was performed at room temperature for 0.5 h).
On completion, the reaction mixture was quenched by addition of 10%
’ EXPERIMENTAL SECTION
General Remarks. All reactions were performed under an argon
atmosphere. 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 plate.
Visualization was achieved by UV light (254 nm). Flash chromatography
was performed using silica gel and gradient solvent system (n-hexane/
EtOAc as eluent). 1H and 13C NMR spectra were measured on 300, 400,
and 500 MHz spectrometers. Chemical shifts (ppm) were recorded with
tetramethylsilane (TMS) as the internal reference standard. Multipli-
cities are given as follows: s (singlet), brs (broad singlet), d (doublet), t
(triplet), dd (doublet of doublets), q (quartet), m (multiplet). The
number of protons (n) for a given resonance is indicated by nH, and
coupling constants are reported as a J value (Hz). Infrared spectra were
recorded on an FTIR spectrometer. Solid samples were examined as a
thin film between NaCl salt plates. 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 on
a LC/HRMS mass spectrometer.
General Procedure for the Synthesis of Propargylic Alco-
hols 1aÀl,n,o,q. To a solution of the appropriate 1-(2-aminophe-
nyl)ketone or aldehyde (1.1 mmol) in pyridine (0.4 mL) was added
p-TsCl (1.6 mmol) at room temperature. The resulting solution was
stirred for 4 h at room temperature. On completion, the reaction mixture
was quenched by addition of H2O (5 mL) and filtered. The resulting
solid was dried and then used directly for the next step. The solid (0.51
mmol) was dissolved in anhydrous THF (8 mL), and a solution of
ethynylmagnesium bromide (0.5 M THF solution; 1.5 mmol) was
added at room temperature. The resulting mixture was allowed to reflux
for 3 h. On completion, the reaction mixture was cooled to room
temperature and treated with saturated NH4Cl (7 mL). After additional
stirring at room temperature for 10 min, EtOAc (15 mL) was added, and
the phases were separated. The aqueous phase was extracted with EtOAc
(3 Â 5 mL), and the combined organic layers were washed with brine
solution, dried over anhydrous Na2SO4, and concentrated under
reduced pressure. Purification by flash column chromatography on silica
gel (eluent: n-hexane/EtOAc = 9:1) gave the title compound.
Procedure for the Synthesis of Propargylic Alcohols 1m
and 1p. To a solution of 1q (0.66 mmol) in CH2Cl2 (5 mL) was added
MnO2 (9.9 mmol) at room temperature. The resulting mixture was
stirred for 3 h at reflux temperature. On completion, the reaction mixture
was cooled to room temperature and filtered through a Celite pad. The
resulting solvent (filterate) was removed under reduced pressure gave
the ketone derivative of 1q, which was used directly for the next step
without purification. For the synthesis of 1m, 2-thienyllithium (1 M
solution in THF, 0.5 mmol) was slowly added to a solution of the ketone
(0.16 mmol) in anhydrous THF (3 mL) at À78 °C; the reaction mixture
was then stirred at À78 °C for 2 h and a further 1 h at room temperature.
For the synthesis of 1p, ethylmagnesium bromide (1 M THF solution,
0.5 mmol) in place of 2-thienyllithium was added at room temperature,
and the reaction mixture was refluxed for 3 h. On completion, the
reaction mixture was quenched by addition of saturated NH4Cl (10 mL)
at room temperature. After additional stirring at room temperature for
10 min, EtOAc (15 mL) was added, and the phases were separated. The
aqueous phase was extracted with EtOAc (3 Â 5 mL), and the combined
organic layers were washed with brine solution, dried over anhydrous
Na2S2O3 5H2O (5 mL) at room temperature and extracted with EtOAc
3
(2 Â 10 mL). The combined organic layers were washed with brine, dried
over Mg2SO4, and concentrated under reduced pressure. Purification by
flash column chromatography on silica gel (n-hexane/EtOAc 24:1 as
eluent) gave the indole-2-carbaldehyde product 2.
General Procedure for Gold(I)-Catalyzed Cycloisomeriza-
tion of Propargylic Alcohols 1a,d,e,j,gÀh,o,q. To a solution of
the gold(I) complex A (13.2 μmol) in acetone (1 mL) was added a
solution of NIS (0.52 mmol) in acetone (0.5 mL) and stirred for 10 min
at room temperature (note: for reactions with 1o and 1q, the resulting
mixture was cooled to À40 °C and 0.34 mmol of NIS was added for 1q).
A solution of 1 (0.26 mmol) in acetone (1 mL) was then added slowly
dropwise, and the reaction mixture was stirred at room temperature (or
À40 °C for 1o and 1q) and monitored by TLC analysis. On completion,
the reaction mixture was quenched by adding 10% Na2S2O3 5H2O
3
(5 mL) and extracted with EtOAc (2 Â 10 mL). The combined organic
layers were washed with brine, dried over Mg2SO4, and concentrated
under reduced pressure. Purification by flash column chromatography
on silica gel (n-hexane/EtOAc 24:1 as eluent) gave the product 3.
Procedure for Gold(I)-Catalyzed Cycloisomerization of
1-Phenyl-1-(2-(tosylamino)phenyl)prop-2-yn-1-ol (1a) in
the Presence of H218O. To a solution of the gold(I) catalyst A
(13.2 μmol) in acetone (1 mL) was added a solution of NIS (0.52
mmol) in acetone (0.5 mL) and the mixture stirred for 10 min at room
temperature. H218O (1 or 3 equiv). A solution of 1a (0.26 mmol) in
acetone (1 mL) was then added slowly dropwise and the reaction
mixture stirred at reflux and monitored by TLC analysis. On comple-
tion, the reaction mixture was quenched by adding 10% Na2S2O3
5
3
H2O (5 mL) and extracted with EtOAc (2 Â 10 mL). The combined
organic layers were washed with brine, dried over Mg2SO4, and
concentrated under reduced pressure. Purification by flash column
chromatography on silica gel (n-hexane/EtOAc 24:1 as eluent) gave
the indole-2-carbaldehyde product 18O-2a.
1-Phenyl-1-(2-(tosylamino)phenyl)prop-2-yn-1-ol (1a):4a yield
89%; yellow oil; 1H NMR (CDCl3, 400 MHz) δ 8.47 (1H, brs),
7.54 (1H, dd, J = 8.32, 12.4 Hz), 7.38 (2H, d, J = 6.6 Hz), 7.29À7.36
(5H, m), 7.21 (1H, d, J = 7.5 Hz), 7.05 (2H, d, J = 8.0 Hz), 6.98 (1H, t,
J = 7.6 Hz) 3.22 (1H, brs), 2.90 (1H, s), 2.33 (3H, s); 13C NMR
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(CDCl3, 100 MHz) δ 143.4, 142.2, 136.3, 135.8, 130.1, 129.6, 129.4,
128.8, 128.7, 128.3, 127.3, 125.8, 122.8, 119.0, 84.4, 77.8, 74.9, 21.5.
1-(5-Methyl-2-(tosylamino)phenyl)-1-phenylprop-2-yn-1-ol (1b):
yield 82%; yellow solid; mp 136À139 °C; 1H NMR (CDCl3, 400 MHz)
δ 8.46 (1H, brs), 7.43 (1H, d, J = 8.3 Hz), 7.24À7.36 (8H, m), 7.00 (3H,
dd, J = 6.9 Hz, J = 7.7 Hz), 3.77 (1H, s), 2.87 (1H, s), 2.31 (3H, s), 2.24
(3H, s); 13C NMR (CDCl3,100 MHz) δ 143.3, 142.5, 136.4, 133.2,
132.6, 130.3, 130.1, 129.5, 129.4, 128.7, 128.2, 127.4, 125.9, 119.3, 84.7,
77.6, 74.9, 21.5, 20.9; IR (NaCl, neat) ν 3419, 3305, 3022, 2113, 1647,
1635, 1498, 1392, 1330, 1157, 1091, 844, 813 cmÀ1; MS (ESI) m/z 414
[M + Na]+; HRMS (ESI) calcd for C23H21NO3SNa (M+ + Na)
414.1140, found 414.1143.
1-(5-Methoxy-2-(tosylamino)phenyl)-1-phenylprop-2-yn-1-ol (1c):
yield 75%; brown solid; mp 144À146 °C; 1H NMR (CDCl3, 400 MHz)
δ 8.05 (1H, brs), 7.49 (1H, d, J = 8.8 Hz), 7.26À7.40 (8H, m), 7.14 (1H,
d, J = 2.8 Hz), 7.06 (2H, d, J = 8.8 Hz), 6.76 (1H, dd, J = 2.8 Hz, J =
8.9 Hz), 3.73 (3H, s), 3.30 (1H, s), 2.87 (1H, s), 2.35 (3H, s); 13C NMR
(CDCl3, 100 MHz) δ 155.4, 143.3, 142.2, 136.5, 132.7, 129.4, 128.7,
128.6, 128.3, 127.3, 125.8, 121.6, 115.4, 113.7, 84.6, 77.5, 74.7, 55.4,
21.5; IR (NaCl, neat) ν 3392, 3292, 3020, 2113, 1153, 1089, 1035, 844,
812 cmÀ1; MS (ESI) m/z 430 [M + Na]+; HRMS (ESI) calcd for
C23H21NO4SNa (M+ + Na) 430.1089, found 430.1082.
7.50 (1H, d, J = 7.5 Hz), 7.47 (1H, dd, J = 1.4 Hz, 7.9 Hz), 7.27 (2H, d,
J = 8.3 Hz), 7.18À7.12 (3H, m), 7.01 (2H, d, J = 8.1 Hz), 6.97 (2H, d,
J = 8.2 Hz), 6.92À6.89 (1H, m), 2.78 (1H, s), 2.29 (3H, s), 2.25
(3H, s); 13C NMR (CDCl3, 125 MHz) δ 143.3, 139.4, 138.1, 136.4,
135.8, 130.2, 129.5, 129.3, 128.8, 127.3, 125.7, 122.8, 119.0, 84.6, 77.5,
74.8, 21.5, 21.2.
1-(4-Bromophenyl)-1-(2-(tosylamino)phenyl)prop-2-yn-1-ol (1i):
yield 87%; brown solid; mp 162À164 °C; 1H NMR (CDCl3, 400 MHz)
δ 8.43 (1H, brs), 7.71 (1H, d, J = 8.2 Hz), 7.65 (1H, d, J = 7.8 Hz), 7.27
(4H, m), 7.14 (2H, d, J = 8.5 Hz), 7.07 (3H, d, J = 8.4 Hz), 3.48 (1H, s),
2.93 (1H, s), 2.36 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 143.6, 141.4,
136.3, 135.9, 131.7, 130.0, 129.6, 129.4, 128.9, 127.3, 127.0, 123.1, 122.6,
119.4, 84.0, 78.3, 74.6, 21.6; IR (NaCl, neat) ν 3437, 3304, 3018, 2113,
1637, 1492, 1396, 1328, 1159, 1091, 891, 819 cmÀ1; MS (ESI) m/z 478
[M + Na]+; HRMS (ESI) calcd for C22H18BrNO3SNa (M+ + Na)
478.0088, found 478.0082.
1-(4-Chlorophenyl)-1-(2-(tosylamino)phenyl)prop-2-yn-1-ol (1j):
yield 82%; yellow solid; mp 169À171 °C; 1H NMR ((CD3)2CO, 300
MHz) δ 9.02 (1H, brs), 7.71 (1H, dd, J = 1.5 Hz, J = 3.8 Hz), 7.68 (1H,
dd, J = 1.6 Hz, J = 4.3 Hz), 7.34 (2H, d, J = 8.3 Hz), 7.32 (1H, d, J = 1.8
Hz), 7.27 (4H, d, J = 5.9 Hz), 7.14 (2H, d, J = 8.0 Hz), 7.03 (1H, td, J =
1.2 Hz, J = 7.7 Hz), 3.52 (1H, s), 2.33 (3H, s); 13C NMR ((CD3)2CO, 75
MHz) δ 143.7, 142.6, 136.7, 136.3, 133.4, 130.3, 129.5, 129.4, 128.9,
128.4, 127.3, 126.9, 122.7, 118.4, 84.6, 78.5, 74.1, 20.7; IR (NaCl, neat)
1-(5-Chloro-2-(tosylamino)phenyl)-1-phenylprop-2-yn-1-ol (1d):
yield 84%; yellow solid; mp 152À154 °C; 1H NMR (CDCl3, 400 MHz)
δ 8.52 (1H, brs), 7.57 (1H, s), 7.49 (1H, d, J = 8.5 Hz), 7.16À7.36 (8H,
ν 3435, 3292, 3018, 2113, 1490, 1396, 1328, 1159, 1091, 893, 821 cmÀ1
;
MS (ESI) m/z 434 [M + Na]+; HRMS (ESI) calcd for C22H18ClNO3S-
m), 7.03 (2H, d, J = 7.3 Hz), 3.80 (1H, s), 2.91 (1H, s), 2.33 (3H, s); 13
C
Na (M+ + Na) 434.0594, found 434.0601.
NMR (CDCl3, 100 MHz): δ 143.7, 141.6, 135.8, 134.4, 131.9, 129.5,
129.4, 128.8, 128.7, 128.6, 128.3, 127.3, 125.8, 120.2, 83.8, 78.3, 74.4,
21.5; IR (NaCl, neat) ν 3406, 3302, 3018, 2113, 1637, 1485, 1332, 1157,
1089, 813 cmÀ1; MS (ESI) m/z 434 [M + Na]+; HRMS (ESI) calcd for
C22H18ClNO3SNa (M+ + Na) 434.0594, found 434.0598.
1-(5-Bromo-2-(tosylamino)phenyl)-1-phenylprop-2-yn-1-ol (1e):
yield 79%; white solid; mp 164À166 °C; 1H NMR (CDCl3, 400 MHz) δ
8.46 (1H, brs), 7.72 (1H, d, J = 2.1 Hz), 7.44 (1H, d, J = 8.8 Hz),
7.26À7.38 (8H, m), 7.04 (2H, d, J = 8.1 Hz), 3.58 (1H, s), 2.93 (1H, s),
2.34 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 143.8, 141.5, 135.8, 135.0,
132.5, 132.1, 131.5, 129.5, 128.9, 128.6, 127.4, 125.8, 120.5, 115.8, 83.8,
78.4, 74.4, 21.5; IR (NaCl, neat) ν 3406, 3292, 3018, 2113, 1595, 1481,
1382, 1321, 1153, 1087, 883, 819 cmÀ1; MS (ESI) m/z 478 [M + Na]+;
HRMS (ESI) calcd for C22H18BrNO3SNa (M+ + Na) 478.0088, found
478.0082.
1-(Biphenyl-4-yl)-1-(2-(tosylamino)phenyl)prop-2-yn-1-ol (1k):
yield 79%; white solid; mp 145À147 °C; 1H NMR (CDCl3, 300 MHz)
δ 8.55 (1H, brs), 7.65 (2H, d, J = 8.3 Hz), 7.61 (2H, d, J = 3.5 Hz),
7.34À7.59 (9H, m), 7.24 (1H, dd, J = 1.5 Hz, J = 8.7 Hz), 7.01À7.06
(1H, m), 6.95 (2H, d, J = 8.1 Hz), 3.41 (1H, s), 2.93 (1H, s), 2.19
(3H, s); 13C NMR ((CD3)2CO, 75 MHz) δ 143.5, 142.7, 140.4, 140.1,
136.7, 136.4, 130.6, 129.4, 129.3, 129.0, 127.6, 127.1, 126.9, 126.8, 126.2,
122.5, 118.0, 85.0, 78.1, 74.5, 20.4; IR (NaCl, neat) ν 3419, 3032, 2113,
1490, 1330, 1157, 1089, 837, 812 cmÀ1; MS (ESI) m/z 476 [M + Na]+;
HRMS (ESI) calcd for C28H23NO3SNa (M+ + Na) 476.1296, found
476.1292.
1-(Naphthalen-2-yl)-1-(2-(tosylamino)phenyl)prop-2-yn-1-ol (1l):
yield 73%; white solid; mp 145À151 °C; 1H NMR (CDCl3, 300 MHz)
δ 8.64 (1H, brs), 7.80 (2H, d, J = 6.3 Hz), 7.69 (4H, dd, J = 7.5 Hz, J = 8.7
Hz), 7.47À7.68 (2H, m), 7.34 (1H, dd, J = 1.9 Hz, J = 8.7 Hz), 7.28 (1H,
dd, J = 1.5 Hz, J = 7.5 Hz), 7.06 (2H, d, J = 8.3 Hz), 7.02 (1H, dd, J = 0.9
Hz, J = 7.6 Hz), 6.57 (2H, d, J = 8.1 Hz), 3.67 (1H, s), 2.93 (1H, s), 2.15
(3H, s); 13C NMR ((CD3)2CO, 75 MHz) δ 143.3, 140.9, 136.4, 136.3,
133.1, 133.0, 130.6, 129.3, 129.1, 129.0, 128.4, 128.3, 127.6, 126.8, 126.5,
124.0, 123.9, 122.6, 118.1, 84.9, 78.4, 74.6, 20.5; IR (NaCl, neat) ν 3414,
1-(3,5-Dimethyl-2-(tosylamino)phenyl)-1-phenylprop-2-yn-1-ol (1f):
yield 77%; white solid; mp 74À78 °C; 1H NMR (CDCl3, 300 MHz) δ
7.65 (2H, d, J = 8.3 Hz), 7.49 (2H, dd, J = 1.8 Hz, J = 8.2 Hz), 7.30À7.37
(3H, m), 7.21 (3H, d, J= 8.1 Hz), 7.02 (1H, brs), 6.96 (1H, s), 4.48 (1H, s),
2.90 (1H, s), 2.40 (3H, s), 2.23 (3H, s), 1.86 (3H, s); 13CNMR(CDCl3, 75
MHz) δ 143.8, 143.6, 139.7, 138.1, 138.0, 136.6, 132.7, 130.2, 129.5, 128.6,
128.4, 128.1, 127.3, 126.3, 86.3, 77.5, 74.4, 21.6, 21.1, 19.5; IR (NaCl, neat)
3304, 3026, 2115, 1647, 1490, 1398, 1332, 1157, 1089, 896, 812 cmÀ1
;
MS (ESI) m/z 450 [M + Na]+; HRMS (ESI) calcd for C26H21NO3SNa
ν 3419, 3302, 3020, 2112, 1637, 1473, 1381, 1321, 1155, 1091, 813 cmÀ1
;
(M+ + Na) 450.1140, found 450.1142.
MS (ESI) m/z 428 [M + Na]+; HRMS (ESI) calcd for C24H23NO3SNa
(M+ + Na) 428.1296, found 428.1290.
1-(Thiophene-2-yl)-1-(2-(tosylamino)phenyl)prop-2-yn-1-ol (1m):
yield 78%; yellow solid; mp 147À150 °C; 1H NMR (CDCl3, 400 MHz)
δ 8.79 (1H, brs), 7.60 (1H, d, J = 8.2 Hz), 7.51À7.46 (3H, m),
7.26À7.20 (2H, m), 7.10 (2H, d, J = 8.0 Hz), 6.99 (1H, t, J = 7.6 Hz),
6.84À6.78 (2H, m), 4.15 (1H, s), 2.87 (1H, s), 2.31 (3H, s); 13C NMR
(CDCl3, 100 MHz) δ 147.1, 143.5, 136.4, 135.9, 129.8, 129.7, 129.5,
128.4, 127.3, 126.8, 126.7, 126.1, 123.0, 119.1, 83.9, 77.1, 72.8, 21.5; IR
(NaCl, neat) ν 3392, 3288, 1635, 1583, 1494, 1371, 1278, 1157, 1087,
1051, 964 cmÀ1; MS (ESI) m/z 406 [M + Na]+; HRMS (ESI) calcd for
C20H17NO3S2Na (M+ + Na) 406.0548, found 406.0545.
1-Phenyl-1-(2-(tosylamino)naphthalen-3-yl)prop-2-yn-1-ol (1g):
yield 83%; yellow solid; mp 200À203 °C; 1H NMR ((CD3)2CO, 400
MHz) δ 9.18 (1H, brs), 8.30 (1H s), 7.97 (1H, s), 7.76 (2H, dd, J = 8.2
Hz, J = 12.7 Hz), 7.43À7.46 (3H, m), 7.31À7.39 (6H, m), 7.07 (2H, dd,
J = 8.1 Hz), 3.59 (1H, s), 3.06 (1H, s), 2.22 (3H, s); 13C NMR
((CD3)2CO, 100 MHz) δ 143.7, 143.3, 136.2, 134.0, 133.6, 131.0,
129.5, 128.9, 128.7, 128.5, 128.1, 128.0, 127.5, 127.3, 126.7, 125.7, 125.3,
114.2, 85.0, 78.5, 74.6, 20.5; IR (NaCl, neat) ν 3381, 3294, 3018,
2117, 1633, 1469, 1336, 1155, 1089, 891, 869 cmÀ1; MS (ESI) m/z 450
[M + Na]+; HRMS (ESI) calcd for C26H21NO3SNa (M+ + Na)
450.1140, found 450.1144.
2-(5-(Tosylamino)benzo[d][1,3]dioxol-6-yl)but-3-yn-2-ol (1n):
yield 90%; yellow solid; mp 130À133 °C; 1H NMR (CDCl3, 300 MHz)
δ 8.97 (1H, brs), 7.72 (2H, d, J = 8.4 Hz), 7.24 (2H, d, J = 8.1 Hz), 7.12
(1H, s), 7.03 (1H, s), 5.90 (2H, s), 3.54 (1H, brs), 2.68 (1H, s), 2.36
1-p-Tolyl-1-(2-(tosylamino)phenyl)prop-2-yn-1-ol (1h):4a. yield
1
80%; yellow gum; H NMR (CDCl3, 500 MHz) δ 8.49 (1H, brs),
7637
dx.doi.org/10.1021/jo201208e |J. Org. Chem. 2011, 76, 7633–7640

The Journal of Organic Chemistry
FEATURED ARTICLE
(3H, s), 1.54 (3H, s); 13C NMR (CDCl3, 75 MHz) δ 147.7, 143.8, 143.8,
136.9, 129.8, 129.6, 127.2, 125.0, 107.3, 102.6, 101.6, 85.8, 74.5, 71.2,
31.3, 21.5; IR (NaCl, neat) ν 3441, 3020, 1627, 1598, 1506, 1487, 1350,
1290, 1253, 1157, 1091, 1041 cmÀ1; MS (ESI) m/z 360 [M + H]+; HRMS
(ESI) calcd for C18H18NO5S (M+ + H) 360.0906, found 360.0917.
2-(2-(Tosylamino)phenyl)but-3-yn-2-ol (1o). yield 93%; white solid;
mp 107À109 °C; 1H NMR (CDCl3, 300 MHz) δ 9.19 (1H, brs), 7.73
(2H, d, J = 8.3 Hz), 7.53 (2H, d, J = 8.0 Hz), 7.20 (3H, d, J = 8.3 Hz), 6.97
(1H, td, J = 1.0 Hz, J = 7.7 Hz), 3.62 (1H, s), 2.69 (1H, s), 2.34 (3H, s),
1.67 (3H, s); 13C NMR (CDCl3, 75 MHz) δ 143.8, 137.0, 135.6, 130.9,
129.7, 129.1, 127.3, 127.2, 123.5, 119.9, 85.7, 74.7, 71.6, 31.2, 21.5;
IR (NaCl, neat) ν 3498, 3307, 3028, 2115, 1635, 1600, 1496, 1375,
1332, 1159, 1091, 871, 813 cmÀ1; MS (ESI) m/z 338 [M + Na]+;
HRMS (ESI) calcd for C17H17NO3SNa (M+ + Na) 338.0827, found
338.0830.
3-(2-(Tosylamino)phenyl)pent-1-yn-3-ol (1p): yield 55%; yellow
solid; mp 125À128 °C; 1H NMR (CDCl3, 500 MHz) δ 9.09 (1H, brs),
7.73 (2H, d, J = 6.8 Hz), 7.60 (1H, dd, J = 1.0 Hz, 8.25 Hz), 7.55 (1H, dd,
J = 1.5 Hz, 7.9 Hz), 7.23À7.19 (3H, m), 7.01À6.98 (1H, td, J = 1.1 Hz,
7.75 Hz), 3.26 (1H, brs), 2.76 (1H, s), 2.35 (3H, s), 1.28À1.75 (1H, m),
1.69À1.61 (1H, m), 0.75 (3H, t, J = 7.4 Hz); 13C NMR (CDCl3, 125
MHz) δ 143.7, 137.5, 135.6, 129.7, 129.6, 129.0, 128.6, 127.1, 123.3,
120.3, 84.3, 76.4, 76.1, 35.6, 21.4, 8.9; IR (NaCl, neat) ν 3423, 3302,
1635, 1598, 1492, 1338, 1288, 1271, 1161, 1091, 1058, 933 cmÀ1; MS
(ESI) m/z 352 [M + Na]+; HRMS (ESI) calcd for C18H19NO3SNa
(M+ + Na) 352.0983, found 352.0990.
1-(2-(Tosylamino)phenyl)prop-2-yn-1-ol (1q): yield 90%; yellow oil;
1H NMR (CDCl3, 400 MHz) δ 7.92 (1H, brs), 7.66 (2H, d, J = 8.0 Hz),
7.52 (1H, d, J = 7.6 Hz), 7.32 (2H, d, J = 8.0 Hz), 7.24 (2H, dd, J = 8.0 Hz,
J = 13.2 Hz), 7.13 (1H, t, J = 7.6 Hz), 5.33 (1H, d, J = 2.4 Hz), 3.61 (1H,
brs), 2.64 (1H, d, J = 2.0 Hz), 2.35 (3H, s); 13C NMR (CDCl3, 100
MHz) δ 144.1, 136.5, 135.2, 131.4, 129.7, 129.6, 128.4, 127.3, 125.6,
123.4, 81.6, 76.4, 62.3, 21.6; IR (NaCl, neat) ν 3423, 3302, 3020, 2121,
1635, 1492, 1400, 1328, 1159, 1091, 833, 813 cmÀ1; MS (ESI) m/z 324
[M + Na]+; HRMS (ESI) calcd for C16H15NO3SNa (M+ + Na)
324.0670, found 324.0671.
3-Phenyl-1-tosyl-1H-indole-2-carbaldehyde (2a): yellow solid; mp
147À150 °C; 1H NMR (CDCl3, 400 MHz) δ 10.22 (1H, s), 8.30 (1H,
d, J = 8.5 Hz), 7.83 (2H, d, J = 8.3 Hz), 7.52À7.58 (2H, m), 7.45 (5H,
m), 7.26 (1H, m), 7.24 (2H, d, J = 6.5 Hz), 2.36 (3H, s); 13C NMR
(CDCl3, 100 MHz) δ 182.4, 145.3, 138.2, 135.8, 135.2, 132.5, 130.5,
130.4, 129.7, 129.3, 129.2, 129.0, 128.4, 127.2, 124.6, 122.6, 115.7, 21.7;
IR (NaCl, neat) ν 3064, 3030, 2920, 1683, 1598, 1543, 1444, 1369, 1172,
1089, 906, 812 cmÀ1; MS (ESI) m/z 376 [M + H]+; HRMS (ESI) calcd
for C22H18NO3S (M+ + H) 376.1007, found 376.1006.
3-Phenyl-1-tosyl-1H-benzo[f]indole-2-carbaldehyde (2g): yellow solid;
1
mp 172À175 °C; H NMR (CDCl3, 400 MHz) δ 10.33 (1H, s), 8.71
(1H, s), 8.04 (1H, d, J = 8.4 Hz), 7.97 (1H, s), 7.83 (1H, d, J = 8.3 Hz), 7.74
(2H, d, J = 8.3 Hz), 7.44 (7H, m), 7.16 (2H, d, J = 8.2 Hz), 2.30 (3H, s); 13
C
NMR (CDCl3, 100 MHz) δ 183.0, 145.2, 136.4, 135.7, 134.7, 134.3, 133.8,
131.0, 130.6, 130.2, 130.0, 129.7, 129.2, 128.5, 128.4, 127.2, 126.8, 125.5, 122.1,
113.3, 21.6; IR (NaCl, neat) ν 3030, 2926, 1681, 1593, 1548, 1489, 1363,
1118, 1085, 948, 918, 875, 844, 812 cmÀ1; MS (ESI) m/z 426 [M + H]+;
HRMS (ESI) calcd for C26H20NO3S (M+ + H) 426.1164, found 426.1161.
3-p-Tolyl-1-tosyl-1H-indole-2-carbaldehyde (2h): yellow solid; mp
147À150 °C; 1H NMR (CDCl3, 300 MHz) δ 10.2 (1H, s), 8.29 (1H, d,
J = 8.4 Hz), 7.82 (2H, d, J = 8.4 Hz), 7.52 (2H, d, J = 7.8 Hz), 7.32 (2H, d,
J = 8.1 Hz), 7.23 (5H, m), 2.42 (3H, s), 2.36 (3H, s); 13C NMR (CDCl3,
75 MHz) δ 182.4, 145.2, 139.0, 138.3, 136.1, 135.2, 132.5, 130.4, 129.7,
129.3, 129.1, 127.2, 124.6, 122.7, 115.7, 79.5, 21.6, 21.4; IR (NaCl, neat)
ν 3026, 2922, 1681, 1597, 1544, 1369, 1174, 1089, 920, 812 cmÀ1
;
MS (ESI) m/z 390 [M + H]+; HRMS (ESI) calcd for C23H20NO3S
(M+ + H) 390.1164, found 390.1166.
3-(4-Bromophenyl)-1-tosyl-1H-indole-2-carbaldehyde (2i): yellow
solid; mp 139À141 °C; 1H NMR (CDCl3, 400 MHz) δ 10.31 (1H, s),
8.29 (1H, d, J = 8.5 Hz), 7.77 (2H, d, J = 8.2 Hz), 7.54 (3H, m), 7.46 (1H,
d, J = 7.4 Hz), 7.30 (3H, m), 7.23 (2H, d, J = 8.0 Hz), 2.36 (3H, s); 13
C
NMR (CDCl3, 100 MHz) δ 182.6, 145.5, 137.8, 134.8, 133.6, 132.4,
132.1, 131.6, 129.8, 129.4, 129.3, 129.1, 127.1, 124.9, 123.3, 122.3, 115.7,
21.7; IR (NaCl, neat) ν 3066, 3020, 2922, 1681, 1595, 1539, 1485, 1371,
1172, 1087, 920, 812 cmÀ1; MS (ESI) m/z 454 [M + H]+; HRMS (ESI)
calcd for C22H17BrNO3S (M+ + H): 454.0113, found 454.0115.
3-(4-Chlorophenyl)-1-tosyl-1H-indole-2-carbaldehyde (2j): white
1
solid; mp 140À143 °C; H NMR (CDCl3, 300 MHz) δ 10.31 (1H,
s), 8.29 (1H, d, J = 8.6 Hz), 7.77 (2H, d, J = 8.4 Hz), 7.54 (1H, td, J = 1.2
Hz, J = 8.5 Hz), 7.38À7.49 (5H, m), 7.29 (1H, d, J = 7.9 Hz), 7.23 (1H,
d, J = 9.3 Hz), 2.36 (3H, s); 13C NMR (CDCl3, 75 MHz) δ 182.6, 162.3,
145.5, 137.8, 135.0, 134.8, 133.6, 132.5, 131.8, 129.8, 129.3, 129.1, 128.9,
128.6, 127.1, 124.9, 122.3, 115.7, 21.7; IR (NaCl, neat) ν 3026, 2922,
1681, 1597, 1541, 1487, 1371, 1174, 1089, 920, 812 cmÀ1; MS (ESI) m/
z 410 [M + H]+; HRMS (ESI) calcd for C22H17ClNO3S (M+ + H)
410.0618, found 410.0619.
3-(Biphenyl-4-yl)-1-tosyl-1H-indole-2-carbaldehyde (2k): yellow
1
solid; mp 137À140 °C; H NMR (CDCl3, 300 MHz) δ 10.28 (1H,
s), 8.31 (1H, d, J = 8.4 Hz), 7.82 (2H, d, J = 8.4 Hz), 7.71À7.53 (8H, m),
7.44À7.48 (2H, m), 7.29À7.39 (2H, m), 7.24 (2H, d, J = 8.1 Hz), 2.37
(3H, s); 13C NMR (CDCl3, 75 MHz) δ 182.6, 145.3, 141.8, 140.4,
138.2, 135.3, 135.1, 132.5, 131.0, 129.8, 129.2, 128.9, 127.7, 127.2, 127.1,
127.0, 124.7, 122.7, 115.8, 36.6, 24.7, 21.7; IR (NaCl, neat) ν 3066, 3030,
2958, 2924, 1683, 1597, 1544, 1508, 1487, 1444, 1371, 1172, 1089, 921,
846, 812 cmÀ1; MS (ESI) m/z 452 [M + H]+; HRMS (ESI) calcd for
C28H22NO3S (M+ + H) 452.1320, found 452.1321.
5-Methyl-3-phenyl-1-tosyl-1H-indole-2-carbaldehyde (2b): yellow
gum; 1H NMR (CDCl3, 400 MHz) δ 10.21 (1H, s), 8.17 (1H, d, J = 8.6
Hz), 7.79 (2H, d, J = 8.2 Hz), 7.45 (5H, m), 7.36 (1H, d, J = 7.0 Hz),
7.22À7.29 (3H, m), 2.38 (3H, s), 2.36 (3H, s); 13C NMR (CDCl3, 100
MHz) δ 182.5, 145.2, 136.5, 135.6, 135.1, 134.6, 132.6, 130.6, 130.5,
129.7, 129.6, 129.5, 129.0, 128.4, 127.2, 122.1, 115.5, 21.7, 21.3; IR
(NaCl, neat) ν 3061, 3026, 2922, 1681, 1597, 1543, 1492, 1369, 1172,
1087, 837, 812 cmÀ1; MS (ESI) m/z 390 [M + H]+; HRMS (ESI) calcd
for C23H20NO3S (M+ + H) 390.1164, found 390.1166.
3-(Naphthalen-2-yl)-1-tosyl-1H-indole-2-carbaldehyde (2l): yellow
oil; 1H NMR (CDCl3, 300 MHz) δ 10.27 (1H, s), 8.33 (1H, d, J = 8.5
Hz), 7.85 (6H, m,), 7.50 (5H, m), 7.25 (3H, m), 2.37 (3H, s); 13C NMR
(CDCl3, 75 MHz) δ 182.5, 145.3, 138.2, 135.7, 135.3, 133.3, 133.0,
132.7, 130.1, 129.8, 129.4, 129.2, 128.2, 128.0, 127.9, 127.8, 127.3, 126.9,
126.6, 124.7, 122.7, 115.8, 76.6, 21.7; IR (NaCl, neat) ν 3055, 3020,
2924, 1676, 1598, 1541, 1442, 1369, 1174, 1089, 962, 925, 862,
812 cmÀ1; MS (ESI) m/z 426 [M + H]+; HRMS (ESI) calcd for
C26H20NO3S (M+ + H) 426.1164, found 426.1164.
3-(Thiophen-2-yl)-1-tosyl-1H-indole-2-carbaldehyde (2m): color-
less gum; 1H NMR (CDCl3, 400 MHz) δ 10.30 (1H, s), 8.29 (1H, d,
J = 8.5 Hz), 7.84 (1H, d, J = 8.1 Hz), 7.79 (2H, d, J = 8.2 Hz), 7.58À7.48
(3H, m), 7.36 (1H, t, J = 7.8 Hz), 7.23 (2H, d, J = 8.1 Hz), 7.19 (1H, t, J =
3.9 Hz), 2.35 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 182.1, 145.3,
137.9, 134.8, 131.0, 130.4, 129.7, 129.2, 129.1, 128.3, 127.6, 127.4, 127.2,
124.8, 122.8, 115.6, 21.6; IR (NaCl, neat) ν 3421, 1681, 1598, 1506,
1492, 1444, 1429, 1369, 1172, 1087, 929, 812 cmÀ1; MS (ESI) m/z 382
5-Methoxy-3-phenyl-1-tosyl-1H-indole-2-carbaldehyde (2c): yel-
1
low solid; mp 129À132 °C; H NMR (CDCl3, 400 MHz) δ 10.23
(1H, s), 8.19 (1H, d, J = 9.2 Hz), 7.76 (2H, d, J = 8.3 Hz), 7.43 (5H, m),
7.22 (2H, d, J = 8.0 Hz), 7.16 (1H, dd, J = 2.6 Hz, J = 9.2 Hz), 6.86 (1H, d,
J = 2.4 Hz), 3.76 (3H, s), 2.36 (3H s); 13C NMR (CDCl3, 100 MHz)
δ 182.6, 157.3, 145.2, 135.4, 134.9, 133.1, 132.8, 130.6, 130.4, 129.7,
128.9, 128.4, 127.1, 119.2, 116.9, 103.4, 55.7, 21.6; IR (NaCl, neat)
ν 3020, 2926, 1681, 1597, 1541, 1492, 1371, 1174, 1087, 812 cmÀ1
;
MS (ESI) m/z 406 [M + H]+; HRMS (ESI) calcd for C23H20NO4S
(M+ + H) 406.1113, found 406.1115.
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FEATURED ARTICLE
[M + H]+; HRMS (ESI) calcd for C20H16NO3S2 (M+ + H) 382.0572,
found 382.0590.
(E)-2-(Iodomethylene)-3-phenyl-1-tosyl-2,3-dihydro-1H-benzo-
[f]indol-3-ol (3g): yellow solid; mp 135À137 °C; 1H NMR (CDCl3,
400 MHz) δ 8.33 (1H, s), 7.88 (1H, d, J = 8.3 Hz), 7.62 (3H, t, J = 8.4
Hz), 7.32À7.48 (4H, m), 7.12À7.25 (5H, m), 7.05 (2H, d, J = 7.4
Hz), 2.90 (1H, s), 2.39 (3H, s); 13C NMR (CDCl3, 100 MHz)
δ 147.8, 145.4, 142.8, 137.6, 135.3, 134.6, 134.0, 131.6, 129.9, 128.3, 128.2,
128.1, 127.6, 127.4, 127.0, 125.5, 125.2, 113.0, 82.5, 64.5, 21.7; IR (NaCl,
neat) ν 3442, 3105, 1633, 1504, 1489, 1446, 1361, 1170, 1153, 1089, 1047,
947 cmÀ1; MS (ESI) m/z 576 [M + Na]+; HRMS (ESI) calcd for
C26H20INO3SNa (M+ + Na) 576.0106, found 576.0103.
7-Methyl-5-tosyl-5H-[1,3]dioxolo[4,5-f]indole-6-carbaldehyde (2n):
colorless gum; 1H NMR (CDCl3, 400 MHz) δ 10.50 (1H, s), 7.71 (1H,
s), 7.58 (2H, d, J = 8.2 Hz), 7.19 (2H, d, J = 8.2 Hz), 6.87 (1H, s) 6.07
(2H, s), 2.45 (3H, s), 2.35 (3H, s); 13C NMR (CDCl3, 100 MHz) δ
184.3, 150.3, 146.3, 145.2, 134.2, 133.5, 132.7, 129.8, 126.7, 125.2, 102.0,
99.1, 96.7, 21.6, 10.8; IR (NaCl, neat) ν 3421, 3018, 1656, 1597, 1529,
1460, 1425, 1365, 1332, 1278, 1178, 1087, 1035, 902, 848 cmÀ1
;
MS (ESI) m/z 358 [M + H]+; HRMS (ESI) calcd for C18H16NO5S
(M+ + H) 358.0749, found 358.0744.
(E)-2-(Iodomethylene)-3-(p-tolyl)-1-tosylindolin-3-ol (3h): colorless
gum; 1H NMR (CDCl3, 400 MHz) δ 7.92 (1H, d, J = 8.3 Hz), 7.58 (2H,
d, J = 8.1 Hz), 7.31 (1H, d, J = 8.0 Hz), 7.30 (1H, s), 7.24 (2H, d, J = 7.7
Hz), 7.07 (1H, t, J = 7.5 Hz), 6.97À6.90 (5H, m), 2.64 (1H, s), 2.41 (3H,
s), 2.27 (3H, s); 13CNMR (CDCl3, 100 MHz) δ 148.0, 145.3, 139.6, 139.3,
137.0, 135.1, 133.6, 130.0, 129.8, 128.8, 127.6, 125.9, 125.3, 125.1, 116.5,
82.8, 65.6, 21.7, 21.1; IR (NaCl, neat) ν3444, 3113, 1710, 1627, 1598, 1462,
1365, 1292, 1172, 1076 cmÀ1; MS (ESI) m/z 540 [M + Na]+; HRMS
(ESI) calcd for C23H20INO3SNa (M+ + Na) 540.0106, found 540.0102.
(E)-3-(4-Chlorophenyl)-2-(iodomethylene)-1-tosylindolin-3-ol (3j):
colorless gum; 1H NMR (CDCl3, 400 MHz) δ 7.93 (1H, d, J = 8.3 Hz),
7.58 (2H, d, J = 8.1 Hz), 7.37 (1H, d, J = 7.9 Hz), 7.33 (1H, s), 7.26 (2H,
d, J = 7.9 Hz), 7.12 (2H, d, J = 8.5 Hz), 7.07 (1H, d, J = 7.4 Hz),
6.96À6.91 (3H, m). 2.50 (1H, s), 2.42 (3H, s); 13C NMR (CDCl3, 100
MHz) δ 147.5, 145.4, 140.7, 139.7, 134.7, 133.5, 133.2, 130.4, 129.8,
128.3, 127.6, 127.1, 126.1, 125.1, 116.7, 82.4, 66.3, 21.6; IR (NaCl, neat)
3-Methyl-1-tosyl-1H-indole-2-carbaldehyde (2o): white solid; mp
193À195 °C; 1H NMR (CDCl3, 300 MHz) δ 10.61 (1H, s), 8.20 (1H, d,
J = 8.5 Hz), 7.55 (3H, d, J = 8.2 Hz), 7.50 (1H, dd, J = 1.1 Hz, J = 8.4 Hz),
7.29 (1H, dd, J = 0.7 Hz, J = 7.9 Hz), 7.12 (2H, d, J = 8.1 Hz), 2.51 (3H, s),
2.30 (3H, s); 13C NMR (CDCl3, 75 MHz) δ 185.3, 145.3, 137.5, 134.2,
133.0, 132.1, 130.6, 129.8, 129.1, 126.7, 124.6, 121.6, 115.8, 21.6, 10.5; IR
(NaCl, neat) ν 3057, 2910, 1672, 1595, 1556, 1490, 1444, 1415, 1363,
1172, 1089, 954, 879, 813 cmÀ1; MS (ESI) m/z 314 [M + H]+; HRMS
(ESI) calcd for C17H16NO3S (M+ + H) 314.0851, found 314.0853.
3-Ethyl-1-tosyl-1H-indole-2-carbaldehyde (2p): colorless gum;
1H NMR (CDCl3, 400 MHz) δ 10.58 (1H, s), 8.22 (1H, d, J = 8.5
Hz), 7.59À7.49 (4H, m), 7.33 (1H, t, J = 7.5 Hz), 7.14 (2H, d, J = 8.2
Hz), 2.99 (2H, q, J = 7.5 Hz), 2.30 (3H, s), 1.18 (3H, t, J = 7.5 Hz); 13C
NMR (CDCl3, 100 MHz) δ 184.9, 145.2, 138.4, 137.8, 134.1, 132.3,
129.7, 129.6, 128.9, 126.7, 124.6, 121.4, 116.0, 21.5, 18.1, 14.4; IR (NaCl,
neat) ν 3439, 1676, 1597, 1550, 1490, 1444, 1411, 1357, 1172, 1087, 981,
906, 810 cmÀ1; MS (ESI) m/z 328 [M + H]+; HRMS (ESI) calcd for
C18H18NO3S (M+ + H) 328.1007, found 328.1013.
ν 3444, 1625, 1597, 1462, 1365, 1292, 1259, 1172, 1089, 1076, 804 cmÀ1
;
MS (ESI) m/z 559.9 [M + Na]+; HRMS (ESI) calcd for C22H17I-
NO3SClNa (M+ + Na) 559.9560, found 559.9556.
1
1-Tosyl-1H-indole-2-carbaldehyde (2q):12 colorless oil; H NMR
(E)-2-(Iodomethylene)-3-methyl-1-tosylindolin-3-ol (3o): colorless
gum; 1H NMR (CDCl3, 400 MHz) δ 7.82 (1H, d, J = 8.2 Hz), 7.48 (2H,
d, J = 8.2 Hz), 7.37 (1H, t, J = 8.2 Hz), 7.25 (1H, d, J = 7.5 Hz), 7.19 (3H,
d, J = 8.2 Hz), 7.08 (1H, s), 2.37 (1H, s), 2.35 (3H, s), 1.10 (3H, s); 13C
NMR (CDCl3, 100 MHz) δ 147.3, 145.0, 139.1, 135.9, 133.8, 130.0,
129.6, 127.4, 126.0, 123.2, 117.2, 79.5, 63.2, 26.5, 21.5; IR (NaCl, neat) ν
3442, 2918, 1670, 1597, 1550, 1492, 1446, 1415, 1367, 1172, 1089, 954,
881, 812 cmÀ1; MS (ESI) m/z 463.9 [M + Na]+; HRMS (ESI) calcd for
C17H16NO3SNaI (M+ + Na) 463.9793, found 463.9795.
(CDCl3, 400 MHz) δ 10.53 (1H, s), 8.24 (1H, d, J = 8.6 Hz), 7.66 (2H,
d, J = 8.3 Hz), 7.63 (1H, d, J = 8.0 Hz), 7.54 (1H, t, J = 7.8 Hz),
7.46 (1H, s), 7.33 (1H, t, J = 7.6 Hz), 7.20 (2H, d, J = 8.2 Hz), 2.32 (3H,
s); 13C NMR (CDCl3, 100 MHz) δ 183.3, 145.6, 138.5, 137.8, 134.6,
129.9, 128.8, 128.2, 126.6, 124.8, 123.6, 118.3, 115.4, 21.5.
(E)-2-(Iodomethylene)-3-phenyl-1-tosylindolin-3-ol (3a): yellow so-
lid; mp 84À86 °C; 1H NMR (CDCl3, 400 MHz) δ 7.91 (1H, d, J = 8.3
Hz), 7.58 (2H, d, J = 8.2 Hz), 7.31 (2H, d, J = 8.2 Hz), 7.24 (2H, d, J = 8.1
Hz), 7.12 (3H m), 7.01 (3H, m), 6.95 (1H, d, J = 7.5 Hz), 2.65 (1H, s),
2.41 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 148.0, 145.3, 142.3, 139.7,
135.1, 133.6, 130.2, 129.8, 128.2, 127.6, 127.3, 126.0, 125.6, 125.3, 116.6,
82.9, 65.9, 21.7; IR (NaCl, neat) ν 3446, 3105, 1807, 1624, 1598, 1462,
1365, 1292, 1257, 1172, 1087, 1074, 810 cmÀ1; MS (ESI) m/z 504
[M + H]+; HRMS (ESI) calcd for C22H19INO3S (M+ + H) 504.0130,
found 504.0135.
1
(E)-2-(Iodomethylene)-1-tosylindolin-3-ol (3q): colorless gum; H
NMR (CDCl3, 400 MHz) δ 7.81 (1H, d, J = 8.2 Hz), 7.52 (2H, d, J = 8.0
Hz), 7.41 (1H, d, J = 7.6 Hz), 7.37 (1H, d, J = 7.5 Hz), 7.26
(1H, s), 7.19À7.16 (3H, m), 5.29, (1H, d, J = 5.6 Hz), 2.34 (3H, s),
1.82 (1H, d, J = 6.5 Hz); 13C NMR (CDCl3, 100 MHz) δ 145.9, 145.0,
142.0, 133.4, 130.6, 129.7, 129.6, 127.3, 125.8, 125.7, 117.1, 73.7, 70.0,
21.6. IR (NaCl, neat) ν 3446, 3018, 1670, 1595, 1490, 1365, 956,
880 cmÀ1; MS (ESI) m/z 450 [M + Na]+; HRMS (ESI) calcd for
C16H14NO3SNaI (M+ + Na) 449.9637, found 449.9622.
(E)-5-Chloro-2-(iodomethylene)-3-phenyl-1-tosylindolin-3-ol (3d):
1
yellow solid; mp 138À141 °C; H NMR (CDCl3, 400 MHz) δ 7.86
(1H, d, J = 8.8 Hz), 7.58 (2H, d, J = 8.0 Hz), 7.14À7.33 (7H, m), 6.98
(2H, d, J = 7.2 Hz), 6.92 (1H, d, J = 1.2 Hz), 2.73 (1H, s), 2.44 (3H, s);
13C NMR (CDCl3, 100 MHz) δ 147.7, 145.6, 141.6, 138.3, 136.6, 133.3,
131.3, 130.4, 130.0, 128.4, 127.7, 127.6, 125.5, 125.4, 117.7, 82.7, 66.2,
21.7; IR (NaCl, neat) ν 3446, 3109, 1637, 1595, 1458, 1363, 1172, 1039,
883, 823 cmÀ1; MS (ESI) m/z 537 [M + H]+; HRMS (ESI) calcd for
C22H18ClINO3S (M+ + H) 537.9741, found 537.9744.
’ ASSOCIATED CONTENT
Supporting Information. 1H and 13C NMR spectra for
S
b
all starting materials and products, LCMS spectrum of 18O-2a,
and X-ray data for 3e (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
(E)-5-Bromo-2-(iodomethylene)-3-phenyl-1-tosylindolin-3-ol (3e):
1
yellow solid; mp 103À106 °C; H NMR (CDCl3, 400 MHz) δ 7.80
’ AUTHOR INFORMATION
(1H, d, J = 8.8 Hz), 7.58 (2H, d, J = 8.2 Hz), 7.42 (1H, dd, J = 1.8 Hz, J =
8.8 Hz), 7.32 (1H, s), 7.14À7.30 (5H, m), 7.06 (1H, d, J = 1.7 Hz), 6.98
(2H, d, J = 7.5 Hz), 2.75 (1H, s), 2.44 (3H, s); 13C NMR (CDCl3, 100
MHz) δ 147.6, 145.6, 141.6, 138.8, 136.9, 133.3, 133.2, 130.0, 128.4,
128.3, 127.7, 127.6, 125.4, 118.8, 118.1, 82.6, 66.1, 21.7; IR (NaCl, neat)
ν 3442, 3109, 1633, 1595, 1417, 1361, 1172, 1128, 1076, 1035, 883,
812 cmÀ1; MS (ESI) m/z 581 [M + H]+; HRMS (ESI) calcd for
C22H18BrINO3S (M+ + H) 581.9236, found 581.9249.
Corresponding Author
*E-mail: waihong@ntu.edu.sg.
’ ACKNOWLEDGMENT
This work is supported by a University Research Committee
Grant (RG55/06) from Nanyang Technological University and a
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The Journal of Organic Chemistry
FEATURED ARTICLE
Science and Engineering Research Council Grant (092 101 0053)
from A*STAR, Singapore. Mr. Anbarasu Kothandaraman is also
gratefully acknowledged for providing the photographs used in the
front cover artwork.
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