Cyclopropyl carbinol rearrangement for benzo-fused nitrogen ring synthesis

Article abstract of DOI:10.1002/chem.201101363

A synthetic method that relies on gold-catalysed cyclopropyl carbinol rearrangement of 2-tosylaminophenyl cyclopropylmethanols to prepare 2,3-dihydro-1H-benzo[b]azepines and 2-vinylindolines efficiently is reported. The reactions were shown to be chemoselective, with secondary and tertiary alcohol substrates exclusively providing benzo-fused five- and seven-membered ring products, respectively. The ring-forming process was also found to proceed in moderate to excellent yields under mild conditions only in the presence of the gold and silver catalyst combination. The mechanism is thought to involve activation of the alcohol by the (p-CF₃C₆H ₄)₃PAuCl/AgOTf (Tf=triflate) catalyst, resulting in ionization of the starting material. The tertiary carbocationic intermediate generated in situ in this manner then triggers ring-opening of the cyclopropane moiety and trapping by the tethered aniline group to give the 2,3-dihydro-1H-benzo[b]azepine. Cyclopropane ring fragmentation of the secondary carbocationic analogue, on the other hand, results in diene formation followed by subsequent intramolecular hydroamination to afford the 2-vinylindoline. Copyright

Full text of DOI:10.1002/chem.201101363

FULL PAPER
DOI: 10.1002/chem.201101363
Cyclopropyl Carbinol Rearrangement for Benzo-Fused Nitrogen Ring
Synthesis
Prasath Kothandaraman, Chuhui Huang, Dewi Susanti, Weidong Rao, and
Philip Wai Hong Chan*[a]
Abstract:
A
synthetic method that
ceed in moderate to excellent yields
under mild conditions only in the pres-
ence of the gold and silver catalyst com-
bination. The mechanism is thought to
involve activation of the alcohol by the
the starting material. The tertiary carbo-
cationic intermediate generated in situ
in this manner then triggers ring-open-
ing of the cyclopropane moiety and
trapping by the tethered aniline group
to give the 2,3-dihydro-1H-benzo[b]aze-
pine. Cyclopropane ring fragmentation
of the secondary carbocationic ana-
logue, on the other hand, results in
diene formation followed by subsequent
relies on gold-catalysed cyclopropyl car-
binol rearrangement of 2-tosylamino-
phenyl cyclopropylmethanols to prepare
2,3-dihydro-1H-benzo[b]azepines and 2-
vinylindolines efficiently is reported.
The reactions were shown to be chemo-
selective, with secondary and tertiary al-
cohol substrates exclusively providing
benzo-fused five- and seven-membered
ring products, respectively. The ring-
forming process was also found to pro-
(p-CF3C6H4)3PAuCl/AgOTf
(Tf=tri-
flate) catalyst, resulting in ionization of
Keywords: alcohols · cyclization ·
gold · homogeneous catalysis · ni-
trogen heterocycles
intramolecular
hydroamination
to
afford the 2-vinylindoline.
Introduction
nophenyl cyclopropylmethanols 1 (Scheme 1). We reasoned
that this class of compounds might also undergo ionization
through coordination of the hydroxy functional group of the
substrate with a gold catalyst. The resultant putative carbo-
cationic species B, formed in situ, would be susceptible to
cyclopropyl carbinol rearrangement (route a in Scheme 1).
Trapping by the tethered aniline moiety when R1 =alkyl or
aryl would then afford the 2,3-dihydro-1H-benzo[b]azepine
product 2 and an alternative method for the preparation of
this N-heterocycle that does not rely on a ring-closing
alkene metathesis strategy.[7]
On the other hand, we anticipated that a carbocationic
species generated from a secondary alcohol containing a dis-
ubstituted cyclopropane moiety would be prone to a more
rapid ring-opening rearrangement process and in situ forma-
tion of the diene 3 (route b in Scheme 1).[8] Subsequent
gold-mediated intramolecular diene hydroamination, a type
Transition-metal-catalysed ring-opening and -expansion of
cyclopropanes offer a highly efficient and convenient syn-
thetic route to nitrogen heterocycles.[1] By exploitation of
the inherent ring strain in these three-membered cyclic
structures, no pre-functionalization is required and the reac-
tions can, in theory, be atom-economical and afford minimal
amounts of waste products. The field has received an im-
mense amount of attention over the years, with a myriad of
impressive metal-mediated methods for the synthesis of N-
heterocycles having been developed.
Approaches that make use of a cyclopropylmethanol-
based strategy, in contrast, have been less widely investigat-
ed.[2–4] Although we have recently delineated one such pro-
cess, which allowed the conversion of cyclopropylmethanols
and aryl sulfonamides into pyrrolidines with the aid of gold
catalysis,[3,5] as shown in Scheme 1, applications to other ni-
trogen ring systems have remained rare. In this context and
as part of an ongoing program exploring the scope of gold
catalysis in heterocyclic synthesis,[6] further exploration of
this chemistry guided us to the readily available 2-tosylami-
ꢀ
of C N bond-forming process of which there are only a
handful of examples in the literature,[9] would then be ex-
pected to deliver the 2-vinylindoline 4.[10] Here we describe
the details of this chemistry, which offers an expedient and
chemoselective approach to these two structurally important
bioactive classes of benzo-fused nitrogen heterocycles
through gold-catalysed cyclopropyl carbinol rearrangement
of 2-tosylaminophenyl cyclopropylmethanols.
[a] P. Kothandaraman, C. Huang, D. Susanti, Dr. W. Rao,
Prof. Dr. P. W. H. Chan
Division of Chemistry and Biological Chemistry
School of Physical and Mathematical Sciences
Nanyang Technological University
Singapore 637371 (Singapore)
Results and Discussion
Fax : (+65)6791-1961
E-mail: waihong@ntu.edu.sg
We began by examining the cyclopropyl carbinol rearrange-
ment of 1-cyclopropyl-1-[2-(tosylamino)phenyl]ethanol (1a,
Table 1) in the presence of a variety of Lewis and Brønsted
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101363.
Chem. Eur. J. 2011, 17, 10081 – 10088
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
10081

acid catalysts to establish the
reaction conditions. The best
result was obtained by treating
1a with (p-CF3C6H4)3PAuCl
(5 mol%)
and
AgOTf
(5 mol%) in toluene at reflux
for 2 h, which gave 5-methyl-1-
tosyl-2,3-dihydro-1H-benzo[b]-
AHCTUNGERTGaNNUN zepine (2a) in 81% yield
(Table 1, entry 1). The struc-
ture of the nitrogen ring prod-
uct
1H NMR spectroscopy and X-
ray crystallography (Fig-
ure 1).[11] In contrast, repetition
was
determined
by
AHCTUNGTRENNUNG
of the reaction in other sol-
vents was found to be marked-
ly less effective (Table 1, en-
tries 2–5). Use of chlorinated
solvents, such as CH2Cl2 or 1,2-
dichloroethane, as well as 1,4-
dioxane, afforded the vinylcy-
clopropane (VCP) by-product
5 as either the sole or the
major adduct in 24–78% yields
(Table 1, entries 2–4). Chang-
ing the solvent from toluene to
Scheme 1. Cyclopropyl carbinol rearrangement for benzo-fused nitrogen ring synthesis.
MeNO2 was found to result in no reaction (based on TLC
and H NMR analysis of the crude mixture) and recovery of
Table 1. Optimization of the reaction conditions.[a]
1
the substrate (Table 1, entry 5). Similarly, a survey of other
Lewis and Brønsted acid catalysts did not provide any im-
provements (Table 1, entries 6–22). In all but one of these
last experiments, the VCP by-product was again obtained as
either the sole or the major product or no reaction was ob-
served. The analogous reaction of 1a catalysed by AuCl
(5 mol%) and AgOTf (5 mol%) in toluene was the only
other instance in which we found 2a was produced in a high
Entry
Yield [%][b]
Catalyst
Solvent
2a
5
1[c]
2
3
4
5
(p-CF3C6H4)3PAuCl/AgOTf
(p-CF3C6H4)3PAuCl/AgOTf
(p-CF3C6H4)3PAuCl/AgOTf
(p-CF3C6H4)3PAuCl/AgOTf
(p-CF3C6H4)3PAuCl/AgOTf
Ph3PAuCl/AgOTf
AuCl/AgOTf
AuCl3/AgOTf
(p-CF3C6H4)3PAuCl
Ph3PAuCl
PhMe
CH2Cl2
(CH2Cl)2
81
–
10
18
–
–
72
10
12
–
–
44
78
24
–
81
–
1,4-dioxane
MeNO2
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
[d]
6
7[c]
8
36
–
9
10
[d]
5
–
11
12
13
14
15
16
17
18
19
20
21
22
AuCl
AuCl3
AgOTf
AgSbF6
8[d]
–
19
[d]
29
63
–
[d]
–
–
–
–
–
–
–
–
7
Cu
A
73
53
51
63
76
34
60
67
Yb
ACHTUNGTRENNUNG
FeCl3
InCl3
ZnCl2
BF3·Et2O
p-TsOH·H2O
TfOH
[a] All reactions were performed with 1a (0.2 mmol) in the presence of
the catalyst (5 mol%) at reflux for 18 h. [b] Yield of the isolated product.
[c] Reaction performed for 2 h. [d] Recovery of 1a in 52–80% yield. Ts=
p-toluenesulfonyl.
Figure 1. ORTEP drawing of 2a with thermal ellipsoids at 50% probabil-
ity levels.[11]
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Chem. Eur. J. 2011, 17, 10081 – 10088

Benzo-Fused Nitrogen Ring Synthesis
FULL PAPER
yield (72%, Table 1, entry 7). More notably, the contrasting
catalytic activities observed in the reactions mediated by
TfOH, AgOTf and other metal triflates also provided evi-
dence to rule out a Brønsted acid promoted process and
that the cationic AuI complex is the catalytic species.
To investigate the scope of these conditions, we next eval-
uated their generality for a series of tertiary 2-tosylamino-
phenyl cyclopropylmethanols; the results are summarized in
Table 2. In general, we were pleased to find the reaction
nucleophilicity of the aniline moiety was found to play a
role in the reactivity. We found that a substrate containing
an electron-withdrawing group, as in 1g and 1h, would
afford a slightly lower product yield than its counterparts
with an electron-neutral or electron-donating group at the
same position, as in 1b and 1 f. Under the standard condi-
tions, the disubstituted cyclopropane 1k was the only exam-
ple in which a mixture of decomposition products was ob-
1
tained (based on TLC and H NMR analysis of the crude
mixture).
With the reaction conditions for 2,3-dihydro-1H-benzo[b]
azepines established, we next examined the scope of this
new methodology for the synthesis of 2-vinylindolines
(Table 3). As shown above (Scheme 1), we anticipated that
Table 2. (p-CF3C6H4)3PAuCl/AgOTf-catalysed cyclopropyl carbinol rear-
rangements of 1b–k.[a,b]
Table 3. (p-CF3C6H4)3PAuCl/AgOTf-catalysed synthesis of the 2-vinylin-
dolines 4.[a,b]
[a] All reactions were performed with 1 (0.3 mmol) in the presence of (p-
CF3C6H4)3PAuCl/AgOTf (5 mol%) in PhMe at reflux. For reaction times,
please refer to the Experimental Section. [b] Values in parentheses repre-
sent yields of isolated products (%). [c] Mixture of unknown side prod-
1
ucts (based on H NMR analysis of the crude mixture) obtained after 2 h.
[a] All reactions were performed with 1 (0.3 mmol) in the presence of (4-
CF3C6H4)3PAuCl/AgOTf (5 mol%) in PhMe at reflux. For reaction times,
please refer to the Experimental Section. [b] Values in parentheses repre-
sent yields of isolated products (%). [c] Mixture of unknown side prod-
ucts (based on 1H NMR analysis of the crude mixture) obtained after
1.5 h.
conditions to be broad, delivering a variety of substituted
2,3-dihydro-1H-benzo[b]azepines in good to excellent yields.
Starting alcohols with pendant phenyl rings and their deriva-
tives with electron-withdrawing or electron-donating groups
at their para positions were found to react well, affording
the corresponding products 2b–e in excellent yields of 83–
87%. Similarly, the 2,3-dihydro-1H-benzo[b]azepines 2 f–j,
containing substituents on their benzo-fused ring structures,
were obtained in good to excellent yields of 46–92% from
the corresponding alcoholic substrates 1 f–j. The structures
of 2b and 2j were confirmed by X-ray crystallographic anal-
ysis (see Figures S43 and S44 in the Supporting Informa-
tion). Notably, these cyclizations also demonstrated that the
such control in product chemoselectivity should be achieva-
ble simply by switching from a tertiary to a secondary alco-
hol as substrate. With this in mind, we first tested the reac-
tion behaviour of (2-phenylcyclopropyl)-1-[2-(tosylamino)-
phenyl]methanol (1l, Table 3) in the presence of (p-
CF3C6H4)3PAuCl (5 mol%) and AgOTf (5 mol%) under the
standard conditions and found that (E)-2-styryl-1-tosylindo-
line (4a) could be obtained as the sole product in 82%
yield. Under similar conditions, repetition of the reaction
Chem. Eur. J. 2011, 17, 10081 – 10088
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10083

P. W. H. Chan et al.
with the other secondary alcohols 1m–r, variously contain-
ing an electron-withdrawing, an electron-donating or a steri-
cally bulky aryl group on the cyclopropane ring, gave the
corresponding 2-vinylindoline products 4b–g in excellent
yields of 78–92%. The trans structure of 4g was also con-
firmed by X-ray crystal structure analysis (Figure 2) and no
CF3C6H4)3PAuCl (5 mol%) and AgOTf (5 mol%) under the
standard conditions was first examined (Scheme 2a). This
test resulted only in the recovery of the VCP substrate in
near quantitative yield and led us to surmise that an alterna-
tive pathway involving an intermediate of the type 5 was un-
likely for reactions of tertiary substrates containing an alkyl
group at the carbinol carbon. Interestingly, this contrasted
with a previous study by Togni and co-workers, who had
demonstrated one example of a closely related VCP readily
undergoing tandem ring-opening/intramolecular hydroami-
nation with TsNH2 to give the corresponding pyrrolidine
adduct in 64% yield.[12]
The likely involvement of a diene intermediate in reac-
tions with secondary alcohols, on the other hand, was sup-
ported by our findings when we investigated the cyclization
of 1l in the presence of (p-CF3C6H4)3PAuCl/AgOTf
(5 mol%) under the conditions shown in Scheme 2b at
shorter reaction times. This revealed the production of the
disubstituted trans diene 3a, structurally determined by X-
ray crystallography (see Figure S45 in the Supporting Infor-
mation), along with 4a (yields of 62 and 30%, respectively).
On exposure of compound 3a once more to the standard
conditions of (p-CF3C6H4)3PAuCl/AgOTf (5 mol%) in tolu-
ene at reflux for 1 h, the expected 2-vinylindoline 4a was
obtained in 84% yield, which is comparable to that directly
produced from 1l shown in Table 3. The reactivities of the
secondary alcohols examined in Table 3 additionally suggest
that the diene formation process occurs in a stepwise
manner and thus involves a transient carbocationic species.
This would also explain the poor results obtained with com-
pounds 1s and 1t, because the ability to stabilize such an in-
termediate through resonance stabilization would be expect-
ed to diminish rapidly on going from 1l–r!1s!1t.
Figure 2. ORTEP drawing of 4g with thermal ellipsoids at 50% probabil-
ity levels.[11]
other side products were detected by TLC and 1H NMR
analysis of the crude mixtures. In our hands, the only instan-
ces that were less successful were the (p-CF3C6H4)3PAuCl/
AgOTf-catalysed cyclopropyl carbinol rearrangements of
secondary alcohols containing
either an n-pentane group or
no substituents on the cyclo-
propane ring, as in 1s and 1t.
The reaction of 1s gave 4h in a
low yield of 23%, whereas that
of 1t resulted in a mixture of
decomposition products (based
1
on TLC and H NMR analysis
of the crude mixture).
In addition to the above re-
sults, we conducted the follow-
ing control experiments to pro-
vide further support for the
mechanism
outlined
in
Scheme 1, as well as to dis-
count the possibility of other
pathways. In view of the com-
petitive formation of the VCP
side product 5 from reactions
of 1a under certain conditions
as described in Table 1, the re-
action behaviour of this inter-
mediate in the presence of (p-
Scheme 2. (p-CF3C6H4)3PAuCl/AgOTf-catalysed reactions of 1b, 1l, 3a, 3b, and 5.
10084
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Benzo-Fused Nitrogen Ring Synthesis
FULL PAPER
For tertiary alcohols, the mechanism leading to the 2,3-di-
hydro-1H-benzo[b]azepines put forward in Scheme 1 was
supported by repetition of the cyclopropyl carbinol rear-
rangement 1b under the conditions shown in Scheme 2c at
shorter reaction times. This showed that 2b was obtained,
along with recovery of the substrate (yields of 58 and 35%,
respectively), but not the trisubstituted diene 3b. Indeed,
this was further corroborated by the fact that the 1,2-dihy-
droquinoline 6 was obtained as the sole product in 92%
yield when a toluene solution containing a 1:1 cis/trans iso-
meric mixture of 3b[13] was subjected to (p-CF3C6H4)3PAuCl
and AgOTf (5 mol%) under the conditions shown in
Scheme 2d.
manner to give the thermodynamically more stable 1,2-dihy-
droquinoline adduct. Additionally, the fact that the trans
isomer of 3b can also undergo intramolecular hydroamina-
ꢀ
tion suggests that Au C bond formation is further advanced
ꢀ
than N C bond formation in the transition state depicted in
Scheme 3. This would not be inconceivable given that the
resultant developing carbocationic charge can be stabilized
by the allylic moiety.
Conclusion
We have demonstrated for the first time that cyclopropyl
carbinol rearrangement is an effective and chemoselective
strategy for the construction of benzo-fused nitrogen hetero-
cycles. The reaction was shown to tolerate a diverse set of
substrate alcohols and to proceed efficiently only in the
presence of the gold and silver catalyst combination, giving
2,3-dihydro-1H-benzo[b]azepines and 2-vinylindolines for
application in natural product synthesis and as versatile priv-
ileged scaffolds in medicinal chemistry. Previous synthetic
approaches to these benzo-fused nitrogen ring compounds
have relied on multistep routes; our method is rapid and
makes use of starting materials and a catalytic system that is
readily available, ecologically benign and simple.
It is interesting to note that the contrasting product selec-
tivities found in these control experiments additionally pro-
vide an insight into the role of steric effects on chemoselec-
tivity in transition-metal-catalysed intramolecular diene hy-
ꢀ
droaminations. This is particularly so because such C N
bond-forming processes have not so far been extensively
studied.[14] As illustrated in Scheme 3, our studies suggest
ꢀ
that formation of the C N bond proceeds preferentially at
the internal C=C bond of the diene when R1 =H and R2 =
alkyl or aryl, despite the reaction having to undergo an un-
favourable 5-endo-trig pathway. We surmise that this could
be so that unfavourable steric interactions between the
metal and the R2 group and between the R2 group and the
ꢀ
N H bond can be kept to a minimum upon cyclization. On
the other hand, such steric interactions are apparently
absent when R1 =alkyl or aryl and R2 =H as in 3b and it is
the difference in steric factors between the two alkene moi-
eties that comes to the fore. Under reflux conditions, the hy-
droamination process can now proceed at the sterically less
hindered terminal C=C bond of the diene in a 6-exo-trig
Experimental Section
General remarks: All reactions were performed under argon or nitrogen.
Unless specified, all reagents and starting materials were purchased from
commercial sources and used as received. All substituted cyclopropyl-
AHCTUNGERTGmNNUN ethanol substrates and compound 3b used in this work were prepared
by literature procedures.[15] Solvents were purified by standard literature
procedures. Analytical TLC was per-
formed with precoated silica gel plates
(Merck 60 F254). Visualization was
achieved by use of UV light (254 nm).
Flash chromatography was performed
with silica gel and with gradient sol-
vent systems (n-hexane/EtOAc) as
1
eluents. H and 13C NMR spectra were
measured with Bruker Avance spec-
trometers (300, 400, and 500 MHz).
Chemical shifts (ppm) were recorded
with tetramethylsilane (TMS) as the
internal reference standard. Multiplici-
ties are given as:
s (singlet), brs
(broad singlet), d (doublet), t (triplet),
dd (doublet of doublets) or m (multip-
let). The number of protons (n) for a
given resonance is indicated by nH
and coupling constants are reported as
J values in Hz. Infrared spectra were
recorded with a Shimadzu IR Prestige-
21 FTIR spectrometer. Solid and
liquid samples were examined as KBr
discs or as thin films between NaCl
salt plates. Low-resolution mass spec-
tra were determined with a Finnigan
LCQ XP MAX mass spectrometer and
are reported in units of mass to charge
ratio (m/z). High-resolution mass spec-
Scheme 3. Possible transition states for (p-CF3C6H4)3PAuCl/AgOTf-catalysed intramolecular hydroaminations
of the dienes 3a and 3b.
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10085

P. W. H. Chan et al.
tra (HRMS) were obtained with a Finnigan MAT95XP LC/HRMS mass
spectrometer.
127.3, 127.1, 121.2, 57.7, 26.8, 21.3 ppm; IR (KBr): n˜ =2911, 2878, 2365,
2330, 1489, 1442, 1339, 1161 cmꢀ1; MS (ESI): m/z: 454 [M+H]+; HRMS
(ESI) calcd for C23H21NO2SBr [M+H]+: 454.0476; found: 454.0474.
General procedure for optimizing the Lewis and Brønsted acid catalysed
cyclopropyl carbinol rearrangement of 1a to 2a: For reactions with a
gold/silver catalyst combination, the gold (15 mmol) and silver (15 mmol)
catalysts were first stirred in toluene (1.5 mL) at room temperature for
10 min. In all other cases the catalyst was added to the appropriate sol-
5-p-Tolyl-1-tosyl-2,3-dihydro-1H-benzo[b]azepine (2e): Reaction time=
1
3 h; yellow solid; m.p.: 159–1638C; H NMR (CDCl3, 400 MHz): d=7.61
(d, J=7.8 Hz, 1H), 7.50 (d, J=7.76 Hz, 2H), 7.21–7.33 (m, 2H), 6.93–
7.00 (m, 4H), 6.78 (d, J=7.44 Hz, 2H), 6.18 (t, J=6.84 Hz, 1H), 4.30
(brs, 2H), 2.33 (s, 3H), 2.25–2.27 (m, 2H), 2.21 ppm (s, 3H); 13C NMR
(CDCl3, 100 MHz): d=142.7, 142.6, 139.6, 137.8, 137.7, 137.6, 136.9,
131.3, 130.5, 129.1, 128.5, 128.1, 127.8, 127.7, 127.4, 125.7, 57.7, 26.8, 21.3,
21.1 ppm; IR (KBr): n˜ =3030, 2958, 2932, 2908, 2879, 2855, 1481, 1441,
1339, 1325, 1163 cmꢀ1; MS (ESI): m/z: 390 [M+H]+; HRMS (ESI) calcd
for C24H24NO2S: 390.1528 [M+H]+; found: 390.1530.
vent prior to addition of the starting material.
A toluene solution
(1.5 mL) containing 1a (0.3 mmol) was slowly added dropwise, and the
reaction mixture was stirred at reflux temperature and monitored to
completion by TLC analysis. The solvent was removed under reduced
pressure. Purification by flash column chromatography on silica gel
(eluent: n-hexane/EtOAc 20:1) gave the title compound.
General procedure for the (4-CF3C6H4)3PAuCl/AgOTf-catalysed cyclo-
propyl carbinol rearrangement of 1: A solution of (4-CF3C6H4)3PAuCl
(15 mmol) and AgOTf (15 mmol) in toluene (1.5 mL) was stirred under
Ar at room temperature for 10 min and a solution of 1 (0.3 mmol) in tol-
uene (1.5 mL) was slowly added dropwise. The reaction mixture was then
brought to reflux and stirred at this temperature until completion (TLC
analysis). The solvent was removed under reduced pressure. Purification
by flash column chromatography on silica gel (n-hexane/EtOAc 20:1 as
7-Methyl-5-phenyl-1-tosyl-2,3-dihydro-1H-benzo[b]azepine (2 f): Reac-
tion time=2 h; white gum; 1H NMR (CDCl3, 400 MHz): d=7.45–7.51
(m, 3H), 7.11–7.25 (m, 4H), 6.94 (dd, J=8.12, 16.8 Hz, 4H), 6.72 (d, J=
1.28 Hz, 1H), 6.21 (t, J=6.96 Hz, 1H), 4.21 (brs, 2H), 2.24 (s, 3H), 2.21
(s, 3H), 2.25–2.17 ppm (m, 2H); 13C NMR (CDCl3, 100 MHz): d=143.0,
142.7, 140.5, 139.2, 137.9, 134.9, 131.1, 130.8, 129.1, 129.0, 127.8, 127.8,
127.3, 127.1, 126.4, 57.7, 26.7, 21.3, 21.0 ppm; IR (NaCl, neat): n˜ =3022,
2926, 2872, 2854, 1492, 1339, 1159 cmꢀ1; MS (ESI): m/z: 390 [M+H]+;
HRMS (ESI) calcd for C24H24NO2S: 390.1528 [M+H]+; found: 390.1530.
eluent) gave either the 2,3-dihydro-1H-benzo[b]ACTHNUTRGNEUGaN zepine or the 2-vinylin-
doline product.
7-Bromo-5-phenyl-1-tosyl-2,3-dihydro-1H-benzo[b]azepine (2g): Reac-
tion time=2.5 h; colourless gum; 1H NMR (CDCl3, 300 MHz): d=7.41–
7.50 (m, 4H), 7.15–7.25 (m, 4H), 7.06 (d, J=2.1 Hz, 1H), 6.97 (d, J=
8.07 Hz, 2H), 6.86 (dd, J=1.2, 7.65 Hz, 2H), 6.27 (t, J=6.96 Hz, 1H),
4.22 (brs, 2H), 2.26–2.35 (m, 2H), 2.22 ppm (s, 3H); 13C NMR (CDCl3,
75 MHz): d=143.1, 142.0, 141.5, 139.9, 137.5, 136.7, 133.2, 132.9, 131.3,
129.3, 129.0, 128.2, 128.0, 127.7, 127.5, 127.3, 122.0, 57.6, 26.6, 21.3 ppm;
IR (NaCl, neat): n˜ =2928, 2882, 1479, 1447, 1339, 1159, 1084 cmꢀ1; MS
(ESI): m/z: 454 [M+H]+; HRMS (ESI) calcd for C23H21NO2SBr:
454.0476 [M+H]+; found: 454.0474.
General procedure for the (4-CF3C6H4)3PAuCl/AgOTf-catalysed intra-
molecular hydroamination of 3 or 5: A solution of (4-CF3C6H4)3PAuCl
(15 mmol) and AgOTf (15 mmol) in toluene (1.5 mL) was stirred under
Ar at room temperature for 10 min and a solution of 3 or 5 (0.3 mmol) in
toluene (1.5 mL) was slowly added dropwise. The reaction mixture was
then brought to reflux and stirred at this temperature until completion
(TLC analysis). The solvent was removed under reduced pressure. Purifi-
cation by flash column chromatography on silica gel (n-hexane/EtOAc
20:1 as eluent) variously gave the 2,3-dihydro-1H-benzo[b]azepine, the 2-
vinylindoline or the 1,2-dihydroquinoline product or recovery of the
starting material.
5-Methyl-1-tosyl-2,3-dihydro-1H-benzo[b]azepine (2a):[7i] Yellow oil;
1H NMR (CDCl3, 300 MHz): d=7.53 (dd, J=1.74, 7.23 Hz, 1H), 7.43 (d,
J=8.25 Hz, 2H), 7.26–7.32 (m, 2H), 7.13–7.17 (m, 3H), 5.63–5.59 (td, J=
1.38, 6.6 Hz, 1H), 4.13 (brs, 2H), 2.37 (s, 3H), 2.02–2.11 (m, 2H),
1.54 ppm (s, 3H); 13C NMR (CDCl3, 75 MHz): d=142.6, 140.8, 137.8,
136.4, 136.2, 131.9, 129.0, 128.2, 127.6, 127.3, 127.1, 125.7, 57.2, 26.3, 22.1,
21.4 ppm; MS (ESI): m/z: 314 [M+H]+.
7-Chloro-5-phenyl-1-tosyl-2,3-dihydro-1H-benzo[b]azepine (2h): Reac-
tion time=3 h; yellow solid; m.p.: 104–1078C; 1H NMR (CDCl3,
300 MHz): d=7.56 (d, J=8.52 Hz, 1H), 7.50 (d, J=8.25 Hz, 2H), 7.30–
7.16 (m, 4H), 6.98 (d, J=8.06 Hz, 2H), 6.90 (d, J=2.47 Hz, 1H), 6.86–
6.83 (dd, J=1.26, 7.71 Hz, 2H), 6.27 (t, J=6.96 Hz, 1H), 4.23 (brs, 2H),
2.24–2.31 (m, 2H), 2.22 ppm (s, 3H); 13C NMR (CDCl3, 75 MHz): d=
143.0, 142.0, 141.1, 139.9, 137.5, 136.2, 133.9, 132.6, 130.3, 129.3, 128.3,
128.0, 127.7, 127.7, 127.5, 127.3, 57.6, 26.7, 21.4 ppm; IR (KBr): n˜ =2918,
2876, 1477, 1340, 1161, 773 cmꢀ1; MS (ESI): m/z: 410 [M+H]+; HRMS
(ESI) calcd for C23H21NO2SCl: 410.0982 [M+H]+; found: 410.0988.
5-Phenyl-1-tosyl-2,3-dihydro-1H-benzo[b]azepine (2b): Reaction time=
2 h; yellow solid; m.p.: 141–1458C; H NMR (CDCl3, 300 MHz): d=7.61
1
5-Phenyl-1-tosyl-2,3-dihydro-1H-naphthoACTHNGUTERN[UNG 2,3-b]azepine (2i): Reaction
(d, J=7.8 Hz, 1H), 7.51 (d, J=8.13 Hz, 2H), 7.15–7.33 (m, 5H), 6.87–
6.95 (m, 5H), 6.23 (t, J=6.90 Hz, 1H), 4.23 (brs, 2H), 2.23–2.30 (m, 2H),
2.20 ppm (s, 3H); 13C NMR (CDCl3, 75 MHz): d=142.8, 140.6, 139.4,
137.8, 137.7, 131.3, 130.5, 129.2, 128.2, 127.9, 127.8, 127.8, 127.3, 127.2,
126.6, 57.6, 26.9, 21.3 ppm; IR (KBr): n˜ =3080, 3051, 2974, 2878, 1487,
1341, 1161 cmꢀ1; MS (ESI): m/z: 376 [M+H]+; HRMS (ESI) calcd for
C23H22NO2S: 376.1371 [M+H]+; found: 376.1375.
time=2.5 h; yellow gum; 1H NMR (CDCl3, 400 MHz): d=8.09 (s, 1H),
7.87 (d, J=7.8 Hz, 1H), 7.64 (d, J=7.92 Hz, 1H), 7.51–7.40 (m, 4H), 7.38
(s, 1H), 7.27–7.18 (m, 3H), 6.96–6.93 (m, 4H), 6.25 (t, J=6.96 Hz, 1H),
4.22 (brs, 2H), 2.25–2.38 (m, 2H), 2.21 ppm (s, 3H); 13C NMR (CDCl3,
100 MHz): d=142.9, 142.8, 141.1, 137.8, 137.6, 135.0, 132.8, 132.5, 130.1,
130.0, 129.2, 128.0, 127.9, 127.9, 127.7, 127.4, 127.3, 126.7, 126.5, 125.9,
56.1, 26.7, 21.4 ppm; IR (NaCl, neat): n˜ =3057, 2954, 2875, 1708, 1666,
1631, 1597, 1492, 1444, 1338, 1159, 1087, 1010, 956 cmꢀ1; MS (ESI): m/z:
426 [M+H]+; HRMS (ESI) calcd for C27H24NO2S: 426.1528 [M+H]+;
found: 426.1530.
5-(4-Chlorophenyl)-1-tosyl-2,3-dihydro-1H-benzo[b]azepine (2c): Reac-
tion time=3 h; white solid; m.p.: 168–1718C; 1H NMR (CDCl3,
300 MHz): d=7.59 (dd, J=1.19, 7.8 Hz, 1H), 7.49 (d, J=8.22 Hz, 2H),
7.22–7.35 (m, 3H), 7.16 (d, J=8.5 Hz, 2H), 6.97 (d, J=8.1 Hz, 2H), 6.90
(dd, J=1.52, 7.64 Hz, 1H), 6.82 (d, J=8.52 Hz, 2H), 6.25 (t, J=6.96 Hz,
1H), 4.30 (brs, 2H), 2.26–2.33 (m, 2H), 2.23 ppm (s, 3H); 13C NMR
(CDCl3, 75 MHz): d=142.9, 141.7, 139.1, 138.9, 137.9, 137.6, 133.1, 131.4,
130.3, 129.2, 129.0, 128.4, 128.1, 128.0, 127.3, 127.0, 57.7, 26.8, 21.3 ppm;
IR (KBr): n˜ =2959, 2933, 2913, 2880, 2856, 1491, 1481, 1342, 1323, 1161,
1111, 1038 cmꢀ1; MS (ESI): m/z: 410 [M+H]+; HRMS (ESI) calcd for
C23H21NO2SCl: 410.0982 [M+H]+; found: 410.0984.
9-Methyl-5-tosyl-6,7-dihydro-5H-[1,3]dioxolo[4’,5’:4,5]benzoACTHUNTGRNEUNG[1,2-b]aze-
pine (2j): Reaction time=17 h; colourless solid; m.p.: 165–1688C;
1H NMR (CDCl3, 400 MHz): d=7.45 (d, J=8.24 Hz, 2H), 7.18 (d, J=
8.12 Hz, 2H), 6.99 (s, 1H), 6.57 (s, 1H), 6.0 (s, 2H), 5.57 (td, J=1.28,
6.72 Hz, 1H), 4.37 (brs, 2H), 2.38 (s, 3H), 2.04 (q, J=6.44 Hz, 2H),
1.42 ppm (s, 3H); 13C NMR (CDCl3, 100 MHz): d=147.7, 146.5, 142.6,
137.7, 136.7, 135.2, 129.0, 127.4, 125.1, 112.4, 106.3, 101.7, 58.0, 26.1, 21.9,
21.4 ppm; IR (NaCl, neat): n˜ =3394, 3020, 2856, 1598, 1483, 1419, 1384,
1336, 1246, 1157, 1085, 966 cmꢀ1; MS (ESI): m/z: 358 [M+H]+; HRMS
(ESI) calcd for C19H20NO4S: 358.1113 [M+H]+; found: 358.1115.
5-(4-Bromophenyl)-1-tosyl-2,3-dihydro-1H-benzo[b]azepine (2d): Reac-
tion time=3 h; white solid; m.p.: 171–1758C; 1H NMR (CDCl3,
300 MHz): d=7.59 (d, J=7.8 Hz, 1H), 7.49 (d, J=8.16 Hz, 2H), 7.23–
7.35 (m, 4H), 6.97 (d, J=8.04 Hz, 2H), 6.90 (d, J=7.56 Hz, 1H), 6.76 (d,
J=8.4 Hz, 2H), 6.26 (t, J=6.93 Hz, 1H), 4.30 (brs, 2H), 2.28–2.32 (m,
2H), 2.23 ppm (s, 3H); 13C NMR (CDCl3, 75 MHz): d=142.9, 141.8,
139.4, 139.0, 137.9, 137.6, 131.5, 130.9, 130.2, 129.3, 129.2, 128.5, 128.1,
4-Methyl-N-[2-((1E,3E)-4-phenylbuta-1,3-dienyl)phenyl]benzenesulfona-
1
mide (3a): Colourless solid; H NMR (CDCl3, 400 MHz): d=7.63 (d, J=
8.04 Hz, 2H), 7.45–7.40 (m, 3H), 7.36 (t, J=7.44 Hz, 2H), 7.29–7.16 (m,
6H), 6.78–6.43 (m, 5H), 2.32 ppm (s, 3H); 13C NMR (CDCl3, 100 MHz):
d=144.0, 137.0, 136.4, 133.8, 133.0, 132.9, 132.4, 129.6, 128.8, 128.7, 128.2,
10086
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ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 10081 – 10088

Benzo-Fused Nitrogen Ring Synthesis
FULL PAPER
127.9, 127.3, 126.9, 126.4, 126.3, 21.5 ppm; IR (NaCl, neat): n˜ =3261,
(m, 1H), 3.16 (dd, J=9.54, 15.99 Hz, 1H), 2.80 (dd, J=2.43, 16.05 Hz,
1H), 2.31 ppm (s, 3H); 13C NMR (CDCl3, 75 MHz): d=143.8, 141.4,
135.8, 133.7, 133.5, 133.0, 131.3, 131.1, 129.5, 129.0, 128.0, 128.0, 127.9,
127.6, 127.2, 126.8, 126.2, 125.9, 125.2, 124.3, 123.6, 116.5, 64.0, 35.5,
21.4 ppm; IR (NaCl, neat): n˜ =2961, 2926, 2855, 1466, 1462, 1398, 1354,
1166, 895 cmꢀ1; MS (ESI): m/z: 426 [M+H]+; HRMS (ESI) calcd for
C27H24NO2S: 426.1528 [M+H]+; found: 426.1529.
3061, 3026, 1670, 1597, 1492, 1448, 1400, 1330, 1161, 1089, 989, 920,
813 cmꢀ1
;
MS (ESI): m/z: 376 [M+H]+; HRMS (ESI) calcd for
C23H22NO2S: 376.1371 [M+H]+; found: 376.1369.
4-Methyl-N-[2-(1-phenylbuta-1,3-dienyl)phenyl]benzenesulfonamide
(3b):[13] Yellow oil; 1H NMR (CDCl3, 400 MHz): d=7.76 (d, J=8.2 Hz,
2H), 7.60 (d, J=8.2 Hz, 1H), 7.00–7.47 (m, 22H), 6.82 (d, J=11.0 Hz,
1H), 6.47–5.60 (m, 2H), 6.26 (s, 1H), 5.80–5.89 (m, 2H), 5.40 (d, J=
16.8 Hz, 1H), 5.24 (t, J=8.7 Hz, 2H), 5.10 (d, J=10.1 Hz, 1H), 2.37 (s,
3H), 2.34 ppm (s, 3H); 13C NMR (CDCl3, 100 MHz): d=143.7, 143.6,
139.0, 138.5, 138.1, 137.2, 136.1, 136.0, 136.0, 134.7, 134.3, 133.6, 133.5,
132.6, 131.3, 130.8, 130.8, 129.6, 129.5, 129.4, 129.3, 129.0, 128.9, 128.7,
128.4, 128.2, 127.3, 127.2, 126.3, 125.3, 124.4, 123.0, 120.9, 120.7, 119.8,
21.5; MS (ESI): m/z: 376 [M+H]+.
(E)-2-Styryl-1-tosylindoline (4a):[10i] Reaction time=3 h; yellow gum;
1H NMR (CDCl3, 300 MHz): d=7.68 (d, J=8.07 Hz, 1H), 7.62 (d, J=
8.1 Hz, 2H), 7.20–7.32 (m, 6H), 7.15 (d, J=7.98 Hz, 2H), 6.99–7.08 (m,
2H), 6.71 (d, J=15.75 Hz, 1H), 6.19 (dd, J=7.08, 15.72 Hz, 1H), 4.93–
4.99 (m, 1H), 3.12 (dd, J=9.57, 16 Hz, 1H), 2.76 (dd, J=2.15, 16 Hz,
1H), 2.33 ppm (s, 3H); 13C NMR (CDCl3, 75 MHz): d=143.8, 141.4,
136.3, 135.7, 131.1, 129.5, 128.7, 128.4, 127.8, 127.8, 127.2, 126.6, 125.1,
124.3, 116.5, 63.9, 35.5, 21.5 ppm; MS (ESI): m/z: 376 [M+H]+.
(E)-1-Tosyl-2-(2,4,6-trimethylstyryl)indoline (4g): Reaction time=2 h;
white solid; m.p.: 113–1168C; 1H NMR (CDCl3, 300 MHz): d=7.68 (s,
1H), 7.65 (d, J=8.37 Hz, 2H), 7.16–7.24 (m, 3H), 6.98–7.07 (m, 2H),
6.82 (s, 2H), 6.68 (d, J=16.02 Hz, 1H), 5.78 (dd, J=6.87, 16.02 Hz, 1H),
4.86–4.93 (m, 1H), 3.11 (dd, J=9.63, 16.05 Hz, 1H), 2.76 (dd, J=3.42,
16.04 Hz, 1H), 2.35 (s, 3H), 2.24 (s, 3H), 2.22 ppm (s, 6H); 13C NMR
(CDCl3, 75 MHz): d=143.8, 141.6, 136.2, 135.9, 135.5, 133.6, 133.0, 131.1,
129.6, 128.9, 128.4, 127.8, 127.1, 125.0, 124.4, 116.7, 64.2, 35.7, 21.5, 20.9,
20.7 ppm; IR (KBr): n˜ =3023, 2955, 2926, 2857, 1480, 1463, 1346, 1331,
1159 cmꢀ1
;
MS (ESI): m/z: 418 [M+H]+; HRMS (ESI) calcd for
C26H28NO2S: 418.1841 [M+H]+; found: 418.1843.
(E)-2-(Hept-1-enyl)-1-tosylindoline (4h): Reaction time=17 h; white
gum; 1H NMR (CDCl3, 400 MHz): d=7.63 (d, J=8.24 Hz, 1H), 7.60 (d,
J=8.24 Hz, 2H), 7.22 (d, J=7.36 Hz, 1H), 7.18 (d, J=8.24 Hz, 2H),
7.05–6.98 (m, 2H), 5.80 (quintet, J=7.8 Hz, 1H), 5.50 (dd, J=7.36,
15.6 Hz, 1H), 4.75–4.71 (m, 1H), 2.99 (dd, J=9.64, 16.48 Hz, 1H), 2.63
(dd, J=2.77, 16.04 Hz, 1H), 2.35 (s, 3H), 2.02–1.95 (m, 2H), 1.35–1.22
(m, 6H), 0.84 ppm (t, J=7.1 Hz, 3H); 13C NMR (CDCl3, 100 MHz): d=
143.6, 141.4, 135.8, 132.7, 131.4, 129.4, 129.2, 127.6, 127.1, 125.0, 124.2,
116.6, 63.8, 35.5, 31.9, 31.4, 28.5, 22.4, 21.5, 14.0 ppm; IR (NaCl, neat):
n˜ =2959, 2928, 2857, 1477, 1460, 1352, 1167 cmꢀ1; MS (ESI): m/z: 370
[M+H]+; HRMS (ESI) calcd for C22H28NO2S: 370.1841 [M+H]+; found:
370.1841.
(E)-2-(4-Fluorostyryl)-1-tosylindoline (4b): Reaction time=3 h; colour-
1
less gum; H NMR (CDCl3, 300 MHz): d=7.68 (d, J=8.07 Hz, 1H), 7.62
(d, J=8.22 Hz, 2H), 7.20–7.30 (m, 3H), 7.16 (d, J=8.13 Hz, 2H), 6.93–
7.08 (m, 4H), 6.68 (d, J=15.75 Hz, 1H), 6.12 (dd, J=6.99, 15.75 Hz,
1H), 4.91–4.97 (m, 1H), 3.11 (dd, J=9.6, 16.05 Hz, 1H), 2.74 (dd, J=2.7,
16.05 Hz, 1H), 2.34 ppm (s, 3H); 13C NMR (CDCl3, 75 MHz): d=162.3
(d, JC,F =241.0 Hz, 1C), 143.8, 141.3, 135.7, 131.1, 129.9, 129.5, 128.2,
128.1, 127.9, 127.1, 125.1, 124.4, 116.6, 115.5 (d, JC,F =22.5 Hz, 1C), 63.7,
35.4, 21.5 ppm; IR (NaCl, neat): n˜ =2961, 2926, 1601, 1477, 1462, 1354,
1166, 1013 cmꢀ1; MS (ESI): m/z: 394 [M+H]+; HRMS (ESI) calcd for
C23H21NO2SF: 394.1277 [M+H]+; found: 394.1278.
N-[2-(1-Cyclopropylvinyl)phenyl]-4-methylbenzenesulfonamide (5): Col-
ourless gum; 1H NMR (CDCl3, 300 MHz): d=7.65–7.61 (m, 3H),7.18 (d,
J=8.16 Hz, 2H), 7.03–6.94 (m, 3H), 5.12 (s, 1H), 4.47 (d, J=1.27 Hz,
1H), 2.35 (s, 3H), 1.41–1.28 (m, 1H), 0.68–0.62 (m, 2H), 0.32–0.26 ppm
(m, 2H); 13C NMR (CDCl3, 75 MHz): d=147.7, 143.8, 136.3, 133.9,
131.7, 129.5, 129.2, 128.2, 127.3, 123.8, 119.3, 113.5, 21.5, 17.0, 6.5 ppm;
IR (NaCl, neat): n˜ =3081, 3065, 3007, 2978, 2359, 2332, 1645, 1574, 1584,
1497, 1323, 1307, 1208, 1166, 1090, 760, 658 cmꢀ1; MS (ESI): m/z: 314
[M+H]+; HRMS (ESI) calcd for C18H20NO2S: 314.1215 [M+H]+; found:
314.1217.
2-Methyl-4-phenyl-1-tosyl-1,2-dihydroquinoline (6):[13] White solid;
1H NMR (CDCl3, 500 MHz): d=7.81 (d, J=8.04 Hz, 1H), 7.23–7.34 (m,
6H), 7.12 (t, J=7.5 Hz, 1H), 7.02 (d, J=8.0 Hz, 2H), 6.86 (d, J=7.7 Hz,
1H), 6.72 (d, J=5.9 Hz, 2H), 5.62 (d, J=6.0 Hz, 1H), 5.08–5.14 (m, 1H),
2.27 (s, 3H), 1.20 ppm (d, J=6.9 Hz, 3H); 13C NMR (CDCl3, 125 MHz):
d=143.3, 138.2, 136.4, 135.9, 133.0, 129.9, 129.0, 128.8, 128.2, 128.0, 127.5,
127.5, 126.5, 125.8, 50.8, 21.4, 19.3 ppm; MS (ESI): m/z: 398 [M+Na]+.
(E)-2-(4-Chlorostyryl)-1-tosylindoline (4c): Reaction time=3 h; yellow
gum; 1H NMR (CDCl3, 400 MHz): d=7.68 (d, J=7.68 Hz, 1H), 7.61 (d,
J=7.71 Hz, 2H), 7.22–7.26 (m, 5H), 7.16 (d, J=7.53 Hz, 2H), 7.01–7.06
(m, 2H) , 6.67 (d, J=15.84 Hz, 1H), 6.17 (dd, J=6.90, 15.81 Hz, 1H,),
4.94–4.96 (m, 1H), 3.11 (dd, J=10.29, 16.09 Hz, 1H), 2.75 (dd, J=2.07,
16.3 Hz, 1H), 2.34 ppm (s, 3H); 13C NMR (CDCl3, 75 MHz): d=143.9,
141.3, 135.6, 134.8, 133.4, 131.0, 129.9, 129.5, 129.4, 128.6, 127.9, 127.8,
127.1, 125.2, 124.4, 116.6, 63.6, 35.4, 21.5 ppm; IR (NaCl, neat): n˜ =2924,
2855, 1478, 1460, 1354, 1167 cmꢀ1; MS (ESI): m/z: 410 [M+H]+; HRMS
(ESI) calcd for C23H21NO2SCl: 410.0982 [M+H]+; found: 410.0991.
(E)-2-(4-Bromostyryl)-1-tosylindoline (4d): Reaction time=3 h; brown
gum; 1H NMR (CDCl3, 300 MHz): d=7.68 (d, J=7.92 Hz, 1H), 7.62 (d,
J=8.04 Hz, 2H), 7.41 (d, J=8.31 Hz, 2H), 7.02–7.26 (m, 6H), 6.66 (d,
J=15.72 Hz, 1H), 6.19 (dd, J=6.9, 15.78 Hz, 1H), 4.91–4.96 (m, 1H),
3.11 (dd, J=9.54, 16.05 Hz, 1H), 2.74 (d, J=16.47 Hz, 1H), 2.34 ppm (s,
3H); 13C NMR (CDCl3, 75 MHz): d=143.9, 141.3, 135.6, 135.2, 133.0,
131.5, 129.9, 129.5, 129.6, 128.1, 127.9, 127.1, 125.1, 124.4, 121.5, 116.6,
63.6, 35.4, 21.5 ppm; IR (NaCl, neat): n˜ =2963, 2926, 2870, 1643, 1487,
1477, 1462, 1354, 1166, 1072, 1028 cmꢀ1; MS (ESI): m/z: 454 [M+H]+;
HRMS (ESI) calcd for C23H21NO2SBr: 454.0476 [M+H]+; found:
454.0470.
Acknowledgements
This work is supported by a University Research Committee Grant
(RG55/06) from Nanyang Technological University (NTU), and a Sci-
ence and Engineering Research Council Grant (092 101 0053) from
A*STAR, Singapore. An Undergraduate Research Experience on
Campus stipend (to D.S.) from NTU is also gratefully acknowledged.
(E)-2-(4-Methylstyryl)-1-tosylindoline (4e): Reaction time=2.5 h; yellow
gum; 1H NMR (CDCl3, 300 MHz): d=7.67 (d, J=8.1 Hz, 1H), 7.63 (d,
J=8.25 Hz, 2H), 6.98–7.25 (m, 9H), 6.67 (d, J=15.72 Hz, 1H), 6.13–6.06
(dd, J=7.23, 15.75 Hz, 1H), 4.92–4.98 (m, 1H), 3.11 (dd, J=9.57,
16.07 Hz, 1H), 2.75 (dd, J=2.63, 16.04 Hz, 1H), 2.33 (s, 3H), 2.31 ppm
(s, 3H); 13C NMR (CDCl3, 75 MHz): d=143.7, 141.4, 137.6, 135.8, 133.5,
131.2, 131.1, 129.5, 129.1, 127.8, 127.6, 127.2, 126.5, 125.1, 124.3, 116.5,
64.0, 35.5, 21.5, 21.2 ppm; IR (NaCl, neat): n˜ =2963, 2924, 1477, 1460,
1354, 1166 cmꢀ1; MS (ESI): m/z: 390 [M+H]+; HRMS (ESI) calcd for
C24H24NO2S: 390.1528 [M+H]+; found: 390.1526.
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Received: May 4, 2011
Published online: July 21, 2011
10088
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Chem. Eur. J. 2011, 17, 10081 – 10088