Cyclization of N-Arylacrylamides via Radical Arylsulfenylation of Carbon-Carbon Double Bonds with Sulfonyl Hydrazides

Article abstract of DOI:10.1021/acs.joc.5b02322

An unprecedented tandem radical sulfenylation/cyclization reaction of N-arylacrylamides with sulfonyl hydrazides has been developed in the presence of iodine for the selective synthesis of 3-(sulfenylmethyl)oxindoles and 3-sulfenyl-3,4-dihydroquinolin-2(1H)-ones. Preliminary mechanistic studies showed that sulfonyl hydrazides decomposed completely at an early stage to thiosulfonates and disulfides, both of which underwent tandem radical sulfenylation/cyclization with N-arylacrylamides at a late stage.

Full text of DOI:10.1021/acs.joc.5b02322

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Note
Cyclization of N-Arylacrylamides via Radical Arylsulfenylation
of Carbon-Carbon Double Bonds with Sulfonyl Hydrazides
Fu-Xiang Wang, and Shi-Kai Tian
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b02322 • Publication Date (Web): 19 Nov 2015
Downloaded from http://pubs.acs.org on November 23, 2015
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Cyclization of N-Arylacrylamides via Radical Arylsulfenylation of
Carbon-Carbon Double Bonds with Sulfonyl Hydrazides
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Fu-Xiang Wang and Shi-Kai Tian*
Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026,
China
E-mail: tiansk@ustc.edu.cn
ABSTRACT: An unprecedented tandem radical sulfenylation/cyclization reaction of
N-arylacrylamides with sulfonyl hydrazides has been developed in the presence of iodine for the
selective synthesis of 3-(sulfenylmethyl)oxindoles and 3-sulfenyl-3,4-dihydroquinolin-2(1H)-ones.
Preliminary mechanistic studies showed that sulfonyl hydrazides decomposed completely at an early
stage to thiosulfonates and disulfides, both of which underwent tandem radical
sulfenylation/cyclization with N-arylacrylamides at a late stage.
Sulfonyl hydrazides have recently emerged as useful sulfenylating agents for the
1
2
functionalization of carbon-hydrogen bonds, carbon-carbon multiple bonds, carbon-heteroatom
3
4
bonds, and phosphorus-hydrogen bonds. When compared to commonly employed sulfenylating
agents such as thiols, disulfides, sulfenyl halides, sulfenate esters, and sulfenamides, sulfonyl
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hydrazides are much more amenable to handling because, in general, they are readily accessible
solids, free of unpleasant odor, and compatible with moisture. Technically, the sulfenylation with
sulfonyl hydrazides does not require external reductants to decrease the valence of sulfur from +6 to
0
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0
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0
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7
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9
0
+
2 in that the NHNH
2
moiety is utilized to remove the two oxygen atoms from the SO
2
group to
generate sulfur electrophiles as well as water and molecular nitrogen as byproducts.
1a,2b,3b,5
As part of our efforts in exploring the synthetic utilities of monosubstituted hydrazines,
we have recently developed an iodine-catalyzed oxysulfenylation reaction of alkenes with sulfonyl
hydrazides and alcohols, which, however, is not applicable to electron-deficient alkenes such as
2
b
α,-unsaturated amides. On the other hand, arenesulfonyl hydrazides were reported recently by Li,
Xu, and coworkers to undergo tandem radical sulfonylation/cyclization with N-arylacrylamides in
6
the presence of TBHP, KI, and 18-crown-6 to afford 3-(sulfonylmethyl)oxindoles [Scheme 1 (a)]. It
is noteworthy that N-arylacrylamides serve as versatile building blocks for the construction of
7
functionalized oxindoles, which has been found in many biologically relevant compounds. In this
context, we wondered if iodine could render such a tandem process. However, to our surprise,
sulfenylation rather than sulfonylation took place between sulfonyl hydrazides and
N-arylacrylamides in the presence of iodine. Importantly, this tandem sulfenylation/cyclization
reaction proceeded in radical pathway to afford either 3-(sulfenylmethyl)oxindoles or
8
,9
3
-sulfenyl-3,4-dihydroquinolin-2(1H)-ones with high regioselectivity [Scheme 1 (b)].
Scheme 1. Cyclization of N-Arylacrylamides with Sulfonyl Hydrazides
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(
a) Li and Xu:6
O
O
TBHP, KI
8-crown-6
S
O
S
1
Ar
+
Ar
NHNH2
O
N
N
O
O
Ar = 4-MeC6H4, Ph
(b) This work:
O
I2
S
S
0
1
2
3
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9
0
1
2
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0
1
2
3
4
5
6
7
8
9
0
+
S
NHNH2
or
O
N
O
O
N
N
O
Initially, we employed 20 mol% iodine to catalyze the model reaction of N-arylacrylamide 1a
with sulfonyl hydrazide 2a in 1,2-dichloroethane. The reaction mixture was heated under air in a
o
sealed tube at 90 C for 24 h and 3-(sulfenylmethyl)oxindole 3a was isolated in 49% yield (Table 1,
entry 1). Prolonging the reaction time to 48 h improved the yield to 73%, and on the other hand,
o
elevating the temperature to 120 C improved the yield to 86% (Table 1, entries 2 and 3). Since
iodine is inexpensive, we increased its amount to 1 equivalent and found that the yield was improved
to 97% (Table 1, entry 4). The oxygen in air proved unnecessary according to the control experiment
performed under nitrogen, which gave 3-(sulfenylmethyl)oxindole 3a in 94% yield (Table 1, entry 5).
Moreover, performing the reaction under oxygen led to a lower yield because a higher concentration
of molecular oxygen could accelerate the decomposition of the sulfonyl hydrazide into a sulfonic
1
0
acid via the intermediacy of a sulfinic acid (Table 1, entry 6). Replacing iodine with NIS
(
N-iodosuccinimide) dramatically decreased the yield and even no desired product was isolated
n
when using either Bu
4
NI or HI as the catalyst (Table 1, entries 7-9). Finally, a number of common
organic solvents were examined and no better yield was obtained (Table 1, entries 10-16).
a
Table 1. Optimization of Reaction Conditions
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o
b
entry catalyst (equiv)
solvent
temp ( C) time (h) yield (%)
1
2
3
4
I
I
I
2
2
2
I
I
I
(0.2)
(0.2)
(0.2)
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
90
90
120
90
90
90
90
90
90
90
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90
24
48
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49
73
86
97
94
84
37
0
0
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0
1
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4
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0
1
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9
0
1
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0
1
2
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4
5
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9
0
2
(1)
(1)
(1)
c
5
2
2
d
6
7
NIS (1)
n
8
9
Bu
4
NI (1)
HI (1)
0
10
I
I
I
I
I
I
I
2
2
2
2
2
2
2
(1)
(1)
(1)
(1)
(1)
(1)
(1)
CHCl
3
95
63
54
87
0
11
PhMe
1
2
dioxane
13
3
CH CN
1
4
5
DMF
DMSO
EtOH
1
0
16
0
a
Reaction conditions: N-arylacrylamide 1a (0.20 mmol), sulfonyl hydrazide 2a (0.24 mmol),
b
c
catalyst (0.2-1 equiv), solvent (0.50 mL), under air at 90 ºC (oil bath) for 24 h. Isolated yield. The
d
reaction was run under nitrogen. The reaction was run under oxygen.
Under the optimized conditions, a range of -unsubstituted N-arylacrylamides smoothly
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underwent 5-exo-trig cyclization via iodine-catalyzed sulfenylation with sulfonyl hydrazides and
structurally diverse 3-(sulfenylmethyl)oxindoles were isolated in moderate to excellent yields (Table
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9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
, 3a-w). In general, the reaction with aromatic sulfonyl hydrazides gave much higher yields than
0
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4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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4
5
6
7
8
9
0
1
2
3
4
5
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9
0
1
2
3
4
5
6
7
8
9
0
that with aliphatic ones (3a-i versus 3j) and notably, the cyclization proceeded with high
regioselectivity regarding the carbon-carbon bond formation of the aromatic ring (3r and 3s).
Moreover, the reaction is highly sensitive to the nature of N-substituents in substrates 1 and no
2
desired cyclization was observed when R was hydrogen or an electron-withdrawing group such as a
p-toluenesulfonyl group or an acetyl group.
Table 2. Sulfenylation of N-Arylacrylamides with Sulfonyl Hydrazides Leading to
a
Functionalized Oxindoles
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R3
N
Me
R1
S
Me
Me
Me
S
Me
O
O
0
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0
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N
Me
3x, 66%b
v, R1 = H, R3 = CH OH, 40%
Me
3
2
3w, R = Me, R3 = Ph, 97%
1
a
Reaction conditions: N-arylacrylamide 1 (0.20 mmol), sulfonyl hydrazide 2 (0.24 mmol), iodine
o
b
(
0.20 mmol), in DCE (0.50 mL) under air at 90 C (oil bath) for 24 h. Iodine (0.40 mmol) was
used.
There are two cyclization modes, 5-exo-trig versus 6-endo-trig, identified for -substituted
N-arylacrylamides in their sulfenylation reaction with sulfonyl hydrazides, which required two
3
4
equivalents of iodine to achieve better yields. When R and R were both alkyl groups, a
3
-(sulfenylmethyl)oxindole was isolated as the only cyclization product (Table 2, 3x). In contrast,
the reaction with a -aryl-N-arylacrylamide or an α-unsubstituted -alkyl-N-arylacrylamide only
afforded a 3-sulfenyl-3,4-dihydroquinolin-2(1H)-one, whose structure was further confirmed by
1
1
Raney
Ni-mediated
desulfuration
(Scheme
2).
It
is
noteworthy
that
3
-sulfenyl-3,4-dihydroquinolin-2(1H)-ones 4a-c were produced with very high diastereoselectivity
1
2
according to NMR spectroscopic analysis.
Scheme 2. Sulfenylation of N-Arylacrylamides with Sulfonyl Hydrazides Leading to
Functionalized 3,4-Dihydroquinolin-2(1H)-ones
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The cyclization reaction failed to proceed with α,-unsubstituted N-arylacrylamides. For
example, no cyclization product was detected at all in the reaction of N-arylacrylamide 1s with
sulfonyl hydrazide 2a (eq 1). Instead, the reaction gave bisthioether 6a in 34% yield. On the other
hand, TsNHNHCOPh (2aa) did not undergo cyclization with N-arylacrylamide 1a and this result
suggests that the NHNH
2
group is essential for the sulfonyl hydrazide to serve as an effective
sulfenylating agent (eq 2).
1
To gain insights into the reaction mechanism, we carried out H NMR spectroscopic analysis of
the reaction mixture of N-arylacrylamide 1c with sulfonyl hydrazide 2a in deuterated chloroform and
found that the sulfonyl hydrazide decomposed completely at an early stage to a 60:40 mixture of
10
thiosulfonate 7a and disulfide 8a, both of which were gradually converted to the desired oxindole
3l at a late stage (Table 3).
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1
Table 3. H NMR Spectroscopic Analysis of the Reaction Mixture
0
1
2
3
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5
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8
9
0
1
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9
0
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9
0
1
2
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4
5
6
7
8
9
0
entry
time (h)
2a (%)
7a (%)
55
8a (%)
35
3l (%)
0
1
2
3
4
5
0.5
1
10
0
56
38
6
2
0
49
36
15
45
95
5
0
31
24
24
0
0
5
Both intermediates 7a and 8a were isolated and underwent tandem sulfenylation/cyclization
with N-arylacrylamide 1a to give the desired oxindole product in good yields (Scheme 3). Moreover,
treatment of thiosulfonate 7a with one equivalent of iodine gave disulfide 8a in 35% yield under the
1
standard conditions. Although sulfinic acid 9a was not detected by the aforementioned H NMR
spectroscopic analysis (Table 3), it was reported previously to be generated through the
1
0
decomposition of the corresponding sulfonyl hydrazide upon heating. Therefore, we carried out the
reaction of sulfinic acid 9a with N-arylacrylamide 1a and found that 3-(sulfenylmethyl)oxindole 3a
was produced albeit in a lower yield. Moreover, in the presence of iodine sulfinic acid 9a was
converted to thiosulfonate 7a in 60% yield together with disulfide 8a in 15% yield.
Scheme 3. Transformations of Intermediates
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Addition of one equivalent of 2,6-di-tert-butyl-4-methylphenol (BHT) to the reaction mixture
of N-arylacrylamide 1a, sulfonyl hydrazide 2a, and iodine significantly decreased the yield (from 97%
to 34%) for the formation of the desired cyclization product. Moreover, replacement of BHT with
2
,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) almost completely inhibited the desired reaction.
These results suggest that the reaction may proceed via a radical pathway, which is substantially
supported by the following experiment. The electron paramagnetic resonance (EPR) spectrum of the
same reaction mixture displayed the resonance characteristic of a tertiary carbon radical having
1
2
-hydrogens with an absorption maximum at g = 2.0050 (Figure 1).
Figure 1. EPR Spectrum of the Reaction Mixture.
1
a,7
According to the above experimental results and previous studies, we propose the following
reaction pathways for the tandem sulfenylation/cyclization of N-arylacrylamides with sulfonyl
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hydrazides, wherein iodine plays multiple roles as an oxidant, a reductant, and a radical initiator
(Scheme 4). Initially, sulfonyl hydrazide 2 reacts with iodine to give sulfinic acid 9 and sulfenyl
1a
iodide 11. The two intermediates undergo nucleophilic substitution to give thiosulfonate 7, which is
0
1
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0
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2
3
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8
9
0
1
2
3
4
5
6
7
8
9
0
reduced by iodine to give disulfide 8. Alternatively, thiosulfonate 7 is also generated through
reduction of sulfinic acid 9 with iodine. In these steps, iodine is converted to HI and HOI, the two of
which react to give water and regenerate iodine. Both thiosulfonate 7 and disulfide 8 are attacked by
1
3
iodine radical, generated from iodine upon heating, to give sulfenyl radical 13. Regioselective
addition of radical 13 to N-arylacrylamide 1 lead to the formation of alkyl radical 14 or 16,
depending on which one is more stable. Cyclization of radical 14 followed by aromatization gives
7
3
-(sulfenylmethyl)oxindole 3. On the other hand, tandem cyclization/aromatization of radical 16
9
3
gives 3-sulfenyl-3,4-dihydroquinolin-2(1H)-one 4. However, when R is hydrogen, the
conformation required for the cyclization is unfavorable and consequently, radical 14 prefers to
couple with radical 13 to give bisthioether 6.
Scheme 4. Proposed Reaction Pathways
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In summary, we have developed an unprecedented tandem sulfenylation/cyclization reaction of
N-arylacrylamides with sulfonyl hydrazides selectively leading to 3-(sulfenylmethyl)oxindoles and
3
-sulfenyl-3,4-dihydroquinolin-2(1H)-ones. In the presence of iodine, -unsubstituted
N-arylacrylamides underwent sulfenylation with sulfonyl hydrazides followed by 5-exo-trig
cyclization to afford structurally diverse 3-(sulfenylmethyl)oxindoles in moderate to excellent yields.
In contrast, the reaction with -substituted N-arylacrylamides afforded either
3-(sulfenylmethyl)oxindoles
or
3-sulfenyl-3,4-dihydroquinolin-2(1H)-ones
with
high
regioselectivity depending on the nature of α- and -substituents. Preliminary mechanistic studies
showed that sulfonyl hydrazides decomposed completely at an early stage to thiosulfonates and
disulfides, both of which underwent tandem radical sulfenylation/cyclization with N-arylacrylamides
at a late stage.
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EXPERIMENTAL SECTION
1
13
General Information. H NMR and C NMR spectra were recorded using tetramethylsilane
as an internal reference. Chemical shifts (δ) and coupling constants (J) were expressed in ppm and
Hz, respectively. High resolution mass spectra (HRMS) were recorded on a LC-TOF spectrometer
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using electron spray ionization (ESI) techniques. N-Arylacrylamides 1, sulfonyl hydrazides 2
1
5
1a,2b
(
except 2a), thiosulfonate 7a, disulfide 8a, sulfinic acid 9a, and compound 2aa
were prepared
according to literature procedures.
General Procedure for the Sulfenylation of N-Arylacrylamides with Sulfonyl Hydrazides
Table 2, Scheme 2, and Equation 1). A mixture of N-arylacrylamide 1 (0.20 mmol), sulfonyl
(
hydrazide 2 (0.24 mmol; For the synthesis of bisthioether 6a: 0.48 mmol), and iodine (50.8 mg, 0.20
mmol; For the synthesis of oxindole 3x and dihydroquinolin-2(1H)-one 4: 101.6 mg, 0.40 mmol) in
1
,2-dichloroethane (0.50 mL) was heated at 90 ºC (oil bath) under air for 24 h. The mixture was
cooled to room temperature, and purified directly by silica gel chromatography, eluting with ethyl
acetate/petroleum ether (1:1 to 1:10), to give oxindole 3, 3,4-dihydroquinolin-2(1H)-one 4, or
bisthioether 6a. The structure of compounds 3a, 3x, and 4a-c was further confirmed by desulfuration
(see below). The relative stereochemistry of compounds 4a and 5a was assigned by 2D NOESY
spectroscopic ananlysis and that of compounds 4b-c was assigned according to the vicinal
proton-proton NMR coupling constants.
1
1
,3-Dimethyl-3-((p-tolylthio)methyl)indolin-2-one (3a): Colorless oil (57.6 mg, 97%); H
NMR (400 MHz, CDCl
3
) δ 7.30-7.27 (m, 1H), 7.19 (d, J = 6.8 Hz, 1H), 7.10 (d, J = 8.0 Hz, 2H),
7
3
.02-6.96 (m, 3H), 6.86 (d, J = 7.6 Hz, 1H), 3.38 (d, J = 12.7 Hz, 1H), 3.33 (d, J = 12.7 Hz, 1H),
13
3
.21 (s, 3H), 2.28 (s, 3H), 1.43 (s, 3H); C NMR (100 MHz, CDCl ) δ 179.1, 143.4, 136.6, 132.4,
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31.2, 129.5, 128.2, 123.3, 122.5, 108.0, 49.1, 43.4, 26.3, 23.0, 21.0; HRMS (ESI) calcd for
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
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5
5
5
6
+
+
C
18
H20NOS (M+H) 298.1260, found 298.1257.
1
1
,3-Dimethyl-3-((phenylthio)methyl)indolin-2-one (3b): Colorless oil (50.9 mg, 90%); H
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
NMR (400 MHz, CDCl
3
) δ 7.30-7.27 (m, 1H), 7.22-7.12 (m, 6H), 7.01-6.95 (m, 1H), 6.86 (d, J = 7.6
1
3
Hz, 1H), 3.42 (d, J = 12.7 Hz, 1H), 3.37 (d, J = 12.7 Hz, 1H), 3.21 (s, 3H), 1.45 (s, 3H); C NMR
(
100 MHz, CDCl ) δ 179.0, 143.4, 136.1, 132.3, 130.5, 128.7, 128.3, 126.4, 123.3, 122.5, 108.0,
3
+
+
4
9.0, 42.8, 26.3, 23.0; HRMS (ESI) calcd for C17H18NOS (M+H) 284.1104, found 284.1102.
3-(((4-Methoxyphenyl)thio)methyl)-1,3-dimethylindolin-2-one (3c): Colorless oil (46.9 mg,
1
7
5%); H NMR (400 MHz, CDCl
3
) δ 7.31-7.27 (m, 1H), 7.17-7.10 (m, 3H), 7.02-6.96 (m, 1H), 6.86
(
d, J = 8.0 Hz, 1H), 6.71 (d, J = 8.8 Hz, 2H), 3.76 (s, 3H), 3.31 (s, 2H), 3.21 (s, 3H), 1.41 (s, 3H);
1
3
3
C NMR (100 MHz, CDCl ) δ 179.1, 159.0, 143.5, 133.9, 132.4, 128.2, 126.4, 123.3, 122.5, 114.3,
+
+
1
08.0, 55.3, 49.3, 44.5, 26.3, 23.1; HRMS (ESI) calcd for C18
14.1207.
2
H20NO S (M+H) 314.1209, found
3
3-(((4-Fluorophenyl)thio)methyl)-1,3-dimethylindolin-2-one (3d): Colorless oil (48.8 mg, 81%);
H NMR (400 MHz, CDCl ) δ 7.31-7.25 (m, 1H), 7.17-7.09 (m, 3H), 7.00-6.94 (m, 1H), 6.90-6.82
m, 3H), 3.35 (s, 2H), 3.22 (s, 3H), 1.42 (s, 3H); C NMR (100 MHz, CDCl
245.3 Hz), 143.5, 133.5 (d, J = 8.1 Hz), 132.1, 131.0, 128.3, 122.9 (d, J = 69.7 Hz), 115.7 (d, J =
1
3
13
(
3
) δ 179.0, 162.0 (d, J =
+
+
2
1.7 Hz), 108.0, 49.3, 43.9, 26.3, 23.2; HRMS (ESI) calcd for C17
found 302.1009.
3-(((4-Chlorophenyl)thio)methyl)-1,3-dimethylindolin-2-one (3e): Colorless oil (55.8 mg, 88%);
H17FNOS (M+H) 302.1009,
1
H NMR (400 MHz, CDCl
3
) δ 7.32-7.28 (m, 1H), 7.15-7.07 (m, 5H), 7.01-6.95 (m, 1H), 6.86 (d, J =
13
8
.0 Hz, 1H), 3.39 (d, J = 12.8 Hz, 1H), 3.35 (d, J = 12.8 Hz, 1H), 3.21 (s, 3H), 1.44 (s, 3H); C
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NMR (100 MHz, CDCl
3
) δ 178.9, 143.4, 134.6, 132.5, 132.1, 132.0, 128.8, 128.4, 123.2, 122.5,
+
+
108.1, 49.1, 43.0, 26.3, 23.1; HRMS (ESI) calcd for C17
H
17ClNOS (M+H) 318.0714, found
3
18.0717.
-(((4-Bromophenyl)thio)methyl)-1,3-dimethylindolin-2-one (3f): Colorless oil (60.0 mg, 83%);
H NMR (400 MHz, CDCl ) δ 7.47 (d, J = 8.4 Hz, 2H), 7.32-7.27 (m, 1H), 7.14 (d, J = 7.6 Hz, 1H),
.02-6.96 (m, 1H), 6.90 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 7.6 Hz, 1H), 3.39 (d, J = 12.8 Hz, 1H), 3.35
0
1
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0
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6
7
8
9
0
3
1
3
7
13
(d, J = 12.8 Hz, 1H), 3.21 (s, 3H), 1.44 (s, 3H); C NMR (100 MHz, CDCl
3
) δ 178.9, 143.4, 135.3,
132.1, 132.0, 131.7, 128.4, 123.2, 122.5, 120.5, 108.1, 49.1, 42.8, 26.3, 23.1; HRMS (ESI) calcd for
+
+
C
17
H
17BrNOS (M+H) 362.0209, found 362.0206.
-(((4-Iodophenyl)thio)methyl)-1,3-dimethylindolin-2-one (3g): Colorless oil (73.6 mg, 90%);
H NMR (400 MHz, CDCl ) δ 7.47 (d, J = 8.4 Hz, 2H), 7.31-7.25 (m, 1H), 7.14 (d, J = 7.6 Hz, 1H),
.01-6.96 (m, 1H), 6.90 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 7.6 Hz, 1H), 3.39 (d, J = 12.8 Hz, 1H), 3.35
3
1
3
7
13
(d, J = 12.8 Hz, 1H), 3.21 (s, 3H), 1.44 (s, 3H); C NMR (100 MHz, CDCl
3
) δ 178.9, 143.4, 137.6,
136.2, 132.1, 132.0, 128.4, 123.2, 122.6, 108.1, 91.5, 49.0, 42.6, 26.3, 23.1; HRMS (ESI) calcd for
+
+
17
C H17INOS (M+H) 410.0070, found 410.0064.
1
3
-((Mesitylthio)methyl)-1,3,5-trimethylindolin-2-one (3h): Colorless oil (59.7 mg, 88%); H
NMR (400 MHz, CDCl
3
) δ 7.06 (d, J = 7.9 Hz, 1H), 6.98 (s, 1H), 6.80 (s, 2H), 6.72 (d, J = 7.9 Hz,
1
1
H), 3.19 (s, 3H), 3.11 (d, J = 12.2 Hz, 1H), 3.05 (d, J = 12.2 Hz, 1H), 2.29 (s, 9H), 2.20 (s, 3H),
13
.38 (s, 3H); C NMR (100 MHz, CDCl
3
) δ 179.0, 142.3, 141.1, 137.7, 132.5, 131.9, 130.4, 128.7,
+
128.4, 123.9, 107.7, 49.0, 42.8, 26.2, 23.5, 21.6, 21.1, 20.9; HRMS (ESI) calcd for C21H26NOS
+
(
M+H) 340.1730, found 340.1727.
1
,3-Dimethyl-3-((naphthalen-1-ylthio)methyl)indolin-2-one (3i): Colorless oil (51.3 mg, 77%);
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H NMR (400 MHz, CDCl
3
) δ 8.23-8.19 (m, 1H), 7.81-7.76 (m, 1H), 7.68 (d, J = 8.0 Hz, 1H),
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
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5
5
5
5
6
7.49-7.41 (m, 3H), 7.29 (d, J = 7.6 Hz, 1H), 7.22-7.18 (m, 1H), 7.10 (d, J = 7.6 Hz, 1H), 6.94-6.89
(
m, 1H), 6.78 (d, J = 7.6 Hz, 1H), 3.46 (d, J = 12.8 Hz, 1H), 3.41 (d, J = 12.8 Hz, 1H), 3.15 (s, 3H),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
13
1
3
.42 (s, 3H); C NMR (100 MHz, CDCl ) δ 178.9, 143.4, 133.9, 133.4, 133.0, 132.3, 130.8, 128.4,
128.1, 126.3, 126.0, 125.4, 123.2, 122.3, 108.1, 49.3, 43.2, 26.2, 23.3; HRMS (ESI) calcd for
+
+
21
C H20NOS (M+H) 334.1260, found 334.1257.
1
1
,3-Dimethyl-3-((octylthio)methyl)indolin-2-one (3j): Colorless oil (32.5 mg, 51%); H NMR
(400 MHz, CDCl
3
) δ 7.25-7.18 (m, 2H), 7.03-6.97 (m, 1H), 6.79 (d, J = 7.6 Hz, 1H), 3.17 (s, 3H),
2
1
.95 (d, J = 12.8 Hz, 1H), 2.84 (d, J = 12.8 Hz, 1H), 2.25 (t, J = 7.2 Hz, 2H), 1.37-1.33 (m, 4H),
13
3
.23-1.13 (m, 11H), 0.80 (t, J = 6.8 Hz, 3H); C NMR (100 MHz, CDCl ) δ 179.6, 143.5, 133.0,
128.2, 123.0, 122.4, 108.0, 31.8, 29.2, 29.1, 28.7, 26.3, 22.9, 22.6, 14.1; HRMS (ESI) calcd for
+
+
19
C H30NOS (M+H) 320.2043, found 320.2039.
1
1
,3,5-Trimethyl-3-((p-tolylthio)methyl)indolin-2-one (3k): Colorless oil (52.2 mg, 84%); H
NMR (400 MHz, CDCl
3
) δ 7.08-7.01 (m, 3H), 6.95 (d, J = 8.0 Hz, 2H), 6.88 (s, 1H), 6.72 (d, J = 8.0
Hz, 1H), 3.35 (d, J = 13.0 Hz, 1H), 3.30 (d, J = 13.0 Hz, 1H), 3.19 (s, 3H), 2.26 (s, 3H), 2.22 (s, 3H),
13
1
.40 (s, 3H); C NMR (100 MHz, CDCl
128.3, 124.2, 107.7, 49.3, 43.4, 26.3, 23.1, 21.0; HRMS (ESI) calcd for C19
12.1417, found 312.1415.
-Methoxy-1,3-dimethyl-3-((p-tolylthio)methyl)indolin-2-one (3l): Colorless oil (59.5 mg,
3
) δ 179.0, 141.0, 136.4, 132.4, 132.2, 131.9, 131.3, 129.4,
+
+
H
22NOS (M+H)
3
5
1
91%); H NMR (400 MHz, CDCl
3
) δ 7.07 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 6.80-6.70 (m,
3
1
H), 3.71 (s, 3H), 3.35 (d, J = 12.8 Hz, 1H), 3.32 (d, J = 12.8 Hz, 1H), 3.19 (s, 3H), 2.27 (s, 3H),
13
3
.41 (s, 3H); C NMR (100 MHz, CDCl ) δ 178.8, 155.9, 136.9, 136.6, 133.6, 132.4, 131.3, 129.4,
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5
5
5
5
6
+
+
1
12.5, 110.7, 108.2, 55.6, 49.7, 43.5, 26.3, 23.1, 21.0; HRMS (ESI) calcd for C19
2
H22NO S (M+H)
328.1366, found 328.1362.
5
-Fluoro-1,3-dimethyl-3-((p-tolylthio)methyl)indolin-2-one (3m): Colorless oil (46.6 mg, 74%);
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
H NMR (400 MHz, CDCl ) δ 7.07 (d, J = 7.8 Hz, 2H), 6.98 (d, J = 7.8 Hz, 2H), 6.93 (dd, J = 8.8,
3
2.4 Hz, 1H), 6.85 (dd, J = 8.0, 2.4 Hz, 1H), 6.74 (dd, J = 8.4, 4.0 Hz, 1H), 3.34 (d, J = 13.2 Hz, 1H),
13
3
3
.30 (d, J = 13.2 Hz, 1H), 3.19 (s, 3H), 2.27 (s, 3H), 1.40 (s, 3H); C NMR (100 MHz, CDCl ) δ
1
78.7, 159.2 (d, J = 239.1 Hz), 139.4, 136.9, 134.0 (d, J = 8.0 Hz), 132.0, 131.4, 129.5, 114.3 (d, J =
23.4 Hz), 111.6 (d, J = 24.7 Hz), 108.3 (d, J = 8.1 Hz), 49.8, 43.3, 26.4, 23.0, 21.0; HRMS (ESI)
+
+
calcd for C18
-Chloro-1,3-dimethyl-3-((p-tolylthio)methyl)indolin-2-one (3n): Colorless oil (50.3 mg, 76%);
H NMR (400 MHz, CDCl ) δ 7.19 (dd, J = 8.4, 2.0 Hz, 1H), 7.03 (d, J = 8.4 Hz, 2H), 6.98-6.94 (m,
H), 6.74 (d, J = 8.4 Hz, 1H), 3.32 (s, 2H), 3.19 (s, 3H), 2.28 (s, 3H), 1.39 (s, 3H); C NMR (100
H19FNOS (M+H) 316.1166, found 316.1164.
5
1
3
13
3
3
MHz, CDCl ) δ 178.6, 142.0, 137.0, 133.9, 131.9, 131.5, 129.5, 128.0, 127.9, 124.0, 108.8, 49.8,
+
+
43.3, 26.3, 23.0, 21.0; HRMS (ESI) calcd for C18H19ClNOS (M+H) 332.0870, found 332.0866.
5
-Bromo-1,3-dimethyl-3-((p-tolylthio)methyl)indolin-2-one (3o): Colorless oil (71.3 mg, 95%);
H NMR (400 MHz, CDCl ) δ 7.33 (dd, J = 8.4, 2.0 Hz, 1H), 7.08 (d, J = 2.0 Hz, 1H), 7.02 (d, J =
8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 6.69 (d, J = 8.4 Hz, 1H), 3.31 (s, 2H), 3.19 (s, 3H), 2.28 (s,
1
3
1
3
3
1
H), 1.38 (s, 3H); C NMR (100 MHz, CDCl
3
) δ 178.5, 142.5, 137.0, 134.2, 131.8, 131.5, 130.8,
+
29.5, 126.7, 115.2, 109.3, 49.7, 43.3, 26.3 23.0, 21.1; HRMS (ESI) calcd for C18H19BrNOS
+
(M+H) 376.0365, found 376.0361.
5
-Iodo-1,3-dimethyl-3-((p-tolylthio)methyl)indolin-2-one (3p): Colorless oil (79.5 mg, 94%);
1
H NMR (400 MHz, CDCl ) δ 7.52 (dd, J = 8.4, 2.0 Hz, 1H), 7.22 (d, J = 1.6 Hz, 1H), 7.00 (d, J =
3
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.4 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 6.60 (d, J = 8.0 Hz, 1H), 3.33 (d, J = 13.2 Hz, 1H), 3.29 (d, J
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
= 13.2 Hz, 1H), 3.19 (s, 3H), 2.30 (s, 3H), 1.37 (s, 3H); C NMR (100 MHz, CDCl
3
) δ 178.3, 143.2,
1
37.0, 136.8, 134.5, 132.3, 131.8, 131.5, 129.5, 109.9, 85.1, 49.6, 43.4, 26.3, 23.0, 21.2; HRMS (ESI)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
+
calcd for C18H19INOS (M+H) 424.0227, found 424.0222.
1
1,3,7-Trimethyl-3-((p-tolylthio)methyl)indolin-2-one (3q): Colorless oil (51.6 mg, 83%); H
NMR (400 MHz, CDCl
H), 3.33 (s, 2H), 2.59 (s, 3H), 2.27 (s, 3H), 1.40 (s, 3H); C NMR (100 MHz, CDCl
141.2, 136.5, 133.0, 132.5, 131.9, 131.2, 129.5, 122.4, 121.1, 119.6, 48.3, 43.7, 29.6, 23.5, 21.0, 19.1;
3
) δ 7.11 (d, J = 8.4 Hz, 2H), 7.05-6.97 (m, 4H), 6.91-6.85 (m, 1H), 3.48 (s,
1
3
3
3
) δ 179.8,
+
+
HRMS (ESI) calcd for C19
H22NOS (M+H) 312.1417, found 312.1412.
5
,6-Dimethoxy-1,3-dimethyl-3-((p-tolylthio)methyl)indolin-2-one (3r): Colorless oil (54.3 mg,
1
3
76%); H NMR (400 MHz, CDCl ) δ 7.06 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 6.66 (s, 1H),
1
3
6
.49 (s, 1H), 3.94 (s, 3H), 3.72 (s, 3H), 3.32 (s, 2H), 3.22 (s, 3H), 2.27 (s, 3H), 1.40 (s, 3H); C
3
NMR (100 MHz, CDCl ) δ 179.4, 149.5, 145.0, 137.0, 136.6, 132.6, 131.3, 129.4, 123.0, 108.4, 94.1,
+
+
56.4, 49.6, 43.7, 29.7, 26.4, 23.2, 21.0; HRMS (ESI) calcd for C20
found 358.1469.
3
H24NO S (M+H) 358.1471,
1
,3-Dimethyl-1-((p-tolylthio)methyl)-1H-benzo[e]indol-2(3H)-one (3s): Colorless oil (49.9 mg,
1
72%); H NMR (400 MHz, CDCl
3
) δ 7.83 (d, J = 8.8 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.67 (d, J =
.4 Hz, 1H), 7.40-7.35 (m, 1H), 7.31-7.25 (m, 1H), 7.19 (d, J = 8.8 Hz, 1H), 6.83 (d, J = 8.0 Hz, 2H),
.70 (d, J = 8.0 Hz, 2H), 3.79 (d, J = 13.0 Hz, 1H), 3.61 (d, J = 13.0 Hz, 1H), 3.31 (s, 3H), 2.14 (s,
8
6
1
3
3H), 1.65 (s, 3H); C NMR (100 MHz, CDCl
3
) δ 180.3, 136.4, 131.6, 131.2, 130.4, 129.7, 129.6,
1
29.0, 127.0, 123.5, 123.2, 121.7, 109.4, 51.2, 43.2, 26.5, 23.4, 20.9; HRMS (ESI) calcd for
+
+
C
22
H22NOS (M+H) 348.1417, found 348.1415.
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,8-Dimethyl-1-((p-tolylthio)methyl)-5,6-dihydro-1H-pyrrolo[3,2,1-ij]quinolin-2(4H)-one (3t):
1
Colorless oil (47.2 mg, 70%); H NMR (400 MHz, CDCl
3
) δ 7.10 (d, J = 8.0 Hz, 2H), 6.97 (d, J =
8
.0 Hz, 2H), 6.82 (s, 1H), 6.77 (s, 1H), 3.76-3.63 (m, 2H), 3.36 (d, J = 12.8 Hz, 1H), 3.30 (d, J =
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
1
2.8 Hz, 1H), 2.82-2.67 (m, 2H), 2.27 (s, 3H), 2.22 (s, 3H), 2.07-1.94 (m, 2H), 1.41 (s, 3H); C
NMR (100 MHz, CDCl
3
) δ 177.8, 136.7, 136.4, 132.6, 131.4, 131.1, 130.9, 129.4, 127.3, 122.0,
+
+
1
19.7, 50.6, 43.3, 38.9, 24.5, 22.8, 21.4, 21.3, 21.0; HRMS (ESI) calcd for C21
H
24NOS (M+H)
3
38.1573, found 338.1569.
1
1-Benzyl-3-methyl-3-((p-tolylthio)methyl)indolin-2-one (3u): Colorless oil (47.7 mg, 64%); H
NMR (400 MHz, CDCl
8.0 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 6.94-6.88 (m, 1H), 6.69 (d, J = 7.6 Hz, 1H), 5.05 (d, J =
15.7 Hz, 1H), 4.83 (d, J = 15.7 Hz, 1H), 3.47 (d, J = 12.7 Hz, 1H), 3.41 (d, J = 12.7 Hz, 1H), 2.27 (s,
3
) δ 7.39-7.35 (m, 2H), 7.32-7.22 (m, 3H), 7.13 (d, J = 8.0 Hz, 2H), 7.09 (d, J
=
1
3
3
H), 1.48 (s, 3H); C NMR (100 MHz, CDCl
3
) δ 179.3, 142.5, 136.6, 135.8, 132.6, 132.3, 131.1,
1
29.5, 128.7, 128.1, 127.5, 127.3, 123.3, 122.5, 109.1, 49.3, 43.9, 43.5, 23.5, 21.0; HRMS (ESI)
+
+
calcd for C24H24NOS (M+H) 374.1573, found 374.1570.
3
-(Hydroxymethyl)-1-methyl-3-((p-tolylthio)methyl)indolin-2-one (3v): Colorless oil (25.0 mg,
1
4
0%); H NMR (400 MHz, CDCl
3
) δ 7.35-7.29 (m, 1H), 7.22 (d, J = 7.2 Hz, 1H), 7.11 (d, J = 8.0 Hz,
2H), 7.05-6.97 (m, 3H), 6.88 (d, J = 8.0 Hz, 1H), 3.91 (d, J = 11.2 Hz, 1H), 3.78 (d, J = 11.2 Hz, 1H),
1
3
3
.53 (d, J = 13.1 Hz, 1H), 3.50 (d, J = 13.1 Hz, 1H), 3.21 (s, 3H), 2.28 (s, 3H), 2.01 (s, br, 1H); C
NMR (100 MHz, CDCl ) δ 177.9, 144.2, 136.8, 132.1, 131.3, 129.5, 128.9, 128.4, 123.9, 122.7,
108.3, 66.3, 54.5, 38.9, 26.3, 21.0; HRMS (ESI) calcd for C18
14.1210.
,5-Dimethyl-3-phenyl-3-((p-tolylthio)methyl)indolin-2-one (3w): Colorless oil (72.4 mg, 97%);
3
+
+
H
2
20NO S (M+H) 314.1209, found
3
1
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H NMR (400 MHz, CDCl
3
) δ 7.31 (d, J = 7.6 Hz, 1H), 7.22-7.12 (m, 4H), 7.04-6.96 (m, 3H),
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
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3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
6.89-6.85 (m, 3H), 6.70 (d, J = 7.6 Hz, 1H), 3.74 (d, J = 13.2 Hz, 1H), 3.71 (d, J = 13.2 Hz, 1H),
13
3
3
.12 (s, 3H), 2.18 (s, 3H), 2.15 (s, 3H); C NMR (100 MHz, CDCl ) δ 177.0, 141.9, 139.0, 136.6,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
32.4, 131.9, 131.5, 130.1, 129.3, 128.8, 128.5, 127.6, 126.9, 126.4, 107.9, 57.2, 43.7, 26.5, 21.1,
+
+
20.9; HRMS (ESI) calcd for C24H24NOS (M+H) 374.1573, found 374.1569.
1
,3,5-Trimethyl-3-(1-(p-tolylthio)ethyl)indolin-2-one (3x): Obtained as an inseparable mixture
of two diastereomers (We failed to determine the diastereomeric ratio by either NMR or HPLC
1
analysis); Colorless oil (42.9 mg, 66%); H NMR (400 MHz, CDCl
3
) δ 7.37-7.33 (m, 3H), 7.12-7.08
(
m, 3H), 6.74 (d, J = 8.0 Hz, 1H), 3.59 (q, J = 6.8 Hz, 1H), 3.20 (s, 3H), 2.37 (s, 3H), 2.33 (s, 3H),
1
3
1
3
.55 (s, 3H), 0.99 (d, J = 6.8 Hz, 3H); C NMR (100 MHz, CDCl ) δ 179.3, 141.0, 137.2, 132.4,
132.2, 132.1, 131.6, 129.8, 128.4, 125.3, 107.6, 52.9, 52.4, 26.2, 23.2, 21.3, 21.1, 18.2; HRMS (ESI)
+
+
calcd for C20H24NOS (M+H) 326.1573, found 326.1573.
cis-1,3,6-Trimethyl-4-phenyl-3-(p-tolylthio)-3,4-dihydroquinolin-2(1H)-one (4a): Colorless oil
1
(51.1 mg, 66%); H NMR (400 MHz, CDCl
3
) δ 7.25-7.13 (m, 5H), 7.12-7.06 (m, 3H), 7.00-6.93 (m,
1
3
4
H), 4.05 (s, 1H), 3.46 (s, 3H), 2.32 (s, 3H), 2.27 (s, 3H), 1.25 (s, 3H); C NMR (100 MHz, CDCl
3
)
δ 168.5, 140.0, 139.7, 137.1, 137.0, 132.8, 129.7, 129.4, 128.9, 128.6, 128.0, 127.4, 127.3, 127.0,
+
+
114.6, 54.7, 54.6, 30.1, 22.4, 21.3, 20.6; HRMS (ESI) calcd for C25
found 388.1732.
H26NOS (M+H) 388.1730,
cis-1,6-Dimethyl-4-phenyl-3-(p-tolylthio)-3,4-dihydroquinolin-2(1H)-one (4b): Colorless oil
1
(61.9 mg, 83%); H NMR (400 MHz, CDCl
3
) δ 7.40-7.35 (m, 2H), 7.27-7.08 (m, 6H), 7.01 (s, 1H),
1
3
6
.97-6.91 (m, 3H), 4.31-4.29 (m, 1H), 4.14 (d, J = 2.0 Hz, 1H), 3.34 (s, 3H), 2.32 (s, 6H); C NMR
(
100 MHz, CDCl ) δ 166.6, 140.4, 138.3, 137.3, 133.5, 133.2, 130.4, 129.8, 129.4, 129.0, 128.9,
3
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+
+
1
27.3, 127.1, 124.8, 114.9, 54.2, 48.5, 29.8, 21.2, 20.7; HRMS (ESI) calcd for C24H24NOS (M+H)
374.1573, found 374.1576.
cis-1,4,6-Trimethyl-3-(p-tolylthio)-3,4-dihydroquinolin-2(1H)-one (4c): Colorless oil (39.8 mg,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
6
4%); H NMR (400 MHz, CDCl
3
) δ 7.32 (d, J = 8.0 Hz, 2H), 7.09-7.05 (m, 3H), 6.97 (d, J = 2.0 Hz,
1H), 6.87 (d, J = 8.0 Hz, 1H), 3.80 (d, J = 2.0 Hz, 1H), 3.35 (s, 3H), 3.13-3.07 (m, 1H), 2.33 (s, 3H),
13
2
3
.31 (s, 3H), 1.22 (d, J = 7.2 Hz, 3H); C NMR (100 MHz, CDCl ) δ 167.2, 138.1, 136.0, 133.4,
1
32.9, 129.7, 129.5, 129.0, 128.3, 128.1, 114.8, 53.9, 38.3, 29.7, 21.2, 20.9, 20.7; HRMS (ESI) calcd
+
+
for C19H22NOS (M+H) 312.1417, found 312.1419.
1
N-Methyl-N-phenyl-2,3-bis(p-tolylthio)propanamide (6a): Colorless oil (27.7 mg, 34%); H
NMR (400 MHz, CDCl ) δ 7.27-7.21 (m, 1H), 7.20-7.14 (m, 2H), 7.09 (d, J = 6.8 Hz, 2H), 6.98 (d, J
= 8.0 Hz, 2H), 6.90 (d, J = 8.0 Hz, 4H), 6.83 (d, J = 8.4 Hz, 2H),3.67 (dd, J = 11.2, 3.2 Hz, 1H), 3.50
3
(
dd, J = 13.6, 11.2 Hz, 1H), 3.30 (s, 3H), 3.07 (dd, J = 13.6, 3.2 Hz, 1H), 2.32 (s, 3H), 2.29 (s, 3H);
1
3
3
C NMR (100 MHz, CDCl ) δ 169.3, 142.9, 138.4, 135.7, 133.7, 131.7, 129.7, 129.5, 129.3, 128.9,
+
+
128.8, 127.7, 47.5, 37.7, 35.4, 21.1, 21.0; HRMS (ESI) calcd for C24
found 408.1445.
2
H26NOS (M+H) 408.1450,
Desulfuration of Compounds 3a, 3x, and 4a-c. A mixture of compound 3a (3x or 4a-c) (0.20
11
mmol) and Raney nickel (2.0 g) in ethanol (25 mL) was refluxed for 3 h. After the nickel was
filtered and washed with ethanol, the combined filtrate and washing solutions were evaporated under
reduced pressure. The residue was purified directly by silica gel chromatography, eluting with ethyl
acetate/petroleum ether (1:3 to 1:10), to give oxindole 3aa (or 3xa) (Known compounds) or
3
,4-dihydroquinolin-2(1H)-one 5a-c.
trans-1,3,6-Trimethyl-4-phenyl-3,4-dihydroquinolin-2(1H)-one (5a): Colorless oil (52.5 mg,
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9%); H NMR (400 MHz, CDCl
4.00 (d, J = 6.0 Hz, 1H), 3.43 (s, 3H), 3.06-2.97 (m, 1H), 2.25 (s, 3H), 1.14 (d, J = 7.2 Hz, 3H); C
NMR (100 MHz, CDCl ) δ 171.4, 139.3, 137.8, 132.6, 129.5, 129.1, 128.6, 128.3, 128.2, 127.1,
15.2, 48.4, 40.0, 29.8, 20.6, 13.1; HRMS (ESI) calcd for C18
266.1539.
3
) δ 7.27-7.16 (m, 3H), 7.08 (d, J = 9.6 Hz, 1H), 7.03-6.95 (m, 4H),
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
+
1
H
20NO (M+H) 266.1539, found
1
1
,6-Dimethyl-4-phenyl-3,4-dihydroquinolin-2(1H)-one (5b): Colorless oil (50.2 mg, quant.); H
NMR (400 MHz, CDCl
3
) δ 7.36-7.30 (m, 2H), 7.28-7.23 (m, 1H), 7.15 (d, J = 7.2 Hz, 2H), 7.09 (d, J
= 8.0 Hz, 1H), 6.95 (d, J = 8.0 Hz, 1H), 6.74 (s, 1H), 4.19 (t, J = 7.2 Hz, 1H), 3.37 (s, 3H), 2.94 (d, J
1
3
=
7.2 Hz, 2H), 2.24 (s, 3H); C NMR (100 MHz, CDCl
28.7, 128.3, 127.8, 127.1, 114.8, 41.5, 39.0, 29.6, 20.6; HRMS (ESI) calcd for C17
252.1383, found 252.1378.
3
) δ 169.2, 141.3, 138.0, 132.6, 128.9, 128.8,
+
+
1
H
18NO (M+H)
1
1
,4,6-Trimethyl-3,4-dihydroquinolin-2(1H)-one (5c): Colorless oil (37.8 mg, quant.); H NMR
(
400 MHz, CDCl
3
) δ 6.98 (d, J = 8.4 Hz, 1H), 6.94 (s, 1H), 6.81 (d, J = 8.4 Hz, 1H), 3.28 (s, 3H),
2.99-2.89 (m, 1H), 2.64 (dd, J =15.6, 5.2 Hz, 1H), 2.37 (dd, J =15.6, 7.6 Hz, 1H), 2.25 (s, 3H), 1.20
1
3
(
d, J = 7.2 Hz, 3H); C NMR (100 MHz, CDCl
3
) δ 169.8, 137.4, 132.6, 130.9, 127.7, 127.0, 114.7,
+
+
3
9.2, 30.3, 29.4, 20.7, 19.3; HRMS (ESI) calcd for C12H16NO (M+H) 190.1226, found 190.1228.
ACKNOWLEDGMENT
We are grateful for the financial support from the National Natural Science Foundation of
China (21472178 and 21232007) and the National Key Basic Research Program of China
(
2014CB931800).
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Supporting Information. Copies of H NMR, C NMR, and 2D NOESY spectra for products
and EPR analysis. This material is available free of charge via the Internet at http://pubs.acs.org.
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