Synthesis of CF3CH2-Containing Indolines by Transition-Metal-Free Aryltrifluoromethylation of Unactivated Alkenes

Article abstract of DOI:10.1021/acs.joc.8b01861

With an unactivated double bond as the radical acceptor, allyl amines underwent a metal-free trifluoromethylation/cyclization cascade with CF₃SO₂Na (Langlois' reagent), affording CF₃CH₂-containing indolines and tetrahydroisoquinolines, whose practical syntheses are significant challenges. This protocol features mild conditions, low cost, and a broad substrate scope.

Full text of DOI:10.1021/acs.joc.8b01861

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Article
Synthesis of CF3CH2-Containing Indolines by Transition
Metal-Free Aryltrifluoromethylation of Unactivated Alkenes
Deqiang Liang, Qishan Dong, Penghui Xu, Ying Dong, Weili Li, and Yinhai Ma
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01861 • Publication Date (Web): 10 Sep 2018
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Page 1 of 11
The Journal of Organic Chemistry
Synthesis of CF3CH2-Containing Indolines by Transition Metal-Free
Aryltrifluoromethylation of Unactivated Alkenes
Deqiang Liang,*,†,§ Qishan Dong,† Penghui Xu,† Ying Dong,‡ Weili Li,§ and Yinhai Ma†
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†Department of Chemistry, Kunming University, Kunming 650214, China
‡College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China
§Yunnan Engineering Technology Research Center for Plastic Films, Kunming 650214, China
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ABSTRACT: With unactivated double bond as the radical acceptor, allyl amines underwent metal-free
trifluoromethylation/cyclization cascade with CF3SO2Na (Langlois' reagent), affording CF3CH2-containing indolines and
tetrahydroisoquinolines, whose practical syntheses are significant challenges. This protocol features mild conditions, low cost, and
broad substrate scope.
conditions (Scheme 2).8,13 The reduction of oxindoles might
INTRODUCTION
afford related indolines as well, yet it suffers from severe
functional group intolerance.14 Therefore, it is highly desirable
The polyfluoroalkyl-containing compounds, which show
to develop a general, practical, and cost-effective method for
the synthesis of the title CF3CH2-containing indolines.
improved biological, physical, and chemical properties
compared to that of their C-H counterparts, are finding
increasing applications in pharmaceuticals, agrochemicals and
material science.1 Significant efforts have been directed toward
the incorporation of a polyfluoroalkyl group into various
organic systems.2 In this context, trifluoromethylative vicinal
difunctionalization of activated alkenes has proven to be a
powerful strategy to access molecule complexity,3-6 while
trifluoromethylation of unactivated ones remains more
rudimentary.7,8
Scheme 2. Previous Syntheses of 3-(2,2,2-Trifluoroethyl) Indolines
Scheme 1. Synthesis of CF3CH2-Containing Oxindoles from N-
Arylacrylamides
Indolic motifs are core structures of many natural alkaloids
and clinical drugs,9 and it is more challenging in indole
chemistry to elaborate an indoline framework than to
synthesize other indolic variants such as oxindole.10 For
example, CF3CH2-containing oxindoles can be readily accessed
either through trifluoromethylation/cyclization cascade of
activated alkenes of N-arylacrylamides5 (Scheme 1) or acryl
sulfonamides,6 or through derivatization reaction of their
parent oxindoles,11 whereas the synthesis of 3-(2,2,2-
trifluoroethyl) indolines still remains a significant challenge,
probably because unactivated alkenes are prone to
polymerization and double bond transfer.12 Very few examples
of 3-(2,2,2-trifluoroethyl) indoline synthesis have been
disclosed, and they are associated with tedious procedures,
narrow substrate scope, high cost, and/or harsh/toxic
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In connection with our continuous efforts in the synthesis of
performing the reaction in other tested solvents, including
biologically active molecules,15 herein, we report a metal-free
tandem trifluoromethylation/arylation of unactivated alkenes,
which leads to CF3CH2-containing indolines and 1,2,3,4-
tetrahydrofuran (THF, entry 3), MeNO2, MeCN, CH2Cl2,
toluene and EtOH (entries 4-8). A comparison of a series of
oxidants was also conducted. While tert-butyl hydroperoxide
(TBHP, entry 10) is less active than K2S2O8 in this cyclization,
use of Oxone (entry 9), di-tert-butyl peroxide (DTBP, entry
11), phenyliodine diacetate (PIDA, entry 12), or m-
chloroperbenzoic acid (mCPBA, entry 13) gave product 2a1 in
0-6% yields. At room temperature under otherwise identical
conditions, this aryltrifluoromethylation did not proceed, and
only the decomposition of substrate 1a1 was observed (entry
14). With reduced loading of K2S2O8 (entry 15) or CF3SO2Na
(entry 16), indoline 2a1 was yielded in compromised yields.
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tetrahydroisoquinolines.
A
methodology for 4-(2,2,2-
trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline synthesis is also
highly valuable, because there is only one report on such a
synthesis, in which only one example was presented.16 The
inexpensive and stable solid CF3SO2Na (Langlois' reagent)
was used as the radical trifluoromethylating agent, and this
protocol features mild conditions, easy operation, low cost,
and broad substrate scope.
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RESULTS AND DISCUSSION
Table 2. Synthesis of 3-(2,2,2-Trifluoroethyl) Indolinesa
Table 1. Optimization of the Reaction Conditionsa
Entry
1
Oxidant
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
Oxone
TBHPd
DTBP
Solvent
DMSO
DMF
Yield (%)
83
68 (13)b
2
3
THF
nr
4
MeNO2
MeCN
CH2Cl2
toluene
EtOH
nr
5
nr
6
0 (4)b (65)c
0 (7)b (78)c
7
8
nr
9
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
0 (12)b (66)c
72 (9)b
6 (70)b
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11
12
13
14e
15f
16g
PIDA
nr
mCPBA
K2S2O8
K2S2O8
K2S2O8
nr
0 (32)b (48)c
66
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aReaction conditions: 1a1 (1.0 mmol), CF3SO2Na (2.0 mmol),
oxidant (1.5 mmol), solvent (3.0 mL), 50 °C, 24 h. bIsolation of N-
phenylacetamide. cRecovery of 1a1. d5.0−6.0 mol/L in decane.
eThe reaction was performed at ambient temperature. fThe
reaction was performed with 1.1 equiv of K2S2O8. The reaction
was performed with 1.5 equiv of CF3SO2Na.
g
We began
our studies by investigating the
aryltrifluoromethylation of N-(2-methylallyl) acetanilide 1a1
(Table 1). To our delight, exposure of 1a1 to 2 equiv of
CF3SO2Na and 1.5 equiv of K2S2O8 in 50 °C dimethylsulfoxide
(DMSO, entry 1) furnished 3-(2,2,2-trifluoroethyl) indoline
2a1 in 83% yield. Using N,N-dimethylformamide (DMF, entry
2) as the solvent, 2a1 was delivered in 68% yield, along with
acetanilide, arising from the oxidative N-deprotection, formed
in 13% yield. Indoline 2a1 could not be obtained by
aReaction conditions: 1 (1.0 mmol), CF3SO2Na (2.0 mmol),
K2S2O8 (1.5 mmol), DMSO (3.0 mL), 50 °C, 24 h.
Under the optimized reaction conditions, a variety of
trifluoromethylated indolines 2 were prepared from various
allylated anilines 1 (Table 2). N-(2-methylallyl) acetanilides
bearing a methyl, bromo, or phenyl group at the para position
of the N-aryl group reacted with CF3SO2Na to afford 5-
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The Journal of Organic Chemistry
Our initial studies focused on the trifluoromethylative
substituted indolines 2a2-4 in 64-86% yields. Propionyl- and
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3
4
5
6
7
8
octanoyl-protected indolines 2b1,2 were both furnished in high
yields from corresponding anilides. Sulfonyl protecting groups
(PGs) were also tolerated, and methylsulfonyl-, ethylsulfonyl-,
cyclization of N-(2-methylallyl) substrates, in order to steer
clear of potentially competing formal 6-endo-trig cyclization,
which is also favoured according to Baldwin's rule.17 After we
achieved excellent exo selectivity in all the above reactions,
simple N-allyl aniline was also evaluated as the substrate. To
phenylsulfonyl-,
tosyl-,
o-tolylsulfonyl-,
(4-
bromophenyl)sulfonyl-, or N,N-dimethylsulfamoyl-protected
allylated anilines having an electron-neutral, -rich, or -deficient
N-aryl group all participated in this tandem reaction smoothly,
affording the desired CF3CH2-containing indolines 2c-h in
moderate to high yields. The structure of 2e1 was
unambiguously confirmed by X-ray crystallography (Figure S1,
see the Supporting Information). N-Allyl acetanilide with an
ortho-substituent on the N-aryl ring proved to be a challenging
substrate, providing corresponding 7-methyl indoline 2i in
only a poor yield as a result of steric conflict. With anilines
bearing a meta-substituted N-aryl group, poor regioselectivity
was observed, and 4-substituted indolines 2j-l and
regioisomeric 6-substituted counterparts 2j'-l' were
simultaneously produced. Interestingly, more encumbered
products 2j-l are major isomers. At this stage, the origin of such
a selectivity remains unclear, yet it might be associated with
intermediate stability. Unfortunately, we failed to isolate any
pure product from the complex reaction mixture of 3-
chlorobenzoyl-protected N-allyl aniline, which is probably
because both phenyl rings might serve as the radical acceptor
during reaction. An electron-withdrawing N-PG is essential,
for the use of N-methyl-N-(2-methylallyl)aniline also gave a
complex mixture, probably due to overreaction as a result of
the electron-rich nature of the substrate.
our
surprise,
subjecting
N-allyl-N-(4-
bromophenyl)methanesulfonamide
5
to our standard
conditions delivered 5-exo-trig product 6 exclusively in 91%
yield (Scheme 3).
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Scheme 4. Proposed Reaction Mechanism
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To probe the radical nature of this transformation, radical
trapping experiments were conducted (Scheme 4a). As might
be expected, the model reaction under standard conditions was
almost completely suppressed by adding 4 equiv of 2,2,6,6-
tetramethylpiperidine-1-oxyl (TEMPO), 2,6-di-tert-butyl-4-
methylphenol (BHT), or 1,1-diphenylethylene (DPE) as the
radical scavenger, and DPE-CF3 adduct 7 was isolated in 32%
yield in the DPE experiment. On the basis of the above results
and previous reports,5g,h,18 a tentative mechanism is proposed
(Scheme 4b). At the beginning, CF3SO2Na reacts with K2S2O8
to deliver sulfate dianion, sulfate radical anion, and
trifluoromethanesulfonyl radical. The decomposition of the
radical releases a molecule of SO2 to furnish trifluoromethyl
radical, the addition of which to the unactivated double bond
of 1a1 gives alkyl radical A.5a,7,8e,f,17a,b Ring closure ensues,
through intramolecular radical tapping by the phenyl ring,
producing dearomatizated aryl radical B.5,6,8e Subsequent
hydrogen atom transfer from B to sulfate radical anion releases
indoline 2a1 as well as the hydrogen sulfate anion.
Table
3.
Synthesis
of
CF3CH2-Containing
1,2,3,4-
Tetrahydroisoquinolinesa
CONCLUSIONS
aReaction conditions: 3 (1.0 mmol), CF3SO2Na (2.0 mmol),
K2S2O8 (1.5 mmol), DMSO (3.0 mL), 50 °C, 24 h.
In conclusion, a metal-free trifluoromethylation/cyclization
radical cascade of allyl amines using unactivated double bond
as the radical acceptor has been developed. This reaction
provides direct access to CF3CH2-containing indolines and
1,2,3,4-tetrahydroisoquinolines, and notable advantages
include mild conditions, simple operation, low cost, and broad
substrate scope.
This protocol could be extended to N-allylated
benzylamines
3
(Table 3). For example, 4-(2,2,2-
trifluoroethyl)-1,2,3,4-tetrahydroisoquinolines 4a-d were
obtained from N-allyl benzylamines protected by
phenylsulfonyl, or o-tolylsulfonyl group, with yields ranging
from 41-65%.
Scheme 3. Trifluoromethylation/Cyclization of Simple N-Allyl
Aniline
EXPERIMENTAL SECTION
General. Chemicals were all purchased from commercial
sources and used without treatment. Reactions were
monitored by Thin Layer Chromatography (TLC) using silica
gel F254 plates. Products were purified by column
chromatography over 300-400 mesh silica gel under a positive
1
pressure of air. H, 13C, DEPT, 19F and 2D NMR spectra were
3
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Page 4 of 11
recorded at 25 °C on a Bruker AscendTM 400 spectrometer
using TMS as internal standard. High-resolution mass spectra
(HRMS) were obtained using a Bruker microTOF II Focus
spectrometer (ESI).
7.32-7.35 (m, 2H), 7.43 (dd, J = 7.8, 7.4 Hz, 2H), 7.49 (dd, J
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2
3
4
5
6
7
8
= 1.7, 8.4 Hz, 1H), 7.54-7.56 (m, 2H), 8.26 (d, J = 8.4 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 168.6, 140.7,
140.7, 138.2, 137.4, 128.8, 127.7, 127.2, 126.9, 126.3 (q, 1J(C–F)
4
= 277.0 Hz), 120.7, 117.5, 61.3 (q, J(C–F) = 1.4 Hz), 43.3 (q,
Synthesis of CF3CH2-containing indolines and 1,2,3,4-
tetrahydroisoquinolines (2a1 as an example). A 35-mL Schlenk
tube, equipped with a magnetic stirring bar, was charged with
CF3SO2Na (312 mg, 2.0 mmol), K2S2O8 (405 mg, 1.5 mmol),
and N-(2-methylallyl)-N-phenylacetamide 1a (189 mg, 1.0
mmol), followed by the addition of DMSO (3.0 mL). The
mixture was stirred at 50 °C for 24 h, then it was quenched
with saturated aqueous Na2S2O3 (2.0 mL) and water (15.0
mL), and extracted with CH2Cl2 (10.0 mL) three times. The
residue obtained after evaporation of the solvent was purified
by column chromatography on silica gel (petroleum ether–
ethyl acetate = 30:1, v/v) to afford 1-(3-methyl-3-(2,2,2-
trifluoroethyl)indolin-1-yl)ethan-1-one 2a1 as a pale yellow oil
(214 mg, 83% yield).
2J(C–F) = 26.7 Hz), 41.2, 26.1, 24.2; 19F NMR (376 MHz,
CDCl3) δ = -60.35 (t, J(H–F) = 11.2, 3F); HRMS (ESI-TOF)
Calcd for C19H19F3NO+ ([M+H]+) 334.1413. Found 334.1413.
2b1, 1-(5-bromo-3-methyl-3-(2,2,2-trifluoroethyl)indolin-
1
1-yl)propan-1-one, white solid: mp 69-70 °C. H NMR (400
9
MHz, CDCl3) δ = 1.23 (t, J = 7.3 Hz, 3H), 1.46 (s, 3H), 2.38-
2.59 (m, 4H), 3.82 (d, J = 10.8 Hz, 1H), 4.11 (d, J = 10.8 Hz,
1H), 7.22 (s, 1H), 7.36 (dd, J = 1.3, 8.6 Hz, 1H), 8.13 (d, J =
8.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 172.1,
140.7, 139.6, 131.7, 126.1 (q, 1J(C–F) = 277.1 Hz), 125.3, 118.7,
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116.1, 60.1 (q, J(C–F) = 1.1 Hz), 43.1 (q, J(C–F) = 26.9 Hz),
41.1, 29.2, 26.1, 8.6; 19F NMR (376 MHz, CDCl3) δ = -60.40
(t, J(H–F)
= 12.0, 3F); HRMS (ESI-TOF) Calcd for
C14H16BrF3NO+ ([M+H]+) 350.0362. Found 350.0364.
2a1, 1-(3-methyl-3-(2,2,2-trifluoroethyl)indolin-1-yl)ethan-
1-one, white solid: mp 73-74 °C. 1H NMR (400 MHz, DMSO-
d6) δ = 1.37 (s, 3H), 2.16 (s, 3H), 2.63-2.76 (m, 1H), 2.81-
2.93 (m, 1H), 3.90 (d, J = 10.8 Hz, 1H), 4.14 (d, J = 10.8 Hz,
1H), 7.04 (ddd, J = 0.7, 7.4, 7.4 Hz, 1H), 7.20 (ddd, J = 0.9,
7.4, 7.4 Hz, 1H), 7.36 (d, J = 7.4 Hz, 1H), 8.03 (d, J = 7.4 Hz,
1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ = 169.1, 141.8,
138.2, 128.4, 127.3 (q, 1J(C–F) = 277.1 Hz), 123.9, 123.6, 116.3,
60.7, 42.1 (q, 2J(C–F) = 25.4 Hz), 40.9 (q, 3J(C–F) = 1.3 Hz), 27.3,
2b2, 1-(5-bromo-3-methyl-3-(2,2,2-trifluoroethyl)indolin-
1
1-yl)octan-1-one, white crystal: mp 92-93 °C. H NMR (400
MHz, CDCl3) δ = 0.89 (t, J = 7.0 Hz, 3H), 1.25-1.42 (m, 8H),
1.46 (s, 3H), 1.72 (tt, J = 7.6, 7.4 Hz, 2H), 2.37-2.58 (m, 4H),
3.82 (d, J = 10.8 Hz, 1H), 4.12 (d, J = 10.8 Hz, 1H), 7.22 (d, J
= 1.4 Hz, 1H), 7.36 (dd, J = 2.0, 8.6 Hz, 1H), 8.13 (d, J = 8.6
Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 171.6, 140.7,
139.6, 131.7, 126.1 (q, 1J(C–F) = 277.0 Hz), 125.2, 118.8, 116.2,
60.3 (q, 4J(C–F) = 2.0 Hz), 43.1 (q, 2J(C–F) = 26.9 Hz), 41.1, 35.9,
31.7, 29.3, 29.1, 26.0, 24.5, 22.6, 14.1; 19F NMR (376 MHz,
CDCl3) δ = -60.38 (t, J(H–F) = 10.9, 3F); HRMS (ESI-TOF)
Calcd for C19H26BrF3NO+ ([M+H]+) 420.1144. Found
420.1143.
24.4; 19F NMR (376 MHz, DMSO-d6) δ = -59.18 (t, J(H–F)
=
11.9, 3F); HRMS (ESI-TOF) Calcd for C13H15F3NO+
([M+H]+) 258.1100. Found 258.1103.
2a2,
1-(3,5-dimethyl-3-(2,2,2-trifluoroethyl)indolin-1-
yl)ethan-1-one, colorless oil. 1H NMR (400 MHz, CDCl3) δ =
1.46 (s, 3H), 2.23 (s, 3H), 2.33 (s, 3H), 2.37-2.61 (m, 2H),
3.81 (d, J = 10.8 Hz, 1H), 4.09 (d, J = 10.8 Hz, 1H), 6.91 (s,
1H), 7.05 (dd, J = 1.0, 8.2 Hz, 1H), 8.07 (d, J = 8.2 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ = 168.4, 139.0, 137.7,
2c1,
3,5-dimethyl-1-(methylsulfonyl)-3-(2,2,2-
trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz,
CDCl3) δ = 1.47 (d, J = 0.8 Hz, 3H), 2.33 (s, 3H), 2.39-2.62
(m, 2H), 2.90 (s, 3H), 3.74 (d, J = 10.4 Hz, 1H), 3.95 (d, J =
10.4 Hz, 1H), 6.95 (s, 1H), 7.05-7.07 (m, 1H), 7.29 (d, J = 8.2
Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 138.2, 137.4,
1
133.8, 129.2, 126.3 (q, J(C–F) = 276.9 Hz), 122.5, 117.0, 61.1
4
2
3
(q, J(C–F) = 2.0 Hz), 43.2 (q, J(C–F) = 26.7 Hz), 41.0 (q, J(C–F)
= 1.4 Hz), 26.0 (q, 4J(C–F) = 0.9 Hz), 24.1, 21.1; 19F NMR (376
MHz, CDCl3) δ = -60.43 (t, J(H–F) = 10.9, 3F); HRMS (ESI-
TOF) Calcd for C14H17F3NO+ ([M+H]+) 272.1257. Found
272.1272.
1
133.7, 129.6, 126.1 (q, J(C–F) = 277.0 Hz), 123.6, 113.3, 62.0
4
2
3
(q, J(C–F) = 2.1 Hz), 42.6 (q, J(C–F) = 27.0 Hz), 41.0 (q, J(C–F)
= 1.7 Hz), 34.4, 25.6 (q, 4J(C–F) = 1.5 Hz), 21.0; 19F NMR (376
MHz, CDCl3) δ = -60.27 (t, J(H–F) = 11.2, 3F); HRMS (ESI-
TOF) Calcd for C13H17F3NO2S+ ([M+H]+) 308.0927. Found
308.0923.
2a3, 1-(5-bromo-3-methyl-3-(2,2,2-trifluoroethyl)indolin-1-
yl)ethan-1-one, colorless oil. 1H NMR (400 MHz, CDCl3) δ =
1.47 (s, 3H), 2.23 (s, 3H), 2.39-2.60 (m, 2H), 3.83 (d, J =
10.8 Hz, 1H), 4.13 (d, J = 10.8 Hz, 1H), 7.23 (d, J = 1.8 Hz,
1H), 7.35 (dd, J = 2.0, 8.6 Hz, 1H), 8.09 (d, J = 8.6 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ = 168.7, 140.5, 139.7,
2c2,
5-bromo-3-methyl-1-(methylsulfonyl)-3-(2,2,2-
trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz,
CDCl3) δ = 1.48 (s, 3H), 2.42-2.62 (m, 2H), 2.93 (s, 3H),
3.77 (d, J = 10.5 Hz, 1H), 3.99 (d, J = 10.5 Hz, 1H), 7.27 (d, J
= 1.9 Hz, 1H), 7.29 (d, J = 8.6 Hz, 1H), 7.37 (dd, J = 2.0, 8.6
Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.8, 139.4,
1
131.6, 125.3, 126.1 (q, J(C–F) = 277.0 Hz), 118.7, 116.3, 61.0
4
2
3
(q, J(C–F) = 1.8 Hz), 42.9 (q, J(C–F) = 26.9 Hz), 41.1 (q, J(C–F)
= 1.1 Hz), 26.1, 24.1; 19F NMR (376 MHz, CDCl3) δ = -60.41
132.0, 126.4, 125.9 (q, J(C–F) = 276.9 Hz), 116.4, 115.0, 61.9
1
4
2
3
(t, J(H–F)
=
11.2, 3F); HRMS (ESI-TOF) Calcd for
(q, J(C–F) = 2.1 Hz), 42.5 (q, J(C–F) = 27.2 Hz), 41.0 (q, J(C–F)
= 1.7 Hz), 35.0, 25.8 (q, 4J(C–F) = 1.5 Hz); 19F NMR (376 MHz,
CDCl3) δ = -60.21 (t, J(H–F) = 10.8, 3F); HRMS (ESI-TOF)
Calcd for C12H14BrF3NO2S+ ([M+H]+) 371.9875. Found
371.9877.
C13H14BrF3NO+ ([M+H]+) 336.0205. Found 336.0209.
2a4, 1-(3-methyl-5-phenyl-3-(2,2,2-trifluoroethyl)indolin-
1-yl)ethan-1-one, white crystal: mp 165-166 °C. 1H NMR (400
MHz, CDCl3) δ = 1.53 (s, 3H), 2.27 (s, 3H), 2.47-2.68 (m,
2H), 3.87 (d, J = 10.8 Hz, 1H), 4.16 (d, J = 10.8 Hz, 1H),
4
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The Journal of Organic Chemistry
3-methyl-1-(methylsulfonyl)-5-phenyl-3-(2,2,2- = 140.4, 140.1, 137.7, 137.0, 128.9, 128.0, 127.3, 126.9, 126.1
2c3,
trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz,
CDCl3) δ = 1.53 (s, 3H), 2.46-2.69 (m, 2H), 2.95 (s, 3H),
3.81 (d, J = 10.5 Hz, 1H), 4.03 (d, J = 10.5 Hz, 1H), 7.32-7.36
(m, 2H), 7.41-7.45 (m, 2H), 7.47-7.48 (m, 2H), 7.51-7.54 (m,
(q, J(C–F) = 277.0 Hz), 121.8, 113.6, 62.1 (q, J(C–F) = 2.1 Hz),
1
4
1
2
3
4
5
6
7
8
44.5, 42.7 (q, 2J(C–F) = 27.0 Hz), 41.2 (q, 3J(C–F) = 1.6 Hz), 25.8
4
(q, J(C–F) = 1.4 Hz), 7.8; 19F NMR (376 MHz, CDCl3) δ = -
60.20 (t, J(H–F) = 10.9, 3F); HRMS (ESI-TOF) Calcd for
2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.3, 139.9,
C19H21F3NO2S+ ([M+H]+) 384.1240. Found 384.1241.
1
137.9, 137.5, 128.9, 128.1, 127.4, 126.9, 126.1 (q, J(C–F)
=
2e1,
3-methyl-1-(phenylsulfonyl)-3-(2,2,2-
277.0 Hz), 121.9, 113.7, 62.2 (q, 4J(C–F) = 2.1 Hz), 42.7 (q, 2J(C–
1
trifluoroethyl)indoline, white solid: mp 121-122 °C. H NMR
(400 MHz, CDCl3) δ = 1.22 (d, J = 0.8 Hz, 3H), 1.97-2.09 (m,
1H), 2.25-2.37 (m, 1H), 3.71 (d, J = 11.0 Hz, 1H), 3.96 (d, J
= 11.0 Hz, 1H), 7.00-7.06 (m, 2H), 7.24-7.29 (m, 1H), 7.45-
7.49 (m, 2H), 7.57 (dddd, J = 1.2, 1.2, 6.8, 6.6 Hz, 1H), 7.69
(d, J = 8.2 Hz, 1H), 7.82-7.85 (m, 2H); 13C{1H} NMR (100
MHz, CDCl3) δ = 140.3, 137.9, 136.9, 133.4, 129.2, 128.9,
3
4
= 27.0 Hz), 41.1 (q, J(C–F) = 1.7 Hz), 34.9, 25.8 (q, J(C–F)
=
=
F)
1.4 Hz); 19F NMR (376 MHz, CDCl3) δ = -60.14 (t, J(H–F)
9
11.1, 3F); HRMS (ESI-TOF) Calcd for C18H19F3NO2S+
([M+H]+) 370.1083. Found 370.1084.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2d1,
1-(ethylsulfonyl)-3-methyl-3-(2,2,2-
trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz,
CDCl3) δ = 1.42 (t, J = 7.4 Hz, 3H), 1.47 (d, J = 0.8 Hz, 3H),
2.41-2.62 (m, 2H), 3.15 (q, J = 7.4 Hz, 2H), 3.82 (d, J = 10.5
Hz, 1H), 4.05 (d, J = 10.5 Hz, 1H), 7.05 (ddd, J = 0.9, 7.5, 7.5
Hz, 1H), 7.14 (dd, J = 0.9, 7.5 Hz, 1H), 7.23 (ddd, J = 1.3, 7.4,
7.4 Hz, 1H), 7.37 (d, J = 8.1 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ = 140.7, 137.0, 129.0, 126.1 (q, 1J(C–F) = 277.0
1
127.2, 126.0 (q, J(C–F) = 277.1 Hz), 124.1, 122.7, 115.0, 61.3
4
2
3
(q, J(C–F) = 2.2 Hz), 42.7 (q, J(C–F) = 26.9 Hz), 41.0 (q, J(C–F)
= 1.7 Hz), 25.2 (q, J(C–F) = 1.6 Hz); 19F NMR (376 MHz,
4
CDCl3) δ = -60.38 (t, J(H–F) = 11.2, 3F); HRMS (ESI-TOF)
Calcd for C17H17F3NO2S+ ([M+H]+) 356.0927. Found
356.0928.
4
Hz), 123.5, 123.0, 113.4, 61.8 (q, J(C–F) = 2.1 Hz), 44.4, 42.7
2e2,
5-bromo-3-methyl-1-(phenylsulfonyl)-3-(2,2,2-
2
3
4
1
(q, J(C–F) = 27.0 Hz), 41.1 (q, J(C–F) = 1.7 Hz), 25.7 (q, J(C–F)
trifluoroethyl)indoline, white solid: mp 135-136 °C. H NMR
(400 MHz, CDCl3) δ = 1.21 (d, J = 0.6 Hz, 3H), 1.96-2.08 (m,
1H), 2.22-2.34 (m, 1H), 3.70 (d, J = 11.1 Hz, 1H), 3.96 (d, J
= 11.1 Hz, 1H), 7.13 (d, J = 2.0 Hz, 1H), 7.37 (dd, J = 2.0, 8.6
Hz, 1H), 7.48-7.51 (m, 2H), 7.57-7.62 (m, 2H), 7.80-7.83 (m,
= 1.5 Hz), 7.7; 19F NMR (376 MHz, CDCl3) δ = -60.28 (t, J(H–
= 11.2, 3F); HRMS (ESI-TOF) Calcd for C13H17F3NO2S+
F)
([M+H]+) 308.0927. Found 308.0926.
2d2,
5-bromo-1-(ethylsulfonyl)-3-methyl-3-(2,2,2-
1
trifluoroethyl)indoline, pale yellow oil. H NMR (400 MHz,
CDCl3) δ = 1.42 (t, J = 7.4 Hz, 3H), 1.47 (d, J = 0.6 Hz, 3H),
2.40-2.60 (m, 2H), 3.14 (q, J = 7.4 Hz, 2H), 3.82 (d, J = 10.6
Hz, 1H), 4.05 (d, J = 10.6 Hz, 1H), 7.24 (d, J = 1.9 Hz, 1H),
7.26 (d, J = 8.6 Hz, 1H), 7.34 (dd, J = 2.0, 8.6 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ = 140.1, 139.2, 131.9,
126.3, 125.9 (q, 1J(C–F) = 276.9 Hz), 115.9, 115.0, 61.9 (q, 4J(C–F)
= 2.1 Hz), 44.7, 42.6 (q, 2J(C–F) = 27.2 Hz), 41.1 (q, 3J(C–F) = 1.7
2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.1, 139.6,
1
136.6, 133.7, 131.9, 129.3, 127.2, 126.1, 125.8 (q, J(C–F)
=
277.1 Hz), 116.7, 116.5, 61.4 (q, 4J(C–F) = 2.2 Hz), 42.6 (q, 2J(C–
3
4
= 27.1 Hz), 41.1 (q, J(C–F) = 1.7 Hz), 25.2 (q, J(C–F) = 1.5
F)
Hz); 19F NMR (376 MHz, CDCl3) δ = -60.34 (t, J(H–F) = 10.8,
3F); HRMS (ESI-TOF) Calcd for C17H16BrF3NO2S+
([M+H]+) 434.0032. Found 434.0035.
2f1, 3-methyl-1-tosyl-3-(2,2,2-trifluoroethyl)indoline, white
crystal: mp 128-129 °C. 1H NMR (400 MHz, CDCl3) δ = 1.24
(d, J = 0.9 Hz, 3H), 1.96-2.09 (m, 1H), 2.22-2.34 (m, 1H),
2.38 (s, 3H), 3.69 (d, J = 11.0 Hz, 1H), 3.94 (d, J = 11.1 Hz,
1H), 7.00-7.05 (m, 2H), 7.24-7.28 (m, 3H), 7.68 (d, J = 8.1
Hz, 1H), 7.72 (ddd, J = 1.6, 1.6, 8.3 Hz, 2H); 13C{1H} NMR
(100 MHz, CDCl3) δ = 144.4, 140.4, 137.9, 133.8, 129.8,
128.9, 127.3, 126.0 (q, 1J(C–F) = 277.0 Hz), 124.0, 122.7, 115.0,
Hz), 25.8 (q, J(C–F) = 1.5 Hz), 7.7; 19F NMR (376 MHz,
CDCl3) δ = -60.27 (t, J(H–F) = 11.1, 3F); HRMS (ESI-TOF)
Calcd for C13H16BrF3NO2S+ ([M+H]+) 386.0032. Found
386.0032.
4
2d3,
1-(ethylsulfonyl)-3-methyl-3-(2,2,2-
trifluoroethyl)indoline-5-carbonitrile, colorless oil. 1H NMR
(400 MHz, CDCl3) δ = 1.44 (t, J = 7.4 Hz, 3H), 1.50 (s, 3H),
2.43-2.63 (m, 2H), 3.20 (q, J = 7.4 Hz, 2H), 3.90 (d, J = 10.3
Hz, 1H), 4.13 (d, J = 10.6 Hz, 1H), 7.40 (d, J = 1.5 Hz, 1H),
7.47 (dd, J = 0.3, 8.4 Hz, 1H), 7.55 (dd, J = 1.6, 8.5 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ = 144.8, 137.8, 133.9,
4
2
61.3 (q, J(C–F) = 2.1 Hz), 42.7 (q, J(C–F) = 26.9 Hz), 41.0 (q,
3J(C–F) = 1.6 Hz), 25.1 (q, 4J(C–F) = 1.5 Hz), 21.5; 19F NMR (376
MHz, CDCl3) δ = -60.39 (t, J(H–F) = 10.9, 3F); HRMS (ESI-
TOF) Calcd for C18H19F3NO2S+ ([M+H]+) 370.1083. Found
370.1082.
1
127.0, 125.7 (q, J(C–F) = 277.0 Hz), 118.6, 113.6, 106.5, 61.8
4
2
(q, J(C–F) = 2.1 Hz), 45.7, 42.7 (q, J(C–F) = 27.3 Hz), 40.9 (q,
2f2,
1-((4-bromophenyl)sulfonyl)-3-methyl-3-(2,2,2-
3J(C–F) = 1.7 Hz), 26.3 (q, J(C–F) = 1.3 Hz), 7.7; 19F NMR (376
4
trifluoroethyl)indoline, white crystal: mp 121-122 °C. 1H
NMR (400 MHz, CDCl3) δ = 1.26 (d, J = 0.8 Hz, 3H), 2.06-
2.18 (m, 1H), 2.32-2.44 (m, 1H), 3.69 (d, J = 10.9 Hz, 1H),
3.93 (d, J = 10.9 Hz, 1H), 7.03-7.08 (m, 2H), 7.24-7.29 (m,
1H), 7.60-7.66 (m, 3H), 7.70 (ddd, J = 2.2, 2.0, 8.7 Hz, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ = 140.0, 137.8, 135.8,
132.5, 129.0, 128.7, 128.6, 126.0 (q, 1J(C–F) = 276.9 Hz), 124.3,
MHz, CDCl3) δ = -60.24 (t, J(H–F) = 11.5, 3F); HRMS (ESI-
TOF) Calcd for C14H16F3N2O2S+ ([M+H]+) 333.0879. Found
333.0882.
2d4,
1-(ethylsulfonyl)-3-methyl-5-phenyl-3-(2,2,2-
trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz,
CDCl3) δ = 1.45 (t, J = 7.4 Hz, 3H), 1.52 (s, 3H), 2.46-2.68
(m, 2H), 3.18 (q, J = 7.4 Hz, 2H), 3.87 (d, J = 10.5 Hz, 1H),
4.10 (d, J = 10.5 Hz, 1H), 7.32-7.36 (m, 2H), 7.41-7.47 (m,
4H), 7.51-7.54 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ
4
2
122.9, 114.7, 61.4 (q, J(C–F) = 2.2 Hz), 42.7 (q, J(C–F) = 26.9
Hz), 41.0 (q, J(C–F) = 1.6 Hz), 25.4 (q, J(C–F) = 1.6 Hz); 19F
3
4
NMR (376 MHz, CDCl3) δ = -60.35 (t, J(H–F) = 11.1, 3F);
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Page 6 of 11
1
HRMS (ESI-TOF) Calcd for C17H16BrF3NO2S+ ([M+H]+)
434.0032. Found 434.0048.
2g1, 3-methyl-1-(o-tolylsulfonyl)-3-(2,2,2-
94 °C. H NMR (400 MHz, CDCl3) δ = 1.52 (s, 3H), 2.46-
1
2
3
4
5
6
7
8
2.67 (m, 2H), 2.94 (s, 6H), 3.82 (d, J = 10.3 Hz, 1H), 4.06 (d,
J = 10.3 Hz, 1H), 7.30 (d, J = 1.4 Hz, 1H), 7.33 (dddd, J = 1.2,
1.2, 7.3, 7.3 Hz, 1H), 7.41-7.47 (m, 4H), 7.52-7.54 (m, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ = 141.0, 140.6, 137.5,
136.6, 128.8, 127.8, 127.2, 126.9, 126.2 (q, 1J(C–F) = 277.1 Hz),
1
trifluoroethyl)indoline, white solid: mp 114-115 °C. H NMR
(400 MHz, CDCl3) δ = 1.34 (d, J = 0.7 Hz, 3H), 2.18-2.31 (m,
1H), 2.36-2.48 (m, 1H), 2.61 (s, 3H), 3.76 (d, J = 10.9 Hz,
1H), 4.01 (d, J = 10.9 Hz, 1H), 7.04 (ddd, J = 0.9, 7.6, 7.3 Hz,
1H), 7.09 (dd, J = 1.3, 7.5 Hz, 1H), 7.21 (ddd, J = 1.6, 7.3, 7.2
Hz, 1H), 7.33 (dd, J = 7.5, 8.2 Hz, 2H), 7.44 (d, J = 8.1 Hz,
1H), 7.48 (ddd, J = 1.2, 7.6, 7.5 Hz, 1H), 7.98 (d, J = 8.1 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 141.0, 138.1,
137.6, 137.1, 133.3, 133.0, 129.4, 128.7, 126.4, 126.0 (q, 1J(C–F)
4
2
121.4, 114.1, 62.4 (q, J(C–F) = 2.1 Hz), 42.8 (q, J(C–F) = 26.9
3
4
Hz), 41.1 (q, J(C–F) = 1.6 Hz), 38.3, 25.5 (q, J(C–F) = 1.3 Hz);
19F NMR (376 MHz, CDCl3) δ = -60.27 (t, J(H–F) = 11.1, 3F);
HRMS (ESI-TOF) Calcd for C19H22F3N2O2S+ ([M+H]+)
399.1349. Found 399.1368.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2i,
1-(3,7-dimethyl-3-(2,2,2-trifluoroethyl)indolin-1-
4
= 277.0 Hz), 123.8, 122.7, 114.8, 61.1 (q, J(C–F) = 2.1 Hz),
yl)ethan-1-one, colorless oil. 1H NMR (400 MHz, CDCl3) δ =
1.41 (d, J = 0.8 Hz, 3H), 2.26-2.38 (m, 7H), 2.44-2.57 (m,
1H), 3.85 (brd, J = 9.8 Hz, 1H), 4.11 (d, J = 11.1 Hz, 1H),
6.94-6.98 (m, 1H), 7.07-7.12 (m, 2H); 13C{1H} NMR (100
MHz, CDCl3) δ = 168.9 (br), 141.0 (br), 140.3 (br), 130.8,
2
3
42.6 (q, J(C–F) = 26.9 Hz), 41.1 (q, J(C–F) = 1.7 Hz), 25.1 (q,
4J(C–F) = 1.5 Hz), 20.8; 19F NMR (376 MHz, CDCl3) δ = -60.42
(t, J(H–F)
C18H19F3NO2S+ ([M+H]+) 370.1083. Found 370.1081.
2g2, 5-chloro-3-methyl-1-(o-tolylsulfonyl)-3-(2,2,2-
= 11.3, 3F); HRMS (ESI-TOF) Calcd for
1
129.6 (br), 126.4 (q, J(C–F) = 276.9 Hz), 125.8, 119.0 (br),
62.4 (br), 42.2 (br), 41.6 (q, 2J(C–F) = 27.0 Hz), 23.6 (br), 23.4
trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz,
CDCl3) δ = 1.32 (s, 3H), 2.17-2.29 (m, 1H), 2.32-2.44 (m,
1H), 2.60 (s, 3H), 3.73 (d, J = 10.9 Hz, 1H), 3.99 (d, J = 10.9
Hz, 1H), 7.04 (d, J = 2.1 Hz, 1H), 7.17 (dd, J = 2.1, 8.6 Hz,
1H), 7.33 (dd, J = 7.4, 7.2 Hz, 2H), 7.40 (d, J = 8.6 Hz, 1H),
7.48 (ddd, J = 1.2, 7.5, 7.5 Hz, 1H), 7.94-7.96 (m, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ = 139.7, 139.4, 138.1,
136.7, 133.5, 133.1, 129.5, 128.9, 128.8, 126.5, 125.8 (q, 1J(C–F)
(br), 20.4 (br); 19F NMR (376 MHz, CDCl3) δ = -60.41 (t, J(H–
= 11.1, 3F); HRMS (ESI-TOF) Calcd for C14H17F3NO+
F)
([M+H]+) 272.1257. Found 272.1260.
2j,
4-chloro-1-(ethylsulfonyl)-3-methyl-3-(2,2,2-
trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz,
CDCl3) δ = 1.42 (t, J = 7.4 Hz, 3H), 1.62 (s, 3H), 2.66-2.78
(m, 1H), 2.86-2.98 (m, 1H), 3.13-3.19 (m, 2H), 3.83 (d, J =
10.7 Hz, 1H), 4.16 (d, J = 10.7 Hz, 1H), 6.98 (dd, J = 0.8, 8.0
Hz, 1H), 7.17 (dd, J = 8.1, 8.1 Hz, 1H), 7.32 (dd, J = 0.8, 8.2
Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 143.0, 131.9,
4
= 277.0 Hz), 123.2, 115.9, 61.2 (q, J(C–F) = 2.2 Hz), 42.5 (q,
3
4
2J(C–F) = 27.2 Hz), 41.2 (q, J(C–F) = 1.7 Hz), 25.1 (q, J(C–F)
=
1.4 Hz), 20.8; 19F NMR (376 MHz, CDCl3) δ = -60.41 (t, J(H–F)
= 11.1, 3F); HRMS (ESI-TOF) Calcd for C18H18ClF3NO2S+
([M+H]+) 404.0693. Found 404.0675.
1
131.0, 130.3, 126.1 (q, J(C–F) = 277.0 Hz), 124.9, 111.9, 61.3
4
3
(q, J(C–F) = 2.3 Hz), 44.7, 42.4 (q, J(C–F) = 1.8 Hz), 40.4 (q,
2J(C–F) = 26.7 Hz), 24.7 (q, 4J(C–F) = 1.3 Hz), 7.7; 19F NMR (376
MHz, CDCl3) δ = -60.35 (t, J(H–F) = 10.9, 3F); HRMS (ESI-
TOF) Calcd for C13H16ClF3NO2S+ ([M+H]+) 342.0537.
Found 342.0539.
2h1, N,N,3,5-tetramethyl-3-(2,2,2-trifluoroethyl)indoline-
1
1-sulfonamide, pale yellow oil. H NMR (400 MHz, CDCl3) δ
= 1.45 (d, J = 0.9 Hz, 3H), 2.31 (s, 3H), 2.38-2.60 (m, 2H),
2.90 (s, 6H), 3.74 (d, J = 10.4 Hz, 1H), 3.99 (d, J = 10.4 Hz,
1H), 6.91 (s, 1H), 7.00-7.03 (m, 1H), 7.24 (d, J = 8.2 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ = 139.2, 137.1, 132.8,
129.3, 126.3 (q, 1J(C–F) = 277.0 Hz), 123.2, 113.8, 62.2 (q, 4J(C–F)
= 2.1 Hz), 42.7 (q, 2J(C–F) = 26.8 Hz), 41.1 (q, 3J(C–F) = 1.7 Hz),
2j',
6-chloro-1-(ethylsulfonyl)-3-methyl-3-(2,2,2-
trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz,
CDCl3) δ = 1.44 (t, J = 7.4 Hz, 3H), 1.46 (s, 3H), 2.39-2.59
(m, 2H), 3.16 (q, J = 7.4 Hz, 2H), 3.84 (d, J = 10.5 Hz, 1H),
4.06 (d, J = 10.5 Hz, 1H), 7.01 (dd, J = 1.6, 8.1 Hz, 1H), 7.04
(d, J = 7.9 Hz, 1H), 7.39 (dd, J = 0.4, 1.6 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ = 141.9, 135.4, 134.8, 125.9 (q,
4
38.2, 25.4 (q, J(C–F) = 1.5 Hz), 20.9; 19F NMR (376 MHz,
CDCl3) δ = -60.34 (t, J(H–F) = 11.0, 3F); HRMS (ESI-TOF)
Calcd for C14H20F3N2O2S+ ([M+H]+) 337.1192. Found
337.1195.
1J(C–F) = 277.0 Hz), 123.9, 123.5, 113.8, 62.1 (q, J(C–F) = 2.1
4
Hz), 44.8, 42.6 (q, 2J(C–F) = 27.1 Hz), 40.8 (q, 3J(C–F) = 1.7 Hz),
25.9 (q, 4J(C–F) = 1.5 Hz), 7.7; 19F NMR (376 MHz, CDCl3) δ =
-60.29 (t, J(H–F) = 11.0, 3F); HRMS (ESI-TOF) Calcd for
C13H16ClF3NO2S+ ([M+H]+) 342.0537. Found 342.0533.
2h2,
5-bromo-N,N,3-trimethyl-3-(2,2,2-
trifluoroethyl)indoline-1-sulfonamide, white solid: mp 82-
1
83 °C. H NMR (400 MHz, CDCl3) δ = 1.47 (d, J = 0.9 Hz,
3H), 2.39-2.58 (m, 2H), 2.91 (s, 6H), 3.75 (d, J = 10.4 Hz,
1H), 4.00 (d, J = 10.4 Hz, 1H), 7.20 (d, J = 2.0 Hz, 1H), 7.24
(d, J = 8.6 Hz, 1H), 7.33 (dd, J = 2.0, 8.6 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ = 140.9, 139.0, 131.7, 126.0 (q,
2k,
5-bromo-1-(ethylsulfonyl)-3,4-dimethyl-3-(2,2,2-
trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz,
CDCl3) δ = 1.42 (t, J = 7.4 Hz, 3H), 1.58 (s, 3H), 2.42 (s, 3H),
2.59 (q, J(H–F) = 11.2 Hz, 2H), 3.13 (q, J = 7.5 Hz, 2H), 3.72 (d,
J = 10.6 Hz, 1H), 4.15 (d, J = 10.6 Hz, 1H), 7.14 (d, J = 8.6
Hz, 1H), 7.43 (d, J = 8.6 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ = 140.9, 135.0, 134.5, 133.1, 125.9 (q, 1J(C–F) = 277.2
Hz), 120.4, 112.5, 61.7 (q, 4J(C–F) = 2.2 Hz), 44.4, 42.3 (q, 3J(C–F)
= 1.7 Hz), 41.1 (q, 2J(C–F) = 26.5 Hz), 24.9 (q, 4J(C–F) = 1.3 Hz),
4
1J(C–F) = 276.9 Hz), 125.9, 115.52, 115.48, 62.2 (q, J(C–F) = 2.1
Hz), 42.6 (q, 2J(C–F) = 27.1 Hz), 41.1 (q, 3J(C–F) = 1.7 Hz), 38.2,
4
25.5 (q, J(C–F) = 1.4 Hz); 19F NMR (376 MHz, CDCl3) δ = -
60.33 (t, J(H–F) = 11.8, 3F); HRMS (ESI-TOF) Calcd for
C13H17BrF3N2O2S+ ([M+H]+) 401.0141. Found 401.0144.
2h3,
N,N,3-trimethyl-5-phenyl-3-(2,2,2-
19.2, 7.7; 19F NMR (376 MHz, CDCl3) δ = -60.31 (t, J(H–F)
=
trifluoroethyl)indoline-1-sulfonamide, white solid: mp 93-
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The Journal of Organic Chemistry
10.8, 3F); HRMS (ESI-TOF) Calcd for C14H18BrF3NO2S+
([M+H]+) 400.0188. Found 400.0189.
7.29-7.39 (m, 3H), 7.49 (ddd, J = 1.4, 7.5, 7.5 Hz, 1H), 7.98
(dd, J = 1.3, 7.9 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
= 140.0, 138.1, 135.3, 133.3, 133.0, 130.8, 130.4, 127.4, 127.1,
126.7, 126.4, 126.3, 126.1 (q, 1J(C–F) = 277.2 Hz), 53.1 (q, 4J(C–F)
= 1.7 Hz), 47.4, 42.4 (q, 2J(C–F) = 26.6 Hz), 36.5 (q, 3J(C–F) = 1.4
1
2
3
4
5
6
7
8
2k',
5-bromo-1-(ethylsulfonyl)-3,6-dimethyl-3-(2,2,2-
trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz,
CDCl3) δ = 1.43 (t, J = 7.4 Hz, 3H), 1.45 (d, J = 0.6 Hz, 3H),
2.37 (s, 3H), 2.41-2.59 (m, 2H), 3.14 (q, J = 7.4 Hz, 2H), 3.81
(d, J = 10.5 Hz, 1H), 4.04 (d, J = 10.5 Hz, 1H), 7.257 (s, 1H),
7.265 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.2,
138.7, 136.5, 126.7, 125.9 (q, 1J(C–F) = 276.9 Hz), 118.4, 115.4,
62.1 (q, 4J(C–F) = 2.1 Hz), 44.5, 42.7 (q, 2J(C–F) = 27.1 Hz), 40.8
4
Hz), 24.3 (q, J(C–F) = 1.3 Hz), 20.9; 19F NMR (376 MHz,
CDCl3) δ = -59.50 (t, J(H–F) = 11.3, 3F); HRMS (ESI-TOF)
Calcd for C19H21F3NO2S+ ([M+H]+) 384.1240. Found
384.1253.
4c,
4,6-dimethyl-2-(o-tolylsulfonyl)-4-(2,2,2-
9
3
4
(q, J(C–F) = 1.7 Hz), 25.9 (q, J(C–F) = 1.4 Hz), 23.4, 7.7; 19F
NMR (376 MHz, CDCl3) δ = -60.31 (t, J(H–F) = 11.2, 3F);
HRMS (ESI-TOF) Calcd for C14H18BrF3NO2S+ ([M+H]+)
400.0188. Found 400.0189.
trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline, colorless oil. 1H
NMR (400 MHz, CDCl3) δ = 1.39 (d, J = 0.6 Hz, 3H), 2.31 (s,
3H), 2.35-2.51 (m, 2H), 2.66 (s, 3H), 3.00 (d, J = 12.5 Hz,
1H), 3.61 (d, J = 12.4 Hz, 1H), 4.24 (d, J = 14.8 Hz, 1H), 4.50
(d, J = 14.8 Hz, 1H), 6.94 (d, J = 7.9 Hz, 1H), 7.01 (dd, J =
0.8, 7.9 Hz, 1H), 7.09 (s, 1H), 7.31-7.37 (m, 2H), 7.48 (ddd, J
= 1.2, 7.5, 7.5 Hz, 1H), 7.97 (dd, J = 1.1, 8.0 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ = 140.0, 138.1, 137.1, 135.4, 133.2,
133.0, 130.4, 128.0, 127.7, 126.7, 126.6, 126.3, 126.1 (q, 1J(C–F)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2l,
5-bromo-3,4-dimethyl-1-(methylsulfonyl)-3-(2,2,2-
trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz,
CDCl3) δ = 1.59 (d, J = 0.8 Hz, 3H), 2.42 (s, 3H), 2.60 (q, J(H–
F) = 11.0 Hz, 2H), 2.92 (s, 3H), 3.64 (d, J = 10.6 Hz, 1H), 4.10
(d, J = 10.6 Hz, 1H), 7.18 (d, J = 8.6 Hz, 1H), 7.46 (d, J = 8.6
Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.7, 135.2,
4
2
= 277.3 Hz), 53.1 (q, J(C–F) = 1.7 Hz), 47.3, 42.4 (q, J(C–F)
=
3
4
1
26.5 Hz), 36.4 (q, J(C–F) = 1.4 Hz), 24.3 (q, J(C–F) = 1.1 Hz),
134.7, 133.2, 125.9 (q, J(C–F) = 277.1 Hz), 120.9, 112.4, 61.7
21.3, 20.9; 19F NMR (376 MHz, CDCl3) δ = -59.48 (t, J(H–F)
=
3
(q, 4J(C–F) = 2.2 Hz), 42.2 (q, J(C–F) = 1.7 Hz), 41.1 (q, 2J(C–F)
=
11.4, 3F); HRMS (ESI-TOF) Calcd for C20H23F3NO2S+
([M+H]+) 398.1396. Found 398.1394.
26.6 Hz), 34.7, 25.0 (q, J(C–F) = 1.3 Hz), 19.1; 19F NMR (376
MHz, CDCl3) δ = -60.28 (t, J(H–F) = 10.8, 3F); HRMS (ESI-
TOF) Calcd for C13H16BrF3NO2S+ ([M+H]+) 386.0032.
Found 386.0031.
4
4d,
6-chloro-4-methyl-2-(o-tolylsulfonyl)-4-(2,2,2-
trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline, colorless oil. 1H
NMR (400 MHz, CDCl3) δ = 1.40 (d, J = 0.6 Hz, 3H), 2.31-
2.54 (m, 2H), 2.66 (s, 3H), 3.00 (d, J = 12.6 Hz, 1H), 3.62 (d,
J = 12.6 Hz, 1H), 4.24 (d, J = 15.2 Hz, 1H), 4.51 (d, J = 15.2
Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H), 7.18 (dd, J = 2.1, 8.3 Hz,
1H), 7.28 (d, J = 2.0 Hz, 1H), 7.33-7.39 (m, 2H), 7.50 (ddd, J
= 1.3, 7.5, 7.5 Hz, 1H), 7.97 (dd, J = 1.1, 7.9 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ = 142.0, 138.1, 135.2, 133.4, 133.2,
133.0, 130.4, 129.3, 128.1, 127.5, 126.6, 126.4, 125.9 (q, 1J(C–F)
2l',
5-bromo-3,6-dimethyl-1-(methylsulfonyl)-3-(2,2,2-
trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz,
CDCl3) δ = 1.46 (s, 3H), 2.39 (s, 3H), 2.42-2.60 (m, 2H),
2.93 (s, 3H), 3.76 (d, J = 10.5 Hz, 1H), 3.97 (d, J = 10.5 Hz,
1H), 7.28 (s, 1H), 7.31 (s, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ = 139.9, 138.9, 136.7, 126.9, 125.9 (q, 1J(C–F) = 277.0
4
2
Hz), 118.9, 115.5, 62.1 (q, J(C–F) = 2.0 Hz), 42.6 (q, J(C–F)
=
3
4
27.1 Hz), 40.8 (q, J(C–F) = 1.7 Hz), 34.9, 25.9 (q, J(C–F) = 1.4
4
2
Hz), 23.4; 19F NMR (376 MHz, CDCl3) δ = -60.27 (t, J(H–F)
=
= 277.2 Hz), 52.8 (q, J(C–F) = 1.7 Hz), 47.1, 42.8 (q, J(C–F)
=
3
4
11.2, 3F); HRMS (ESI-TOF) Calcd for C13H16BrF3NO2S+
([M+H]+) 386.0032. Found 386.0030.
26.8 Hz), 36.7 (q, J(C–F) = 1.4 Hz), 24.3 (q, J(C–F) = 1.2 Hz),
20.9; 19F NMR (376 MHz, CDCl3) δ = -59.45 (t, J(H–F) = 11.6,
3F); HRMS (ESI-TOF) Calcd for C19H20ClF3NO2S+
([M+H]+) 418.0850. Found 418.0832.
4a,
4-methyl-2-(phenylsulfonyl)-4-(2,2,2-trifluoroethyl)-
1,2,3,4-tetrahydroisoquinoline, white solid: mp 133-134 °C.
1H NMR (400 MHz, CDCl3) δ = 1.47 (d, J = 1.0 Hz, 3H),
2.46-2.71 (m, 2H), 2.79 (d, J = 12.0 Hz, 1H), 3.62 (d, J = 12.0
Hz, 1H), 4.03 (d, J = 14.8 Hz, 1H), 4.46 (d, J = 14.8 Hz, 1H),
7.01-7.04 (m, 1H), 7.16-7.24 (m, 2H), 7.31 (d, J = 7.6 Hz,
1H), 7.56-7.66 (m, 3H), 7.86-7.89 (m, 2H); 13C{1H} NMR
(100 MHz, CDCl3) δ = 139.8, 135.8, 133.1, 130.5, 129.3,
127.8, 127.4, 127.1, 126.5, 126.4, 126.3 (q, 1J(C–F) = 277.1 Hz),
53.6 (q, 4J(C–F) = 1.6 Hz), 48.3, 42.7 (q, 2J(C–F) = 26.6 Hz), 36.5
6,
5-bromo-1-(methylsulfonyl)-3-(2,2,2-
1
trifluoroethyl)indoline, white solid: mp 100-101 °C. H NMR
(400 MHz, CDCl3) δ = 2.31-2.45 (m, 1H), 2.56-2.69 (m, 1H),
2.91 (s, 3H), 3.67-3.74 (m, 1H), 3.77 (dd, J = 7.6, 10.5 Hz,
1H), 4.20 (dd, J = 9.1, 9.9 Hz, 1H), 7.31 (d, J = 8.6 Hz, 1H),
7.33 (s, 1H), 7.39 (ddd, J = 0.5, 1.9, 8.6 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ = 140.9, 134.1, 132.2, 127.7, 125.9
1
4
(q, J(C–F) = 275.8 Hz), 116.6, 115.3, 56.1 (q, J(C–F) = 1.4 Hz),
38.3 (q, J(C–F) = 28.3 Hz), 35.1, 34.5 (q, J(C–F) = 2.8 Hz); 19F
NMR (376 MHz, CDCl3) δ = -64.64 (t, J(H–F) = 10.5, 3F);
HRMS (ESI-TOF) Calcd for C11H12BrF3NO2S+ ([M+H]+)
357.9719. Found 357.9722.
2
3
3
4
(q, J(C–F) = 1.4 Hz), 24.5 (q, J(C–F) = 1.2 Hz); 19F NMR (376
MHz, CDCl3) δ = -59.21 (t, J(H–F) = 11.6, 3F); HRMS (ESI-
TOF) Calcd for C18H19F3NO2S+ ([M+H]+) 370.1083. Found
370.1086.
7, (3,3,3-trifluoroprop-1-ene-1,1-diyl)dibenzene, colorless
4b,
4-methyl-2-(o-tolylsulfonyl)-4-(2,2,2-trifluoroethyl)-
1
oil. H NMR (400 MHz, CDCl3) δ = 6.13 (q, J(H–F) = 8.2 Hz,
1,2,3,4-tetrahydroisoquinoline, white solid: mp 127-128 °C.
1H NMR (400 MHz, CDCl3) δ = 1.41 (d, J = 1.1 Hz, 3H),
2.33-2.55 (m, 2H), 2.67 (s, 3H), 3.02 (d, J = 12.5 Hz, 1H),
3.63 (dd, J = 0.9, 12.5 Hz, 1H), 4.29 (d, J = 15.1 Hz, 1H), 4.56
(d, J = 15.0 Hz, 1H), 7.05-7.07 (m, 1H), 7.18-7.25 (m, 2H),
1H), 7.23-7.26 (m, 4H), 7.30-7.41 (m, 6H); 13C{1H} NMR
(100 MHz, CDCl3) δ = 152.5 (q, 3J(C–F) = 5.6 Hz), 140.1, 137.3,
4
129.4, 129.1 (q, J(C–F) = 1.8 Hz), 128.48, 128.47, 128.03,
1
2
127.96, 123.1 (q, J(C–F) = 269.0 Hz), 115.4 (q, J(C–F) = 33.6
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Hz); 19F NMR (376 MHz, CDCl3) δ = -55.60 (d, J(H–F) = 8.3,
MHz, CDCl3) δ = 1.38 (t, J = 7.4 Hz, 3H), 1.72 (s, 3H), 3.11
(q, J = 7.4 Hz, 2H), 4.37 (s, 2H), 4.84 (s, 1H), 4.86 (s, 1H),
+
3F); HRMS (ESI-TOF) Calcd for C15H12F3 ([M+H]+)
1
2
3
4
5
249.0886. Found 249.0887.
7.51 (ddd, J = 2.2, 1.8, 8.7 Hz, 2H), 7.67 (ddd, J = 2.2, 2.0, 8.7
Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 143.4, 139.3,
133.1, 127.0, 118.2, 115.4, 110.2, 56.1, 46.1, 19.7, 8.0; HRMS
(ESI-TOF) Calcd for C13H17N2O2S+ ([M+H]+) 265.1005.
Found 265.1003.
Synthesis of allyl amines 1, 3 and 5. Allyl amines were prepared
by the methods shown in Scheme S1 (see the Supporting
Information).
6
General procedure (1a2 as an example). A 100-mL flask,
equipped with a magnetic stirring bar, was charged with p-
toluidine (1.607 g, 15.0 mmol), CH2Cl2 (50.0 mL), and Et3N
(4.170 mL, 30.0 mmol), followed by the addition of acetyl
chloride (1.273 mL, 18.0 mmol). The reaction mixture was
stirred at room temperature. After p-toluidine was consumed,
as indicated by TLC, the reaction mixture was quenched with
aqueous NaHCO3 (100 mL) and extracted with CH2Cl2 (100
mL) three times. The combined organic phase was washed
with brine (50 mL) two times. After removal of solvents, the
solid of the crude product was further purified by washing with
petroleum ether/ethyl acetate mixture (5:1, v/v), affording N-
(p-tolyl)acetamide as a white crystal (2.104 g, 94% yield). To
a stirred solution of N-(p-tolyl)acetamide (1.492 g, 10.0 mmol)
and NaOH (600 mg, 15.0 mmol) in DMF (30.0 mL) was
added 3-bromo-2-methylprop-1-ene (1.311 mL, 13.0 mmol),
and the mixture was stirred at ambient temperature. After N-
(p-tolyl)acetamide was consumed, as indicated by TLC, the
reaction mixture was quenched with brine (60 mL), and
extracted with CH2Cl2 three times. The residue obtained after
evaporation of the solvent was purified by column
chromatography on silica gel (petroleum ether–ethyl acetate =
20:1, v/v) to afford N-(2-methylallyl)-N-(p-tolyl)acetamide
1a2 as a colorless oil (1.830 g, 90% yield).
7
8
9
1d4,
N-([1,1'-biphenyl]-4-yl)-N-(2-
methylallyl)ethanesulfonamide, white solid: mp 146-147 °C.
1H NMR (400 MHz, CDCl3) δ = 1.41 (t, J = 7.4 Hz, 3H), 1.79
(s, 3H), 3.08 (q, J = 7.4 Hz, 2H), 4.33 (s, 2H), 4.84 (s, 2H),
7.35 (dddd, J = 1.2, 1.2, 7.4, 7.3 Hz, 1H), 7.40-7.46 (m, 4H),
7.55-7.60 (m, 4H); 13C{1H} NMR (100 MHz, CDCl3) δ =
140.4, 140.2, 140.0, 138.2, 128.9, 128.3, 127.9, 127.6, 127.1,
115.0, 57.2, 45.3, 19.9, 8.1; HRMS (ESI-TOF) Calcd for
C18H22NO2S+ ([M+H]+) 316.1366. Found 316.1354.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1g1,
2-methyl-N-(2-methylallyl)-N-
phenylbenzenesulfonamide, white solid: mp 56-57 °C. 1H
NMR (400 MHz, CDCl3) δ = 1.75 (s, 3H), 2.30 (s, 3H), 4.20
(s, 2H), 4.73 (s, 1H), 4.76 (s, 1H), 7.08-7.13 (m, 2H), 7.20-
7.29 (m, 5H), 7.41 (ddd, J = 1.3, 7.5, 7.5 Hz, 1H), 7.79 (dd, J
= 1.2, 8.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ =
139.9, 138.6, 138.1, 136.8, 132.7, 132.6, 130.3, 128.8, 128.6,
127.6, 126.1, 115.3, 57.0, 20.8, 20.0; HRMS (ESI-TOF) Calcd
for C17H20NO2S+ ([M+H]+) 302.1209. Found 302.1203.
1g2,
N-(4-chlorophenyl)-2-methyl-N-(2-
methylallyl)benzenesulfonamide, white solid: mp 58-59 °C. 1H
NMR (400 MHz, CDCl3) δ = 1.73 (s, 3H), 2.35 (s, 3H), 4.16
(s, 2H), 4.71 (s, 1H), 4.78 (s, 1H), 7.04 (ddd, J = 3.0, 2.1, 8.8
Hz, 2H), 7.21-7.28 (m, 4H), 7.43 (ddd, J = 1.3, 7.6, 7.6 Hz,
1H), 7.76 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ = 139.6, 138.0, 137.2, 136.5, 133.4, 133.0, 132.7,
130.4, 129.8, 129.1, 126.2, 115.8, 57.0, 20.8, 19.9; HRMS
(ESI-TOF) Calcd for C17H19ClNO2S+ ([M+H]+) 336.0820.
Found 336.0823.
1a4, N-([1,1'-biphenyl]-4-yl)-N-(2-methylallyl)acetamide,
1
colorless oil. H NMR (400 MHz, CDCl3) δ = 1.78 (s, 3H),
1.96 (s, 3H), 4.32 (s, 2H), 4.75 (s, 1H), 4.85 (s, 1H), 7.23 (d,
J = 8.2 Hz, 2H), 7.37 (dd, J = 7.3, 7.3 Hz, 1H), 7.45 (dd, J =
7.7, 7.4 Hz, 2H), 7.58-7.61 (m, 4H); 13C{1H} NMR (100
MHz, CDCl3) δ = 170.4, 142.3, 140.8, 140.6, 140.0, 128.9,
128.11, 128.05, 127.7, 127.1, 113.1, 55.0, 22.9, 20.4; HRMS
(ESI-TOF) Calcd for C18H20NO+ ([M+H]+) 266.1539. Found
266.1538.
1h1,
N,N-dimethyl-N'-(2-methylallyl)-N'-(p-
tolyl)sulphamide, pale yellow oil. 1H NMR (400 MHz, CDCl3)
δ = 1.75 (s, 3H), 2.31 (s, 3H), 2.73 (s, 6H), 4.20 (s, 2H), 4.76
(s, 2H), 7.14 (d, J = 8.3 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ = 140.4, 137.5, 137.3,
129.7, 128.0, 114.7, 58.5, 38.3, 21.1, 20.0; HRMS (ESI-TOF)
Calcd for C13H21N2O2S+ ([M+H]+) 269.1318. Found 269.1335.
1c2,
N-(4-bromophenyl)-N-(2-
methylallyl)methanesulfonamide, white crystal: mp 77-78 °C.
1H NMR (400 MHz, CDCl3) δ = 1.74 (s, 3H), 2.90 (s, 3H),
4.22 (s, 2H), 4.80 (s, 1H), 4.83 (s, 1H), 7.22 (ddd, J = 3.0, 2.1,
8.8 Hz, 2H), 7.51 (ddd, J = 3.0, 2.1, 8.8 Hz, 2H); 13C{1H}
NMR (100 MHz, CDCl3) δ = 139.5, 138.0, 132.5, 129.6, 121.7,
115.6, 56.6, 37.3, 19.8; HRMS (ESI-TOF) Calcd for
C11H15BrNO2S+ ([M+H]+) 304.0001. Found 304.0004.
1h2,
N'-(4-bromophenyl)-N,N-dimethyl-N'-(2-
1
methylallyl)sulphamide, pale yellow oil. H NMR (400 MHz,
CDCl3) δ = 1.74 (s, 3H), 2.77 (s, 6H), 4.19 (s, 2H), 4.76 (s,
1H), 4.79 (s, 1H), 7.26 (ddd, J = 3.0, 2.1, 8.8 Hz, 2H), 7.47
(ddd, J = 3.0, 2.1, 8.8 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ = 139.9, 139.3, 132.2, 129.6, 121.0, 115.3, 58.2, 38.3,
20.0; HRMS (ESI-TOF) Calcd for C12H18BrN2O2S+ ([M+H]+)
333.0267. Found 333.0262.
1d1, N-(2-methylallyl)-N-phenylethanesulfonamide, pale
1
yellow solid: mp 78-79 °C. H NMR (400 MHz, CDCl3) δ =
1.39 (t, J = 7.4 Hz, 3H), 1.76 (s, 3H), 3.04 (q, J = 7.4 Hz, 2H),
4.29 (s, 2H), 4.79 (s, 2H), 7.27-7.32 (m, 1H), 7.34-7.39 (m,
4H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.2, 139.1,
129.2, 128.2, 127.6, 114.9, 57.3, 45.2, 19.8, 8.0; HRMS (ESI-
TOF) Calcd for C12H18NO2S+ ([M+H]+) 240.1053. Found
240.1068.
1
1i, N-(2-methylallyl)-N-(o-tolyl)acetamide, red oil. H NMR
(400 MHz, CDCl3) δ = 1.79-1.80 (m, 6H), 2.23 (s, 3H), 3.48
(d, J = 14.5 Hz, 1H), 4.67-4.68 (m, 1H), 4.82-4.86 (m, 2H),
7.07 (dd, J = 1.4, 7.8 Hz, 1H), 7.18-7.26 (m, 2H), 7.27-7.30
(m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 170.6, 141.6,
140.7, 135.4, 131.4, 129.0, 128.3, 127.0, 113.8, 53.9, 22.3, 20.7,
1d3,
N-(4-cyanophenyl)-N-(2-
methylallyl)ethanesulfonamide, colorless oil. 1H NMR (400
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The Journal of Organic Chemistry
3c,
17.5; HRMS (ESI-TOF) Calcd for C13H18NO+ ([M+H]+)
2-methyl-N-(2-methylallyl)-N-(4-
methylbenzyl)benzenesulfonamide, pale yellow solid: mp 43-
44 °C. H NMR (400 MHz, CDCl3) δ = 1.55 (s, 3H), 2.30 (s,
1
2
3
4
5
6
7
8
204.1383. Found 204.1387.
1
1j, N-(3-chlorophenyl)-N-(2-methylallyl)ethanesulfonamide,
1
3H), 2.58 (s, 3H), 3.71 (s, 2H), 4.33 (s, 2H), 4.80 (s, 1H),
4.93 (s, 1H), 6.91 (d, J = 8.0 Hz, 2H), 7.04 (d, J = 7.8 Hz, 2H),
7.30 (dd, J = 7.9, 7.6 Hz, 2H), 7.45 (ddd, J = 1.1, 7.5, 7.5 Hz,
1H), 7.99 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ = 139.8, 138.7, 137.6, 137.5, 132.7, 132.6, 132.5,
130.1, 129.1, 128.9, 126.1, 115.1, 51.7, 49.0, 21.1, 20.5, 19.8;
HRMS (ESI-TOF) Calcd for C19H24NO2S+ ([M+H]+)
330.1522. Found 330.1538.
pale yellow oil. H NMR (400 MHz, CDCl3) δ = 1.39 (t, J =
7.4 Hz, 3H), 1.75 (s, 3H), 3.06 (q, J = 7.4 Hz, 2H), 4.28 (s,
2H), 4.81 (s, 1H), 4.83 (s, 1H), 7.25-7.33 (m, 3H), 7.35-7.36
(m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.3, 139.7,
134.6, 130.1, 128.0, 127.8, 126.2, 115.3, 57.1, 45.5, 19.8, 8.0;
HRMS (ESI-TOF) Calcd for C12H17ClNO2S+ ([M+H]+)
274.0663. Found 274.0663.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1k,
N-(4-bromo-3-methylphenyl)-N-(2-
3d,
N-(4-chlorobenzyl)-2-methyl-N-(2-
methylallyl)ethanesulfonamide, pale yellow solid: mp 51-52 °C.
1H NMR (400 MHz, CDCl3) δ = 1.38 (t, J = 7.4 Hz, 3H), 1.75
(s, 3H), 2.39 (s, 3H), 3.03 (q, J = 7.4 Hz, 2H), 4.25 (s, 2H),
4.79 (s, 1H), 4.82 (s, 1H), 7.03 (dd, J = 2.5, 8.5 Hz, 1H), 7.23
(d, J = 2.5 Hz, 1H), 7.51 (d, J = 8.5 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ = 139.9, 139.1, 138.2, 133.0, 130.5,
126.6, 123.9, 115.2, 57.2, 45.3, 23.1, 19.8, 8.0; HRMS (ESI-
TOF) Calcd for C13H19BrNO2S+ ([M+H]+) 332.0314. Found
332.0316.
1
methylallyl)benzenesulfonamide, colorless oil. H NMR (400
MHz, CDCl3) δ = 1.51 (s, 3H), 2.58 (s, 3H), 3.69 (s, 2H),
4.35 (s, 2H), 4.77 (s, 1H), 4.91 (s, 1H), 7.02 (d, J = 8.4 Hz,
2H), 7.22 (ddd, J = 2.4, 1.8, 8.4 Hz, 2H), 7.31 (dd, J = 7.2, 7.4
Hz, 2H), 7.46 (ddd, J = 1.2, 7.6, 7.6 Hz, 1H), 7.97-7.99 (m,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.6, 138.3,
137.6, 134.3, 133.6, 132.9, 132.7, 130.2, 130.1, 128.6, 126.2,
115.6, 52.2, 48.8, 20.5, 19.7; HRMS (ESI-TOF) Calcd for
C18H21ClNO2S+ ([M+H]+) 350.0976. Found 350.0974.
1l,
N-(4-bromo-3-methylphenyl)-N-(2-
5, N-allyl-N-(4-bromophenyl)methanesulfonamide, pale
yellow semisolid. H NMR (400 MHz, CDCl3) δ = 2.91 (s,
methylallyl)methanesulfonamide, pale yellow solid: mp 66-
1
1
67 °C. H NMR (400 MHz, CDCl3) δ = 1.75 (s, 3H), 2.39 (s,
3H), 4.27 (ddd, J = 1.2, 1.2, 6.4 Hz, 2H), 5.15-5.20 (m, 2H),
5.76-5.86 (m, 1H), 7.21 (ddd, J = 3.0, 2.1, 8.8 Hz, 2H), 7.52
(ddd, J = 3.0, 2.1, 8.8 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ = 138.3, 132.6, 132.5, 130.0, 121.9, 119.6, 53.6, 38.2;
HRMS (ESI-TOF) Calcd for C10H13BrNO2S+ ([M+H]+)
289.9845. Found 289.9831.
3H), 2.90 (s, 3H), 4.21 (s, 2H), 4.81 (s, 1H), 4.83 (s, 1H),
7.02 (dd, J = 2.6, 8.5 Hz, 1H), 7.21 (d, J = 2.4 Hz, 1H), 7.52
(d, J = 8.5 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ =
139.7, 139.2, 138.1, 133.0, 130.5, 126.5, 124.2, 115.3, 56.7,
37.3, 23.1, 19.8; HRMS (ESI-TOF) Calcd for C12H17BrNO2S+
([M+H]+) 318.0158. Found 318.0159.
1m,
N-(4-bromophenyl)-3-chloro-N-(2-
AUTHOR INFORMATION
Corresponding Author
1
methylallyl)benzamide, white solid: mp 104-105 °C. H NMR
(400 MHz, CDCl3) δ = 1.80 (s, 3H), 4.46 (s, 2H), 4.87 (s,
1H), 4.92 (s, 1H), 6.91 (d, J = 8.4 Hz, 2H), 7.08-7.14 (m, 2H),
7.24-7.27 (m, 1H), 7.34 (d, J = 8.6 Hz, 2H), 7.40 (s, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ = 168.8, 142.3, 140.5,
137.4, 134.2, 132.3, 130.1, 129.2, 128.9, 128.5, 126.6, 120.4,
113.1, 55.7, 20.4; HRMS (ESI-TOF) Calcd for
C17H16BrClNO+ ([M+H]+) 364.0098. Found 364.0094.
*liangdq695@nenu.edu.cn, ldq5871@126.com
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Financial support from the National Natural Science Foundation
of China (No. 21702083) is gratefully acknowledged.
3a, N-benzyl-N-(2-methylallyl)benzenesulfonamide, pale
yellow oil. 1H NMR (400 MHz, CDCl3) δ = 1.52 (s, 3H), 3.71
(s, 2H), 4.35 (s, 2H), 4.70 (s, 1H), 4.82 (s, 1H), 7.14-7.18 (s,
2H), 7.21-7.26 (m, 3H), 7.47-7.51 (m, 2H), 7.56 (dddd, J =
1.3, 1.3, 7.4, 7.3 Hz, 1H), 7.82-7.85 (m, 2H); 13C{1H} NMR
(100 MHz, CDCl3) δ = 140.6, 139.9, 135.9, 132.5, 129.0,
128.7, 128.4, 127.7, 127.2, 114.9, 53.3, 50.6, 19.9; HRMS
(ESI-TOF) Calcd for C17H20NO2S+ ([M+H]+) 302.1209.
Found 302.1210.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website.
X-ray crystallograpy data for 2e1 (CIF)
Spectroscopic data (PDF)
3b,
N-benzyl-2-methyl-N-(2-
REFERENCES
1
methylallyl)benzenesulfonamide, colorless oil. H NMR (400
MHz, CDCl3) δ = 1.55 (s, 3H), 2.58 (s, 3H), 3.73 (s, 2H),
4.38 (s, 2H), 4.79 (s, 1H), 4.93 (s, 1H), 7.03-7.05 (m, 2H),
7.22-7.25 (m, 3H), 7.30 (dd, J = 7.7, 7.6 Hz, 2H), 7.46 (ddd, J
= 1.1, 7.6, 7.6 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H); 13C{1H}
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