Cu-Mediated Synthesis of Indolines and Dihydroisoquinolinones through Arylperfluoroalkylation of Unactivated Alkenes

Article abstract of DOI:10.1002/ejoc.201900680

The copper-mediated fluroalkylation/cyclization of N-allyl anilines has been described using fluoroalkyl iodides as fluoroalkylation reagents for the first time. The reaction provides an efficient and direct access to 3-fluoroalkyl indolines in moderate to good yields with unactivated double bonds as the radical acceptor. This protocol combines a simple experimental procedure with low-costing fluoroalkylated sources and excellent functional group tolerance.

Full text of DOI:10.1002/ejoc.201900680

DOI: 10.1002/ejoc.201900680
Full Paper
Fluroalkylation
Cu-Mediated Synthesis of Indolines and Dihydroisoquinolinones
through Arylperfluoroalkylation of Unactivated Alkenes
Dandan Li,*[a] Yan Wang,[b] Zhenzhen Jia,[a] Zhaocheng Ou,[a] Yongrui Dong,[b] Cunjie Lv,[a]
Guangbin Fu,[a] and Deqiang Liang*[b]
Abstract: The copper-mediated fluroalkylation/cyclization of moderate to good yields with unactivated double bonds as the
N-allyl anilines has been described using fluoroalkyl iodides as radical acceptor. This protocol combines a simple experimental
fluoroalkylation reagents for the first time. The reaction pro- procedure with low-costing fluoroalkylated sources and excel-
vides an efficient and direct access to 3-fluoroalkyl indolines in lent functional group tolerance.
Introduction
perfluoroalkylation for the synthesis of heterocycles. In 2018,
our group[9] developed the synthesis of CF3CH2-containing ind-
olines by transition-metal-free aryltrifluoromethylation of unac-
tivated alkenes. Inspired by recent advances in difunctionaliza-
tion of unactivated alkene,[3a,8–10] and in continuation of our
interest in the synthesis of biologically active compounds,[9–11]
we speculate that Rf acts as a free radical initiator mediated by
copper without ligand and N-allyl acts as a free radical acceptor
to achieve the construction of fluorinated indoline structures
by free radical cascade reaction. Herein, a new radical cascade
reaction and towards the formation of fluorinated indoline is
described in this work.
Fluoroalkyl-containing compounds often play unique roles in
pharmaceuticals, agrochemicals, and materials because the in-
troduction of fluorinated groups can dramatically modify the
solubility, metabolic stability, and bioavailability of target mol-
ecules.[1] Therefore, continuous endeavors have been focused
on developing efficient methods for the synthesis of organo-
fluorine compounds.[2] Over the past years, difunctionalization
of alkenes to incorporate perfluoroalkyl (Rf) group has attracted
considerable attention and has emerged as a powerful strategy
for the construction of functionalized Rf-containing com-
pounds.[3] However, most of the perfluoroalkylative reactions
are limited to the difunctionalization of activated olefins.[4]
Therefore, it remains a challenge for the perfluoroalkylative di-
functionalization of unactivated alkenes.
Results and Discussion
Initially, we chose perfluorobutyl iodide (2a) as the source of
the C4F9 group and N-(2-methylallyl)-N-phenylacetamide (1a) to
optimize the reaction conditions (Table 1). Firstly, various cop-
per sources were tested to mediate the arylperfluoroalkylation
at 120 °C in DMSO. However, either no or only a trace amount
of the desired product was obtained (entries 1–6). Gratifyingly,
when 1.5 equiv. of Cu powder was added to the reaction, we
could get the desired product 3aa in 68 % yield (entry 7). More-
over, the effect of solvent was also explored. DCE, CH3CN, or
PhMe were not suitable for this transformation (entries 8–10).
Other solvents such as 1,4-dioxane and DMF failed to give a
better yield than DMSO (entries 11–12). These results indicated
that DMSO was the most effective solvent for this reaction. As
expected, the reaction failed to provide any desired product
without Cu (entry 13). Reducing the metal Cu loading to
1.1 equiv., the yield of 3aa dropped slightly to 64 % (entry 14).
When the temperature was reduced to 80 °C, only 11 % of the
target product was obtained even after a prolonged reaction
time (entry 15). In addition, we also attempted to investigate
the effect of perfluorobutyl iodide loading (2a). By decreasing
the amount of 2a, a diminished yield of the desired product
was obtained (entry 16). To our pleasure, the yield of 3aa in-
creased to 74 % by using 3.0 equiv. of 2a (entry 17). When the
Indoles, including indolines and oxindoles, are valuable
structural motifs that widely existed in bioactive natural prod-
ucts, and clinical drugs.[5] Developing convenient and efficient
methods for the construction of indole skeleton has long been
received significant attention in industrial and academic society.
Compared with the approaches for indole blocks, the pathway
for synthesis of indoline scaffolds is rather limited and mainly
restricted to the de-aromatization of indole.[6] Moreover, an-
other method for preparing indoline frameworks through the
reduction of oxoindoles either require the use of harsh reaction
conditions or suffer from poor tolerance of functional groups.[7]
Therefore, it is essential to develop novel and highly efficient
methods for the synthesis of indoline scaffolds. In 2016,
Cheng and Yuan group[8] have reported the Pd-catalyzed aryl-
[a] School of Chemistry and Chemical Engineering, Xuchang University,
No. 88, Bayi Road, Xuchang, Henan 461000, P. R. China.
E-mail: dandanli2015@outlook.com
https://huaxue.xcu.edu.cn/info/1013/3673.htm
[b] Department of Chemistry, Kunming University,
Kunming 650214, P. R. China.
E-mail: liangdq695@nenu.edu.cn
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201900680.
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amount of 2a was further increased to 3.5 equiv., the yield of to the methyl group, we were unable to obtain any target prod-
3aa was not substantially improved (entry 18). Therefore, uct. Interestingly, the substrate N-benzyl-2-methylprop-2-en-1-
1 equiv. of 1a, 1.5 equiv. of Cu, and 3 equiv. of 2a at 120 °C in amine substituted with o-tolylsulfonyl group could also be tol-
DMSO (3 mL) for 6 h were chosen as the optimized conditions erated to give the six-membered product in a highly selective
for the Cu-mediated arylperfluoroalkylation reaction.
manner (3xa). Moreover, if the methyl group R1 was replaced by
a hydrogen atom, we still obtained the corresponding indolines
(3ya–3za). Furthermore, the reaction could be successfully ex-
tended to longer chain perfluoroiodo alkanes (C6F13I and
C8F17I), affording the corresponding products in good to excel-
lent yields (3ab–3ac). In addition, when BrCF2CO2Et was em-
ployed as a fluoroalkylating agent, 55 % yield of indoline deriva-
tive (3ad) obtained. We also attempted CF3I and CH3I as sub-
Table 1. Optimization of the reaction conditions.[a]
Entry
[Cu]
Solvent
t [h]
Yield[%][b]
Table 2. Cu-mediated arylperfluoroalkylation reaction of alkenes.[a,b]
1
2
3
4
5
6
7
8
CuBr
CuCl
CuI
Cu2O
CuO
CuCl2
Cu
Cu
Cu
Cu
Cu
Cu
–
Cu
Cu
Cu
Cu
Cu
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DCE
MeCN
PhMe
1,4-dioxane
DMF
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
12
12
12
12
12
12
6
6
6
6
6
12
6
6
24
6
6
trace
trace
NR
NR
NR
NR
68
NR
NR
NR
11
31
NR
64
11
49
9
10
11
12
13
14[c]
15[d]
16[e]
17[f]
18[g]
74
75
6
[a] Reaction conditions: 0.5 mmol of 1a, 1.0 mmol of 2a, and 1.5 equiv. of
[Cu]-catalyst in 3 mL of solvent at 120 °C. [b] Isolated yield. [c] 1.1 equiv. of
Cu used. [d] At 80 °C. [e] 1.5 equiv. of 2a used. [f] 3.0 equiv. of 2a used.
[g] 3.5 equiv. of 2a used.
With the optimal conditions in hand, we turned to investi-
gate the scope and the limitations of the reactions. As shown
in Table 2, alkenes with various substitution on the phenyl ring
well tolerated in this transformation, leading to the correspond-
ing perfluoroalkylated indolines (3aa–3da) in moderate to
good yields. It should be noted that the substrate containing
pyridin-4-amine could be smoothly converted into the desired
product 3ea in 71 % yield. The effect of protecting groups on
the nitrogen atom was further examined. N-(2-methylallyl)
anilines protected by propionyl group reacted with 2a
smoothly to provide the corresponding indolines (3fa–3ga) in
60–76 % yields. Similarly, long-chain protecting groups such as
butyl, and octanoyl also showed good reactivity in this transfor-
mation (3ha–3ja). Boc-protected indoline 3ka could be ob-
tained in high yields under the standard conditions. By using
3-chlorobenzoyl group as protecting group, 2a can react selec-
tively with the benzene ring of the N-phenyl group instead of
the benzene ring of the 3-chlorobenzoyl group, furnishing the
product 3la in 62 % yield. Meanwhile, various sulfonyl protect-
ing groups including alkylsulfonyl (such as methylsulfonyl, eth-
ylsulfonyl, and N,N-dimethylsulfamoyl) and arylsulfonyl groups
(phenylsulfonyl, tosyl, and o-tolylsulfonyl) could be applied in
this protocol, bringing out the desired products 3ma–3wa in
32–79 % yields. Disappointingly, changing the protecting group
[a] Reaction conditions: 0.5 mmol of 1, 1.5 mmol of 2, and 1.5 equiv. of Cu
in 3 mL of DMSO at 120 °C for 6 h. [b] Isolated yield.
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strates, however, either no or a trace amount of products were ylene under the standard conditions, we still could obtain the
detected.
Encouraged by the above-mentioned results, we next ex-
plored the scope of allylamine protected by benzoyl groups
nC4F9-adduct product 6 in 45 % yield. These results indicated
that nC4F9 radical could be formed under these conditions.
Based on the above experimental results and literature re-
(Table 3). The substrate 4a bearing a methyl group on N atom ports,[8,10a,10b,12] a plausible mechanism for Cu-mediated aryl-
was tolerated under the standard conditions, affording the cor- perfluoroalkylation process was outlined in Scheme 2. First, RfX
responding six-ring product in 57 % yield (5aa). Moreover, two reacts with Cu to produce perfluoroalkyl radical Rf·, which un-
kinds of N-allylated benzylamines were also investigated. Unlike dergoes the addition with 1 to give the intermediate A. Then,
the o-tolylsulfonyl protected benzylamine (Table 2, 2w), the intermediate A is converted to intermediate B through the
benzoyl protected benzylamines selectively underwent ring clo- intramolecular radical cyclization. Finally, the generated Rf·
sure reaction with the phenyl ring of the benzoyl group, rather selectively abstracts a hydrogen atom from the intermediate B
than the phenyl ring of benzylamine group (5ba–5ca).
to deliver the target product 3aa. It should be noted that a
mechanism involving Cu(I)-catalyzed perfluoroalkylation path-
way[10c,13] could not be completely excluded.
Table 3. Synthesis of nC4F9-containing dihydroisoquinolinones by Cu-medi-
ated aryltrifluoromethylation of unactivated alkenes.[a,b]
Scheme 2. Plausible mechanism.
[a] Reaction conditions: 0.5 mmol of 4, 1.5 mmol of 2, and 1.5 equiv. of Cu
in 3 mL of DMSO at 120 °C for 6 h. [b] Isolated yield.
Conclusions
In order to gain insights into the reaction mechanism, several
control experiments were conducted (Scheme 1). When radical
scavenger (2,2,6,6–tetramethylpiperidin–1-yl)oxy (TEMPO) was
added into the reaction system, no desired target product
could be observed under the standard reaction conditions
(Scheme 1). When 1,1-diphenylethylene was added as a radical
scavenger, the reaction was totally inhibited and the nC4F9-ad-
duct product 6 was isolated in 16 % yield. Then, replacing the
N-(2-methylallyl)-N-phenylacetamide (1a) with 1,1-diphenyleth-
A new copper-mediated cascade cyclization of N-allyl anilines
with fluoroalkyl iodides has been demonstrated for the first
time. This reaction allows the direct access to 3-fluoroalkyl ind-
olines in moderate to good yields with unactivated double
bonds as the radical acceptor. This synthetic method exhibits
simple operation, good functional group tolerance, and low-
cost fluoroalkylated sources. Moreover, the preliminary mecha-
nistic studies disclose that the reaction may proceed via a radi-
cal pathway.
Experimental Section
General Information: Unless otherwise noted, all commercial ma-
1
terials and solvents were used without further purification. H NMR
and 13C NMR spectra were referenced to TMS and residue CHCl3 at
0.00 ppm and 77.16 ppm, respectively. High-resolution mass spec-
tra (HRMS) were measured with ESI in positive mode.
General Procedure for the Synthesis of N-Allyl Anilines or Sulf-
onamides Substrates (2b as an Example):[14] A mixture of p-tolu-
idine (1.607 g, 15.0 mmol), CH2Cl2 (50.0 mL), and Et3N (4.170 mL,
30.0 mmol), was placed in a round-bottom flask equipped with a
magnetic stir bar. To this mixture was added 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 or-
ganic phase was washed with brine (50 mL) two times. After re-
moval of solvents, the solid of the crude product was further puri-
fied by washing with a petroleum ether/ethyl acetate mixture (5:1,
Scheme 1. Control experiments.
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v/v), affording N-(p-tolyl)acetamide as a white crystal. To a stirred
solution of N-(ptolyl)acetamide (1.492 g, 10.0 mmol) and NaOH
(600 mg, 15.0 mmol) in DMF (30.0 mL) was added 3-bromo-2-meth-
1.51 (d, J = 2.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ = 168.45,
138.98, 138.15, 133.97, 129.44, 122.62, 117.23, 61.64 (d, J = 6.3 Hz),
41.81, 39.41 (t, J = 20.4 Hz), 26.67 (d, J = 3.7 Hz), 24.25, 21.24; 19F
ylprop-1-ene (1.311 mL, 13.0 mmol), and the mixture was stirred at NMR (376 MHz, CDCl3) δ = –81.01 (t, J = 11.4 Hz, 3F), –107.82 to
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 ob-
tained 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 2a as a colorless
oil.
–114.39 (m, 2F), –124.47 to –124.56 (m, 2F), –125.59 to –125.85 (m,
2F); HRMS (ESI): m/z [M + H]+ calcd. for C17H17F9NO: 433.1161, found
433.1163.
1-(5-Chloro-3-methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)-
indolin-1-yl)ethanone (3ca): Yield 82 % (180.8 mg), white solid,
m.p. 89–90 °C. 1H NMR (400 MHz, CDCl3) δ = 8.16 (d, J = 8.6 Hz,
1H), 7.22 (dd, J = 8.6, 2.2 Hz, 1H), 7.10 (d, J = 2.2 Hz, 1H), 4.11 (d,
J = 10.9 Hz, 1H), 3.91 (dd, J = 10.9, 1.6 Hz, 1H), 2.55–2.39 (m, 2H),
2.24 (s, 3H), 1.53 (d, J = 2.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ =
168.74, 139.97, 139.73, 129.09, 128.94, 122.52, 118.50, 61.57 (d, J =
6.2 Hz), 41.86, 39.28 (t, J = 20.5 Hz), 26.77 (d, J = 3.7 Hz), 24.18; 19F
NMR (376 MHz, CDCl3) δ = –81.05 (t, J = 11.4 Hz, 3F), –108.02 to
–114.08 (m, 2F), –124.41 to –124.55 (m, 2F), –125.70 to –125.80 (m,
2F); HRMS (ESI): m/z [M + H]+ calcd. for C16H14ClF9NO: 442.0615,
found 442.0619.
General Procedure for the Cu-Mediated Synthesis of Indolines
and Dihydroisoquinolinones: A mixture of N-allyl anilines 1a (1b–
z and 4a–c, 0.5 mmol), Cu (1.0 mmol, 63.5 mg) and RfX (1.5 mmol)
in DMSO (3 mL) was stirred at 120 °C. The reaction was monitored
by TLC and stopped at the desired time. After the reaction was
finished, the mixture was filtered by a silica gel plug with ethyl
acetate (30 mL) as the eluent. The filtrate was washed with satu-
rated brine (3 × 10 mL) and the organic phase was dried with
Na2SO4, filtered, and concentrated under reduced pressure. The resi-
due was separated on a silica gel column with petroleum ether/
ethyl acetate as the eluent to get product 3aa (3ba–3za, 3ab–ac,
and 5aa–ca).
1-(3-Methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)-5-phenyl-
indolin-1-yl)ethanone(3da): Yield 58 % (140.0 mg), white solid,
1
m.p. 151–152 °C. H NMR (400 MHz, CDCl3) δ = 8.28 (d, J = 8.4 Hz,
1H), 7.56 (dd, J = 8.3, 1.3 Hz, 2H), 7.51 (dd, J = 8.4, 1.9 Hz, 1H), 7.44
(t, J = 7.6 Hz, 2H), 7.37–7.31 (m, 2H), 4.14 (d, J = 10.8 Hz, 1H), 3.94
(dd, J = 10.8, 1.6 Hz, 1H), 2.63–2.46 (m, 2H), 2.27 (s, 3H), 1.58 (d, J =
2.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ = 168.74, 140.73, 140.64,
138.68, 137.57, 128.96, 127.92, 127.33, 127.02, 120.78, 117.63, 61.75
(d, J = 6.5 Hz), 41.90, 39.44, 26.82 (d, J = 3.7 Hz), 24.31; 19F NMR
(376 MHz, CDCl3) δ = –81.02 (t, J = 11.4 Hz, 3F), –107.80 to –114.22
(m, 2F), –124.40 to –124.50 (m, 2F), –125.59 to –125.82 (m, 2F);
Experimental Details: N-(2-methylallyl)-N-phenylacetamide 1a
(0.5 mmol), Cu (1.0 mmol, 63.5 mg), nC4H9I 2a (1.5 mmol, 258.2 μL),
and 1,1-diphenylethenein (1.0 mmol, 176.5 μL) in DMSO (3 mL) was
stirred at 120 °C. The reaction was monitored by TLC and stopped
at the desired time. After the reaction was finished, the mixture was
filtered by a silica gel plug with ethyl acetate (30 mL) as the eluent.
The filtrate was washed with saturated brine (3 × 10 mL) and the
organic phase was dried with Na2SO4, filtered, and concentrated HRMS (ESI): m/z [M + H]+ calcd. for C22H19F9NO: 484.1317, found
under reduced pressure. The residue was separated on a silica gel
column with petroleum ether/ethyl acetate as the eluent to get
product 6 (16 %, 31.9 mg).
484.1319.
1-(3-Methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)-2,3-dihydro-
1H-pyrrolo[3,2-c]pyridin-1-yl)ethanone (3ea): Yield 71 %
(144.8 mg), white solid, m.p. 103–104 °C. 1H NMR (400 MHz, CDCl3)
δ = 8.51–8.36 (m, 2H), 8.04 (d, J = 5.6 Hz, 1H), 4.14 (d, J = 10.9 Hz,
1H), 3.93 (d, J = 10.9 Hz, 1H), 2.67–2.46 (m, 2H), 2.27 (s, 3H), 1.59 (s,
3H); 13C NMR (101 MHz, CDCl3) δ = 169.70, 150.86, 147.94, 144.22,
133.26, 111.69, 65.38–60.33 (m), 41.11, 39.46 (t, J = 20.4 Hz) 27.37
(d, J = 3.1 Hz), 24.33; 19F NMR (376 MHz, CDCl3) δ = –81.05 (t, J =
nC4H9I 2a (1.5 mmol, 258.2 μL), Cu (1.0 mmol, 63.5 mg), and 1,1-
diphenylethenein (1.0 mmol, 176.5 μL) in DMSO (3 mL) was stirred
at 120 °C. The reaction was monitored by TLC and stopped at the
desired time. After the reaction was finished, the mixture was fil-
tered by a silica gel plug with ethyl acetate (30 mL) as the eluent.
The filtrate was washed with saturated brine (3 × 10 mL) and the
organic phase was dried with Na2SO4, filtered, and concentrated 11.7 Hz, 3F), –108.16 to –113.86 (m, 2F), –124.41 to –124.51 (m, 2F),
under reduced pressure. The residue was separated on a silica gel
column with petroleum ether/ethyl acetate as the eluent to get
product 6 (45 %, 89.7 mg).
–125.62 to –125.82 (m, 2F); HRMS (ESI): m/z [M + H]+ calcd. for
C15H14F9N2O: 409.0957, found 409.0958.
1-(3,5-Dimethyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)indolin-1-
yl)propan-1-one (3fa): Yield 76 % (165.0 mg), white solid, m.p.
106–107 °C. 1H NMR (400 MHz, CDCl3) δ = 8.24 (d, J = 8.2 Hz, 1H),
1-(3-Methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)indolin-1-yl)-
ethanone (3aa): Yield 74 % (150.5 mg), white solid, m.p. 103–
1
104 °C. H NMR (400 MHz, CDCl3) δ = 8.22 (d, J = 8.1 Hz, 1H), 7.29– 7.19 (dd, J = 8.3, 1.8 Hz, 1H), 7.05 (s, 1H), 4.19 (d, J = 10.8 Hz, 1H),
7.25 (m, 1H), 7.14 (d, J = 6.1 Hz, 1H), 7.09 (td, J = 7.4, 1.1 Hz, 1H),
4.10 (d, J = 10.9 Hz, 1H), 3.89 (dd, J = 10.9, 1.5 Hz, 1H), 2.58–2.40
(m, 2H), 2.25 (s, 3H), 1.53 (d, J = 2.4 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ = 168.81, 141.28, 137.98, 128.98, 124.27, 122.10, 117.49,
61.50 (d, J = 6.2 Hz), 41.83, 39.41 (t, J = 20.6 Hz), 26.78 (d, J = 3.8 Hz),
24.38. 19F NMR (376 MHz, CDCl3) δ = –81.01 (t, J = 12.3 Hz, 3F),
–107.46 to –114.59 (m, 2F), –124.46 to –124.58 (m, 2F), –125.60 to
3.99 (d, J = 10.8 Hz, 1H), 2.63–2.53 (m, 4H), 2.46 (s, 3H), 1.36 (t, J =
7.4 Hz, 3H);13C NMR (101 MHz, CDCl3) δ = 171.88, 139.21, 138.05,
133.81, 129.45, 122.60, 117.17, 60.69 (d, J = 6.4 Hz), 41.81, 39.37 (t,
J = 20.3 Hz), 29.26, 26.59 (d, J = 3.6 Hz), 21.22, 8.84; 19F NMR
(376 MHz, CDCl3) δ = –80.90 (t, J = 11.5 Hz, 3F), –107.95 to
–114.06(m, 2F), –124.39 to –124.49 (m, 2F), –125.56 to –125.77 (m,
2F); HRMS (ESI): m/z [M + H]+ calcd. for C18H19F9NO: 436.1317, found
–125.83 (m, 2F); HRMS (ESI): m/z [M + H]+ calcd. for C16H15F9NO: 436.1319.
408.1004, found 408.1007.
1-(5-Chloro-3-methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)-
1-(3,5-Dimethyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)indolin-1-
yl)ethanone (3ba): Yield 80 % (172.8 mg), white solid, m.p. 119–
120 °C. 11H NMR (400 MHz, CDCl3) δ = 8.09 (d, J = 8.2 Hz, 1H), 7.07
(dd, J = 8.4, 1.6 Hz, 1H), 6.93 (s, 1H), 4.07 (d, J = 10.8 Hz, 1H), 3.88
(dd, J = 10.9, 1.6 Hz, 1H), 2.52–2.40 (m, 2H), 2.34 (s, 3H), 2.23 (s, 3H),
indolin-1-yl)propan-1-one (3ga): Yield 60 % (136.8 mg), white
solid, m.p. 104–105 °C. 1H NMR (400 MHz, CDCl3) δ = 8.19 (d, J =
8.7 Hz, 1H), 7.23 (dd, J = 8.7, 2.2 Hz, 1H), 7.09 (d, J = 2.3 Hz, 1H),
4.10 (d, J = 10.8 Hz, 1H), 3.89 (d, J = 10.9 Hz, 1H), 2.50–2.40 (m, 4H),
1.51 (s, 3H), 1.24 (t, J = 7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ =
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172.18, 140.19, 139.62, 128.96, 128.92, 122.50, 118.43, 60.65 (d, J =
6.5 Hz), 41.87, 39.25 (t, J = 20.4 Hz), 29.28, 26.73 (d, J = 3.6 Hz), 8.73.
19F NMR (376 MHz, CDCl3) δ = –81.01 (t, J = 12.0 Hz, 3F), –107.95
to –114.06 (m, 2F), –124.39 to –124.53 (m, 2F), –125.57 to –125.77
(m, 2F); HRMS (ESI): m/z [M + H]+ calcd. for C17H16ClF9NO: 456.0771,
found 456.0776.
2.66–2.29 (m, 2H), 1.55(d, J = 2.0 Hz, 3H); 13C NMR (101 MHz, CDCl3)
δ = 167.30, 140.77, 138.95, 138.02, 134.91, 130.83, 130.14, 128.56,
127.46, 125.21, 124.81, 122.47, 117.66, 62.58, 41.54, 38.84 (t, J =
20.6 Hz), 26.08; 19F NMR (376 MHz, CDCl3) δ = –80.04 (t, J = 10.5 Hz,
3F), –108.63 to –114.06 (m, 2F), –124.42 to –124.52 (m, 2F), –125.60
to –125.80 (m, 2F). HRMS (ESI): m/z [M + H]+ calcd. for
C21H16ClF9NO: 504.0771, found 504.0776.
1-(5-Chloro-3-methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)-
indolin-1-yl)-2,2-dimethylpropan-1-one (3ha): Yield 86 %
(207.7 mg), white solid, m.p. 100–101 °C. H NMR (400 MHz, CDCl3)
5-Chloro-3-methyl-1-(methylsulfonyl)-3-(2,2,3,3,4,4,5,5,5-nona-
fluoropentyl)indoline (3ma): Yield 65 % (150.2 mg), yellow oil. H
1
1
δ = 8.17 (d, J = 8.7 Hz, 1H), 7.22 (dd, J = 8.8, 2.2 Hz, 1H), 7.09 (d,
J = 2.2 Hz, 1H), 4.30 (d, J = 10.8 Hz, 1H), 4.07 (dd, J = 10.8, 1.6 Hz,
NMR (400 MHz, CDCl3) δ = 7.36 (d, J = 8.6 Hz, 1H), 7.23 (dd, J = 8.6,
2.1 Hz, 1H), 7.14 (d, J = 2.1 Hz, 1H), 3.99 (dd, J = 10.7, 0.9 Hz, 1H),
1H), 2.50–2.31 (m, 2H), 1.52 (d, J = 2.6 Hz, 3H), 1.37 (s, 9H); 13C NMR 3.85 (dd, J = 10.6, 1.7 Hz, 1H), 2.93 (s, 3H), 2.58–2.39 (m, 2H), 1.54
(101 MHz, CDCl3) δ = 176.71, 141.74, 139.62, 129.22, 128.73, 122.12,
120.02, 61.65 (d, J = 6.6 Hz) 42.53, 40.28, 38.14 (t, J = 20.6 Hz), 27.67,
(d, J = 2.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ = 139.49, 139.19,
129.33, 129.31, 123.63, 114.72, 62.43 (d, J = 5.9 Hz), 41.81, 38.75 (t,
24.80, 24.76. 19F NMR (376 MHz, CDCl3) δ = –81.02 (t, J = 11.2 Hz, J = 20.6 Hz), 35.19, 26.44 (d, J = 3.1 Hz); 19F NMR (376 MHz, CDCl3)
3F), –107.73 to –114.73 (m, 2F), –124.44 to –124.53 (m, 2F), –125.38 δ = –81.06 (t, J = 10.9 Hz, 3F), –108.08 to –113.61 (m, 2F), –124.38
to –126.08 (m, 2F); HRMS (ESI): m/z [M + H]+ calcd. for
C19H20ClF9NO: 484.1084, found 484.1087.
to –124.44 (m, 2F), –125.62 to –125.79 (m, 2F). HRMS (ESI): m/z [M
+ H]+ calcd. for C15H14ClF9NO2S: 478.0285, found 478.0288.
1-(5-Chloro-3-methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)- 3-Methyl-1-(methylsulfonyl)-3-(2,2,3,3,4,4,5,5,5-nonafluoro-
indolin-1-yl)octan-1-one (3ia): Yield 66 % (173.4 mg), white solid,
m.p. 92–93 °C. 1H NMR (400 MHz, CDCl3) δ = 8.19 (d, J = 8.7 Hz,
1H), 7.22 (dd, J = 8.6, 2.2 Hz, 1H), 7.09 (d, J = 2.2 Hz, 1H), 4.11 (d,
J = 10.8 Hz, 1H), 3.90 (d, J = 10.8 Hz, 1H), 2.57–2.27 (m, 4H), 1.76–
pentyl)-5-phenylindoline (3na): Yield 75 % (194.5 mg), white solid,
m.p. 115–116 °C. H NMR (400 MHz, CDCl3) δ = 7.57–7.51 (m, 2H),
7.49 (d, J = 1.2 Hz, 2H), 7.44 (t, J = 7.6 Hz, 2H), 7.38–7.32 (m, 2H),
4.02 (dd, J = 10.6, 0.9 Hz, 1H), 3.89 (dd, J = 10.6, 1.7 Hz, 1H), 2.96
1
1.69 (m, 2H), 1.52 (d, J = 2.3 Hz, 3H), 1.42–1.25 (m, 8H), 0.92–0.85 (s, 3H), 2.66–2.44 (m, 2H), 1.59 (d, J = 2.2 Hz, 3H); 13C NMR (101 MHz,
(m, 3H); 13C NMR (101 MHz, CDCl3) δ = 171.66, 140.19, 139.68, CDCl3) δ = 140.43, 139.83, 138.41, 137.70, 129.05, 128.31, 127.54,
128.93, 122.47, 118.52, 60.80 (d, J = 6.4 Hz), 41.85, 39.22 (t, J = 127.04, 121.94, 113.87, 62.58 (d, J = 5.9 Hz), 41.85, 38.96, 35.08,
20.5 Hz), 36.03, 31.82, 29.41, 29.26, 26.65 (d, J = 3.7 Hz), 24.65, 22.76, 26.48 (d, J = 3.5 Hz); 19F NMR (376 MHz, CDCl3) δ = –81.02 (t, J =
14.19. 19F NMR (376 MHz, CDCl3) δ = –81.02 (t, J = 11.4 Hz, 3F), 11.7 Hz, 3F), –107.91 to –113.66 (m, 2F), –124.32 to –124.40 (m, 2F),
–107.96 to –114.07 (m, 2F), –124.33 to –124.56 (m, 2F), –125.57 to
–125.79 (m, 2F); HRMS (ESI): m/z [M + H]+ calcd. for C22H26ClF9NO:
526.1554, found 526.1557.
–125.57 to –125.74 (m, 2F); HRMS (ESI): m/z [M + H]+ calcd. for
C21H19F9NO2S: 520.0987, found 520.0989.
5-Chloro-1-(ethylsulfonyl)-3-methyl-3-(2,2,3,3,4,4,5,5,5-nona-
1-(5-Bromo-3-methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)- fluoropentyl)indoline (3oa): Yield 76 % (186.6 mg), yellow oil. 1H
indolin-1-yl)octan-1-one (3ja): Yield 59 % (167.9 mg), white solid,
NMR (400 MHz, CDCl3) δ = 7.33 (d, J = 8.6 Hz, 1H), 7.20 (dd, J = 8.5,
2.1 Hz, 1H), 7.12 (d, J = 2.1 Hz, 1H), 4.09–4.01 (m, 1H), 3.90 (dd, J =
m.p. 96–97 °C. 1H NMR (400 MHz, CDCl3) δ = 8.14 (d, J = 8.7 Hz,
1H), 7.37 (dd, J = 8.6, 2.0 Hz, 1H), 7.24 (d, J = 2.0 Hz, 1H), 4.10 (d, 10.6, 1.7 Hz, 1H), 3.14 (q, J = 7.4 Hz, 2H), 2.57–2.39 (m, 2H), 1.53 (d,
J = 10.8 Hz, 1H), 3.89 (d, J = 10.8 Hz, 1H), 2.57–2.30 (m, 4H), 1.73 (p,
J = 7.4 Hz, 2H), 1.51 (s, 3H), 1.42–1.25 (m, 8H), 0.93–0.84 (m, 3H);
13C NMR (101 MHz, CDCl3) δ = 171.71, 140.68, 140.06, 131.88,
J = 2.2 Hz, 3H), 1.42 (t, J = 7.4 Hz, 3H); 13C NMR (101 MHz, CDCl3)
δ = 139.49, 139.29, 129.14, 128.83, 123.51, 114.69, 62.41 (d, J =
6.1 Hz), 44.88, 41.90, 38.79 (t, J = 20.5 Hz), 26.40 (d, J = 3.5 Hz), 7.84;
125.37, 118.99, 116.33, 60.76 (d, J = 6.2 Hz), 41.84, 39.26 (t, J = 19F NMR (376 MHz, CDCl3) δ = –81.06 (t, J = 11.3 Hz, 3F), –107.97
20.5 Hz), 36.07, 31.83, 29.41, 29.26, 26.69 (d, J = 3.4 Hz), 24.64, 22.76, to –113.79 (m, 2F), –124.40 to –124.49 (m, 2F), –125.61 to –125.79
14.19; 19F NMR (376 MHz, CDCl3) δ = –80.86 to –81.17 (m, 3F),
–107.93 to –114.06 (m, 2F), –124.37 to –124.47 (m, 2F), –125.56 to
–125.77 (m, 2F);HRMS (ESI): m/z [M + H]+ calcd. for C22H26BrF9NO:
570.1049, found 570.1050.
(m, 2F); HRMS (ESI): m/z [M + H] + calcd. for C16H16ClF9NO2S:
492.0441, found 492.0446.
1-(Ethylsulfonyl)-3-methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoro-
pentyl)-5-phenylindoline (3pa): Yield 74 % (197.2 mg), white solid,
m.p. 109–110 °C. 1H NMR (400 MHz, CDCl3) δ = 7.57–7.50 (m, 2H),
7.50–7.40 (m, 4H), 7.35 (d, J = 7.2 Hz, 2H), 4.09 (d, J = 10.6 Hz, 1H),
3.95 (dd, J = 10.6, 1.7 Hz, 1H), 3.18 (q, J = 7.4 Hz, 2H), 2.65–2.44 (m,
2H), 1.58 (d, J = 2.2 Hz, 3H), 1.45 (t, J = 7.4 Hz, 3H); 13C NMR
(101 MHz, CDCl3) δ = 140.51, 140.10, 138.23, 137.24, 129.02, 128.15,
tert-Butyl-5-chloro-3-methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoro-
pentyl)indoline-1-carboxylate (3ka): Yield 84 % (209.6 mg), white
solid, m.p. 77–78 °C. 1H NMR (400 MHz, CDCl3) δ = 7.80 (s, 1H), 7.18
(dd, J = 8.6, 2.2 Hz, 1H), 7.06 (d, J = 2.2 Hz, 1H), 4.01 (d, J = 11.7 Hz,
1H), 3.84 (d, J = 11.9 Hz, 1H), 2.56–2.29 (m, 2H), 1.57 (s, 9H), 1.48 (d,
J = 2.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ = 152.30, 140.08, 127.45, 127.00, 121.85, 113.80, 62.56 (d, J = 6.1 Hz), 44.71, 41.92,
139.52, 128.71, 127.66, 122.79, 116.23, 81.61, 60.60 (d, J = 5.9 Hz),
39.00 (t, J = 20.5 Hz), 26.44 (d, J = 3.4 Hz), 7.89; 19F NMR (376 MHz,
CDCl3) δ = –80.03 (t, J = 11.3 Hz, 3F), –107.80 to –113.84 (m, 2F),
41.08, 39.39 (t, J = 20.5 Hz), 28.50, 26.84 (d, J = 2.9 Hz); 19F NMR
(376 MHz, CDCl3) δ = –81.09 (t, J = 10.2 Hz, 3F), –107.99 to –114.18 –124.36 to –124.42 (m, 2F), –125.57 to –125.75 (m, 2F); HRMS (ESI):
(m, 2F), –124.46 to –124.55 (m, 2F), –125.70 to –125.83 (m, 2F); m/z [M + H]+ calcd. for C22H21F9NO2S: 534.1144, found 534.1147.
HRMS (ESI): m/z [M + H]+ calcd. for C19H20F9NO2: 500.1033, found
4,6-Dichloro-1-(ethylsulfonyl)-3-methyl-3-(2,2,3,3,4,4,5,5,5-
500.1037.
nonafluoropentyl)indoline (3qa): Yield 72 % (188.9 mg), colorless
(3-Chlorophenyl)(3-methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropent- oil. 1H NMR (400 MHz, CDCl3) δ = 7.35 (d, J = 1.8 Hz, 1H), 7.00 (d,
yl)indolin-1-yl)methanone (3la): Yield 62 % (160.1 mg), colorless
oil. 1H NMR (400 MHz, CDCl3) δ = 8.14 (s, 1H), 7.54 (t, J = 1.4 Hz,
1H), 7.50–7.47 (m, 1H), 7.41 (d, J = 5.0 Hz, 2H), 7.29–7.16 (m, 2H),
7.12 (d, J = 7.4 Hz, 1H), 4.12 (d, J = 11.4 Hz, 1H), 4.02–3.70 (m, 1H),
J = 1.8 Hz, 1H), 4.17 (d, J = 10.8 Hz, 1H), 3.90 (d, J = 10.7 Hz, 1H),
3.22–3.13 (m, 2H), 2.89–2.65 (m, 2H), 1.65 (d, J = 1.6 Hz, 3H), 1.43
(t, J = 7.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ = 143.84, 135.81,
131.52, 130.82, 124.64, 112.48, 62.20 (dd, J = 4.9, 2.7 Hz), 45.37,
Eur. J. Org. Chem. 0000, 0–0
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
42.77, 36.56, 25.64 (d, J = 2.8 Hz), 7.79; 19F NMR (376 MHz, CDCl3)
δ = –81.05 (t, J = 12.0 Hz, 3F), –109.29 to –113.66 (m, 2F), –124.51
to –124.62 (m, 2F), –125.67 to –125.80 (m, 2F); HRMS (ESI): m/z [M
+ H]+ calcd. for C16H15Cl2F9NO2S: 526.0051, found 526.0051.
(376 MHz, CDCl3) δ = –80.97 to –81.06 (t, J = 11.3 Hz, 3F), –107.70
to –114.42 (m, 2F), –124.47 to –124.56 (m, 2F), –125.64 to –125.84
(m, 2F); HRMS (ESI): m/z [M + H + calcd. for C22H21F9NO2S: 534.1144,
found 534.1147.
N,N,3-trimethyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)-5-phen-
ylindoline-1-sulfonamide (3ra): Yield 71 % (194.6 mg), yellow
solid, m.p. 123–124 °C. 1H NMR (400 MHz, CDCl3) δ = 7.58–7.51 (m,
2H), 7.50–7.39 (m, 4H), 7.37–7.30 (m, 2H), 4.05 (d, J = 10.5 Hz, 1H),
3.88 (dd, J = 10.5, 1.8 Hz, 1H), 2.94 (s, 6H), 2.63–2.43 (m, 2H), 1.58
(d, J = 2.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ = 140.98, 140.68,
5-Chloro-3-methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)-1-
(o-tolylsulfonyl)indoline (3wa): Yield 51 % (283.3 mg), colorless
oil. 1H NMR (400 MHz, CDCl3) δ = 7.96 (dd, J = 7.9, 1.5 Hz, 1H), 7.48
(td, J = 7.5, 1.4 Hz, 1H), 7.40 (d, J = 8.6 Hz, 1H), 7.33 (t, J = 7.8 Hz,
2H), 7.18 (dd, J = 8.6, 2.1 Hz, 1H), 7.07 (d, J = 2.1 Hz, 1H), 3.97 (dd,
J = 10.9, 0.9 Hz, 1H), 3.80 (dd, J = 11.0, 1.7 Hz, 1H), 2.60 (s, 3H),
138.07, 136.86, 129.00, 128.00, 127.34, 127.01, 121.47, 114.35, 62.81 2.42–2.24 (m, 2H), 1.37 (d, J = 2.4 Hz, 3H); 13C NMR (101 MHz, CDCl3)
(d, J = 6.4 Hz), 41.92, 39.20, 39.00, 38.80, 38.39, 26.15 (d, J = 3.4 Hz); δ = 139.81, 139.71, 138.25, 136.90, 133.62, 133.20, 129.65, 129.07,
19F NMR (376 MHz, CDCl3) δ = –80.90 to –81.00 (m, J = 10.9 Hz, 3F), 129.01, 126.60, 123.33, 115.98, 61.71 (d, J = 6.4 Hz), 41.98, 38.78 (t,
–107.78 to –114.40 (m, 2F), –124.40 to –124.50 (m, 2F), –125.57 to
J = 20.5 Hz), 25.92 (d, J = 3.7 Hz), 20.89; 19F NMR (376 MHz, CDCl3)
–125.78 (m, 2F); HRMS (ESI): m/z [M + H]+ calcd. for C22H22F9N2O2S: δ = –81.04 (t, J = 11.6 Hz, 3F), –107.82 to –114.23 (m, 2F), –124.42
549.1253, found 549.1253.
to –124.48 (m, 2F), –125.63 to –125.82 (m, 2F); HRMS (ESI): m/z [M
+ H]+ calcd. for C21H18ClF9NO2S: 554.0598, found 554.0599.
3-Methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)-1-(phenylsulf-
onyl)indoline (3sa): Yield 74 % (186.8 mg), yellow oil. 1H NMR
(400 MHz, CDCl3) δ = 7.90–7.79 (m, 2H), 7.71 (d, J = 8.1 Hz, 1H),
7.56 (t, J = 7.4 Hz, 1H), 7.46 (dd, J = 8.5, 7.0 Hz, 2H), 7.29–7.24 (m,
1H), 7.10–6.99 (m, 2H), 3.99–3.90 (m, 1H), 3.80 (dd, J = 11.1, 1.6 Hz,
4-Methyl-4-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)-2-(o-tolylsulf-
onyl)-1,2,3,4-tetrahydroisoquinoline (3xa): Yield 25 % (66.7 mg),
colorless oil. 1H NMR (400 MHz, CDCl3) δ = 7.99 (dd, J = 7.9, 1.4 Hz,
1H), 7.48 (td, J = 7.5, 1.4 Hz, 1H), 7.37 (d, J = 7.8 Hz, 1H), 7.32 (dd,
1H), 2.41–2.07 (m, 2H), 1.26 (d, J = 2.5 Hz, 3H); 13C NMR (101 MHz, J = 8.0, 3.8 Hz, 2H), 7.27–7.18 (m, 2H), 7.07– 7.05 (m, 1H), 4.52 (d,
CDCl3) δ = 140.31, 138.19, 136.99, 133.55, 129.29, 129.09, 127.30,
J = 15.1 Hz, 1H), 4.31 (d, J = 15.1 Hz, 1H), 3.67 (d, J = 12.5 Hz, 1H),
124.25, 122.96, 114.97, 61.84 (d, J = 6.2 Hz), 41.75, 39.07, 26.21 (d, 3.10 (d, J = 12.5 Hz, 1H), 2.67 (s, 3H), 2.67–2.45 (m, 1H), 2.39–2.25
J = 3.6 Hz); 19F NMR (376 MHz, CDCl3) δ = –81.12 (t, J = 10.9 Hz, (m, 1H), 1.48 (d, J = 2.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ =
3F), –107.75 to –114.16 (m, 2F), –124.46 to –124.56 (m, 2F), –125.69 140.39, 138.32, 135.35, 133.36, 133.11, 130.84, 130.56, 127.62,
to –125.90 (m, 2F); HRMS (ESI): m/z [M + H]+ calcd. for
C20H17F9NO2S: 506.0831, found 506.0836.
127.23, 126.85, 126.49, 126.38, 53.72 (d, J = 4.3 Hz), 47.59, 38.08 (t,
J = 20.0 Hz), 37.59, 25.33 (d, J = 4.4 Hz), 20.93; 19F NMR (376 MHz,
CDCl3) δ = –81.12 (t, J = 10.7 Hz, 3F), –107.72 to –114.42 (m, 2F),
–124.04 to –124.24 (m, 2F), –125.65 to –125.83 (m, 2F); HRMS (ESI):
m/z [M + H]+ calcd. for C22H21F9NO2S: 534.1144, found 534.1144.
3-Methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)-1-tosylindoline
1
(3ta): Yield 79 % (205.1 mg), pale yellow oil. H NMR (400 MHz,
CDCl3) δ = 7.70 (t, J = 8.4 Hz, 3H), 7.26 (t, J = 8.9 Hz, 3H), 7.04 (q,
J = 3.8 Hz, 2H), 3.92 (d, J = 11.1 Hz, 1H), 3.78 (dd, J = 11.1, 1.5 Hz,
1H), 2.46–2.02 (m, 5H), 1.28 (d, J = 2.4 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ = 144.55, 140.46, 138.19, 134.01, 129.89, 129.05, 127.36,
1-(5-Chloro-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)indolin-1-yl)-
ethanone (3ya): Yield 48 % (102.6 mg), white solid, m.p. 83–84 °C.
1H NMR (400 MHz, CDCl3) δ = 8.17 (d, J = 8.7 Hz, 1H), 7.23 (dd, J =
124.13, 122.94, 115.01, 61.85 (d, J = 6.1 Hz), 41.73, 39.09, 26.14 (d, 8.7, 2.1 Hz, 1H), 7.17–7.10 (m, 1H), 4.41–4.28 (m, 1H), 3.97–3.79 (m,
J = 3.3 Hz), 21.55; 19F NMR (376 MHz, CDCl3) δ = –81.12 (t, J =
11.3 Hz, 3F), –107.78 to –114.19 (m, 2F), –124.48 to –124.57 (m, 2F),
–125.15 to –125.91 (m, 2F); HRMS (ESI): m/z [M + H]+ calcd. for
2H), 2.61 (dt, J = 30.9, 12.7 Hz, 1H), 2.45–2.30 (m, 1H), 2.24 (s, 3H);
13C NMR (101 MHz, CDCl3) δ = 168.68, 141.33, 133.77, 129.04,
123.85, 118.33, 55.41 (d, J = 4.4 Hz) 36.05 (t, J = 21.0 Hz), 34.10–
32.85 (m), 24.22; 19F NMR (376 MHz, CDCl3) δ = –80.96 (t, J =
11.3 Hz, 3F), –111.86 to –114.15 (m, 2F), –124.22 to –124.33 (m, 2F),
–125.75 to –125.90 (m, 2F); HRMS (ESI): m/z [M + H]+ calcd. for
C15H12ClF9NO: 428.0458, found 428.0460.
C21H19F9NO2S: 520.0987, found 520.0988.
3-Methyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)-1-(o-tolylsulf-
onyl)indoline (3ua): Yield 32 % (83.2 mg), yellow oil. 1H NMR
(400 MHz, CDCl3) δ = 7.99 (d, J = 8.1 Hz, 1H), 7.52–7.39 (m, 2H),
7.32 (t, J = 8.1 Hz, 2H), 7.21 (t, J = 7.7 Hz, 1H), 7.11 (d, J = 7.5 Hz,
5-Chloro-1-(ethylsulfonyl)-3-(2,2,3,3,4,4,5,5,5-nonafluoropent-
1H), 7.04 (t, J = 7.4 Hz, 1H), 3.99 (d, J = 10.9 Hz, 1H), 3.82 (d, J = yl)indoline (3za): Yield 57 % (136.1 mg), yellow solid, m.p. 87–
11.6 Hz, 1H), 2.73–2.50 (m, 3H), 2.48–2.22 (m, 2H), 1.39 (d, J = 2.4 Hz, 88 °C. 1H NMR (400 MHz, CDCl3) δ = 7.33 (dd, J = 8.6, 1.5 Hz, 1H),
3H); 13C NMR (101 MHz, CDCl3) δ = 141.05, 138.26, 137.93, 137.32,
7.21 (dd, J = 8.6, 2.2 Hz, 1H), 7.17 (d, J = 2.0 Hz, 1H), 4.38–4.23 (m,
133.40, 133.11, 129.62, 128.96, 126.50, 123.88, 122.88, 114.89, 61.58 1H), 3.90–3.75 (m, 2H), 3.16–3.10 (m, 2H), 2.70–2.50 (m, 1H), 2.48–
(d, J = 6.3 Hz), 41.89, 38.94 (t, J = 20.6 Hz), 25.95 (d, J = 3.8 Hz)
2.27 (m, 1H), 1.46–1.34 (m, 3H); 13C NMR (101 MHz, CDCl3) δ =
140.74, 133.81, 129.25, 129.00, 124.79, 114.87, (d, J = 4.6 Hz), 45.53–
20.87; 19F NMR (376 MHz, CDCl3) δ = –81.05 (t, J = 11.3 Hz, 3F),
–107.76 to –114.36 (m, 2F), –124.45 to –124.52 (m, 2F), –125.64– 44.40 (m), 35.42 (t, J = 21.4 Hz), 33.59 (d, J = 3.2 Hz), 7.85; 19F NMR
125.84 (m, 2F); HRMS (ESI): m/z [M + H]+ calcd. for C21H19F9NO2S:
520.0987, found 520.0988.
(376 MHz, CDCl3) δ = –81.06 (t, J = 11.3 Hz, 3F), –111.93 to –114.14
(m, 2F), –124.24 to –124.36 (m, 2F), –125.81 to –125.96 (m, 2F);
HRMS (ESI): m/z [M + H]+ calcd. for C15H14ClF9NO2S: 478.0285, found
478.0287.
3,5-Dimethyl-3-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)-1-(o-tolyl-
sulfonyl)indoline (3va): Yield 39 % (104.0 mg), yellow oil. 1H NMR
(400 MHz, CDCl3) δ = 7.97 (dd, J = 8.2, 1.2 Hz, 1H), 7.50–7.42 (m,
1H), 7.36–7.27 (m, 3H), 7.02–7.01 (m, 1H), 6.89 (d, J = 1.7 Hz, 1H),
3.96 (dd, J = 11.0, 1.0 Hz, 1H), 3.80 (dd, J = 11.0, 1.7 Hz, 1H), 2.61
1-(3-Methyl-3-(2,2,3,3,4,4,5,5,6,6,7,7,7-tridecafluoroheptyl)-
indolin-1-yl)ethanone (3ab): Yield 83 % (201.5 mg), white solid,
m.p. 126–127 °C. 1H NMR (400 MHz, CDCl3) δ = 8.22 (d, J = 8.1 Hz,
(s, 3H), 2.45–2.21 (m, 5H), 1.36 (d, J = 2.5 Hz, 3H); 13C NMR (101 MHz, 1H), 7.31–7.23 (m, 1H), 7.14 (s, 1H), 7.09 (dd, J = 7.4, 1.1 Hz, 1H),
CDCl3) δ = 138.66, 138.24, 138.19, 137.34, 133.71, 133.29, 133.07,
129.62, 129.47, 126.45, 123.40, 114.80, 61.70 (d, J = 6.7 Hz), 41.92,
38.95 (t, J = 20.4 Hz), 29.85, 25.84, 21.02 (d, J = 15.8 Hz); 19F NMR
4.10 (d, J = 10.8 Hz, 1H), 3.94–3.85 (m, 1H), 2.57–2.40 (m, 2H), 2.25
(s, 3H), 1.53 (d, J = 2.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ =
168.79, 141.29, 138.00, 128.96, 124.26, 122.09, 117.49, 61.50 (d, J =
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6.4 Hz), 41.85, 39.52 (t, J = 20.4 Hz), 26.75 (d, J = 3.7 Hz), 24.32; 19F 7.37–7.32 (m, 2H), 7.30–7.26 (m, 1H), 7.26–7.22 (m, 1H), 4.99 (d, J =
NMR (376 MHz, CDCl3) δ = –80.59 to –80.89 (t, J = 11.3 Hz, 3F),
–107.64 to –113.92 (m, 2F), –121.47 to –12163, (m, 2F), –122.73 to
–122.86 (m, 2F), –123.53 to –123.64 (m, 2F), –126.01 to –126.18 (m,
2F); HRMS (ESI): m/z [M + H]+ calcd. for C18H15F13NO: 508.0941,
found 508.0947.
14.6 Hz, 1H), 4.53 (d, J = 14.6 Hz, 1H), 3.51–3.37 (m, 2H), 2.43–2.07
(m, 2H), 1.56 (d, J = 2.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ =
164.36, 144.35, 138.80, 134.81, 132.83, 130.19, 129.43, 128.70,
128.15, 128.06, 127.89, 126.83, 124.22, 55.68 (d, J = 3.9 Hz), 50.38,
36.91 (t, J = 20.3 Hz), 36.09, 22.86 (d, J = 2.0 Hz); 19F NMR (376 MHz,
CDCl3) δ = –81.06 (t, J = 11.9 Hz, 3F), –110.00 to –113.50 (m, 2F),
–124.00 to –124.33 (m, 2F), –125.54 to –125.95 (m, 2F); HRMS (ESI):
m/z [M + H]+ calcd. for C22H18ClF9NO: 518.0928; found: 518.0932.
1-(3-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,9-Heptadecafluorononyl)-3-
methylindolin-1-yl)ethanone (3ac): Yield 50 % (151.8 mg), white
solid. 1H NMR (400 MHz, CDCl3) δ = 8.22 (d, J = 8.1 Hz, 1H), 7.30–
7.24 (m, 1H), 7.13 (s, 1H), 7.09 (dd, J = 7.4, 1.1 Hz, 1H), 4.08 (s, 1H),
3.94–3.85 (m, 1H), 2.61–2.38 (m, 2H), 2.25 (s, 3H), 1.53 (d, J = 2.4 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ = 168.79, 141.29, 138.01, 128.97,
124.26, 122.09, 117.50, 61.51 (d, J = 6.3 Hz), 41.86, 39.53 (t, J =
20.4 Hz), 26.75 (d, J = 3.6 Hz), 24.33; 19F NMR (376 MHz, CDCl3) δ =
–80.73(t, J = 11.3 Hz, 3F). –107.63 to –113.90 (m, 2F), –121.30 to
–121.86 (m, 2F), –122.30 to –123.56 (m, 6F), –123.54 (d, J = 15.0 Hz,
2F), –126.07 (dd, J = 20.1, 11.7 Hz, 2F). to –80.85 (m, 3F); HRMS (ESI):
m/z [M + H] + calcd. for C20H15F17NO: 608.0877, found 608.0879.
(3,3,4,4,5,5,6,6,6-Nonafluorohex-1-ene-1,1-diyl)dibenzene (6):
Yield 45 % (89.7 mg), white solid, m.p. 71–72 °C. 1H NMR (400 MHz,
CDCl3) δ = 7.43–7.30 (m, 6H), 7.25–7.21 (m, 4H), 6.09 (t, J = 14.7 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ = 154.59 (t, J = 4.5 Hz), 140.89,
140.87, 137.62, 129.67, 129.16 (t, J = 2.8 Hz), 128.66, 128.49, 128.09,
128.01, 112.79 (t, J = 21.1 Hz); 19F NMR (376 MHz, CDCl3) δ = –81.05
(t, J = 10.9 Hz, 3F), –103.71 to –103.83 (m, 2F), –123.89 to –123.98
(m, 2F), –125.61 to –125.68 (m, 2F); HRMS (ESI): m/z [M + H]+ calcd.
for C18H12F9: 399.0790; found: 399.0794.
Ethyl 3-(1-acetyl-3-methylindolin-3-yl)-2,2-difluoropropanoate
(3ad): Yield 55 % (85.6 mg), yellow solid, m.p. 208–209 °C. 1H NMR
(400 MHz, CDCl3) δ = 8.20 (d, J = 8.1 Hz, 1H), 7.26–7.21 (m, 1H),
7.11 (d, J = 1.4 Hz, 1H), 7.05 (td, J = 7.5, 1.1 Hz, 1H), 4.24–4.11 (m,
3H), 3.82 (d, J = 10.7 Hz, 1H), 2.63–2.37 (m, 2H), 2.24 (s, 3H), 1.47 (d,
J = 1.6 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3)
Acknowledgments
This work was supported by the National Natural Science Foun-
dation of China (21702083), the Program for Innovative Re-
search Team (in Science and Technology) in Universities of
δ = 164.36, 144.35, 138.80, 134.81, 132.83, 130.19, 129.43, 128.70, Yunnan Province, and the Yunnan Ten Thousand Talent Program
128.15, 128.06, 127.89, 126.83, 124.22, 55.68 (d, J = 3.9 Hz), 50.38,
38.35–35.53 (m) 22.86; 13C NMR (101 MHz, CDCl3) δ = 168.83,
164.31, 163.99, 163.67, 141.65, 137.82, 128.75, 124.01, 122.40,
118.58, 117.37, 116.08, 113.57, 63.38, 61.45 (d, J = 4.5 Hz), 43.59 (t,
J = 22.0 Hz), 41.71, 27.08 (d, J = 2.6 Hz), 24.36, 13.96; 19F NMR
(376 MHz, CDCl3) δ = –100.40 to –104.22 (m, 2F); HRMS (ESI): m/z
[M + H]+ calcd. for C16H20F2NO3: 312.1406, found 312.1409.
for Young Top-Notch Talents, and the key project of education
department of Henan Province (Nos. 17A150050).
Keywords: Copper · Fluoroalkylation · Homogeneous
catalysis · Nitrogen heterocycles · Radical reactions
(S)-2,4-Dimethyl-4-(2,2,3,3,4,4,5,5,5-nonafluoropentyl)-3,4-di-
hydroisoquinolin-1(2H)-one (5aa): Yield 57 % (85.6 mg), pale yel-
low oil. 1H NMR (400 MHz, CDCl3) δ = 8.14 (dd, J = 7.8, 1.5 Hz, 1H),
7.52 (td, J = 7.6, 1.6 Hz, 1H), 7.40 (td, J = 7.5, 1.2 Hz, 1H), 7.36–7.30
(m, 1H), 3.58 (d, J = 13.0 Hz, 1H), 3.49 (d, J = 13.0 Hz, 1H), 3.18 (s,
3H), 2.57–2.42 (m, 1H), 2.30–2.16 (m, 1H), 1.62 (d, J = 2.4 Hz, 3H);
13C NMR (101 MHz, CDCl3) δ = 164.52, 144.76, 132.49, 129.07,
128.08, 127.91, 123.85, 57.52 (d, J = 4.2 Hz), 37.15, 36.95 (t, J =
20.4 Hz), 35.12, 22.73 (d, J = 5.0 Hz); 19F NMR (376 MHz, CDCl3) δ =
–81.04 (t, J = 10.9 Hz, 3F), –110.61 to –113.28 (m, 2F), –124.29 to
–124.40 (m, 2F), –125.69 to –125.82 (m, 2F); HRMS (ESI): m/z [M +
H]+ calcd. for C16H15F9NO: 408.1004; found: 408.1006.
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1
(85.6 mg), white solid, m.p. 103–104 °C. H NMR (400 MHz, CDCl3)
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J = 13.1 Hz, 2H), 2.35–2.09 (m, 2H), 1.51 (d, J = 1.9 Hz, 3H); 13C NMR
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129.26, 128.94, 128.76, 128.05, 126.14, 55.72 (d, J = 3.2 Hz), 50.76,
36.89 (t, J = 20.2 Hz), 35.76, 22.85 (t, J = 2.9 Hz); 19F NMR (376 MHz,
[D]Chloroform) δ = –81.13 (t, J = 10.5 Hz, 3F), –109.91 to –113.38
(m, 2F), –124.27 to –124.37 (m, 2F), –125.69 – - 125.82 (m, 2F); HRMS
(ESI): m/z [M + H]+ calcd. for C22H18ClF9NO: 518.0928; found:
518.0931.
(S)-2-(3-Chlorobenzyl)-4-methyl-4-(2,2,3,3,4,4,5,5,5-nonafluoro-
pentyl)-3,4-dihydroisoquinolin-1(2H)-one (5ca): Yield 56 %
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Received: May 9, 2019
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Fluroalkylation
D. Li,* Y. Wang, Z. Jia, Z. Ou,
Y. Dong, C. Lv, G. Fu, D. Liang* ...... 1–9
Cu-Mediated Synthesis of Indolines
and Dihydroisoquinolinones through
Arylperfluoroalkylation of Unacti-
vated Alkenes
The copper-mediated fluroalkylation/ moderate to good yields. This protocol
cyclization of N-allyl anilines has been combines a simple experimental pro-
described with unactivated double cedure with low-costing fluoroalkyl-
bonds as the radical acceptor. The re- ated sources and excellent functional
action provides an efficient and direct group tolerance.
access to 3-fluoroalkyl indolines in
DOI: 10.1002/ejoc.201900680
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