Aryltrifluoromethylative cyclization of unactivated alkenes by the use of PhICF3Cl under catalyst-free conditions

Article abstract of DOI:10.1039/c8ob03189d

A concise and catalyst-free aryltrifluoromethylative cyclization of unactivated alkenes has been developed herein. The use of PhICF₃Cl as a powerful trifluoromethylating agent allows easy transformations. A set of trifluoroethylated carbocycles and aza-hereocycles were efficiently synthesized in good yield and selectivity. A broad substrate scope, mild reaction conditions, and easy operation would make this method well-suited for applications.

Full text of DOI:10.1039/c8ob03189d

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: J. Guo, C. Xu, X.
Liu and M. Wang, Org. Biomol. Chem., 2019, DOI: 10.1039/C8OB03189D.
This is an Accepted Manuscript, which has been through the
Volume 14 Number
1 7 January 2016 Pages 1–372
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
www.rsc.org/obc
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 1 of 7
View Article Online
DOI: 10.1039/C8OB03189D
Journal Name
ARTICLE
Aryltrifluoromethylative Cyclization of Unactivated Alkenes by the
Use of PhICF3Cl under Catalyst-Free Condition
Jia Guo,a Cong Xu,b Xiaowei Liu,a and Mang Wang*,a,c
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A concise and catalyst-free aryltrifluoromethylative cyclization of unactivated alkenes has been developed herein. The use
of PhICF3Cl as powerful trifluoromethylating agent allows the easy transformations. A set of trifluoroethylated carbocycles
and aza-hereocycles were efficiently synthesized in good yield and selectivity. Broad substrate scope, mild reaction
conditions, and easy operation would make the method well-suited for applications.
www.rsc.org/
Introduction
TG
TG
[CF3]
The introduction of the trifluoromethyl group into organic
molecules is one of the hottest topics in current organic
synthesis1,2 due to the presence of CF3 framework in a striking
number of pharmaceuticals, agrochemicals, and materials.3
Many elegant trifluoromethylation reactions have been
developed but most of them occurred in the presence of at
least a catalyst or an activator. In view of the practicability,
mild and catalyst-free methods would be a synthetically
enabling strategy for simplifying access to trifluoromethylated
compounds. To achieve this purpose, the use of a readily
available and capable trifluoromethylating agent is
undoubtedly a key factor.
CF3
TG: Trapping Group
A. known methods for the generation of CF3 active species
catalyst or initiator
[CF3] active species
CF3 source
B. competitive -deprotonation existed in the reaction of simple alkenes
[CF3]
CF3
CF3
vs
H
H
trifluoromethylative
functionalization
deprotonative
trifluoromethylation
Recently, trifluoromethylation-triggered cyclization of
alkenes has emerged as
trifluoroethylated cyclic compounds of commercial and
physiological importance.2 It is true that known approaches for
a
convenient access to
C. this work
catalyst-free,
selective,
mild,
efficient
spontaneous generation
PhICF3 + Cl
PhICF3Cl
the generation of the active CF3 initiator from
a
trifluoromethylating reagent require the assistance of a
catalyst or an activator (Scheme 1A).4-9 Catalyst-free process
remains challenge. For example, when hypervalent iodine-
based CF3 reagents, the Togni’s reagents, were used for such
cyclizations, they were generally reduced to be a CF3 radical by
accepting an electron from the catalyst and then participated
in the reaction.4a-o In a few cases, electrophilic CF3 species was
also proposed to undergo an ionic cyclization pathway.4p-t
PhICF3
Ph
CF3
CF3
I
H
Scheme 1 Trifluoromethylation-triggered cyclization of alkenes.
On the other hand, trifluoromethylative difunctionalization
reactions of activated alkenes, such as acryloanilides and
styrenes, have been proven to afford the desired
difunctionalized products efficiently. By comparison, the
reactions of unactivated alkenes bearing an allylic proton
a. Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis,
College of Chemistry, Northeast Normal University, 5268 Renmin Street,
Changchun (China).
b.
National Engineering Laboratory for Druggable Gene and Protein Screening,
would
encounter
a
competitively
deprotonative
School of Life Sciences, Northeast Normal University, 2555 Jingyue Street,
Changchun (China).
trifluoromethylation (Scheme 1B).10 In 2012, Buchwald
successfully used 2,2’-biquinoline ligand to inhibit such allylic
c. State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Weijin
Road 94, Tianjin (China). E-mail: wangm452@nenu.edu.cn
trifluoromethylation
oxycyclization of unsaturated acids/alcohols.4a And in 2013,
in
their
trifluoromethylation-
†Electronic
Supplementary
Information
(ESI)
available:
See
DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 7
ARTICLE
Journal Name
CF3
Sodeoka suggested that the well orbital interactions between
the alkene and aryl group could make the intramolecular
aryltrifluoromethylation of unconjugated alkenes linked by an
aryl group the predominant process in the Cu(I)/Togni II
catalytic system.4q
We recently prepared a CF3-based λ3-iodane, PhICF3Cl, by a
ligand exchange reaction of PhI(OCOCF3)2, TMSCF3, and NaCl
for the first time.11 Compared with neutral cyclic analogs (the
Togni’s reagents1c), noncyclic PhICF3Cl has been proved to
have an enhanced CF3-transfer ability in electrophilic
trifluoromethylation reactions.11,12 With the aim of developing
View Article Online
R3
DOI: 10.1039/C8OB03189D
R1
R3
solvent, N2
T oC, 12 h
R1
+ PhICF3Cl
R2
R2
1, n = 0; 3, n = 1
R2
R2
n
n
2, 4
2a, R1 = H, R3 = Me, 90%
2b, R1 = H, R3 = H, 85% (97%)
2c, R1 = Me, R3 = Me, 87%
2d, R1 = Me, R3 = H, 80%
2e, R1 = tBu, R3 = Me, 88%
2f, R1 = Ph, R3 = Me, 86%
2g, R1 = Cl, R3 = Me, 83%
2h, R1 = NO2, R3 = Me, 80%
2i, R1 = NO2, R3 = H, 57% (70%)
CF3
R3
R1
1ana
CO2Et
CO2Et
R3
R1
2j, R1 = CN, R3 = H, 58%
2k, R1 = Br, R3 = H, 50%
CO2Et
CO2Et
PhICF3Cl
to
be
efficient
and
readily
available
CF3
CF3
trifluoromethylating reagent, we further explored its synthetic
applications. Considering its innate electrophilicity, we
envisioned a cyclization of alkenes including a sequential
trifluoromethylation and arylation process by using PhICF3Cl as
the electrophilic initiator (Scheme 1C). Herein, we report this
catalyst-free and selective cyclization process with a broad
range of unactivated alkene substrates.
R1
R3
R3
+
CO2Et
CO2Et
CO2Et
R1
CO2Et
2l + 2l', R1 = OMe, R3 = Me,
CF3
R3
2l. 30%, (39%),
2l'. 50%, (60%),
2l : 2l' = 1:1.5c
CO2Et
2m, R1 = Cl, R3 = Me, 40% (55%)
CO2Et
CF3
R1
Results and discussion
CO2Et
CO2Et
We set out to study the trifluoromethylation-cyclization of 5-
arylpentenes 1a using PhICF3Cl as the electrophile (Table 1).
The reaction could give the desired product 2a in different
solvents without any catalyst at 60 oC (entries 1−6), among
which DMF led to the best result. Lower temperature (entries
7-9) and shorter reaction time (entries 10, 11) proved to
decrease the yield of 2a. Furthemore, nitrogen atmosphere
achieved better transformation of 1a to 2a (entry 6 versus 12).
2n, 81%
CF3
1oqb
R1
2o, R1 = H, (80%)
2p R1 = F, (71%)
2q, R1 = OMe, (89%)
R1
CF3
R3
4a, R1 = H, R3 = H, 67% (75%)
4b, R1 = H, R3 = Me, 47% (58%)
4c, R1 = OMe, R3 = H, (72%)
4d, R1 = Br, R3 = H, 50%
R1
Table 1 Screen of the reaction conditionsa
3afb
R3
CO2Et
CO2Et
CF3
R1
CF3
solvent
T (oC), t (h)
EtO2C
CO2Et
+
PhICF3Cl
CO2Et
CO2Et
CO2Et
CO2Et
4e, 65% (77%)
CO2Et
1a
2a
CO2Et
Entry
Solvent
T (oC)
t (h)
Yield (%)b
1
MeCN
NMP
THF
60
60
60
60
60
60
50
40
30
60
60
60
12
12
12
12
12
12
12
12
12
10
8
25
31
44
73
78
98
88
78
18
87
79
51
Scheme 2. Aryltrifluoromethylation of arylalkenes. 1/3 (0.3 mmol), DMF (3 mL).
Isolated yields. Yields in brackets are 19F NMR yields using PhCF3 as an internal
standard. a With 1.5 equivalent PhICF3Cl. b With 2.0 equivalent PhICF3Cl. c The ratio of 2l
to 2l’ was determined by 19F NMR spectroscopy.
2
3
4
1,4-dioxane
DCM
DMF
5
6
Then, we investigated the scope of trifluoromethylative
cyclizations of 1 under the optimal reaction conditions (table 1,
entry 6). To our delight, when 5-arylpentenes 1bn were
7
DMF
8
DMF
9
DMF
10
11
12c
DMF
tested,
all
the
desired
trifluoroethylated
DMF
tetrahydronaphthalenes 2bn were obtained in good isolated
yields, respectively, in which alkenes 1b, 1d and 1ik without
R3-susbtituent could also give corresponding 2 efficiently.
Among them, 1l afforded two isomers of 2l and 2l’ as the
products. The lower yield was obtained for the substrate that
DMF
12
Reaction conditions: 1a (0.1 mmol), PhICF3Cl (0.15 mmol), solvent (1 mL). 19F
NMR yields using PhCF3 as an internal standard. c In the air.
a
b
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 7
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
possessed ortho-substitution to the desired product. For
ARTICLE
deprotonation of II gives trifluoromethylated product 2h along
View Article Online
DOI: 10.1039/C8OB03189D
alkenes 1oq, the conversions of them into 2oq were with the elimination of PhI (Scheme 5). The same as the
experimental results reported by Sodeoka, the formations of
tetrahydronaphthalenes 2 were more efficient than that of
dihydroindenes 4. The arylative cyclization was suggested to
be the rate determining step.4q
efficient, while they were not completely separated from the
reaction mixture. Similar to the work of Sodeoka,
dihydroindenes 4ae could be obtained as the main products
but in relatively lower yields when 4-arylbutenes 3af were
selected towards the catalyst-free conditions. Additionally, we
tested the reactions of ((3-methylbut-3-en-1-yl)oxy)benzene
and (3-methylbut-3-en-1-yl)(phenyl)sulfane with PhICF3Cl
under the standard reaction conditions, respectively. But no
desired cyclic products were detected in this case.
additive
+
1h
+
PhICF3Cl
2h
N
DMF, 60 oC, 12 h
OCF3
TEMPO-CF3
entry additive equiv yield of 2h TEMPO-CF3
As described above, an efficient catalyst-free intramolecular
aryltrifluoromethylation of arylalkenes 1 and 3 has been
developed by using PhICF3Cl as the CF3 reagent. Next, we
extended the method to N-allylanilines 5 to synthesize
trifluoromethylated indoline derivatives. As presented in
Scheme 3, the reactions of 5 and PhICF3Cl could also proceed
under catalyst-free conditions and deliver 6ai as the
trifluoromethylative cyclization products in 64-90% isolated
yields, respectively. By comparison, our method could not be
applied to N-allylanilines 5 with no R2 substituent. And
substrate 5g without R3 substituent also gave 6g in lower yield.
1
2
3
--
--
91%
90%
59%
--
--
0
BHT
1.5
TEMPO 1.5
Scheme 4. Mechanism studies with radical scavenger. 1h (0.3 mmol), PhICF3Cl
(0.45mmol). DMF (3.0 mL). 19F NMR yields using PhCF3 as an internal standard.
PhICF3Cl
Ph
Cl
I
CF3
CF3
R3
O2N
O2N
R1
R3
R1
PhICF3
DMF, N2, 60 oC, 12 h
CO2Et
CO2Et
CO2Et
CO2Et
N
R2
N
R2
I
1h
5
6
6a, R1 = Me, R2 = Ts, R3 = Me, 86%
6b, R1 = OMe, R2 = Ts, R3 = Me, 78%
6c, R1 = Br, R2 = Ts, R3 = Me, 71%
6d, R1 = Me, R2 = Boc, R3 = Me, 88%
6e, R1 = Cl, R2 = Boc, R3 = Me, 87%
6f, R1 = OMe, R2 = Boc, R3 = Me, 90%
6g, R1 = Me, R2 = Boc, R3 = H, 64%
6h, R1 = H, R2 = Ph, R3 = Me, 75%
6i, R1 = OMe, R2 = Bz, R3 = Me, 71%
CF3
CF3
I
Ph
HCl
Cl
H
O2N
O2N
CO2Et
CO2Et
CO2Et
CO2Et
-PhI
2h
II
Scheme 3. Aryltrifluoromethylation of N-allylanilines. 5 (0.3 mmol), PhICF3Cl (1.5 eq.),
DMF (3 mL). Isolated yields. Yields in brackets are 19F NMR yields using PhCF3 as an
internal standard.
Scheme 5. Possible Mechanism.
To elucidate the reaction mechanism, control experiments
were performed (Scheme 4). The Reactions of 1h and PhICF3Cl
in the presence of 1.5 equivalents of BHT were conducted. By
the analysis of 19F NMR spectroscopies, 2h could be obtained,
in yields almost comparable to those obtained under the
standard conditions. Comparatively, the addition of 1.5
equivalents of TEMPO into the reaction mixture could not
completely suppress the desired reaction and product 2h was
obtained in 59% yield. The corresponding TEMPO–CF3 adduct
could not be detected in this case (entry 3). The decrease of
the reaction yield may be due to the consumption of oxidative
PhICF3Cl for the formation of oxoammonium salt and
hydroxylamine from TEMPO.13 According to the experimental
results, an ionic process is proposed to include the activation
of the olefin bond by electrophilic [PhICF3]+ species affording
iodonium complex I. Then exo-cyclization occurs via an attack
of the aryl group affording cyclic intermediate II. Finally, the
Conclusions
In summary,
a
catalyst-free aryltrifluoromethylative
cyclization of unactivated alkenes was disclosed herein. The
use of PhICF3Cl as powerful trifluoromethylating agent enables
an easy process for constructing a set of trifluoroethylated
carbocycles and aza-hereocycles. The trifluoromethylation
reaction has been proven to occur in good selectivity. Control
experiments support the suggested ionic mechanism. Broad
substrate scope, mild reaction conditions, and easy operation
make the method well-suited for wide applications.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 7
ARTICLE
Journal Name
(151 MHz, CDCl3): δ = 171.8, 171.3, 149.5, 140.1, V1ie3w0A.0rti,cl1e2O8nl.in7e,
126.5 (q, J = 277.7 Hz), 123.9, 122.7, 61.7, 61.4, 52.4, 45.9 (q, J
= 25.5 Hz), 39.7, 35.4 (q, J = 0.9 Hz), 34.7, 34.6, 31.4 (3C), 29.5,
13.9, 13.9. 19F-NMR (565 MHz, CDCl3): δ = -58.7 (t, J = 11.3 Hz).
HRMS (ESI): Calcd for [C23H31F3O4, M+Na]+: 451.2067,
measured: 451.2072.
Experimental
Typical procedures for catalyst-free intramolecular
aryltrifluoromethylation of unactivated alkenes (taking 1a as
an example):
DOI: 10.1039/C8OB03189D
To a dried polytetrafluoroethene (PTFE) sealed pressure tube
was added 1a (91.3 mg, 0.3 mmol), PhICF3Cl (184.8 mg, 4.5
mmol) and anhydrous DMF (3.0 mL) in sequence under N2.
After the reaction mixture was stirred at 60 °C for 12 h, PhCF3
(30 μL, 0.24 mmol) was added as the internal standard and the
NMR yield of 2a was calculated from 19F-NMR integrals. Then
the mixture was washed with water and brine, extracted by
CH2Cl2. The combined organic phase was dried over anhydrous
MgSO4 and concentrated under reduce pressure. The residue
was purified by silica column chromatography (eluent:
petroleum ether/EtOAc = 20/1 to 15/1, v/v) to give 2a (100.5
mg, 90%) as a yellow oil.
Diethyl-4-methyl-6-phenyl-4-(2,2,2-trifluoroethyl)-3,4-dihyd-
ronaphthalene-2,2(1H)-dicarboxylate (2f). 115.6 mg, 86%
yield. White solid. mp 125-126 ºC. 1H-NMR (600 MHz, CDCl3): δ
= 7.54 (d, J = 8.4 Hz, 2H), 7.42 - 7.45 (m, 3H), 7.39 (dd, J = 7.8
Hz, 1.8 Hz, 1H), 7.34 (t, J = 7.2 Hz, 1H), 7.23 (d, J = 7.8 Hz, 1H),
4.09 - 4.26 (m, 4H), 3.36 (d, J = 16.2 Hz, 1H), 3.18 (d, J = 16.2
Hz, 1H), 2.69 (d, J = 15.0 Hz, 1H), 2.54 - 2.62 (m, 1H), 2.40 -
2.48 (m, 2H), 1.47 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H), 1.22 (t, J = 7.2
Hz, 3H). 13C-NMR (151 MHz, CDCl3): δ = 171.7, 171.3, 141.1,
140.0, 132.3, 129.6, 128.8 (2C), 127.4, 127.2, 127.1 (2C), 126.4
(q, J = 277.5 Hz), 125.8, 124.0, 61.8, 61.5, 52.5, 45.9 (q, J = 25.7
Hz), 39.7, 35.4 (q, J = 0.9 Hz), 34.9, 29.7, 13.9, 13.9. 19F-NMR
(565 MHz, CDCl3): δ = -58.7 (t, J = 11.3 Hz). HRMS (ESI): Calcd
for [C25H27F3O4, M+Na]+: 471.1574, measured: 471.1761.
Characterization data for new products：
Diethyl-4,6-dimethyl-4-(2,2,2-trifluoroethyl)-3,4-dihydronap-
hthalene-2,2(1H)-dicarboxylate (2c). 113.1 mg, 87% yield.
Colourless oil. 1H-NMR (600 MHz, CDCl3): δ = 7.05 (dd, J = 13.2
Hz, 7.8 Hz, 2H), 6.97 (d, J = 7.8 Hz, 1H), 4.06 - 4.24 (m, 4H), 3.26
(d, J = 15.6 Hz, 1H), 3.09 (d, J = 15.6 Hz, 1H), 2.63 (d, J =15.0 Hz,
1H), 2.47 - 2.56 (m, 1H), 2.41 (d, J = 14.4 Hz, 1H), 2.33 - 2.38
(m, 1H), 2.30 (s, 3H), 1.40 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H), 1.20
(t, J = 7.2 Hz, 3H). 13C-NMR (151 MHz, CDCl3): δ = 171.7, 171.3,
140.6, 136.3, 130.0, 129.0, 127.7, 126.5, 126.5 (q, J = 278.1
Hz), 61.7, 61.4, 52.5, 40.6 (q, J = 25.7 Hz), 39.6, 35.2 (q, J = 0.8
Hz), 34.8, 29.5, 21.3, 13.9, 13.9. 19F-NMR (565 MHz, CDCl3): δ =
-58.8 (t, J = 11.3 Hz). HRMS (ESI): Calcd for [C20H25F3O4,
M+Na]+: 409.1597, measured: 459.1606.
Diethyl-6-chloro-4-methyl-4-(2,2,2-trifluoroethyl)-3,4-dihydr-
onaphthalene-2,2(1H)-dicarboxylate (2g). 101.1 mg, 83%
1
yield. White solid. mp 99-100 ºC. H-NMR (600 MHz, CDCl3): δ
= 7.46 (dd, J = 7.8 Hz, 1.2 Hz, 1H), 7.28 (t, J = 7.8 Hz, 2H), 4.20 -
4.25 (m, 2H), 4.07 - 4.19 (m, 2H), 3.39 (d, J = 16.2 Hz, 1H), 3.15
(d, J = 16.2 Hz, 1H), 2.68 (d, J = 14.4 Hz, 1H), 2.46 - 2.54 (m,
1H), 2.37 - 2.45 (m, 2H), 1.43 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H),
1.20 (t, J = 7.2 Hz, 3H). 13C-NMR (151 MHz, CDCl3): δ = 171.1,
170.8, 142.1, 139.3, 130.3, 130.1, 130.1, 125.9 (q, J = 277.4
Hz), 111.0, 62.1, 61.8, 52.2, 45.5 (q, J = 26.0 Hz), 39.4, 35.4 (q, J
= 1.1 Hz), 35.2, 29.8, 13.9, 13.9. 19F-NMR (565 MHz, CDCl3): δ =
-58.9 (t, J = 10.7 Hz). HRMS (ESI): Calcd for [C19H22F3ClO4,
M+Na]+: 429.1050, measured: 429.1045.
Diethyl-6-methyl-4-(2,2,2-trifluoroethyl)-3,4-dihydronaphth-
alene-2,2(1H)-dicarboxylate (2d). 89.3 mg, 80% yield.
1
Colourless oil. H-NMR (600 MHz, CDCl3): δ = 7.05 - 7.08 (m,
1H), 7.02 (d, J = 7.8 Hz, 1H), 6.97 (d, J = 7.8 Hz, 1H), 4.19 - 4.24
(m, 2H), 4.05 - 4.15 (m, 2H), 3.28 - 3.33 (m, 2H), 3.15 (t, J =
13.8 Hz, 1H), 2.83 (dd, J = 13.8 Hz, 6.0 Hz, 1H), 2.76 - 2.79 (m,
1H), 2.30 (d, J = 6.0 Hz, 3H), 2.21 - 2.27 (m, 1H), 1.94 (dd, J =
13.8 Hz, 10.2 Hz, 1H), 1.27 (t, J = 7.2 Hz, 3H), 1.16 (dt, J = 22.2
Hz, 7.2 Hz, 3H). 13C-NMR (151 MHz, CDCl3): δ = 171.6, 170.4,
136.4, 135.9, 133.2, 130.0, 128.9, 128.3 (q, J = 269.7 Hz),
127.6, 61.7, 61.4, 53.7, 41.0 (q, J = 27.2 Hz), 38.4, 34.8, 30.5 (q,
J = 2.3 Hz), 21.2, 14.0, 13.9. 19F-NMR (565 MHz, CDCl3): δ = -
63.5 (t, J = 11.3 Hz). HRMS (ESI): Calcd for [C19H23F3O4, M+Na]+:
395.1440, measured: 395.1444.
Diethyl-4-methyl-6-nitro-4-(2,2,2-trifluoroethyl)-3,4-dihydro-
naphthalene-2,2(1H)-dicarboxylate (2h). 100.1 mg, 80% yield.
1
Yellow solid. mp 74-75 ºC. H-NMR (600 MHz, CDCl3): δ = 8.16
(s, 1H), 8.04 (d, J = 8.4 Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H), 4.24 (q, J
= 8.4 Hz, 2H), 4.08 - 4.19 (m, 2H), 3.45 (d, J = 16.2 Hz, 1H), 3.17
(d, J = 16.2 Hz, 1H), 2.71 (d, J = 14.4 Hz, 1H), 2.52 - 2.60 (m,
1H), 2.43 - 2.50 (m, 2H), 1.47 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H),
1.21 (t, J = 7.2 Hz, 3H). 13C-NMR (151 MHz, CDCl3 ): δ = 171.0,
170.7, 147.1, 142.3, 141.4, 130.2, 125.9 (q, J = 277.5 Hz),
121.8, 121.6, 62.1, 61.9, 52.2, 45.6 (q, J = 26.1 Hz), 39.2, 35.7
(q, J = 0.8 Hz), 35.2, 30.0, 13.9, 13.9. 19F-NMR (565 MHz,
CDCl3): δ = -58.8 (t, J = 10.7 Hz). HRMS (ESI): Calcd for
[C19H22F3NO6, M+Na]+: 440.1291, measured: 440.1293.
Diethyl-6-(tert-butyl)-4-methyl-4-(2,2,2-trifluoroethyl)-3,4-
dihydronaphthalene-2,2(1H)-dicarboxylate (2e). 115.7 mg,
1
88% yield. Colourless oil. H-NMR (600 MHz, CDCl3): δ = 7.23
(d, J = 1.8 Hz, 1H), 7.19 (dd, J = 7.8 Hz, 1.8 Hz, 1H), 7.07 (d, J =
7.8 Hz, 1H), 4.07 - 4.24 (m, 4H), 3.27 (d, J = 16.2 Hz, 1H), 3.12
(d, J = 16.2 Hz, 1H), 2.64 (d, J =14.4 Hz, 1H), 2.46 - 2.54 (m, 1H),
2.42 (d, J = 14.4 Hz, 1H), 2.33 - 2.40 (m, 1H), 1.42 (s, 3H), 1.29
(s, 9H), 1.26 (t, J = 7.2 Hz, 3H), 1.20 (t, J = 7.2 Hz, 3H). 13C-NMR
Diethyl-6-nitro-4-(2,2,2-trifluoroethyl)-3,4-dihydronaphthal-
ene-2,2(1H)-dicarboxylate (2i). 68.9 mg, 57% yield. Yellow oil.
1H-NMR (600 MHz, CDCl3): δ = 8.08 (s, 1H), 8.04 (d, J = 8.4 Hz,
1H), 7.34 (d, J = 8.4 Hz, 1H), 4.24 (q, J = 7.2 Hz, 2H), 4.09 - 4.19
(m, 2H), 3.45 (d, J = 16.8 Hz, 1H), 3.38 (q, J = 8.4 Hz, 1H), 3.25
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 7
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
(d, J = 16.8 Hz, 1H), 2.88 (dd, J = 13.8 Hz, 6.0 Hz, 1H), 2.78 - 1H), 2.33 - 2.53 (m, 3H), 1.41 (s, 3H), 1.28 (t, J = 6.8 Hz, 3H),
View Article Online
13
DOI: 10.1039/C8OB03189D
2.84 (m, 1H), 2.33 - 2.42 (m, 1H), 2.03 (dd, J = 13.2 Hz, 10.8 Hz, 1.21 (t, J = 7.2 Hz, 3H). C-NMR (151 MHz, CDCl3): δ = 171.5,
1H), 1.28 (t, J = 7.2 Hz, 3H), 1.17 (t, J = 7.2 Hz, 3H). 13C-NMR 171.1, 143.1, 134.2, 131.4, 127.7, 127.3, 126.2 (q, J = 279.2
(151 MHz, CDCl3): δ = 170.8, 169.8, 147.0, 142.1, 137.9, 130.3, Hz), 124.6, 61.9, 61.6, 52.0, 45.9 (q, J = 26.1 Hz), 39.0, 35.6,
124.6 (q, J = 276.0 Hz), 121.9, 121.9, 62.1, 61.9, 53.3, 40.1 (q, J 32.0, 29.7, 13.9, 13.9. 19F-NMR (470 MHz, CDCl3): δ = -58.8 (t, J
= 27.8 Hz), 35.2, 34.1, 30.8 (q, J = 2.1 Hz), 14.0, 13.9. 19F-NMR = 12.2 Hz). HRMS (ESI): Calcd for [C19H22ClF3O4, M+Na]+:
(565 MHz, CDCl3): δ = -63.2 (t, J = 10.7 Hz). HRMS (ESI): Calcd 429.1056, measured: 429.1040.
for [C18H20F3NO6, M+Na]+: 426.1135, measured: 426.1135.
Diethyl-1-methyl-1-(2,2,2-trifluoroethyl)-1,4-dihydrophenan-
Diethyl-6-cyano-4-(2,2,2-trifluoroethyl)-3,4-dihydronaphthal- threne-3,3(2H)-dicarboxylate (2n). 115.6 mg, 81% yield.
1
ene-2,2(1H)-dicarboxylate (2j). 66.7mg, 58% yield. Yellow oil. Yellow oil. H-NMR (600 MHz, CDCl3): δ = 8.10 (d, J = 8.4 Hz,
1H-NMR (600 MHz, CDCl3): δ = 7.14 (d, J = 9.0 Hz, 2H), 7.08 (d, J 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 9.0 Hz, 1H), 7.56 (t, J =
= 7.8 Hz, 1H), 4.22 (q, J = 7.2 Hz, 2H), 4.07 - 4.17 (m, 2H), 3.31 7.8 Hz, 1H), 7.49 (t, J = 7.2 Hz, 1H), 7.38 (d, J = 8.4 Hz, 1H), 4.23
(d, J = 15.6 Hz, 2H), 3.13 (d, J = 16.2 Hz, 1H), 2.83 (dd, J = 13.8 - 4.29 (m, 2H), 4.10 - 4.20 (m, 2H), 3.84 (d, J = 16.8 Hz, 1H),
Hz, 7.2 Hz, 1H), 2.68 - 2.76 (m, 1H), 2.24 - 2.34 (m, 1H), 1.95 3.41 (d, J = 16.2 Hz, 1H), 2.80 (d, J = 14.4 Hz, 1H), 2.60 - 2.68
(dd, J = 13.2 Hz, 3.0 Hz, 1H), 1.27 (t, J = 7.2 Hz, 3H), 1.15 (t, J = (m, 1H), 2.57 (d, J = 14.4 Hz, 1H), 2.37 - 2.45 (m, 1H), 1.49 (s,
7.2 Hz, 3H). 13C-NMR (151 MHz, CDCl3): δ = 171.2, 170.1, 3H), 1.31 (t, J = 7.2 Hz, 3H), 1.21 (t, J = 7.2 Hz, 3H). 13C-NMR
138.1, 132.6, 132.6, 130.6, 127.0, 126.6 (q, J = 277.7 Hz), (151 MHz, CDCl3): δ = 171.9, 171.4, 137.4, 132.2, 131.8, 128.4,
126.9, 115.7, 61.9, 61.6, 53.5, 40.7 (q, J = 27.6 Hz), 34.6, 34.5, 128.2, 127.3, 126.5, 126.5 (q, J = 277.7 Hz), 125.7, 123.8,
30.6 (q, J = 2.3 Hz), 14.0, 13.9. 19F-NMR (565 MHz, CDCl3): δ = - 123.4, 61.9, 61.5, 52.1, 45.9 (q, J = 25.7 Hz), 38.6, 35.6 (d, J =
63.5 (t, J = 11.3 Hz). HRMS (ESI): Calcd for [C19H20F3NO4, 0.9 Hz), 30.8, 29.4, 13.9, 13.9. 19F-NMR (600 MHz, CDCl3): δ = -
M+Na]+: 406.1236, measured: 406.1239.
58.6 (t, J = 11.3 Hz). HRMS (ESI): Calcd for [C23H25F3O4, M+Na]+:
445.1597, measured: 445.1596.
Diethyl-7-methoxy-4-methyl-4-(2,2,2-trifluoroethyl)-3,4-dihy-
dronaphthalene-2,2(1H)-dicarboxylate (2l). 36.2mg, 30% Diethyl-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-ind-
yield. Colourless oil. 1H-NMR (600 MHz, CDCl3): δ = 7.08 (d, J = ene-1,1-dicarboxylate (4b). 50.5 mg, 47% yield. Colourless oil.
8.4 Hz, 1H), 6.69 (dd, J = 9.0 Hz, 3.0 Hz, 1H), 6.60 (d, J = 2.4 Hz, 1H-NMR (600 MHz, CDCl3): δ = 7.56 (d, J = 7.8 Hz, 1H), 7.35 (t, J
1H), 4.00 - 4.17 (m, 4H), 3.71 (s, 3H), 3.20 (d, J = 15.6 Hz, 1H), = 7.2 Hz, 1H), 7.30 (t, J = 7.8 Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H),
3.04 (d, J = 16.2 Hz, 1H), 2.56 (d, J = 14.4 Hz, 1H), 2.36 - 2.45 4.20 - 4.27 (m, 4H), 3.03 (d, J = 14.4 Hz, 1H), 2.69 (d, J = 14.4
(m, 1H), 2.33 (d, J = 15.0 Hz, 1H), 2.22 - 2.31 (m, 1H), 1.31 (s, Hz, 1H), 2.37 - 2.52 (m, 2H), 1.42 (s, 3H), 1.28 (t, J = 7.2 Hz, 6H).
3H), 1.19 (t, J = 7.2 Hz, 3H), 1.14 (t, J = 7.2 Hz, 3H). 13C-NMR 13C-NMR (600 MHz, CDCl3): δ = 170.7, 170.6, 150.3, 137.5,
(125 MHz, CDCl3): δ = 171.6, 171.2, 157.9, 134.4, 132.9, 127.2, 129.3, 127.8, 127.1, 126.6 (q, J = 277.2 Hz), 122.6, 64.5, 62.0,
126.3 (q, J = 277.9 Hz), 113.2(2C), 61.7, 61.4, 55.1, 52.4, 46.0 61.9, 45.7, 44.5 (q, J = 26.1 Hz), 43.9 (q, J = 1.5 Hz), 27.3, 14.0,
(q, J = 25.5 Hz), 39.6, 35.3, 34.7, 29.7, 13.9(2C). 19F-NMR (470 14.0. 19F-NMR (565 MHz, CDCl3): δ = -59.9 (t, J = 11.3 Hz).
MHz, CDCl3): δ = -58.9 (t, J = 11.3 Hz). HRMS (ESI): Calcd for HRMS (ESI): Calcd for [C18H21F3O4, M+Na]+: 381.1284,
[C20H25F3O5, M+Na]+: 425.1546, measured: 425.1538.
measured: 381.1292.
Diethyl-5-methoxy-4-methyl-4-(2,2,2-trifluoroethyl)-3,4-dihy- Diethyl-5-bromo-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-ind-
dronaphthalene-2,2(1H)-dicarboxylate (2l‘). 60.3mg, 50% ene-1,1-dicarboxylate (4d). 63.3 mg, 50% yield. Colourless oil.
1
yield. Colourless oil. H-NMR (600 MHz, CDCl3): δ = 7.14 (t, J = 1H-NMR (600 MHz, CDCl3): δ = 7.47 (d, J = 7.8 Hz, 1H),7.44 (d, J
7.8 Hz, 1H), 6.79 (d, J = 7.8 Hz, 1H), 6.72 (d, J = 8.4 Hz, 1H), 4.14 = 8.4 Hz, 1H), 7.35 (s, 1H), 4.26 (q, J = 7.2 Hz, 2H), 4.14 - 4.22
- 4.24 (m, 3H), 4.05 - 4.10 (m, 1H), 3.80 (s, 3H), 3.33 (dd, J = (m, 2H), 3.59 - 3.63 (m, 1H), 3.08 (dd, J = 13.8 Hz, 10.2 Hz, 1H),
15.6 Hz, 2.4 Hz, 1H), 2.99 (d, J = 15.6 Hz, 1H), 2.74 - 2.80 (m, 2.61 - 2.70 (m, 1H), 2.44 (dd, J = 13.2 Hz, 7.8 Hz, 1H), 2.24 -
2H), 2.72 (d, J = 14.4 Hz, 1H), 2.39 (dd, J = 14.4 Hz, 2.4Hz, 1H), 2.33 (m, 1H), 1.29 (t, J = 7.2 Hz, 3H), 1.24 (t, J = 7.2 Hz, 3H). 13C-
1.40 (s, 3H), 1.27 (t, J = 6.6 Hz, 3H), 1.21 (t, J = 6.6 Hz, 3H). 13C- NMR (151 MHz, CDCl3): δ = 170.0, 169.6, 147.0, 138.1, 131.0,
NMR (151 MHz, CDCl3): δ = 171.6, 171.2, 158.1, 135.5, 127.6, 128.5, 126.8, 126.5 (q, J = 277.4 Hz), 123.3, 64.4, 62.1, 62.1,
127.3, 126.9 (q, J = 279.4 Hz), 122.0, 109.6, 61.6, 61.3, 55.0, 40.6, 39.0 (q, J = 28.2 Hz), 36.9 (q, J = 2.6 Hz), 14.1, 14.0. 19F-
51.8, 42.7 (q, J = 25.2 Hz), 41.7 (q, J = 1.8 Hz), 36.1, 35.2, 27.1, NMR (565 MHz, CDCl3): δ = -64.4 (t, J= 10.7 Hz). HRMS (ESI):
14.0, 13.9. 19F-NMR (470 MHz, CDCl3): δ = -59.3 (t, J = 11.8 Hz). Calcd for [C17H18BrF3O4, M+Na]+: 445.0233, measured:
HRMS (ESI): Calcd for [C20H25F3O5, M+Na]+: 425.1546, 445.0246.
measured: 425.1538.
3,5-Dimethyl-1-tosyl-3-(2,2,2-trifluoroethyl)indoline
98.8 mg, 86% yield. Yellow oil. H-NMR (600 MHz, CDCl3): δ =
(6a).
1
Diethyl-8-chloro-4-methyl-4-(2,2,2-trifluoroethyl)-3,4-dihydr-
onaphthalene-2,2(1H)-dicarboxylate (2m). 48.7mg, 40% yield. 7.70 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 7.8 Hz, 1H), 7.25 (d, J = 8.4
1
Colourless oil. H-NMR (600 MHz, CDCl3): δ = 7.26 - 7.29 (m, Hz, 2H), 7.05 (d, J = 8.4 Hz, 1H), 6.80 (s, 1H), 3.92 (d, J = 10.8
1H), 7.13 - 7.19 (m, 2H), 4.06 - 4.26 (m, 4H), 3.68 (dd, J = 16.0 Hz, 1H), 3.67 (d, J = 11.4 Hz, 1H), 2.37 (s, 3H), 2.24 - 2.32 (m,
Hz, 1.2 Hz, 1H), 3.04 (d, J = 16.8 Hz, 1H), 2.64 (d, J = 14.8 Hz, 4H), 1.93 - 2.01 (m, 1H), 1.21 (s, 3H). 13C-NMR (151 MHz,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 6 of 7
ARTICLE
Journal Name
CDCl3): δ = 144.3, 138.1, 138.1, 133.8, 129.7 (2C), 129.4, 127.7, NMR (600 MHz, CDCl3): δ = 7.36 - 7.77 (br. 1H),V7ie.w75Art(icdledO,nJlin=e
127.3 (2C), 126.0 (q, J = 278.7 Hz), 123.3, 114.9, 61.4, 42.7 (q, J 8.4 Hz, 1.8 Hz, 1H), 6.65 (d, J = 2.4 Hz, 1DHO),I:410.0.1103(9s/,C18HO)B,033.17849D-
= 26.9 Hz), 41.0 (q, J = 1.5 Hz), 25.1, 21.5, 21.0. 19F-NMR (565 3.78 (m, 4H), 2.37 - 2.53 (m, 2H), 1.55 (s, 9H), 1.43 (s, 3H). 13C-
MHz, CDCl3): δ = -60.4 (t, J = 10.7 Hz). HRMS (ESI): Calcd for NMR (151 MHz, CDCl3): δ = 155.7, 152.4, 138.6, 138.2, 126.3
[C19H20F3NO2S, M+Na]+: 406.1059, measured: 406.1069.
(q, J = 278.6 Hz), 115.6, 112.8, 109.0, 80.7, 60.1, 55.8, 43.2 (q, J
= 26.9 Hz), 28.5 (3C), 25.9, 25.9. 19F-NMR (470 MHz, CDCl3): δ =
-60.4 (t, J = 11.3 Hz). HRMS (ESI): Calcd for [C17H22F3NO3,
M+Na]+: 368.1444, measured: 368.1447.
5-Methoxy-3-methyl-1-tosyl-3-(2,2,2-trifluoroethyl)indoline
(6b). 93.4 mg, 78% yield. Yellow oil. 1H-NMR (600 MHz, CDCl3):
δ = 7.67 (d, J = 7.8 Hz, 2H), 7.61 (d, J = 9.0 Hz, 1H), 7.25 (d, J = 3-Methyl-1-phenyl-3-(2,2,2-trifluoroethyl)indoline (6h). 65.5
1
8.4 Hz, 2H), 6.79 (dd, J = 9.0 Hz, 3.0 Hz, 1H), 6.54 (d, J = 2.4 Hz, mg, 75% yield. Colorless oil. H-NMR (600 MHz, CDCl3): δ =
1H), 3.94 (d, J = 11.4 Hz, 1H), 3.77 (s, 3H), 3.67 (d, J = 10.8 Hz, 7.36 (t. J = 7.8 Hz, 2H), 7.22 (d, J = 7.8 Hz, 2H), 7.12 - 7.16 (m,
1H), 2.37 (s, 3H), 2.17 - 2.27 (m, 1H), 1.86 - 1.94 (m, 1H), 1.18 2H), 7.10 (d, J = 7.8 Hz, 1H), 7.00 (t, J = 7.2 Hz, 1H), 6.81 (t, J =
(s, 3H). 13C-NMR (151 MHz, CDCl3): δ = 156.9, 144.3, 139.7, 7.2 Hz, 1H), 3.98 (d, J = 9.6 Hz, 1H), 3.73 (d, J = 9.6 Hz, 1H), 2.46
133.8, 133.7, 129.7 (2C), 127.3 (2C), 125.9 (q, J = 277.1 Hz), – 2.60 (m, 2H), 1.50 (s, 3H). 13C-NMR (151 MHz, CDCl3): δ =
116.2, 113.6, 109.0, 61.5, 55.7, 42.7 (q, J = 26.9 Hz), 42.2 (q, J = 145.5, 143.6, 137.4, 129.3 (2C), 128.1, 126.6 (q, J = 278.9 Hz),
1.7 Hz), 25.0, 21.5. 19F-NMR (565 MHz, CDCl3): δ = -60.4 (t, J = 122.6, 121.5, 119.3, 118.0 (2C), 108.5, 64.1, 42.5 (q, J = 26.7
11.3 Hz). HRMS (ESI): Calcd for [C19H20F3NO3S, M+Na]+: Hz), 40.7 (q, J = 1.1 Hz), 24.7. 19F-NMR (470 MHz, CDCl3): δ = -
422.1008, measured: 422.1008.
60.3 (t, J = 12.2 Hz). HRMS (ESI): Calcd for [C17H16F3N, M+Na]+:
313.1174, measured: 313.1167.
5-Bromo-3-methyl-1-tosyl-3-(2,2,2-trifluoroethyl)indoline
(6c). 95.2 mg, 71% yield. Yellow oil. 1H-NMR (600 MHz, CDCl3): (5-Methoxy-3-methyl-3-(2,2,2-trifluoroethyl)indolin-1-yl)(ph-
δ = 7.69 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8,4 Hz, 1H), 7.36 (dd, J = enyl)methanone (6i). 74.4 mg, 71% yield. Colorless oil. 1H-
9.0 Hz, 2.4 Hz, 1H), 7.28 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 1.8 Hz, NMR (600 MHz, CDCl3): δ = 8.20 (d, J = 7.8 Hz, 1H), 7.56 (t, J =
1H), 3.94 (d, J = 10.8 Hz, 1H), 3.68 (d, J = 10.8 Hz, 1H), 2.39 (s, 7.8 Hz, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.37 (d, J = 7.8 Hz, 1H), 7.26
3H), 2.23 - 2.31 (m, 1H), 1.98 - 2.06 (m, 1H), 1.23 (s, 3H). 13C- - 7.29 (m, 2H), 6.96 (d, J = 9.0 Hz, 2H), 3.94 (d, J = 12.6 Hz, 1H),
NMR (151 MHz, CDCl3): δ = 144.7, 140.1, 139.8, 133.6, 131.8, 3.83 (s, 3H), 3.74 (d, J = 12.6 Hz, 1H), 2.51 – 2.70 (m, 2H), 1.60
129.9 (2C), 127.2 (2C), 125.8 (q, J = 276.9 Hz), 126.1, 116.5, (s, 3H). 13C-NMR (151 MHz, CDCl3): δ = 164.0, 158.1, 144.0,
116.5, 61.4, 42.6 (q, J = 28.4 Hz), 41.1 (q, J = 1.7 Hz), 25.2, 21.5. 135.4, 132.6, 129.4, 128.4, 127.8, 126.6 (2C), 126.1 (q, J =
19F-NMR (565 MHz, CDCl3): δ = -60.4 (t, J = 11.3 Hz). HRMS 282.5 Hz), 124.5, 114.0 (2C), 59.0, 55.5, 41.3 (q, J = 25.4 Hz),
(ESI): Calcd for [C18H17BrF3NO2S, M+Na]+: 470.0008, measured: 35.6, 22.3. 19F-NMR (470 MHz, CDCl3): δ = -59.6 (t, J = 12.2 Hz).
470.0007.
HRMS (ESI): Calcd for [C19H18F3NO2, M+Na]+: 372.1182,
measured: 372.1190.
Tert-butyl-3,5-dimethyl-3-(2,2,2-trifluoroethyl)indoline-1-ca-
1
rboxylate (6d). 98.7 mg, 88% yield. Colorless oil. H-NMR (600
Conflicts of interest
There are no conflicts to declare.
MHz, CDCl3): δ = 7.33 - 7.80 (br. 1H), 7.02 (d, J = 8.4 Hz, 1H),
6.89 (s, 1H), 4.00 (d, J = 10.2 Hz, 1H), 3.74 (s, 1H), 2.46 - 2.54
(m, 1H), 2.35 - 2.44 (m, 1H), 2.30 (s, 3H), 1.56 (s, 9H) 1.42 (s,
3H). 13C-NMR (151 MHz, CDCl3): δ = 152.4, 137.3, 132.1, 129.0,
127.3, 125.4, 122.8, 126.3 (q, J = 277.0 Hz), 80.7, 60.1, 43.3 (q,
J = 26.6 Hz), 28.5 (3C), 26.0, 26.0, 20.9. 19F-NMR (565 MHz,
CDCl3): δ = -60.4 (t, J = 11.3 Hz). HRMS (ESI): Calcd for
[C17H22F3NO2, M+Na]+: 352.1495, measured: 352.1490.
Acknowledgements
We thank National Natural Sciences Foundation of China
(21672032, 21802016) for funding supports of this work.
Tert-butyl-5-chloro-3-methyl-3-(2,2,2-trifluoroethyl)indoline-
1-carboxylate (6e). 91.3 mg, 87% yield. Colorless oil. H-NMR
Notes and references
1
1
Selected recent reviews, see, (a) C. Zhang, Adv. Synth. Catal.,
2014, 356, 2895; (b) X. Liu, C. Xu, M. Wang and Q. Liu, Chem.
Rev., 2015, 115, 683; (c) J. Charpentier, N. Früh and A. Togni,
Chem. Rev., 2015, 115, 650; (d) C. Alonso, M. de M. Eduardo,
G. Rubiales and F. Palacios, Chem. Rev., 2015, 115, 1847; (e)
N. Shibata, Bull. Chem. Soc. Jpn., 2016, 89, 1307; (f) G.-B. Li,
C. Zhang, C. Song and Y.-D. Ma Beilstein J. Org. Chem., 2018,
14, 155.
(600 MHz, CDCl3): δ = 7.37 - 7.80 (br. 1H), 7.17 (d, J = 7.8 Hz,
1H), 7.04 (d, J = 1.8 Hz, 1H), 4.03 (d, J = 10,8 Hz, 1H), 3.77 (s,
1H), 2.38 - 2.52 (m, 2H), 1.56 (s, 9H), 1.43 (s, 3H). 13C-NMR
(151 MHz, CDCl3): δ = 152.1, 140.1, 138.9, 128.5, 127.5, 126.1
(q, J = 278.7 Hz), 122.6, 116.0, 81.5, 60.1, 43.2 (q, J = 27.0 Hz),
28.4 (3C), 26.1, 26.1. 19F-NMR (470 MHz, CDCl3): δ = -60.4 (t, J
= 11.3 Hz). HRMS (ESI): Calcd for [C16H19ClF3NO2, M+Na]+:
371.0996, measured: 371.1005.
2
(a) H. Egami and M. Sodeoka, Angew. Chem. Int. Ed., 2014,
53, 8294; (b) E. Merino and C. Nevado, Chem. Soc. Rev.,
2014, 43, 6598; (c) S.-M. Wang, J.-B. Han, C.-P. Zhang, H.-L.
Qin and J.-C. Xiao, Tetrahedron, 2015, 71, 7949; (d) G. S.
Sauer and S. Lin, ACS Catal., 2018, 8, 5175; (e) Y. Tian, S.
Tert-butyl-5-methoxy-3-methyl-3-(2,2,2-trifluoroethyl)indol-
1
ine-1-carboxylate (6f). 99.4 mg, 90% yield. Colorless oil. H-
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 7
Organic & Biomolecular Chemistry
Please do not adjust margins
Journal Name
ARTICLE
Chen, Q,-S. Gu, J.-S. Lin and X.-Y. Liu, Tetrahedron Lett., 2018,
59, 203.
Selected reports on the bioactivities of trifluoromethylated
compounds, see, (a) P. Jeschke, ChemBioChem, 2004, 5, 570;
(b) J.-P. Bégué and D. Bonnet-Delpon, Bioorganic and
Medicinal Chemistry of Fluorine; Wiley-VCH, Hoboken, NJ,
2008; (c) A. Tressaud and G. Haufe, Fluorine and Health:
8
9
Selected examples using CF3I and CF3H, (a) S. Tang, Z.-H. Li,
M.-W. Wang, Z.-P. Li and R.-L. Sheng, Org. BiVoiemwoAlr.ticClehOenmlin.e,
DOI: 10.1039/C8OB03189D
3
2015, 13, 5285; (b) Y. Ye, K. P. S. Cheung, L. He, G. C. Tsui,
Org. Chem. Front., 2018, 5, 1511.
Selected examples using Umemoto’ reagents, (a) Q. Wei, J.-
R. Chen, X.-Q. Hu, X.-C. Yang, B. Lu and W.-J. Xiao, Org. Lett.,
2015, 17, 4464. (b) Y. Yasu, Y. Arai, R. Tomita, T. Koike and M.
Akita, Org. Lett., 2014, 16, 780; (c) X. Sun and S. Yu, Chem.
Commun., 2016, 52, 10898.
Molecular
Imaging,
Biomedical
Materials
and
Pharmaceuticals; Elsevier Science: Amsterdam, 2008; (d) I.
Ojima, Fluorine in Medicinal Chemistry and Chemical Biology; 10 Examples for deprotonative trifluoromethylations of simple
Wiley-Blackwell, Chichester, UK, 2009; (e) K. Müller, C. Faeh
and F. Diederich, Science, 2007, 317, 1881.
alkenes, (a) A. T. Parsons and S. L. Buchwald, Angew. Chem.
Int. Ed., 2011, 50, 9120; (b) J. Xu, Y. Fu, D.-F. Luo, Y.-Y. Jiang,
B. Xiao, Z.-J. Liu, T.-J. Gong and L. Liu, J. Am. Chem. Soc.,
2011, 133, 15300; (c) X. Wang, Y. Ye, S. Zhang, J. Feng, Y. Xu,
Y. Zhang and J. Wang, J. Am. Chem. Soc., 2011, 133, 16410;
(d) L. Chu and F.-L. Qing, Org. Lett., 2012, 14, 2106; (e) R.
Shimizu, H. Egami, Y. Hamashima and M. Sodeoka, Angew.
Chem. Int. Ed., 2012, 51, 4577; (f) S, Mizyta, O. Galicia-López,
K. M. Engle, S. Verhoog, K. Wheelhouse, G. Rassias and V.
Gouverneur, Chem. - Eur. J., 2012, 18, 8583; (g) X. Wu, L. Chu
and F.-L. Qing, Angew. Chem. Int. Ed., 2013, 52, 2198; (h) C.-
H. Chiang, R. Ramu, Y.-J. Tu, C.-L. Yang, K. Y. Ng, W.-I. Luo, C.
H. Chen, Y.-Y. Lu, C.-L. Liu and S. S.-F. Yu, Chem.- Eur. J., 2013,
19, 13680; (i) J. M. Larsson, S. R. Pathipati and K. J. Szabo, J.
Org. Chem., 2013, 78, 7330; j) R. Beniazza, F. Molton, C.
Duboc, A. Tron, N. D. McClenaghan, D. Lastécouères and J.-
M. Vincent, Chem. Commun., 2015, 51, 9571; (k) J. Lei, X. Liu,
S. Zhang, S. Jiang, M. Huang, X. Wu and Q. Zhu, Chem. - Eur.
J., 2015, 21, 6700; (l) M. Asano, R. Tomita, T. Koike and M.
Akita, J. Fluorine Chem., 2015, 179, 83; (m) S. Kawamura and
M. Sodeoka, Angew. Chem. Int. Ed., 2016, 55, 8740; (n) F.
Wang, D. Wang, Y. Zhou, L. Liang, R. Lu, P. Chen, Z. Lin and G.
Liu, Angew. Chem. Int. Ed., 2018, 57, 7140.
4
For selected examples using Togni’s reagents, see, (a) R. Zhu
and S. L. Buchwald, J. Am. Chem. Soc., 2012, 134, 12462; (b)
R. Zhu and S. L. Buchwald, Angew. Chem. Int. Ed., 2013, 52,
12655; (c) Q. Yu and S. Ma, Chem. - Eur. J., 2013, 19, 13304;
(d) H. Egami, S. Kawamura, A. Miyazaki, M. Sodeoka, Angew.
Chem. Int. Ed., 2013, 52, 7841; (e) X. Dong, R. Sang, Q. Wang,
X.-Y. Tang and M. Shi, Chem. - Eur. J., 2013, 19, 16910; (f) P.
Xu, J. Xie, Q. Xue, C. Pan, Y. Cheng and C. Zhu, Chem. - Eur. J.,
2013, 19, 14039; (g) W. Kong, M. Casimiro, E. Merino and C.
Nevado, J. Am. Chem. Soc., 2013, 135, 14480; (h) G. Han, Y.
Liu and Q. Wang, Org. Lett., 2014, 16, 3188; (i) Y.-T. He, L.-H.
Li, Z.-Z. Zhou, H.-L. Hua, Y.-F. Qiu, X.-Y. Liu and Y.-M. Liang,
Org. Lett., 2014, 16, 3896; (j) G. Han, Q. Wang, L. Chen, Y. Liu
and Q. Wang, Adv. Synth. Catal., 2016, 358, 561; (k) P. Xu, J.
Xie, Q. Xue, C. Pan, Y. Cheng and C. Zhu, Chem. - Eur. J., 2013,
19, 14039; (l) Y. An, Y. Li and J. Wu, Org. Chem. Front., 2016,
3, 570; (m) F. Gao, C. Yang, G.-L. Gao, L. Zheng and W. Xia,
Org. Lett., 2015, 17, 3478; (n) Q. Wang, H. Song, Y. Liu, H.
Song and Q. Wang, Adv. Synth. Catal., 2016, 358, 3435; (o) Z.
Liu, Y. Bai, J. Zhang, Y. Yu, Z. Tan and G. Zhu, Chem.
Commun., 2017, 53, 6440; (p) Y.-T. He, L.-H. Li, Y.-F. Yang, Y.-
Q. Wang, J.-Y. Luo, X.-Y. Liu and Y.-M. Liang, Chem. 11 C. Xu, X. Song, J. Guo, S. Chen, J. Gao, J. Jiang, F. Gao, Y. Li
Commun., 2013, 49, 5687; (q) H. Egami, R. Shimizu, S. and M. Wang, Org. Lett., 2018, 20, 3933.
Kawamura and M. Sodeoka, Angew. Chem. Int. Ed., 2013, 52, 12 J. N. Brantley, A. V. Samant and F. D. Toste, ACS Cent. Sci.
4000; (r) P. Gao, X.-B. Yan, T. Tao, F. Yang, T. He, X.-R. Song, 2016, 2, 341.
X.-Y. Liu and Y.-M. Liang, Chem. - Eur. J., 2013, 19, 14420; (s) 13 T. Vogler and A. Studer, Synthesis. 2008, 2008, 1979.
H. Egami, R. Shimizu and M. Sodeoka, J. Fluorine Chem.,
2013, 152, 51; (t) W. Kong, M. Casimiro, N. Fuentes, E.
Merino and C. Nevado, Angew. Chem. Int. Ed., 2013, 52,
13086.
Selected examples using TMSCF3, (a) X. Mu, T. Wu, H.-Y.
Wang, Y.-L. Guo and G. Liu, J. Am. Chem. Soc., 2012, 134,
878; (b) W. Fu, F. Xu, Y. Fu, C. Xu, S. Li and D. Zou, Eur. J. Org.
Chem., 2014, 2014, 709; (c) L. Li, M. Deng, S.-C. Zheng, Y.-P.
Xiong, B. Tan and X.-Y. Liu, Org. Lett., 2014, 16, 504; (d) B.
Chang, Y. Su, D. Huang, K.-H. Wang, W. Zhang, Y. Shi, X.
Zhang and Y. Hu, J. Org. Chem., 2018, 83, 4365.
Selected examples using CF3SO2Na and CF3SO2Cl, (a) F. Yang,
P. Klumphu, Y.-M. Liang and B. H. Lipshutz, Chem. Commun.,
2014, 50, 936; (b) W.-P. Mai, J.-T. Wang, L.-R. Yang, J.-W.
Yuan, Y.-M. Xiao, P. Mao and L.-B. Qu, Org. Lett., 2014, 16,
204; (c) L. Zhang, Z. Li and Z.-Q. Liu, Org. Lett., 2014, 16,
3688; (d) L. Shi, X. Yang, Y. Wang, H. Yang and H. Fu, Adv.
Synth. Catal., 2014, 356, 1021; (e) W. Wei, J. Wen, D. Yang, X.
Liu, M. Guo, R. Dong and H. Wang, J. Org. Chem., 2014, 79,
4225; (f) Y.-Y. Jiang, G.-Y. Dou, K. Xu and C.-C. Zeng, Org.
Chem. Front., 2018, 5, 2573; (g) L. Tang, Z. Yang, X. Chang, J.
Jiao, X. Ma, W. Rao, Q. Zhou and L. Zheng, Org. Lett., 2018,
20, 6520; (h) D. Liang, Q. Dong, P. Xu, Y. Dong, W. Li and Y.
Ma, J. Org. Chem., 2018, 83, 11978; (i) X.-J. Tang, C. S.
Thomoson and W. R. Dolbier Jr, Org. Lett., 2014, 16, 4594; (j)
C. Liu, W. Zhao, Y. Huang, H. Wang and B. Zhang,
Tetrahedron. 2015. 71. 4344.
5
6
7
Example using TfNHNHBoc, J.-Y. Guo, R.-X. Wu, J.-K. Jin and
S.-K. Tian, Org. Lett., 2016, 18, 3850.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins