Regioselective C-H Trifluoromethylation of Aromatic Compounds by Inclusion in Cyclodextrins

Article abstract of DOI:10.1021/acs.orglett.1c01259

A regioselective radical C-H trifluoromethylation of aromatic compounds was developed using cyclodextrins (CDs) as additives. The C-H trifluoromethylation proceeded with high regioselectivity to afford the product in good yield, even on the gram scale. In the presence of CDs, some substrates underwent a single trifluoromethylation selectively, whereas mixtures of single- and double-trifluoromethylated products were formed in the absence of the CD. 1H NMR experiments indicated that the regioselectivity was controlled by the inclusion of a substrate inside the CD cavity.

Full text of DOI:10.1021/acs.orglett.1c01259

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Letter
Regioselective C−H Trifluoromethylation of Aromatic Compounds
by Inclusion in Cyclodextrins
Xu Lu, Ryohei Kawazu, Jizhou Song, Yusuke Yoshigoe, Takeru Torigoe, and Yoichiro Kuninobu*
Cite This: Org. Lett. 2021, 23, 4327−4331
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ABSTRACT: A regioselective radical C−H trifluoromethylation of aromatic
compounds was developed using cyclodextrins (CDs) as additives. The C−H
trifluoromethylation proceeded with high regioselectivity to afford the product in
good yield, even on the gram scale. In the presence of CDs, some substrates
underwent a single trifluoromethylation selectively, whereas mixtures of single- and
1
double-trifluoromethylated products were formed in the absence of the CD. H
NMR experiments indicated that the regioselectivity was controlled by the
inclusion of a substrate inside the CD cavity.
luorinated functional groups, including the trifluoromethyl
(CF3) group, are among the most important functional
F
groups in drugs, agrochemicals, and organic functional
materials. The introduction of the CF3 group(s) results in a
dramatic improvement in the molecular properties of the
compound, such as lipophilicity, metabolic stability, and
bioavailability.1 The ideal method for introducing the CF3
group is direct C−H trifluoromethylation. Radical C−H
trifluoromethylation of five-membered heteroaromatic com-
pounds proceeds regioselectively to afford only single
products.2 On the other hand, radical C−H trifluoromethyla-
tion of six-membered heteroaromatic compounds proceeds at
almost all possible reaction sites, and mixtures of regioisomers
are formed.2c,d We succeeded in the regioselective C−H
trifluoromethylation and related reactions of six-membered
heteroaromatic compounds using CF3 and related anion
sources.3,4 However, regioselective C−H trifluoromethylation
of aromatic compounds is more difficult than that of
heteroaromatic substrates.
The CF3 radical has generally been used in the C−H
trifluoromethylation of aromatic compounds. Trifluoromethy-
lation proceeds at various reaction sites to give mixtures of
regioisomers (Figure 1a).2a,n,5 Although there have been
several reports on ortho-selective C−H trifluoromethylation
of aromatic substrates using a directing group to control the
regioselectivity, there are some drawbacks: (1) the reaction site
is limited to the ortho-position of the substrates, and (2) it is
difficult to remove the directing groups from the products after
the reaction (Figure 1b).6
Figure 1. Several examples of C−H trifluoromethylation of aromatic
compounds.
We hypothesized that regioselective C−H trifluoromethyla-
tion of aromatic compounds could be realized by protecting
several reaction sites using a cyclic molecule as an additive
(Figure 1c). In this reaction system, aromatic molecules are
included inside the cavity of the cyclic molecule, which
protects some potential reaction sites.7 Herein, we report the
regioselective C−H trifluoromethylation of multisubstituted
Received: April 13, 2021
Published: May 14, 2021
https://doi.org/10.1021/acs.orglett.1c01259
© 2021 American Chemical Society
Org. Lett. 2021, 23, 4327−4331
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a
Table 1. Investigation of Cyclodextrins and Several
Transition Metal Salts
Scheme 1. Substrate Scope: Control of Regioselectivity
a
entry
additive
metal salt
none
none
none
none
MnCl2
FeCl3
Fe(NO3)3
CoCl2
NiCl2·6H2O
CuCl2
Cu(OTf)2
yield/% (3a/3a′)
1
2
3
4
5
6
7
8
9
none
56 (2.2)
55 (1.6)
61 (5.1)
48 (4.4)
38 (6.0)
99 (19)
91 (10)
46 (4.8)
77 (4.2)
92 (8.1)
93 (6.7)
α-CD
β-CD
γ-CD
β-CD
β-CD
β-CD
β-CD
β-CD
β-CD
β-CD
10
11
a
Yield was determined by 19F NMR using 2,2,2-trifluoroethanol as an
internal standard. The ratio between trifluoromethylated product 3a
and its regioisomer 3a′ (3a/3a′) is described in parentheses.
aromatic compounds using cyclodextrins (CDs) as the cyclic
molecules, even on the gram scale. Single trifluoromethylation
of the substrates proceeded selectively in the presence of the
CD, whereas both single and double trifluoromethylation
1
occurred in the absence of the CD. H NMR experiments
suggested the inclusion of aromatic substrates inside the CD
cavity.
The difficulty in promoting regioselective radical C−H
trifluoromethylation of aromatic compounds stems from the
high reactivity of the CF3 radical and the occurrence of the
reaction at various sites. Treatment of aromatic substrate 1a
with NaO2SCF3 (2) and tBuOOH in the presence of
Cu(OTf)2 as a catalyst in H2O afforded a mixture of
trifluoromethylated product 3a and its regioisomer 3a′ in
56% combined yield (3a/3a′ = 2.2) (Table 1, entry 1).8 We
considered the use of cyclic compounds as additives to protect
some potential reaction sites of 1a sterically and thus promote
regioselective C−H trifluoromethylation. Although several
cyclic compounds such as calixarenes and pillararenes could
be considered as candidates, C−H trifluoromethylation may
also occur at the aromatic rings of these compounds.
Therefore, we selected CDs because they are inexpensive
and highly water-soluble and do not contain any aromatic
rings. We screened α-, β-, and γ-CDs (Table 1, entries 2−4)
and achieved the best results with β-CD; that is, the ratio of
trifluoromethylated product (3a/3a′) was improved to 5.1
(Table 1, entry 3). These results clearly showed that the size of
the cyclic compound is important for controlling the
regioselectivity. Next, several first-row transition metal salts
were screened (Table 1, entries 5−11). In several entries, the
yield of (3a + 3a′) and the ratio (3a/3a′) were improved, and
the best result was obtained when using a catalytic amount of
a
Yield was determined by 19F NMR using 2,2,2-trifluoroethanol as an
internal standard. The ratio between trifluoromethylated product 3a
and its regioisomer(s) 3a′ (3a/3a′) is described in parentheses. mix =
b
c
complex mixture. Solvent: H2O:MeCN (5/1). With α-cyclodextrin.
d
e
f
With β-cyclodextrin. With γ-cyclodextrin. Without cyclodextrin.
g
Catalyst: Cu(OTf)2 instead of FeCl3. Solvent: aqueous urea (0.10
M).10 Catalyst: Cu(OTf)2 instead of FeCl3. Catalyst: Cu(OTf)2
h
i
instead of FeCl3. Solvent: H2O:MeCN (5/1).
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a
Scheme 2. Substrate Scope: Single Trifluoromethylation
a
Yield was determined by 19F NMR using 2,2,2-trifluoroethanol as an
internal standard. The ratio between single trifluoromethylated
product 3 and double trifluoromethylated product(s) 4 (3/4) is
b
c
described in parentheses. With β-cyclodextrin. Without β-cyclo-
1
d
Figure 2. Partial H NMR spectrum of (a) 4-chlorophenol (0.010
mmol/mL in D2O) and (b) 4-chlorophenol and α-CD (0.010 mmol/
mL in D2O).
dextrin. Catalyst: Cu(OTf)2 instead of FeCl3. Solvent: H2O:MeCN
(5/1).
Scheme 3. Gram-Scale Synthesis of 3a
a
The ratio between trifluoromethylated product 3a and its
regioisomer 3a′ (3a/3a′) is described in parentheses.
Figure 3. Partial 1H NMR spectrum of (a) α-CD (0.010 mmol/mL in
D2O) and (b) α-CD and 4-chlorophenol (0.010 mmol/mL in D2O).
FeCl3 (Table 1, entry 6). Therefore, we performed the
subsequent experiments using FeCl3 as the catalyst.
We then investigated the substrate scope of the aromatic
compounds (Scheme 1). The suitable size of cyclodextrins
existed depending on the size of substrates. The general trend
was as follows: monosubstituted substrates, α-CD; disubsti-
tuted substrates, α- or β-CD; and trisubstituted substrates, β-
or γ-CD. In all cases, the selectivity of the major products was
improved dramatically when using CDs, and regioselective
trifluoromethylation proceeded with good functional group
tolerance. The yields of the trifluoromethylated products
increased in several cases, probably owing to the improved
solubility of the substrates.
The regioselectivity of trifluoromethylated anisole 3b was
improved by the addition of α-CD, and ortho-trifluoromethy-
lated product 3b was obtained as the major product.9 In the
case of 1,2- and 1,4-disubstituted aromatic compounds, C−H
trifluoromethylation proceeded regioselectively when using α-
or β-CD, and the corresponding trifluoromethylated aromatic
compounds 3c−3h were obtained in moderate to excellent
yields with high regioselectivity. C−H trifluoromethylation of
1,3,5- and 1,2,4-trisubstituted aromatic compounds also
proceeded regioselectively in the presence of β- or γ-CD,
and trifluoromethylated compounds 3i−3r were obtained in
moderate to excellent yields. The regioselectivity was not
improved under the reaction conditions using pyridin-3-yl
isobutyrate, 2-acetylfuran, and 2-formylpyrrole as substrates.
Several substrates afforded a mixture of mono- and
ditrifluoromethylated products 3 and 4 in the absence of
CDs (Scheme 2). On the other hand, the ratio of
monotrifluoromethylated products 3s−3u increased dramati-
cally when β-CD was used, and good product yields (63%−
94%) and high monoselectivity were achieved. These results
indicated that the CD protected the second reaction site by
inclusion of the substrates.
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Trifluoromethylation proceeded in excellent yield with high
regioselectivity, even on the gram scale (Scheme 3). Treatment
of a mixture of 1.00 g of 1a and β-CD in H2O with 2,
tBuOOH, and a catalytic amount of FeCl3 at 25 °C gave 1.21 g
of trifluoromethylated product 3a in 90% yield (3a/3a′ = 16).
To confirm the inclusion of aromatic substrates inside the
cavity of the CD in water, 1H NMR experiments were
conducted in D2O at the same concentration as the reaction
mixture (Figures 2 and 3). Proton signals of the aromatic
region of 4-chlorophenol (1e) were downfield-shifted by the
addition of α-CD (Figure 2).11 In addition, a change in the
chemical shifts of the proton signals of α-CD was observed
upon the addition of 1e (Figure 3).11 These results clearly
suggested that 1e was included inside the cavity of α-CD in
water.
Yusuke Yoshigoe − Institute for Materials Chemistry and
Engineering, Kyushu University, Kasuga-shi, Fukuoka 816-
8580, Japan
Takeru Torigoe − Institute for Materials Chemistry and
Engineering and Department of Molecular and Material
Sciences, Interdisciplinary Graduate School of Engineering
Sciences, Kyushu University, Kasuga-shi, Fukuoka 816-8580,
Japan; orcid.org/0000-0002-4902-1596
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c01259
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
In summary, we have successfully developed a regioselective
C−H trifluoromethylation of aromatic compounds using CDs
as additives. The selectivity of the major products was
improved dramatically in the presence of the CDs, and
regioselective trifluoromethylation proceeded with good func-
tional group tolerance, even on the gram scale. The general
trend for the suitability of the CDs was as follows:
monosubstituted substrates, α-CD; disubstituted substrates,
α- or β-CD; and trisubstituted substrates, β- or γ-CD.
Monotrifluoromethylated products were obtained selectively
in the presence of the CD, whereas several aromatic substrates
gave mixtures of mono- and ditrifluoromethylated products.
This work was supported in part by JSPS KAKENHI Grant
Numbers JP 17H03016, 18H04656, and 20H04824, Takeda
Science Foundation, The Mitsubishi Foundation, and Yamada
Science Foundation.
REFERENCES
■
(1) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Fluorine in
Medicinal Chemistry. Chem. Soc. Rev. 2008, 37, 320−330.
(2) (a) Nagib, D. A.; MacMillan, D. W. C. Trifluoromethylation of
Arenes and Heteroarenes by Means of Photoredox Catalysis. Nature
2011, 480, 224−228. (b) Ye, Y.; Lee, S. H.; Sanford, M. S. Silver-
Mediated Trifluoromethylation of Arenes Using TMSCF3. Org. Lett.
2011, 13, 5464−5467. (c) Ji, Y.; Brueckl, T.; Baxter, R. D.; Fujiwara,
Y.; Seiple, I. B.; Su, S.; Blackmond, D. G.; Baran, P. S. Innate C−H
Trifluoromethylation of Heterocycles. Proc. Natl. Acad. Sci. U. S. A.
2011, 108, 14411−14415. (d) Fujiwara, Y.; Dixon, J. A.; O’Hara, F.;
Funder, E. D.; Dixon, D. D.; Rodriguez, R. A.; Baxter, R. D.; Herlé, B.;
Sach, N.; Collins, M. R.; Ishihara, Y.; Baran, P. S. Practical and Innate
Carbon−Hydrogen Functionalization of Heterocycles. Nature 2012,
492, 95−99. (e) Chu, L.; Qing, F.-L. Copper-Catalyzed Direct C−H
Oxidative Trifluoromethylation of Heteroarenes. J. Am. Chem. Soc.
2012, 134, 1298−1304. (f) Iqbal, N.; Choi, S.; Ko, E.; Cho, E. J.
Trifluoromethylation of Heterocycles via Visible Light Photoredox
Catalysis. Tetrahedron Lett. 2012, 53, 2005−2008. (g) Seo, S.; Taylor,
J. B.; Greaney, M. F. Silver-Catalysed Trifluoromethylation of Arenes
at Room Temperature. Chem. Commun. 2013, 49, 6385−6387.
(h) Pitre, S. P.; McTiernan, C. D.; Ismaili, H.; Scaiano, J. C. Metal-
Free Photocatalytic Radical Trifluoromethylation Utilizing Methylene
Blue and Visible Light Irradiation. ACS Catal. 2014, 4, 2530−2535.
(i) Choi, W. J.; Choi, S.; Ohkubo, K.; Fukuzumi, S.; Cho, E. J.; You,
Y. Mechanisms and Applications of Cyclometalated Pt(II) Complexes
in Photoredox Catalytic Trifluoromethylation. Chem. Sci. 2015, 6,
1454−1464. (j) Beatty, J. W.; Douglas, J. J.; Miller, R.; McAtee, R. C.;
Cole, K. P.; Stephenson, C. R. J. Photochemical Perfluoroalkylation
with Pyridine N-Oxides: Mechanistic Insights and Performance on a
Kilogram Scale. Chem. 2016, 1, 456−472. (k) Natte, K.; Jagadeesh, R.
V.; He, L.; Rabeah, J.; Chen, J.; Taeschler, C.; Ellinger, S.; Zaragoza,
F.; Neumann, H.; Brîckner, A.; Beller, M. Palladium-Catalyzed
Trifluoromethylation of (Hetero)Arenes with CF3Br. Angew. Chem.,
Int. Ed. 2016, 55, 2782−2786. (l) Wu, Y.; Zhang, H.-R.; Jin, R.-X.;
Lan, Q.; Wang, X.-S. Nickel-Catalyzed C−H Trifluoromethylation of
Electron-Rich Heteroarenes. Adv. Synth. Catal. 2016, 358, 3528−
3533. (m) Du, Y.; Pearson, R. M.; Lim, C.-H.; Sartor, S. M.; Ryan, M.
D.; Yang, H.; Damrauer, N. H.; Miyake, G. M. Strongly Reducing,
Visible-Light Organic Photoredox Catalysts as Sustainable Alter-
natives to Precious Metals. Chem. - Eur. J. 2017, 23, 10962−10968.
(n) Liu, P.; Liu, W.; Li, C.-J. Catalyst-Free and Redox-Neutral Innate
Trifluoromethylation and Alkylation of Aromatics Enabled by Light. J.
Am. Chem. Soc. 2017, 139, 14315−14321. (o) Harris, C. F.; Kuehner,
C. S.; Bacsa, J.; Soper, J. D. Photoinduced Cobalt(III)-Trifluor-
omethyl Bond Activation Enables Arene C−H Trifluoromethylation.
1
The results of the H NMR experiments indicated that the
aromatic substrate was present inside the cavity of the CD in
water. The investigation of more detailed mechanistic studies is
underway in our group. The use of cyclic compounds such as
CDs is expected to be a useful and efficient strategy to control
the regioselectivity in C−H transformations.12
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c01259.
General experimental procedure and characterization
data for products (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Yoichiro Kuninobu − Institute for Materials Chemistry and
Engineering and Department of Molecular and Material
Sciences, Interdisciplinary Graduate School of Engineering
Sciences, Kyushu University, Kasuga-shi, Fukuoka 816-8580,
Japan; orcid.org/0000-0002-8679-9487;
Email: kuninobu@cm.kyushu-u.ac.jp
Authors
Xu Lu − Department of Molecular and Material Sciences,
Interdisciplinary Graduate School of Engineering Sciences,
Kyushu University, Kasuga-shi, Fukuoka 816-8580, Japan
Ryohei Kawazu − Department of Molecular and Material
Sciences, Interdisciplinary Graduate School of Engineering
Sciences, Kyushu University, Kasuga-shi, Fukuoka 816-8580,
Japan
Jizhou Song − Department of Molecular and Material
Sciences, Interdisciplinary Graduate School of Engineering
Sciences, Kyushu University, Kasuga-shi, Fukuoka 816-8580,
Japan
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pubs.acs.org/OrgLett
Letter
Angew. Chem., Int. Ed. 2018, 57, 1311−1315. (p) Meucci, E. A.;
Nguyen, S. N.; Camasso, N. M.; Chong, E.; Ariafard, A.; Canty, A. J.;
Sanford, M. S. Nickel(IV)-Catalyzed C−H Trifluoromethylation of
(Hetero)arenes. J. Am. Chem. Soc. 2019, 141, 12872−12879.
(3) (a) Nishida, T.; Ida, H.; Kuninobu, Y.; Kanai, M. Regioselective
Trifluoromethylation of N-Heteroaromatic Compounds Using
Trifluoromethyldifluoroborane Activator. Nat. Commun. 2014, 5,
3387. (b) Kuninobu, Y.; Nagase, M.; Kanai, M. Benzylic C(sp3)−H
Perfluoroalkylation of Six-Membered Heteroaromatic Compounds.
Angew. Chem., Int. Ed. 2015, 54, 10263−10266. (c) Nagase, M.;
Kuninobu, Y.; Kanai, M. 4-Position-Selective C−H Perfluoroalkyla-
tion and Perfluoroarylation of Six-Membered Heteroaromatic
Compounds. J. Am. Chem. Soc. 2016, 138, 6103−6106. (d) Shirai,
T.; Kanai, M.; Kuninobu, Y. 2-Position-Selective C−H Perfluor-
oalkylation of Quinoline Derivatives. Org. Lett. 2018, 20, 1593−1596.
(4) For a 2-position-selective C−H trifluoromethylthiolation of six-
membered heteroaromatic compounds, see: Muta, R.; Torigoe, T.;
Kuninobu, Y. 2-Position-Selective Trifluoromethylthiolation of Six-
Membered Heteroaromatic Compounds. Org. Lett. 2019, 21, 4289−
4292.
Solubilization of Cyclodextrins for Analytical Application. Anal. Chem.
1989, 61, 275−279.
(11) The similar change in the chemical shifts was reported in the
̆
case of inclusion of vanillin inside the cavity of β-CD. See: Pîrnau, A.;
Bogdan, N.; Floare, C. G. NMR spectroscopic characterization of β-
cyclodextrin inclusion complex with vanillin. J. Phys. Conf. Ser. 2009,
182, 012013.
(12) A previous version of this manuscript has been deposited on a
preprint server: DOI: 10.26434/chemrxiv.14173655.v1.
(5) (a) Ye, Y.; Lee, S. H.; Sanford, M. S. Silver-Mediated
Trifluoromethylation of Arenes Using TMSCF3. Org. Lett. 2011, 13,
5464−5467. (b) Mejia, E.; Togni, A. Rhenium-Catalyzed Trifluor-
omethylation of Arenes and Heteroarenes by Hypervalent Iodine
Reagents. ACS Catal. 2012, 2, 521−527. (c) Wu, X.; Chu, L.; Qing,
F.-L. PhI(OAc)2-mediated oxidative trifluoromethylation of arenes
with CF3SiMe3 under metal-free conditions. Tetrahedron Lett. 2013,
54, 249−251. (d) Cui, L.; Matusaki, Y.; Tada, N.; Miura, T.; Uno, B.;
Itoh, A. Metal-Free Direct C−H Perfluoroalkylation of Arenes and
Heteroarenes Using a Photoredox Organocatalyst. Adv. Synth. Catal.
2013, 355, 2203−2207. (e) Natte, K.; Jagadeesh, R. V.; He, L.;
Rabeah, J.; Chen, J.; Taeschler, C.; Ellinger, S.; Zaragoza, F.;
Neumann, H.; Bruckner, A.; Beller, M. Palladium-Catalyzed
̈
Trifluoromethylation of (Hetero)Arenes with CH3Br. Angew. Chem.,
Int. Ed. 2016, 55, 2782−2786. (f) Li, L.; Mu, X.; Liu, W.; Wang, Y.;
Mi, Z.; Li, C.-J. Simple and Clean Photoinduced Aromatic
Trifluoromethylation Reaction. J. Am. Chem. Soc. 2016, 138, 5809−
5812. (g) Chang, B.; Shao, H.; Yan, P.; Qiu, W.; Weng, Z.; Yuan, R.
Quinone-Mediated Trifluoromethylation of Arenes and Heteroarenes
with Visible Light. ACS Sustainable Chem. Eng. 2017, 5, 334−341.
(h) Du, Y.; Pearson, R. M.; Lim, C.-H.; Sartor, S. M.; Ryan, M. D.;
Yang, H.; Damrauer, N. H.; Miyake, G. M. Strongly Reducing,
Visible-Light Organic Photoredox Catalysts as Sustainable Alter-
natives to Precious Metals. Chem. - Eur. J. 2017, 23, 10962−10968.
(i) Yang, B.; Yu, D.; Xu, X.-H.; Qing, F. L. Visible-Light Photoredox
Decarboxylation of Perfluoroarene Iodine(III) Trifluoroacetates for
C−H Trifluoromethylation of (Hetero)arenes. ACS Catal. 2018, 8,
2839−2843. For a review, see: (j) Studer, A. A “Renaissance” in
Radical Trifluoromethylation. Angew. Chem., Int. Ed. 2012, 51, 8950−
8958. (k) Egami, H.; Ito, Y.; Ide, T.; Masuda, S.; Hamashima, Y.
Simple Photo-Induced Trifluoromethylation of Aromatic Rings.
Synthesis 2018, 50, 2948−2953.
(6) Wang, X.; Truesdale, L.; Yu, J.-Q. Pd(II)-Catalyzed ortho-
Trifluoromethylation of Arenes Using TFA as a Promoter. J. Am.
Chem. Soc. 2010, 132, 3648−3649.
(7) For pioneering examples of regioselective reactions using cyclic
compounds as additives, see: (a) Breslow, R.; Campbell, P. Selective
Aromatic Substitution within a Cyclodextrin Mixed Complex. J. Am.
Chem. Soc. 1969, 91, 3085−3085. (b) Komiyama, M.; Hirai, H.
Selective Syntheses Using Cyclodextrins as Catalysts. 2. Para-Oriented
Carboxylation of Phenols. J. Am. Chem. Soc. 1984, 106, 174−178.
(8) Langlois, B. R.; Laurent, E.; Roidot, N. Trifluoromethylation of
Aromatic Compounds with Sodium Trifluoromethanesulfinate under
oxidative conditions. Tetrahedron Lett. 1991, 32, 7525−7528.
(9) 3b was formed as a single product in water solvent, whereas the
yield of 3b was low (18%).
(10) The solubility of β-CD in H2O is improved by the addition of
urea. See: Pharr, D. Y.; Fu, Z. S.; Smith, T. K.; Hinze, W. L.
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