TfOH-Promoted Transition-Metal-Free Cascade Trifluoroethylation/Cyclization of Organic Isothiocyanates by Phenyl(2,2,2-trifluoroethyl)iodonium Triflate

Article abstract of DOI:10.1021/acs.orglett.8b02793

An efficient and transition-metal-free method for the synthesis of the structurally diversified trifluoroethylthiol phenanthridines and 3,4-dihydroisoquinolines is described. Various 2-isothiocyanobiaryls and aryl alkyl isothiocyanates reacted with phenyl(2,2,2-trifluoroethyl)iodonium triflate in CH₂Cl₂ in the presence of trifluoromethanesulfonic acid at 40 °C to form the corresponding trifluoroethylation/cyclization products in good to quantitative yields. This work represents the first construction of trifluoroethylthiol phenanthridine and isoquinoline derivatives from isothiocyanates in the absence of transition-metal catalysts by a one-pot procedure.

Full text of DOI:10.1021/acs.orglett.8b02793

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
TfOH-Promoted Transition-Metal-Free Cascade Trifluoroethylation/
Cyclization of Organic Isothiocyanates by Phenyl(2,2,2-
trifluoroethyl)iodonium Triflate
Cheng-Long Zhao,† Qiu-Yan Han,† and Cheng-Pan Zhang*,†,‡
†School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan 430070,
China
‡Department of Chemistry, College of Basic Medicine, Army Medical University, Shapingba, Chongqing 400038, China
S
* Supporting Information
ABSTRACT: An efficient and transition-metal-free method for the synthesis of the structurally diversified trifluoroethylthiol
phenanthridines and 3,4-dihydroisoquinolines is described. Various 2-isothiocyanobiaryls and aryl alkyl isothiocyanates reacted
with phenyl(2,2,2-trifluoroethyl)iodonium triflate in CH2Cl2 in the presence of trifluoromethanesulfonic acid at 40 °C to form
the corresponding trifluoroethylation/cyclization products in good to quantitative yields. This work represents the first
construction of trifluoroethylthiol phenanthridine and isoquinoline derivatives from isothiocyanates in the absence of transition-
metal catalysts by a one-pot procedure.
he installation of bioisosteric fluorine or fluorine-
containing groups into bioactive molecules can dramat-
sources.9 Notably, the catalyst-free reactions of [ArICH2CF3]X
with amines, peptides, alcohols, phenols, thiols, sulfides,
carbohydrates, thioglycosides, fatty acids, phosphines, and
electron-rich arenes have supplied a large number of
trifluoroethylated bioactive molecules.7,8 These studies dem-
onstrate that [ArICH2CF3]X have much more powerful
trifluoroethylation reactivity than other electrophilic
CF3CH2-transfer reagents.
T
ically change their physiochemical and pharmacokinetic
properties.1 Given the benefits invoked by fluorine, a great
variety of fluorine-containing compounds have been utilized in
the search for new pharmaceuticals and agrochemicals.1,2
Among these entities, trifluoroethylated molecules are of
particular interest as a growing number of CF3CH2 compounds
with potent biological activities have emerged in drug
discovery.3 Thus, the development of effective and practical
methods for the synthesis of trifluoroethylated compounds is
of vital importance.3 At present, the transition-metal-catalyzed
or -free trifluoroethylation of a wide range of organic scaffolds,
such as arylboronic acids or esters, aryl iodides, arene, alkynes,
alkenes, anilines, and aryl Grignard reagents, has been
documented.4−7 Reagents used in these reactions include
CF3CH2I, CF3CHN2, CF3CHCl2, (CF3CH2SO2)2Zn,
CF3 CH2 SO2 Na, CF3 CH2 SO2 Cl, CF3 CO2 H, and
[ArICH2CF3]X (Ar = C6H5, 2,4,6-Me3C6H2; X = OTf,
NTf2).4−7 Aryl(2,2,2-trifluoroethyl)iodonium salts
([ArICH2CF3]X), first synthesized by Umemoto, have proven
to be the highly efficient electrophilic trifluoroethylation
reagents for heteroatom and carbon nucleophiles under mild
conditions.7,8 The palladium-catalyzed reactions of aryl(2,2,2-
trifluoroethyl)iodonium triflates with arylboronic acids via
Suzuki−Miyaura cross-coupling or with anilides, aromatic
amides, and indoles via C−H activation have represented the
state-of-the-art transition-metal-catalyzed trifluoroethylation
approaches using [ArICH2CF3][OTf] as the CF3CH2
On the other hand, phenanthridine and isoquinoline
derivatives are privileged compounds found in natural
products, with many of them showing antitumor, antiviral,
antibacterial activities, and/or optoelectronic properties.10,11
A
variety of 6-fluoroalkylated phenanthridines have been
constructed by the radical insertion reactions of numerous
fluoroalkylation reagents into 2-isocyanobiaryls.10c However,
synthesis of fluorinated phenanthridines from 2-isothiocyano-
biaryls via direct fluoroalkylation at the isothiocyano (NCS)
moieties has not been realized. Only a few examples of
preparing nonfluorinated phenanthridines by a copper-
catalyzed tandem arylation/cyclization of 2-biaryl isothiocya-
nates with diaryliodonium salts (at 100 °C) and a Mn(II)-
promoted tandem phosphorylation/cyclization reaction of 2-
biaryl isothiocyanates with phosphine oxides (at 110 °C) have
been reported.12 Although preparation of isoquinoline
derivatives by intramolecular cyclization of aryl alkyl
Received: August 31, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b02793
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Letter
̈
isothiocyanates in the presence of copper catalysts or Bronsted
acids has been explored, the fluorinated versions of these
conversions have never been known.13 Since aryl(2,2,2-
trifluoroethyl)iodonium salts are powerful electrophilic tri-
fluoroethylation reagents toward a variety of nucleophiles,7,8
we wondered whether [ArICH2CF3][OTf] would trigger a
transition-metal-free cascade 2,2,2-trifluoroethylation/cycliza-
tion of organic isothiocyanates. It is a challenging task to
activate isothiocyano groups by iodonium salts without
transition-metal catalysts because the NCS segments in 2-
isothiocyanobiaryls have much poorer nucleophilicity.12
Indeed, reaction of 2-isothiocyanato-1,1′-biphenyl (1a) with
phenyl(2,2,2-trifluoroethyl)iodonium triflate (2a, 2 equiv) in
CH3CN, ClCH2CH2Cl, CH2Cl2, toluene, or 1,4-dioxane at
room temperature or 80 °C for 15 or 24 h gave none or a trace
amount (<1%) of 6-[(2,2,2-trifluoroethyl)thio]phenanthridine
(3a) (Table S2-1). Addition of bases such as K3PO4, KF,
CH3CO2K, and HCO2Na to the reaction mixture of 1a and 2a
in CH3CN at 80 °C afforded none or <1% of 3a as well.
Significantly, if the reaction of 1a and 2a was carried out in
CH3CN in the presence of 1.5 equiv of TfOH at room
temperature for 15 h, 3% of 3a was formed. Furthermore, if the
same reaction with TfOH was run in CH2Cl2 or ClCH2CH2Cl,
3a was obtained in 72% or 52% yields, respectively. These
results suggest that the superacid TfOH could efficiently
promote the trifluoroethylation/cyclization reaction of 1a. The
reaction was neither air- nor moisture-sensitive as the mixtures
of 1a, 2a, and TfOH treated under a nitrogen atmosphere or
an ambient atmosphere provided 3a in comparable yields
(Table S2-2). Finally, treatment of 1a with 2a (2 equiv) in
CH2Cl2 in the presence of TfOH (3 equiv) at room
temperature for 24 h or at 40 °C for 6 h gave 96% or 97%
of 3a (Table S2-2). Other strong acids such as CF3CO2H,
concentrated H2SO4, CH3SO3H, and Tf2NH could also
facilitate the production of 3a (2−50% yield) but showed
much less efficiency compared to TfOH (Table S2-3).
Moreover, the similar reactions using mesityl(2,2,2-
trifluoroethyl)iodonium triflate (2b) as a CF3CH2 source
instead of 2a provided 3a in moderate yields, indicating
relatively poor reactivity of 2b in this transformation (Table
S2-5).
With the optimized conditions in hand (1, 2a (2 equiv),
TfOH (3 equiv), CH2Cl2, rt/24 h or 40 °C/6 h), the substrate
scope of this trifluoroethylation/cyclization reaction was
examined (Scheme 1). To our delight, various 2-isothiocya-
nobiaryls 1b−s bearing either electron-donating or -with-
drawing groups on the aryl rings were all smoothly converted
to furnish the corresponding trifluoroethylthiol phenanthridine
derivatives 3b−s in 39% to >99% yields. The electronic nature
and the position of the substituents on the aryl rings had a
considerable influence on the reaction. The electron-with-
drawing groups (e.g., fluoro, chloro, trifluoromethyl, ester,
nitro, cyano) on either of the aromatic rings of 2-
isothiocyanobiaryls slowed down the trifluoroethylation/
cyclization processes, which afforded 39−73% yields of the
desired products 3e, 3f, 3h−k, 3r, and 3s. Prolonging the
reaction time could somewhat improve the yields of these
derivatives (e.g., 3f, 3i−k). In addition, reaction of 2-
isothiocyanato-4′-methyl-1,1′-biphenyl (1b) or 2-isothiocya-
nato-2′-methyl-1,1′-biphenyl (1m) with 2a under the standard
conditions provided 3b or 3m, respectively, as the sole
product, in quantitative yield, while the same reaction of 2-
isothiocyanato-3′-methyl-1,1′-biphenyl (1n) with 2a afforded a
Scheme 1. Transition-Metal-Free Trifluoroethylation/
Cyclization of Aryl Isothiocyanates by [PhICH2CF3][OTf]
a
in the Presence of TfOH
a
Reaction conditions: 1 (0.2 mmol), 2a (0.4 mmol), TfOH (0.6
b
c
d
mmol), CH2Cl2 (2 mL), 40 °C, 6 h. Isolated yields. 12 h. 24 h. 3
days. TfOH (1.2 mmol), 12 h.
e
mixture of 7-methyl-6-[(2,2,2-trifluoroethyl)thio]-
phenanthridine (3n, 24%) and 9-methyl-6-[(2,2,2-
trifluoroethyl)thio]phenanthridine (3n′, 58%). Similar treat-
ment of 5-(2-isothiocyanatophenyl)benzo[d][1,3]dioxole (1l)
with 2a gave 6-[(2,2,2-trifluoroethyl)thio][1,3]dioxolo[4,5-
j]phenanthridine (3l) in 99% yield. Heteroaromatic systems
were also suitable substrates for the reaction. 4-(2-
Isothiocyanatophenyl)dibenzo[b,d]furan (1t), 2-(2-
isothiocyanatophenyl)thiophene (1u), and 3-(2-
isothiocyanatophenyl)thiophene (1v) reacted with 2a under
the standard conditions to form phenanthridine derivatives
3t−v in good yields. Interestingly, reaction of 2,2′-
diisothiocyanato-1,1′-biphenyl (1w) with 2a in the presence
of 6 equiv of TfOH at room temperature for 12 h supplied 10-
isothiocyanato-6-[(2,2,2-trifluoroethyl)thio]phenanthridine
(3w) in 51% yield, with one NCS group transformed and the
other retained. All these combined suggested good compati-
bility and availability of the reaction.
Furthermore, the TfOH-promoted trifluoroethylation/cycli-
zation reaction was applicable to aryl alkyl isothiocyanates (4)
(Scheme 2). Numerous (2-isothiocyanatoethyl)arenes 4b−j
with either electron-donating or slightly electron-withdrawing
groups on the aromatic rings reacted with 2a in the presence of
3 equiv of TfOH at 40 °C for 2 h to furnish the respective
trifluoroethylthiolated 3,4-dihydroisoquinolines in good yields.
The position of the functionalities on the aryl rings had little
influence on the reaction. The para- or meta-substituted (2-
isothiocyanatoethyl)arenes (e.g., 4b, 4d, 4f) reacted mildly to
give the desired products (5b, 5d, 5f) in yields close to those
obtained from the ortho-substituted analogues 4c, 4e, and 4g.
1-Bromo-3-(2-isothiocyanatoethyl)benzene (4f), 4-(2-isothio-
cyanatoethyl)-1,2-dimethoxybenzene (4h), 5-(2-
isothiocyanatoethyl)benzo[d][1,3]dioxole (4i), and 1,2-di-
chloro-4-(2-isothiocyanatoethyl)benzene (4j) reacted specifi-
B
DOI: 10.1021/acs.orglett.8b02793
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Transition-Metal-Free Trifluoroethylation/
Scheme 3. Control Experiments for the Mechanistic Study
Cyclization of Aryl-Alkyl Isothiocyanates by
[PhICH2CF3][OTf] in the Presence of TfOH
a
TfOH and gave 5b in 82% yield. Likewise, intermediate 4b′
without purification reacted with 2a in the same system to
form 5b in 75% yield. These observations implied that 3,4-
dihydroisoquinoline-1(2H)-thione was likely the key inter-
mediate of the reaction of aryl-alkyl isothiocyanate.
a
Reaction conditions: 4 (0.2 mmol), 2a (0.4 mmol), TfOH (0.6
mmol), CH2Cl2 (2 mL), 40 °C, 2 h. Isolated yields.
cally with 2a at both the electron-rich and the least sterically
hindered aromatic carbon sites to produce isoquinolines 5f and
5h−j, showing excellent regioselectivity. Moreover, reaction of
(3-isothiocyanatopropyl)benzene (4l) with 2a and TfOH
under the standard conditions furnished 1-[(2,2,2-
trifluoroethyl)thio]-4,5-dihydro-3H-benzo[c]azepine (5l),
with a seven-membered ring, in 67% yield. Nevertheless, the
similar reactions of (isothiocyanatomethyl)benzene (4k) and
(4-isothiocyanatobutyl)benzene (4m) with 2a at 40 °C gave
complicated mixtures in which the desired products were not
isolated by column chromatography. It should be mentioned
that all fluorinated 3,4-dihydroisoquinoline derivatives synthe-
sized in Scheme 2 tended to decompose when they were
chromatographed on silica gel or aluminum oxide (especially
the former). To obtain good yields of the products, their
purification by the column chromatography on aluminum
oxide should finish as fast as possible.
To shed light on the reaction mechanism, several control
experiments were carried out. Initially, reaction of 1a with
TfOH in CH2Cl2 in the absence of 2a at 40 °C for 6 h
provided phenanthridine-6(5H)-thione (1a′) in 93% yield,
which was determined by the NMR spectroscopy (see Scheme
3 and the Supporting Information (SI)). Subsequently,
treatment of 1a′ with 2a at 40 °C in CH2Cl2 without TfOH
gave 3a in 98% yield. The overall yield of 3a (91%) was
comparable to that (97%) obtained by the one-pot procedure.
Further investigation revealed that the reaction of 1a′ and 2a
proceeded very fast, which could finish within 5 min (see SI).
The acid was neither beneficial nor harmful to the
trifluoroethylation step. Alternatively, the intermediate 1a′
without isolation reacted with 2a in the same mixture to
provide 3a in 83% yield. These results suggest that
phenanthridine-6(5H)-thione might be the key intermediate
of the reaction of 2-isothiocyanobiaryl. In the case of aryl alkyl
isothiocyanate, a similar reaction of 4b with TfOH in the
absence of 2a afforded 7-methyl-3,4-dihydroisoquinoline-
1(2H)-thione (4b′) in 83% yield (see Scheme 3 and the SI).
Then 4b′ reacted with 2a at 40 °C in CH2Cl2 in the absence of
Furthermore, the standard reaction of 1a or 4a with 2,2,2-
trifluoroethyl trifluoromethanesulfonate (TfOCH2CF3) as a
trifluoroethyl source in the presence of TfOH did not form the
desired product. Instead, the corresponding thioamide (1a′
(82%) or 4a′ (63%)) was isolated in the reaction (see Scheme
3 and the SI), indicating that the transformation stopped at the
cyclization step. Additionally, reaction of 1a (or 4b) with
diphenyliodonium salts under the standard conditions
provided very low yields of 1a′ (or 4b′) as well as the
phenylthiolated product and most of the starting material was
recovered (see SI). All these results combined demonstrated a
much higher electrophilic reactivity of phenyl(2,2,2-
trifluoroethyl)iodonium triflate (2a). TfOCH2CF3 and the
diphenyliodonium salts seemed to slightly or seriously suppress
the formation of thioamide as the reactions of 1a/
TfOCH2CF3/TfOH and 1a/[Ph2I][OTf]/TfOH gave lower
yields of 1a′ (82% and 5%) than that of the blank reaction
(93%) (see the SI). Moreover, the higher yield of 3a from the
one-step reaction (97%) compared to that from the two-step
processes (91% and 83% overall yields) suggested that 2a
might play an important synergetic role in the acid-promoted
cyclization of isothiocyanates. The production of 3a from 1a
and 2a in the absence of TfOH, albeit in trace amounts, also
supported that 2a itself could trigger the cyclization of
isothiocyanates (see the SI). Nevertheless, the exact mecha-
nism of this process remained unclear. In addition, the kinetic
isotope effect (kH/kD) of the cyclization step was studied by
the competitive and parallel reactions of 1a and 2-
isothiocyanato-1,1′-biphenyl-2′,3′,4′,5′,6′-d5 (1a-D) with 2a/
TfOH at room temperature for 1 h (see Scheme 3 and the SI).
The reactions gave a kH/kD value of 1.04 or 1.16, implying that
the C−H bond cleavage was not involved in the rate-
determining step.
Based on the above discussions, a plausible reaction
mechanism was proposed for the TfOH-promoted trifluor-
oethylation/cyclization reactions (Scheme 4). First, isothio-
cyanate (1 or 4) is activated by TfOH via protonation of the
nitrogen atom of the NCS group, forming a cation
C
DOI: 10.1021/acs.orglett.8b02793
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Notes
Scheme 4. A Plausible Reaction Mechanism for the TfOH-
Promoted Trifluoroethylation/Cyclization of
Isothiocyanates
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Wuhan University of Technology, the National
Natural Science Foundation of China (21602165), the
“Chutian Scholar” Program from Department of Education
of Hubei Province (China), the “Hundred Talent” Program of
Hubei Province (China), and the Chongqing Research
Program of Basic and Frontier Technology (cstc2017jcy-
jAX0303, cstc2018jcyjAX0106) for financial support.
REFERENCES
intermediate (6). Intramolecular Friedel−Crafts reaction
between the activated NCS moiety and the adjacent aryl ring
gives a cyclohexadienyl cation 7, which is probably the rate-
determining step of the reaction. Then deprotonation of 7 by
the −OTf anion proceeds quickly and affords a stable
thioamide 1′ or 4′. Finally, trifluoroethylation of the thioamide
intermediate 1′ or 4′ at the sulfur center by 2a followed by
aromatization furnishes the final product 3 or 5 within a few
minutes. Since there was no N-trifluoroethylated product
observed, the reaction at the nitrogen site could be excluded.
In conclusion, we have developed a convenient and efficient
method for the one-pot synthesis of trifluoroethylthiol
phenanthridines and 3,4-dihydroisoquinolines under transi-
tion-metal-free conditions. The cascade trifluoroethylation/
cyclization of 2-isothiocyanobiaryls and aryl alkyl isothiocya-
nates (1 and 4) with phenyl(2,2,2-trifluoroethyl)iodonium
triflate (2a) in CH2Cl2 in the presence of TfOH at 40 °C
afforded a variety of trifluoroethylthiolated phenanthridine and
3,4-dihydroisoquinoline derivatives (3 and 5) in good to
quantitative yields. The reactions were dramatically promoted
by TfOH; its absence led to only trace amounts of the desired
products. The control experiments suggested that phenan-
thridine-6(5H)-thiones and 3,4-dihydroisoquinoline-1(2H)-
thiones might be the key intermediates of the reactions,
respectively, when using TfOH as a promotor. This protocol is
the first report for the production of fluorinated phenan-
thridine and isoquinoline derivatives from isothiocyanates
without using transition metals. The reactions verified again
the powerful electrophilic trifluoroethylation reactivity of
aryl(2,2,2-trifluoroethyl)iodonium salts. Application of these
promising reagents in new trifluoroethylation reactions is
currently underway in our laboratory.
■
(1) (a) Ojima, I. Fluorine in Medicinal Chemistry and Chemical
Biology; Wiley-Blackwell, 2009. (b) Prakash Reddy, V. Organofluorine
Compounds in Biology and Medicine; Elsevier, 2015.
(2) (a) Zhou, Y.; Wang, J.; Gu, Z.; Wang, S.; Zhu, W.; Acena, J. L.;
̃
Soloshonok, V. A.; Izawa, K.; Liu, H. Chem. Rev. 2016, 116, 422.
(b) Yerien, D. E.; Bonesi, S.; Postigo, A. Org. Biomol. Chem. 2016, 14,
8398. (c) Cavaliere, A.; Probst, K. C.; Westwell, A. D.; Slusarczyk, M.
Future Med. Chem. 2017, 9, 1809. (d) Meanwell, N. A. J. Med. Chem.
2018, 61, 5822.
(3) Selected examples: (a) van Oeveren, A.; Motamedi, M.; Mani,
N. S.; Marschke, K. B.; Lopez, F. J.; Schrader, W. T.; Negro-Vilar, A.;
́
Zhi, L. J. Med. Chem. 2006, 49, 6143. (b) Baker, M. T. WO
2008008492A2. (c) Xu, F.; Zacuto, M.; Yoshikawa, N.; Desmond, R.;
Hoerrner, S.; Itoh, T.; Journet, M.; Humphrey, G. R.; Cowden, C.;
Strotman, N.; Devine, P. J. Org. Chem. 2010, 75, 7829. (d) Gujjar, R.;
El Mazouni, F.; White, J.; Creason, S.; Shackleford, D. M.; Deng, X.;
Charman, W. N.; Bathurst, I.; Burrows, J.; Floyd, D. M.; Matthews,
D.; Buckner, F. S.; Charman, S. A.; Phillips, M. A.; Rathod, P. K. J.
Med. Chem. 2011, 54, 3935. (e) Vorberg, R.; Trapp, N.; Zimmerli, D.;
Wagner, B.; Fischer, H.; Kratochwil, N. A.; Kansy, M.; Carreira, E. M.;
Muller, K. ChemMedChem 2016, 11, 2216.
̈
(4) (a) Han, J.-B.; Hao, J.-H.; Zhang, C.-P.; Qin, H.-L. Curr. Org.
Chem. 2015, 19, 1554 and references cited therein . (b) Song, H.-X.;
Han, Q.-Y.; Zhao, C.-L.; Zhang, C.-P. Green Chem. 2018, 20, 1662.
(c) Uneyama, K.; Yamazaki, T. J. Fluorine Chem. 2017, 203, 3.
(5) (a) Zhu, M.; Han, X.; Fu, W.; Wang, Z.; Ji, B.; Hao, X.-Q.; Song,
M.-P.; Xu, C. J. Org. Chem. 2016, 81, 7282. (b) Zhang, X.; Yang, C.
Adv. Synth. Catal. 2015, 357, 2721. (c) Roh, G.-b.; Iqbal, N.; Cho, E.
Chin. J. Chem. 2016, 34, 459. (d) Yu, X.; Cohen, S. M. J. Am. Chem.
Soc. 2016, 138, 12320. (e) Yan, S.-Y.; Zhang, Z.-Z.; Shi, B.-F. Chem.
Commun. 2017, 53, 10287. (f) Zhang, Y.; Du, H.; Zhu, M.; Li, J.; Zou,
D.; Wu, Y.; Wu, Y. Tetrahedron Lett. 2017, 58, 880. (g) Zhang, H.;
Wang, H.-Y.; Luo, Y.; Chen, C.; Cao, Y.; Chen, P.; Guo, Y.-L.; Lan,
Y.; Liu, G. ACS Catal. 2018, 8, 2173. (h) Ohtsuka, Y.; Yamakawa, T.
J. Fluorine Chem. 2016, 185, 96. (i) Zhang, H.; Chen, P.; Liu, G.
Angew. Chem., Int. Ed. 2014, 53, 10174.
ASSOCIATED CONTENT
* Supporting Information
■
S
(6) (a) Luo, H.; Wu, G.; Zhang, Y.; Wang, J. Angew. Chem., Int. Ed.
2015, 54, 14503. (b) Han, E.-J.; Sun, Y.; Shen, Q.; Chen, Q.-Y.; Guo,
Y.; Huang, Y.-G. Org. Chem. Front. 2015, 2, 1379. (c) Fujiwara, Y.;
Dixon, J. A.; O’Hara, F.; Funder, E. D.; Dixon, D. D.; Rodriguez, R.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b02793.
́
A.; Baxter, R. D.; Herle, B.; Sach, N.; Collins, M. R.; Ishihara, Y.;
Screening of the optimal reaction conditions, proce-
dures, characterization data, control experiments, NMR
spectra (PDF)
Baran, P. S. Nature 2012, 492, 95. (d) Tang, X.-J.; Thomoson, C. S.;
Dolbier, W. R., Jr. Org. Lett. 2014, 16, 4594. (e) Andrews, K. G.;
Faizova, R.; Denton, R. M. Nat. Commun. 2017, 8, 15913.
(7) (a) Umemoto, T.; Gotoh, Y. J. Fluorine Chem. 1985, 28, 235.
(b) Umemoto, T.; Gotoh, Y. Bull. Chem. Soc. Jpn. 1991, 64, 2008.
(c) Montanari, V.; Resnati, G. Tetrahedron Lett. 1994, 35, 8015.
(d) DesMarteau, D. D.; Montanari, V. Chem. Commun. 1998, 2241.
(e) DesMarteau, D. D.; Montanari, V. Chem. Lett. 2000, 29, 1052.
(f) Zhang, J.; Martin, G. R.; DesMarteau, D. D. Chem. Commun. 2003,
2334. (g) Lu, C.; DesMarteau, D. D. Chem. Commun. 2008, 208.
(h) Lu, C.; VanDerveer, D.; DesMarteau, D. D. Org. Lett. 2008, 10,
5565.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: cpzhang@whut.edu.cn, zhangchengpan1982@
hotmail.com.
ORCID
Cheng-Pan Zhang: 0000-0002-2803-4611
D
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Organic Letters
Letter
(8) (a) Chu, A.-H. A.; Minciunescu, A.; Montanari, V.; Kumar, K.;
́
Bennett, C. S. Org. Lett. 2014, 16, 1780. (b) Tolnai, G. L.; Szekely, A.;
́
́
́
Mako, Z.; Gati, T.; Daru, J.; Bihari, T.; Stirling, A.; Novak, Z. Chem.
Commun. 2015, 51, 4488. (c) Tolnai, G. L.; Nilsson, U. J.; Olofsson,
B. Angew. Chem., Int. Ed. 2016, 55, 11226. (d) Han, Q.-Y.; Zhao, C.-
L.; Yang, J.; Zhang, C.-P. Green Chem. Lett. Rev. 2017, 10, 162.
(e) Zhao, C.-L.; Yang, J.; Han, Z.-Z.; Zhang, C.-P. J. Fluorine Chem.
2017, 204, 23.
́
́
́
́
(9) (a) Toth, B. L.; Kovacs, S.; Salyi, G.; Novak, Z. Angew. Chem.,
Int. Ed. 2016, 55, 1988. (b) Yang, J.; Han, Q.-Y.; Zhao, C.-L.; Dong,
T.; Hou, Z.-Y.; Qin, H.-L.; Zhang, C.-P. Org. Biomol. Chem. 2016, 14,
́
́
7654. (c) Kovacs, S.; Toth, B. L.; Borsik, G.; Bihari, T.; May, N. V.;
́
Stirling, A.; Novak, Z. Adv. Synth. Catal. 2017, 359, 527. (d) Borah, A.
J.; Shi, Z. Chem. Commun. 2017, 53, 3945. (e) Maraswami, M.;
Pankajakshan, S.; Chen, G.; Loh, T.-P. Org. Lett. 2017, 19, 4223.
(10) (a) Johnstone, T. C.; Park, G. Y.; Lippard, S. J. Anticancer Res.
́
2014, 34 (1B), 471. (b) Tumir, L.-M.; Stojkovic, M. R.; Piantanida, I.
Beilstein J. Org. Chem. 2014, 10, 2930. (c) Zhang, B.; Studer, A. Chem.
Soc. Rev. 2015, 44, 3505.
(11) (a) Haider, S.; Chittiboyina, A. G.; Khan, I. A. Curr. Org. Chem.
2018, 22, 148. (b) Qing, Z.-X.; Yang, P.; Tang, Q.; Cheng, P.; Liu, X.-
B.; Zheng, Y.-J.; Liu, Y.-S.; Zeng, J.-G. Curr. Org. Chem. 2017, 21,
1920. (c) Chrzanowska, M.; Grajewska, A.; Rozwadowska, M. D.
Chem. Rev. 2016, 116, 12369.
(12) (a) Guo, W.; Li, S.; Tang, L.; Li, M.; Wen, L.; Chen, C. Org.
Lett. 2015, 17, 1232. (b) Guo, W.-S.; Dou, Q.; Hou, J.; Wen, L.-R.; Li,
M. J. Org. Chem. 2017, 82, 7015.
(13) (a) Wen, L.-R.; Shen, Q.-Y.; Guo, W.-S.; Li, M. Org. Chem.
Front. 2016, 3, 870. (b) Wen, L.-R.; Dou, Q.; Wang, Y.-C.; Zhang, J.-
W.; Guo, W.-S.; Li, M. J. Org. Chem. 2017, 82, 1428. (c) Gittos, M.
W.; Robinson, M. R.; Verge, J. P.; Davies, R. V.; Iddon, B.; Suschitzky,
H. J. Chem. Soc., Perkin Trans. 1 1976, 1, 33. (d) Smith, P. A. S.; Kan,
R. O. J. Am. Chem. Soc. 1960, 82, 4753. (e) Smith, P. A. S.; Kan, R. O.
́
Org. Synth. 1964, 44, 91. (f) Girard, Y.; Atkinson, J. G.; Belanger, P.
C.; Fuentes, J. J.; Rokach, J.; Rooney, C. S.; Remy, D. C.; Hunt, C. A.
J. Org. Chem. 1983, 48, 3220.
E
DOI: 10.1021/acs.orglett.8b02793
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