Radical-Mediated Dearomatization of Indoles with Sulfinate Reagents for the Synthesis of Fluorinated Spirocyclic Indolines

Article abstract of DOI:10.1021/acs.orglett.7b03155

The dearomative introduction of trifluoromethyl and 1,1-difluoroethyl radicals, generated from their corresponding sulfinate salts, into the C2 position of indole derivatives allows the diastereoselective synthesis of three-dimensional 3,3-spirocyclic indolines over C-H functionalized indoles.

Full text of DOI:10.1021/acs.orglett.7b03155

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX-XXX
Radical-Mediated Dearomatization of Indoles with Sulfinate
Reagents for the Synthesis of Fluorinated Spirocyclic Indolines
Dmytro Ryzhakov, Maxime Jarret, Regis Guillot, Cyrille Kouklovsky, and Guillaume Vincent*
́
Institut de Chimie Molec
Univ. Paris Sud, CNRS, Universite
́
ulaire et des Mater
́
iaux d’Orsay (ICMMO), Equipe Met
́ ̀ ́ ́
hodologie, Synthese et Molecules Therapeutiques,
́
Paris-Saclay, 15, rue Georges Clemenceau, 91405 Orsay, Cedex, France
S
* Supporting Information
ABSTRACT: The dearomative introduction of trifluorometh-
yl and 1,1-difluoroethyl radicals, generated from their
corresponding sulfinate salts, into the C2 position of indole
derivatives allows the diastereoselective synthesis of three-
dimensional 3,3-spirocyclic indolines over C−H functionalized
indoles.
he indole nucleus is the major constituent of a large
Scheme 1. Radical-Mediated C−H Functionalization versus
T
number of molecules with significant biological activity,
including approved drugs or compounds in clinical trials.
Therefore, the indole scaffold is an important structural unit for
the discovery of new drug candidates.1 On the other hand,
fluorine atoms and, in particular the trifluoromethyl unit (CF3)
offer unique biological properties and are encountered in a high
number of commercial medicines.2 The 1,1-difluoroethyl group
is considered to be a metabolically stable bioisoster of the
methoxy group in drug discovery.3 Finally, the pharmaceutical
industry is in need of scaffolds containing saturations (sp3
carbons); three-dimensional drug candidates are more likely to
succeed than flat ones.4 For instance, the spiroindoline scaffold
is encountered in several medicinally relevant molecules.5
Dearomatization reactions are perfectly suited to achieve this
goal, since they could transform rapidly achiral starting
materials into chiral compounds with an important increase
of complexity.6 Most of the time, dearomatization reactions rely
on the innate nucleophilic character of indoles which react with
electrophiles.5,7
We have recently described that the dearomatization of
indoles could be possible via the generation of electrophilic
indole intermediates.8 We now wish to study a radical-mediated
approach.9 Over the years, several functionalization reactions of
heteroarenes, including indoles, were reported which involve
the addition of free radicals into a heteroaromatic substrate 1
which delivers a dearomatized intermediate I with a radical on
the carbon adjacent to the newly formed bond (Scheme
1).10−12 Usually, this radical is then oxidized by single electron
transfer (SET) into a carbocation II which is followed by a very
fast aromatization event via elimination of a proton to yield
functionalized heteroarene 2. In contrast, the challenge is to
intercept carbocation II by a nucleophile before the
aromatization step to obtain 2,3-difunctionalized indoline 3.
Few reports,13,14 including our work,14a described the addition
of radicals, generated from aziridines,13a oxaziridines,13b
azides,13c or phenols,14 at C2 of indoles followed by trapping
of the C3 resulting carbocations before the aromatization. In
order to introduce fluorine-containing carbon-centered radicals
Dearomatization of Indoles
on the indole nucleus, we selected sodium trifluoromethyl
sulfinate,15 since sulfinates are known to easily generate radicals
in mild oxidative conditions via homolytic cleavage of the
relatively weak C−S bond and elimination of SO2 and are
therefore versatile reagents to perform C−H functionalization
of arenes.12 This strategy would allow us to have general access
to original fluorine-containing spiroindolines.16
We selected 3-(3-hydroxypropyl)-NCO2Et-indole 1a as a
model substrate to evaluate our approach (Table 1). In that
case, carbocation II would be intramolecularly intercepted by
an alcohol to yield spirofuranoindoline 3a. Different oxidative
systems to generate the trifluoromethylene radical from sodium
triflyl sulfinate were investigated. With tert-butyl hydroperoxide,
only few amounts of 3a were detected, along with remaining
indole 1a and unidentified products (Table 1, entries 1 and 2).
Only traces of the desired 3a were obtained with hypervalent
iodine reagent PIFA (Table 1, entry 3). A catalytic amount of
silver nitrate and a sup-stoichiometric amount of potassium
persulfate at 80 °C delivered 3a in 30% yield (Table 1, entry 4).
Manganese(III) acetate at 80 °C in acetonitrile afforded 3a in a
gratifyingly 61% yield (Table 1, entry 5). Ceric ammonium
Received: October 10, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b03155
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 1. Optimization of the 3-Oxy-2-trifluoromethylation of
Indole 1a with Sodium Trifluoromethyl Sulfinate
Scheme 2. Synthesis of Fluorinated Spirocyclic Indolines
from Sulfinate Reagents
temp
3a isolated yield
entry
1
oxidant (equiv)
solvent
(°C)
(%)
t-BuOOH (5)
CH3CN/H2O
(2:1)
rt
10%
2
3
4
t-BuOOH (5)
CH3CN
CH3CN
rt
traces
traces
30
a
PIFA (3)
rt
AgNO3 (0.1),
K2S2O8 (2)
CH3CN/H2O
(1:1)
80
5
6
7
8
Mn(OAc)3 (3)
CH3CN
CH3CN
CH3CN
CH3CN
80
61
b
CAN (3)
rt
51
b
CAN (3)
−10
−30
69
b
CAN (3)
slow conversion
a
b
PhI(OCOCF3)2. (NH4)2Ce(NO3)6.
nitrate (CAN) in acetonitrile at room temperature delivered 3a
in 51% yield and also CF3-containing indole 2a and
undetermined compounds (Table 1, entry 6). Performing the
reaction at −10 °C allows the intramolecular trapping by the
alcohol of carbocation II to be favored over its aromatization,
and 3a was isolated in 69% yield (Table 1, entry 7). The
reaction proved to be too slow at −30 °C (Table 1, entry 8).
Remarkably, indoline 3a was obtained as a unique diaster-
oisomer with the CF3 group at C2 and the oxygen at C3 in a
trans relationship as demonstrated by X-ray analysis of crystals
of 3a.17,18
Having found suitable conditions to perform our desired
dearomative 3-oxy-2-trifluoromethylation of indoles, we
evaluated the scope of this reaction (Scheme 2).18 The
influence of the substitution of the nitrogen of the indole
nucleus was first studied. The Boc and acetyl groups were as
well permitted as the CO2Et since 3b17 and 3c were obtained in
74% and 78% yield, while a lower yield was obtained with a
tosyl group (3d, 43%). Different functional groups on the
benzene ring of the indole nucleus were then scrutinized.
Electron-donating groups, such as methoxy at the C5-position
(3e, 55%), methyl at the C5 (3f, 78%) and C7 (3g, 69%)
positions, or halogens such as fluorine (3h, 60%), chlorine (3i,
71%), and bromine (3j, 61%) at C5, were well tolerated. The
reaction also operates with an electron-withdrawing group at
C5, such as a cyano group (3k, 57%).
Next, the nature of the nucleophile was investigated. A
tertiary alcohol was as efficient as a primary one since indoline
3l was obtained in 70% yield. The carboxylic acid was also a
very good oxygenated nucleophile since 3m was isolated in 87%
yield. Trifluoromethylated-lactones containing a 5-methoxy
(3n, 72%), 7-methyl (3o, 80%), and 6-chlorine (3p, 35%)19
group on the benzene part of the indole ring were also
obtained. To solubilize the starting carboxylic acids, the
reaction leading to 3o and 3p were performed in acetone at
a higher dilution.
a
b
0.022 M in acetone. 2.5 equiv of MeCF2SO2Na and 4 equiv of CAN.
indolines containing, respectively, a methyl (3r, 70%),17
a
methoxy (3s, 53%), and a fluorine (3t, 61%) at the C5-position.
Finally, it was possible to introduce a 1,1-difluoroethyl group
in lieu of the trifluoromethyl by using the corresponding
sodium sulfinate.12e Gratifyingly, we obtained moderate yields
of spirofuranoindoline 3u (28%) and spiropyrrolidinoindoline
3v (27%).20
Nitrogenated nucleophiles were also competent to deliver
spiropyrrolidinoindolines. The cyclization of indoles displaying
a N-tosyl amine on the C3-side chain gave 3q in 66% yield and
To further demonstrate the synthetic potential of this
dearomative method, a gram-scale experiment allowed 3f to be
obtained in 73% yield.
B
DOI: 10.1021/acs.orglett.7b03155
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
A mechanism involving free-radical intermediates is indeed
suggested by the incorporation of the trifluomethyl group into
compounds 3 via desulfonation from the sulfinate reagent.21 In
order to gain additional mechanistic insights, we submitted
indole 1b to the oxidative reaction conditions with CAN
without the presence of the trifluoromethylative reagent, and in
that case, the starting indole was rapidly consumed into several
oxidation products, among which hydroxyl indoline 4 and
dimer 5 were isolated and their structures tentatively assigned
(Scheme 3). A radical cation such as III could be postulated to
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: Guillaume.vincent@u-psud.fr.
ORCID
Guillaume Vincent: 0000-0003-3162-1320
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
D.R. and M.J. thank respectively the MENESR and the ANR
for PhD fellowships. We also gratefully acknowledge the
■
Scheme 3. Control Experiment
Universite
́
Paris Sud and the CNRS for financial support.
REFERENCES
■
(1) (a) Indole Ring Synthesis: From Natural Products to Drug
Discovery; Gribble, G. W., Ed.; Wiley: Hoboken, 2016. (b) Kaushik, N.
K.; Kaushik, N.; Attri, P.; Kumar, N.; Kim, C. H.; Verma, A. K.; Choi,
E. H. Molecules 2013, 18, 6620. (c) de Sa Alves, F.; Barreiro, E.; Fraga,
C. A. M. Mini-Rev. Med. Chem. 2009, 9, 782.
(2) (a) Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881.
̈
(b) Hagmann, W. K. J. Med. Chem. 2008, 51, 4359. (c) Purser, S.;
Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37,
320. (d) Wang, J.; Sanchez-Rosello, M.; Acena, J. L.; del Pozo, C.;
́ ́
̃
Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Chem. Rev.
2014, 114, 2432. (e) Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly,
D. J.; Meanwell, N. A. J. Med. Chem. 2015, 58, 8315.
(3) (a) Coteron, J. M.; Marco, M.; Esquivias, J.; Deng, X.; White, K.
L.; White, J.; Koltun, M.; El Mazouni, F.; Kokkonda, S.; Katneni, K.;
Bhamidipati, R.; Shackleford, D. M.; Angulo-Barturen, I.; Ferrer, S. B.;
explain the formation of such compounds. If both the indole 1
and the sulfinate reagent could be oxidized by CAN,22 it is
presumed that the sulfinate reagent should be oxidized faster
than indoles 123,24 and it supports the mechanism depicted in
Scheme 1. However, we cannot exclude an alternative
mechanism which involves the oxidation of 125 and the
sulfinate reagent into, respectively, the radical cation III and the
trifluoromethyl radical, followed by a radical recombination
event into carbocation II.26
In conclusion, we developed a diastereoselective dearomative
3,3-spirocyclization of indoles via the addition of fluorinated-
carbon radicals, generated from sulfinate reagents, at the C2-
position of indoles, in the presence of ceric ammonium nitrate
as the oxidant. The prominent feature of this strategy is the
interception of the transient carbocation at the C3-position
before aromatization into a C2-functionalized indole through
elimination of a proton. This protocol has a broad substrate
scope and tolerates various nucleophiles. We believe that this
method is potentially of high interest in the discovery of
biologically active compounds.
́
Jimenez-Díaz, M. B.; Gamo, F.-J.; Goldsmith, E. J.; Charman, W. N.;
Bathurst, I.; Floyd, D.; Matthews, D.; Burrows, J. N.; Rathod, P. K.;
Charman, S. A.; Phillips, M. A. J. Med. Chem. 2011, 54, 5540.
(b) Anderson, M. O.; Zhang, J.; Liu, Y.; Yao, C.; Phuan, P.-W.;
Verkman, A. S. J. Med. Chem. 2012, 55 (12), 5942.
(4) Lovering, F.; Bikker, J.; Humblet, C. J. Med. Chem. 2009, 52,
6752.
(5) James, M. J.; O’Brien, P.; Taylor, R. J. K.; Unsworth, W. P. Chem.
- Eur. J. 2016, 22, 2856.
(6) (a) Asymmetric Dearomatization Reactions; You, S.-L., Ed.; Wiley-
VCH: Weinheim, 2016. (b) Zheng, C.; You, S.-L. Chem. 2016, 1, 830.
(c) Zhuo, C.-X.; Zhang, W.; You, S.-L. Angew. Chem., Int. Ed. 2012, 51,
12662. (d) Roche, S. P.; Porco, J. A. Angew. Chem., Int. Ed. 2011, 50,
4068.
́
(7) For reviews: (a) Roche, S. P.; Youte Tendoung, J.-J.; Treguier, B.
Tetrahedron 2015, 71, 3549. (b) Sundberg, R. J. In Heterocyclic
Scaffolds II; Gribble, G. W., Ed.; Topics in Heterocyclic Chemistry;
Springer: Berlin Heidelberg, 2010; p 47; for a recent example from us:
(c) Lachkar, D.; Denizot, N.; Bernadat, G.; Ahamada, K.; Beniddir, M.
A.; Dumontet, V.; Gallard, J.-F.; Guillot, R.; Leblanc, K.; N’nang, E. O.;
Turpin, V.; Kouklovsky, C.; Poupon, E.; Evanno, L.; Vincent, G. Nat.
Chem. 2017, 9, 793.
ASSOCIATED CONTENT
■
S
* Supporting Information
(8) (a) Beaud, R.; Guillot, R.; Kouklovsky, C.; Vincent, G. Angew.
Chem., Int. Ed. 2012, 51, 12546. (b) Beaud, R.; Guillot, R.;
Kouklovsky, C.; Vincent, G. Chem. - Eur. J. 2014, 20, 7492.
(c) Nandi, R. K.; Ratsch, F.; Beaud, R.; Guillot, R.; Kouklovsky, C.;
Vincent, G. Chem. Commun. 2016, 52, 5328. (d) Nandi, R. K.; Guillot,
R.; Kouklovsky, C.; Vincent, G. Org. Lett. 2016, 18, 1716. (e) Beaud,
R.; Nandi, R. K.; Perez-Luna, A.; Guillot, R.; Gori, D.; Kouklovsky, C.;
Ghermani, N.-E.; Gandon, V.; Vincent, G. Chem. Commun. 2017, 53,
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b03155.
Experimental procedures, characterizations, and NMR
spectra of all new compounds (PDF)
Accession Codes
̀
5834. (f) Denizot, N.; Pouilhes, A.; Cucca, M.; Beaud, R.; Guillot, R.;
CCDC 1575354−1575356 contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
Kouklovsky, C.; Vincent, G. Org. Lett. 2014, 16, 5752. (g) Denizot, N.;
Guillot, R.; Kouklovsky, C.; Vincent, G. Chem. - Eur. J. 2015, 21,
18953.
(9) For radical-mediated reductive dearomatization of indoles:
(a) Ziegler, F. E.; Jeroncic, L. O. J. Org. Chem. 1991, 56, 3479.
(b) Hilton, S. T.; Ho, T. C. T.; Pljevaljcic, G.; Schulte, M.; Jones, K.
C
DOI: 10.1021/acs.orglett.7b03155
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Chem. Commun. 2001, 209. (c) Flanagan, S. R.; Harrowven, D. C.;
Bradley, M. Tetrahedron Lett. 2003, 44, 1795. (d) Beemelmanns, C.;
Reissig, H.-U. Angew. Chem., Int. Ed. 2010, 49, 8021. (e) Nicolaou, K.
C.; Dalby, S. M.; Majumder, U. J. Am. Chem. Soc. 2008, 130, 14942.
For radical-mediated oxidative dearomatization of indoles without the
possibility of rearomatization: (f) Zuo, Z.; Ma, D. Angew. Chem., Int.
Ed. 2011, 50, 12008. (g) Zi, W.; Zuo, Z.; Ma, D. Acc. Chem. Res. 2015,
48, 702. (h) El Kaïm, L.; Grimaud, L.; Le Goff, X.-F.; Menes-Arzate,
M.; Miranda, L. D. Chem. Commun. 2011, 47, 8145. (i) Yin, H.; Wang,
T.; Jiao, N. Org. Lett. 2014, 16, 2302.
(10) Seminal contribution: (a) Minisci, F.; Bernardi, R.; Bertini, F.;
Galli, R.; Perchinummo, M. Tetrahedron 1971, 27, 3575. For a general
review: (b) Duncton, M. A. J. MedChemComm 2011, 2, 1135. For
selected recent examples: (c) DiRocco, D. A.; Dykstra, K.; Krska, S.;
Vachal, P.; Conway, D. V.; Tudge, M. Angew. Chem., Int. Ed. 2014, 53,
4802. (d) Seiple, I. B.; Su, S.; Rodriguez, R. A.; Gianatassio, R.;
Fujiwara, Y.; Sobel, A. L.; Baran, P. S. J. Am. Chem. Soc. 2010, 132,
13194. (e) Ma, X.; Herzon, S. B. J. Am. Chem. Soc. 2016, 138, 8718.
(f) Klauck, F. J. R.; James, M. J.; Glorius, F. Angew. Chem., Int. Ed.
2017, 56, 12336. (g) Lo, J. C.; Kim, D.; Pan, C.-M.; Edwards, J. T.;
Galstyan, A.; Strassert, C. A.; Studer, A. Chem. Commun. 2016, 52,
5997.
(17) CCDC 1575354−1575356 (3a, 3b, 3r) contain the
supplementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
1
(18) Only one diastereoisomer was detected by H NMR of the
crude mixture after aqueous workup for all compounds. The trans
stereochemistry may be controlled by electronic factors during the
attack of the nucleophile on the carbocation at C3.
(19) The low yield could be attributed to the low solubility of both
the starting indole 1p and the spiroindoline product 3p.
(20) Dimers such as 5 (Scheme 3) were obtained as the main
byproducts and resulted from the oxidation of indoles 1 with CAN.
This result can be explained by the low solubility of the sodium 1,1-
difluoroethyl sulfinate.
(21) Moreover, upon addition of TEMPO as a radical scavenger to
the reaction, no spiroindoline 3b was observed. Instead 59% of 1b was
recovered along with an undefined dimer of 1b.
(22) The redox potential of CAN is 1.61 V vs NHE; for a review on
CAN as a single-electron oxidant: Nair, V.; Deepthi, A. Chem. Rev.
2007, 107, 1862.
Yabe, Y.; Gui, J.; Qin, T.; Gutier
́
rez, S.; Giacoboni, J.; Smith, M. W.;
Holland, P. L.; Baran, P. S. J. Am. Chem. Soc. 2017, 139, 2484.
(23) The oxidation potential of CF3SO2K is 1.05 V vs SCE; see:
Tommasino, J.-B.; Brondex, A.; Medebielle, M.; Thomalla, M.;
́
Langlois, B. R.; Billard, T. Synlett 2002, 1697.
́
́
(h) Gutierrez-Bonet, A.; Remeur, C.; Matsui, J. K.; Molander, G. A. J.
Am. Chem. Soc. 2017, 139, 12251. (i) Matsui, J. K.; Primer, D. N.;
Molander, G. A. Chem. Sci. 2017, 8, 3512.
(24) The oxidation potential of 3-methyl-N-acetylindole has been
(11) For a review on direct trifluoromethylation of C−H bonds:
(a) Liu, H.; Gu, Z.; Jiang, X. Adv. Synth. Catal. 2013, 355, 617. For
selected examples of radical mediated trifluoromethylation of C−H
bonds of arenes: (b) Wiehn, M. S.; Vinogradova, E. V.; Togni, A. J.
Fluorine Chem. 2010, 131, 951. (c) Kino, T.; Nagase, Y.; Ohtsuka, Y.;
Yamamoto, K.; Uraguchi, D.; Tokuhisa, K.; Yamakawa, T. J. Fluorine
Chem. 2010, 131, 98. (d) Nagib, D. A.; MacMillan, D. W. C. Nature
2011, 480, 224. (e) Mejía, E.; Togni, A. ACS Catal. 2012, 2, 521.
(12) (a) Langlois, B. R.; Laurent, E.; Roidot, N. Tetrahedron Lett.
1991, 32, 7525. (b) Ji, Y.; Brueckl, T.; Baxter, R. D.; Fujiwara, Y.;
Seiple, I. B.; Su, S.; Blackmond, D. G.; Baran, P. S. Proc. Natl. Acad. Sci.
U. S. A. 2011, 108, 14411. (c) Fujiwara, Y.; Dixon, J. A.; Rodriguez, R.
A.; Baxter, R. D.; Dixon, D. D.; Collins, M. R.; Blackmond, D. G.;
Baran, P. S. J. Am. Chem. Soc. 2012, 134, 1494. (d) Fujiwara, Y.; Dixon,
J. A.; O’Hara, F.; Funder, E. D.; Dixon, D. D.; Rodriguez, R. A.; Baxter,
determined to be 1.10 V vs Ag/AgCl; see ref 14b.
(25) The redox potentials of the sulfinate reagent and indoles
substituted by electron-withdrawing groups at the nitrogen are close.
Moreover, the presence of electron-donating groups on the indole
nucleus may lower the oxidation potential of the indole since 3-
methyl-5-methoxyl-N-acetylindole has an oxidation potential of 0.98 vs
Ag/AgCl; see ref 14b.
(26) Radical cations generated from indoles substituted at the
nitrogen by electron-withdrawing groups could be persistent and lead
to selective coupling reaction with a transient radical; see ref 14b for a
discussion.
́
R. D.; Herle, B.; Sach, N.; Collins, M. R.; Ishihara, Y.; Baran, P. S.
Nature 2012, 492, 95. (e) Zhou, Q.; Ruffoni, A.; Gianatassio, R.;
Fujiwara, Y.; Sella, E.; Shabat, D.; Baran, P. S. Angew. Chem., Int. Ed.
2013, 52, 3949. (f) Gianatassio, R.; Kawamura, S.; Eprile, C. L.; Foo,
K.; Ge, J.; Burns, A. C.; Collins, M. R.; Baran, P. S. Angew. Chem., Int.
Ed. 2014, 53, 9851. (g) Li, L.; Mu, X.; Liu, W.; Wang, Y.; Mi, Z.; Li,
C.-J. J. Am. Chem. Soc. 2016, 138, 5809.
(13) (a) Ziegler, F. E.; Belema, M. J. Org. Chem. 1994, 59 (26), 7962.
(b) Benkovics, T.; Guzei, I. A.; Yoon, T. P. Angew. Chem., Int. Ed.
2010, 49, 9153. (c) Li, J.; Liu, M.; Li, Q.; Tian, H.; Shi, Y. Org. Biomol.
Chem. 2014, 12, 9769.
(14) (a) Tomakinian, T.; Guillot, R.; Kouklovsky, C.; Vincent, G.
Angew. Chem., Int. Ed. 2014, 53, 11881. For an electrochemical
version, see: (b) Liu, K.; Tang, S.; Huang, P.; Lei, A. Nat. Commun.
2017, 8, 775.
(15) (a) Zhang, C. Adv. Synth. Catal. 2014, 356, 2895. (b) Lefebvre,
Q. Synlett 2016, 28, 19.
(16) For the synthesis of C2-fluorinated indolines by other strategies:
(a) García Ruano, J. L.; Aleman
Monteagudo, S.; Parra, A.; del Pozo, C.; Fustero, S. Angew. Chem.,
Int. Ed. 2008, 47, 7941. (b) Fustero, S.; Sanchez-Rosello, M.; Baez, C.;
del Pozo, C.; del Ruano, J. L. G.; Aleman, J.; Marzo, L.; Parra, A.
́ ́
, J.; Catalan, S.; Marcos, V.;
́
́
́
́
Amino Acids 2011, 41, 559. (c) Yin, X.-P.; Zeng, X.-P.; Liu, Y.-L.; Liao,
F.-M.; Yu, J.-S.; Zhou, F.; Zhou, J. Angew. Chem., Int. Ed. 2014, 53,
13740. (d) Doebelin, C.; Patouret, R.; Garcia-Ordonez, R. D.; Chang,
M. R.; Dharmarajan, V.; Kuruvilla, D. S.; Novick, S. J.; Lin, L.;
Cameron, M. D.; Griffin, P. R.; Kamenecka, T. M. ChemMedChem
2016, 11, 2607. (e) Leifert, D.; Artiukhin, D. G.; Neugebauer, J.;
D
DOI: 10.1021/acs.orglett.7b03155
Org. Lett. XXXX, XXX, XXX−XXX