Multicomponent Oxidative Trifluoromethylation of Alkynes with Photoredox Catalysis: Synthesis of α-Trifluoromethyl Ketones

Article abstract of DOI:10.1021/acs.orglett.8b00410

The direct oxidative addition of CF₃ and H₂O to alkynes was achieved with photoredox catalysis to obtain α-trifluoromethyl ketones via rapid enol-keto tautomerization. The reaction exhibits high functional group tolerance and regioselectivity. Heterocycles of various sizes containing CF₃ were synthesized from the α-CF₃-substituted diketones obtained through the protocol, thereby demonstrating the versatile applicability of the method. Mechanistic studies of the reaction with isotopes provided insight into the reaction pathway.

Full text of DOI:10.1021/acs.orglett.8b00410

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Multicomponent Oxidative Trifluoromethylation of Alkynes with
Photoredox Catalysis: Synthesis of α‑Trifluoromethyl Ketones
Yashwardhan R. Malpani,∇,† Bishyajit Kumar Biswas,∇,§,†,‡ Hong Sik Han,†,‡ Young-Sik Jung,†,‡
and Soo Bong Han*,†,‡
†Division of Bio and Drug Discovery, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong, Daejeon 34114,
Republic of Korea
‡Department of Medicinal and Pharmaceutical Chemistry, University of Science and Technology, 217 Gajeongro, Yuseong, Daejeon
305-355, Republic of Korea
S
* Supporting Information
ABSTRACT: The direct oxidative addition of CF3 and H2O to
alkynes was achieved with photoredox catalysis to obtain α-
trifluoromethyl ketones via rapid enol-keto tautomerization. The
reaction exhibits high functional group tolerance and regioselectiv-
ity. Heterocycles of various sizes containing CF3 were synthesized
from the α-CF3-substituted diketones obtained through the
protocol, thereby demonstrating the versatile applicability of the
method. Mechanistic studies of the reaction with isotopes provided
insight into the reaction pathway.
he incorporation of a fluoro-substituent in organic
existing carbonyl moieties.5 Alternatively, the direct formation
Tmolecules has been studied extensively, because of its of α-CF3 substituted ketones from alkenes was achieved
(Scheme 1, c).6 These bis-functionalization approaches are
highly beneficial, because of the high availability of alkenes and
significant impact on biological properties, such as lipophilicity,
binding affinity, and metabolic stability.1 Among these
no required preformation. Further attempts were made to
extend this attractive approach to alkyne substrates. Hu used
propionic acids in an electrophilic decarboxylative mechanism
with Cu(OAc)2 (Scheme 1d).7 In addition, Maiti reported CF3
radical and O2 incorporation using AgNO3 (Scheme 1e).8
However, these methods still have major limitations, such as
stoichiometric use of Cu(OAc)2 (2 equiv) and high catalytic
loading of AgNO3 (20 mol %). In addition, only terminal
alkynes and alkynyl acids can be employed to produce
unsubstituted α-CF3 ketones (Scheme 1, R2 = H) as a result.
Thus, an atom-economical and versatile method for use with a
broad range of alkynes remained elusive and needed to be
developed to obtain diversely substituted α-CF3 ketones.
Herein, in continuation of our efforts to develop novel CF3-
related bis-functionalization reactions,9 we disclose the multi-
component oxidative trifluoromethylation of various internal
and terminal alkynes with visible light catalysis for the
formation of α-CF3 substituted ketones. To the best of our
knowledge, this reaction is the first direct synthesis of α-CF3
substituted ketones from internal and terminal alkynes using
photoredox catalysis (Scheme 1f).
reactions, the formation of α-CF3 substituted ketones in
particular is very attractive, because of their use as versatile
building blocks for a variety of complex CF3-containing
molecules. The most common route to α-CF3 ketones involves
the use of enolates or enol ethers as substrates. For example, in-
situ-generated Li, Ti, and Zn enolates were used to form α-CF3
ketones in combination with a CF3 radical.2 In addition, silyl
enol ethers were successfully employed by MacMillan and
Kappe (see Scheme 1a).3 Recently, Li and Kamimura reported
the formation of α-CF3 ketones using vinyl triflates via oxidative
radical fragmentation (see Scheme 1b).4 However, these types
of reactions could not proceed without the prerequisite
formation of appropriate enol-type substrates and needed
Scheme 1. Synthesis of α-Trifluoromethyl Ketones
We envisioned the possibility of a regioselective and
chemoselective direct one-step conversion of aryl alkynes
employing visible-light-mediated photoredox catalysis using a
CF3 radical and H2O, as depicted in Scheme 2. Excitation of the
Received: February 5, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b00410
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Proposed Pathway for Direct α-
Trifluoromethylation of Alkynes
Table 1. Optimization of the Oxidative Trifluoromethylation
of Alkynes
a
b
entry
catalyst
solvent
yield (%)
1
2
3
4
5
6
fac-Ir(ppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
Ru(bpy)3
acetone:H2O (9:1, 0.1 M)
acetone:H2O (19:1, 0.1 M)
acetone:H2O (39:1, 0.1 M)
acetone:H2O (39:1, 0.1 M)
acetone:H2O (39:1, 0.1 M)
acetone:H2O (39:1, 0.1 M)
acetone:H2O (39:1, 0.1 M)
acetone:H2O (39:1, 0.1 M)
acetone:H2O (39:1, 0.1 M)
60
69
77
23
[Ru(phen)3]Cl2
Ir(dFppy)3
fac-Ir(ppy)3
fac-Ir(ppy)3
55
60
c
7
81 (77)
0
d
8
e
9
26
photoredox catalyst (from IrIII to *IrIII) with visible light can
generate the CF3 radical from Umemoto’s reagent (E1/2
−0.37 V vs SCE), because of a high reducing power of fac-
=
a
Reactions were carried out under N2 atmosphere at 25 °C for 12 h
using 1a (0.1 mmol), catalyst (2 mol %), and Umemoto’s reagent
Ir(ppy)3 (EI1V/2/*III = −1.73 V vs SCE).10 The CF3 radical can be
captured by alkynes to produce the vinyl radical Int-I.
Regioselecive generation of the vinyl radical is anticipated,
because of the stabilization effect of the adjacent aromatic
ring.9a,11 The resulting vinyl radical species can be oxidized by
b
1
(0.15 mmol). Yields were determined by H NMR using 1,1,2,2-
tetrachloroethane as internal standard (isolated yield after flash silica
c
gel column given in parentheses). Umemoto’s reagent (0.20 mmol).
d
e
In darkness. Without a catalyst.
IrIV to a vinyl cation Int-II since the reduction potential of IrIV
(2c) yields, respectively. In addition, a Boc-protected amine
gave the desired product in moderate yield (2d, 50%). A
tertiary amine substituent such as in dimethyl aniline also
produced the desired product with moderate reactivity (2e,
51% yield). Methoxy- and mesyl-protected alcohols were
efficiently transformed to the α-CF3 substituted ketones in
75% and 63% yields, respectively (2f and 2g). In particular,
unprotected alcohol substituents in the form of phenolic and
benzyl alcohols were also not detrimental to forming the
desired products 2h (81%) and 2i (65%). In addition,
substrates with halide substituents on the aromatic rings were
stably converted to the products (2j−2l) in good to moderate
yields (68%−50%). Unsubstituted (2m) and alkyl-substituted
(2n) aromatic rings proved to be good substrates for the
reaction (70% and 77% yields).
In another set of experiments, we varied the R2 group as in
substrates 3a−3l to investigate the steric effect and functional
tolerance on the alkynic position (see Table 3). Longer alkyl
chains from Me to n-Bu did not hinder the progress of the
reaction to give 4a (71%). Even the bulky cyclopentyl and
cyclohexyl rings were found to be tolerant under the reaction
conditions to give the desired products (4b (80%) and 4c
(63%)). Interestingly, the benzyl product (4d) was obtained in
moderate yield (50%). Noticeably, the bis α-trifluoromethy-
lated ketone (4e, 66%) can be formed when the CF3-containing
alkyne 3e is used as a starting material. It is important to note
here that terminal alkynes were also proven to be efficient
substrates for the transformation, as shown in the examples of
the formation of 4f−4h in good to high yields (55%−70%).
Most interestingly, we could also achieve the formation of the
CF3-containing ketoester 4i in satisfactory yield (62%), thereby
IV/III
is sufficiently high (E
= 0.77 V vs SCE).10,12 This oxidation
1/2
regenerates the catalyst IrIII to close the catalytic cycle. In
addition, the formed vinyl cations can easily be trapped with
−
H2O to generate Int-III. Deprotonation with the anion BF4
produces the enol Int-IV. The desired product could be readily
obtained by enol-keto tautomerization.
Based on the proposed pathway, we attempted the reaction
with the internal alkyne 1a under various photoredox catalytic
conditions (see Table 1). To our delight, the desired product
2a was obtained in 60% yield when H2O and Umemoto’s
reagent were added with a catalytic amount of fac-Ir(ppy)3
under blue LED irradiation (entry 1, Table 1). When the
amount of H2O was decreased, the yield was increased to as
much as 77% (entries 1−3, Table 1). Catalyst screening
enabled fac-Ir(ppy)3 to be identified as the optimal catalyst
(entries 3−6, Table 1).13 The use of two equivalents of
Umemoto’s reagent resulted in improvement with an isolated
yield of 77% (entry 7, Table 1). The absence of light irradiation
completely quenched the reaction, proving that a light-
mediated reaction was involved (entry 8, Table 1). Interest-
ingly, without the catalyst, the reaction yielded 26% of the
product, which is suspected to form via an inefficient radical
pathway, resulting from the direct absorption of light by
Umemoto’s reagent (entry 9, Table 1).9a
Using this optimization protocol, various alkynes were
subjected to the reaction conditions. First, substrates with
substituents on the aromatic rings were tested with 1-phenyl-1-
propyne and its various derivatives (Table 2, 1a−1n). Acetyl
and tosyl protected amines containing alkynes were smoothly
converted to their product in 77% (2a), 81% (2b), and 81%
B
DOI: 10.1021/acs.orglett.8b00410
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 2. Direct Oxidative Trifluoromethylation of Alkynes
1
Table 3. Direct Oxidative Trifluoromethylation of Alkynes
3
a
,b
ab
,
a
Reactions were carried out under N2 atmosphere at 25 °C for 12 h
using alkyne (0.2 mmol), fac-Ir(ppy)3 (2 mol %) and Umemoto’s
b
reagent (0.4 mmol). Isolated yields after column chromatography are
given in parentheses.
a
Reactions were carried out under N2 atmosphere at 25 °C for 12 h
using alkyne (0.2 mmol), fac-Ir(ppy)3 (2 mol %) and Umemoto’s
b
tively.17 Furthermore, simple urea treatment gave the 2-hydroxy
pyrimidine product (5c (52%)). Particularly, the CF3-
incorporated pyrazole (5b) shares the core structure with the
nonsteroidal anti-inflammatory drug (NSAID) Celecoxib and
its structural analogues,18 which highlights the high applicability
of this methodology to the field of medicinal chemistry.
The reaction pathway was examined more closely by
conducting isotope labeled experiments, as shown in Scheme
4. Even though the optimized solvent system is acetone/H2O,
in these experiments MeCN was used instead of acetone,
because the high exchange rates of deuterium with the methyl
protons of acetone19 and 18O with the carbonyl oxygen of
acetone20 would complicate the interpretation. When H218O
was used under the optimized conditions, 18O was incorporated
into 87% of the product 6a (see Scheme 4, eq 1). In addition,
when D2O was used, we observed that 72% of the deuterium
was incorporated in the product 6b (Scheme 4, eq 2). These
isotope studies clearly show that the product is formed as a
reagent (0.4 mmol). Isolated yields after column chromatography are
given in parentheses.
demonstrating the strong tolerability of the reaction and its
extensibility to the synthesis of complex molecules.14 Similarly,
other 1,3-diketo compounds were produced with methyl (4j
(71%)), isopropyl (4k (72%)), and heteroaromatic (4l (55%))
substitutions.
The formation of trifluoromethylated dicarbonyl products
(4i−4l) highlights the importance of the protocol over
previously reported procedures. The strong versatility in the
application of dicarbonyl compounds as synthons is well-
established and was demonstrated here by the synthesis of
various trifluoromethylated heterocyclic compounds,15 using
the diketo product 4m (Scheme 3).16 For example, five-
membered rings, such as isoxazole (5a, 62%) and pyrazole (5b,
57%) were efficiently synthesized by condensation with
hydroxylamine hydrochloride and phenyl hydrazine, respec-
C
DOI: 10.1021/acs.orglett.8b00410
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
ORCID
Scheme 3. Synthesis of CF3-Containing Heterocyclic
Compounds
Young-Sik Jung: 0000-0001-9492-6848
Soo Bong Han: 0000-0002-7831-1832
Present Address
§Department of Pharmacy, Jagannath University Dhaka, 1100,
Bangladesh.
Author Contributions
∇These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by Korea Research Institute of
Chemical Technology (Grant No. KK1803-C00 and KK1706-
G08). B.K.B. and H.S.H. thanks University of Science and
Technology for providing student fellowships.
REFERENCES
■
(1) (a) Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.;
Meanwell, N. A. J. Med. Chem. 2015, 58, 8315. (b) Wang, J.; San
́
chez-
Rosello,
́
M.; Acena, J. L.; del Pozo, C.; Sorochinsky, A. E.; Fustero, S.;
̃
Soloshonok, V. A.; Liu, H. Chem. Rev. 2014, 114, 2432. (c) Hagmann,
W. K. J. Med. Chem. 2008, 51, 4359. (d) O’Hagan, D. Chem. Soc. Rev.
2008, 37, 308. (e) Kirk, K. L. Org. Process Res. Dev. 2008, 12, 305.
(f) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc.
Scheme 4. Isotope-Labeled Experiments
Rev. 2008, 37, 320. (g) Muller, K.; Faeh, C.; Diederich, F. Science 2007,
̈
317, 1881−1886. (h) Shah, P.; Westwell, A. D. J. Enzyme Inhib. Med.
Chem. 2007, 22, 527. (i) Biffinger, J. C.; Kim, H. W.; DiMagno, S. G.
ChemBioChem 2004, 5, 622. (j) Gerebtzoff, G.; Li-Blatter, X.; Fischer,
H.; Frentzel, A.; Seelig, A. ChemBioChem 2004, 5, 676. (k) Dunitz, J.
D. ChemBioChem 2004, 5, 614. (l) Jeschke, P. ChemBioChem 2004, 5,
570. (m) Bohm, H.-J.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn, B.;
̈
Muller, K.; Obst-Sander, U.; Stahl, M. ChemBioChem 2004, 5, 637.
̈
(n) Hung, M. H.; Farnham, W. B.; Feiring, A. E.; Rozen, S.
Fluoropolymers: Synthesis, Vol. 1; Plenum Press: New York, 1999.
(2) (a) Tomita, Y.; Itoh, Y.; Mikami, K. Chem. Lett. 2008, 37, 1080.
(b) Petrik, V.; Cahard, D. Tetrahedron Lett. 2007, 48, 3327. (c) Tomita,
Y.; Ichikawa, Y.; Itoh, Y.; Kawada, K.; Mikami, K. Tetrahedron Lett.
2007, 48, 8922. (d) Itoh, Y.; Houk, K. N.; Mikami, K. J. Org. Chem.
2006, 71, 8918. (e) Itoh, Y.; Mikami, K. Tetrahedron 2006, 62, 7199.
(f) Itoh, Y.; Mikami, K. J. Fluorine Chem. 2006, 127, 539. (g) Itoh, Y.;
Mikami, K. Org. Lett. 2005, 7, 4883.
result of an attack by water and tautomerization of the enol, as
depicted in Scheme 2.
In conclusion, we developed a direct oxidative trifluorome-
thylation using photoredox catalysis to obtain various α-CF3
incorporated ketones from various alkynes. The mechanistic
study revealed that H2O can be used as a nucleophile, and that
enol-keto tautomerization is occurring. The broad scope of
functional group tolerance, operational simplicity, and the
synthesis of various CF3-incorporated heterocyclic compounds
demonstrate the strong versatility of the reaction.
́
(3) (a) Cantillo, D.; de Frutos, O.; Rincon, J. A.; Mateos, C.; Kappe,
C. O. Org. Lett. 2014, 16, 896. (b) Pham, P. V.; Nagib, D. A.;
MacMillan, D. W. C. Angew. Chem., Int. Ed. 2011, 50, 6119.
(c) Jacquet, J.; Blanchard, S.; Derat, E.; Desage-El Murr, M.;
Fensterbank, L. Chem. Sci. 2016, 7, 2030. (d) Li, L.; Chen, Q.-Y.;
Guo, Y. J. Org. Chem. 2014, 79, 5145. (e) Ma, J.-A.; Cahard, D. J. Org.
Chem. 2003, 68, 8726.
(4) (a) Su, X.; Huang, H.; Yuan, Y.; Li, Y. Angew. Chem., Int. Ed.
2017, 56, 1338. (b) Kawamoto, T.; Sasaki, R.; Kamimura, A. Angew.
Chem., Int. Ed. 2017, 56, 1342.
(5) For more examples, see: (a) Deng, Q.-H.; Wadepohl, H.; Gade,
L. H. J. Am. Chem. Soc. 2012, 134, 10769. (b) Herrmann, A. T.; Smith,
L. L.; Zakarian, A. J. Am. Chem. Soc. 2012, 134, 6976. (c) Novak, P.;
́
Lishchynskyi, A.; Grushin, V. V. J. Am. Chem. Soc. 2012, 134, 16167.
(d) Morandi, B.; Carreira, E. M. Angew. Chem., Int. Ed. 2011, 50, 9085.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b00410.
(e) Valero, G.; Companyo,
́
X.; Rios, R. Chem.Eur. J. 2011, 17, 2018.
Experimental procedures and spectroscopic data for all
new compounds (PDF)
(f) Allen, A. E.; MacMillan, D. W. C. J. Am. Chem. Soc. 2010, 132,
4986. (g) Nagib, D. A.; Scott, M. E.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2009, 131, 10875. (h) Sato, K.; Yuki, T.; Yamaguchi, R.; Hamano,
T.; Tarui, A.; Omote, M.; Kumadaki, I.; Ando, A. J. Org. Chem. 2009,
74, 3815. (i) Noritake, S.; Shibata, N.; Nomura, Y.; Huang, Y.;
Matsnev, A.; Nakamura, S.; Toru, T.; Cahard, D. Org. Biomol. Chem.
2009, 7, 3599. (j) Sato, K.; Yuki, T.; Tarui, A.; Omote, M.; Kumadaki,
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: sbhan@krict.re.kr.
D
DOI: 10.1021/acs.orglett.8b00410
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
I.; Ando, A. Tetrahedron Lett. 2008, 49, 3558. (k) Billard, T.; Langlois,
B. R. Eur. J. Org. Chem. 2007, 2007, 891. (l) Sato, K.; Omote, M.;
Ando, A.; Kumadaki, I. Org. Lett. 2004, 6, 4359. (m) Umemoto, T.;
Adachi, K. J. Org. Chem. 1994, 59, 5692.
(6) (a) Deb, A.; Manna, S.; Modak, A.; Patra, T.; Maity, S.; Maiti, D.
Angew. Chem., Int. Ed. 2013, 52, 9747. (b) Tomita, R.; Yasu, Y.; Koike,
T.; Akita, M. Angew. Chem., Int. Ed. 2014, 53, 7144. (c) Zhang, C.-P.;
Wang, Z.-L.; Chen, Q.-Y.; Zhang, C.-T.; Gu, Y.-C.; Xiao, J.-C. Chem.
Commun. 2011, 47, 6632. (d) Wu, Y.-b.; Lu, G.-p.; Yuan, T.; Xu, Z.-b.;
Wan, L.; Cai, C. Chem. Commun. 2016, 52, 13668. (e) Lu, Q.; Liu, C.;
Huang, Z.; Ma, Y.; Zhang, J.; Lei, A. Chem. Commun. 2014, 50, 14101.
(f) Li, L.; Chen, Q.-Y.; Guo, Y. J. Fluorine Chem. 2014, 167, 79.
(7) He, Z.; Zhang, R.; Hu, M.; Li, L.; Ni, C.; Hu, J. Chem. Sci. 2013,
4, 3478.
(8) Maji, A.; Hazra, A.; Maiti, D. Org. Lett. 2014, 16, 4524.
(9) (a) Han, H. S.; Lee, Y. J.; Jung, Y.-S.; Han, S. B. Org. Lett. 2017,
19, 1962. (b) An, W.; Ha, N.; Lee, H. M.; Malpani, Y. R.; Lee, D.-H.;
Jung, Y.-S.; Han, S. B. Adv. Synth. Catal. 2015, 357, 3949. (c) Oh, S.
H.; Malpani, Y. R.; Ha, N.; Jung, Y.-S.; Han, S. B. Org. Lett. 2014, 16,
1310.
(10) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev.
2013, 113, 5322.
(11) (a) Tomita, R.; Koike, T.; Akita, M. Angew. Chem., Int. Ed. 2015,
54, 12923. (b) Galli, C.; Guarnieri, A.; Koch, H.; Mencarelli, P.;
Rappoport, Z. J. Org. Chem. 1997, 62, 4072. (c) Wille, U. Chem. Rev.
2013, 113, 813.
(12) Oxidation state of fac-IrIV(ppy)3 is high and comparable to MnIII
oxidatants, see: Montevecchi, P. C.; Navacchia, M. L. Tetrahedron
2000, 56, 9339.
ox
1/2
(13) fac-Ir(ppy)3 is a powerful reductant (E = − 1.73 V vs SCE). It
has a high luminescence quantum yield (Φem = 0.4), suggesting strong
absorption of light (especially blue LED, λabs = 375 nm), efficient
MLCT, and further cascade process. These properties have made it
highly useful for various photoredox conversions, in comparison to
other photoredox catalysts. See: (a) Dixon, I. M.; Collin, J.-P.; Sauvage,
J.-P.; Flamigni, L.; Encinas, S.; Barigelletti, F. Chem. Soc. Rev. 2000, 29,
385. (b) King, K. A.; Spellane, P. J.; Watts, R. J. J. Am. Chem. Soc. 1985,
107, 1431. (c) Tucker, J. W.; Stephenson, C. R. J. J. Org. Chem. 2012,
77, 1617.
(14) 1,2 diphenylacetylene was also tried, but only 17% (NMR yield,
using 1,1,2,2-tetrachloroethylene as internal standard) of product
forms with many unidentified byproducts.
(15) For examples on synthesis of trifluoromethylated heterocycles,
see: (a) Wu, X.-F.; Neumann, H.; Beller, M. Chem.Asian J. 2012, 7,
1744. (b) Tomashenko, O. A.; Grushin, V. V. Chem. Rev. 2011, 111,
4475. (c) Begue, J.-P.; Bonnet-Delpon, D.; Crousse, B.; Legros, J.
Chem. Soc. Rev. 2005, 34, 562.
(16) See the Supporting Information for detailed procedures.
(17) Ohtsuka, Y.; Uraguchi, D.; Yamamoto, K.; Tokuhisa, K.;
Yamakawa, T. Tetrahedron 2012, 68, 2636. Small quantities (<10%) of
the other regioisomer was observed. See the Supporting Information
for details.
(18) (a) Dadiboyena, S.; Hamme, A. T., II. Curr. Org. Chem. 2012,
16, 1390. (b) Flower, R. J. Nat. Rev. Drug Discovery 2003, 2, 179.
(19) Halford, J. O.; Anderson, L. C.; Bates, J. R.; Swisher, R. D. J. Am.
Chem. Soc. 1935, 57, 1663.
(20) Byrn, M.; Calvin, M. J. Am. Chem. Soc. 1966, 88, 1916.
E
DOI: 10.1021/acs.orglett.8b00410
Org. Lett. XXXX, XXX, XXX−XXX