Ruthenium-Catalyzed Remote C-H Sulfonylation of N-Aryl-2-aminopyridines with Aromatic Sulfonyl Chlorides

Article abstract of DOI:10.1021/acs.orglett.7b03051

A ruthenium-catalyzed remote sulfonylation at the C5 position of the pyridine group of N-aryl-2-aminopyridines with aromatic sulfonyl chlorides is described. The mechanistic and deuterium labeling studies clearly reveal that the ruthenametallacycle is a key intermediate in the reaction, which forms via the C-H bond activation. The DFT calculation supports that the C5 position of the 2-aminopyridine group carries a more negative charge (-0.304) as compared with other carbons in the metalacycle intermediate.

Full text of DOI:10.1021/acs.orglett.7b03051

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX-XXX
Ruthenium-Catalyzed Remote C−H Sulfonylation of N‑Aryl-2-
aminopyridines with Aromatic Sulfonyl Chlorides
Balu Ramesh and Masilamani Jeganmohan*
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India
S
* Supporting Information
ABSTRACT: A ruthenium-catalyzed remote sulfonylation at the C5 position of the pyridine group of N-aryl-2-aminopyridines
with aromatic sulfonyl chlorides is described. The mechanistic and deuterium labeling studies clearly reveal that the
ruthenametallacycle is a key intermediate in the reaction, which forms via the C−H bond activation. The DFT calculation
supports that the C5 position of the 2-aminopyridine group carries a more negative charge (−0.304) as compared with other
carbons in the metalacycle intermediate.
he transition-metal-catalyzed direct functionalization of
Tunactivated C−H bonds of organic molecules has received
considerable attention in organic synthesis for the past two
decades.1−3 Several methods are available in the literature for
activating the C−H bond of organic molecules.1a−c,l Among
them, the chelation-assisted C−H bond activation has gained
tremendous attention due to the high selectivity.1−3 By
employing this method, the ortho C−H bond of aromatics is
successfully functionalized as well as extensively studied.1−3 Very
recently, the meta C−H bond functionalization of aromatics has
gained tremendous attention.4,5 Generally, the meta C−H bond
Figure 1. Ru-catalyzed remote C−H functionalization.
functionalization can be achieved by (a) the designed template
directing group strategy,4a−e (b) norbornene-mediated trans-
Generally, the sulfonylated pyridines are prepared by the reaction
formation,4f,g and (c) a ruthenium-catalyzed functionalization.5 It
is important to note the unique reactivity of ruthenium metal as
compared with other metals.1,2 The Ru−C aryl σ-bond of the key
metalacycle intermediate induces functionalization at the ortho
C−H bond3 or meta C−H bond5 to the directing group based on
the incoming electrophile. For this transformation, the readily
available directing groups such as 2-pyridyl, pyrazolyl, imidazolyl,
pyrimidyl, and azo can be used.5 In recent years, the meta selective
alkylation, sulfonylation, bromination, and nitration of aromatics
are performed successfully.5 Very recently, Frost’s group
disclosed an unusual ruthenium-catalyzed remote C-6 alkylation
of substituted indoles with alkyl halides.6
Herein, we report an unusual ruthenium-catalyzed remote C−
H sulfonylation at the C5 position ofthe pyridine group of N-aryl-
2-aminopyridines with aromatic sulfonylchlorides via C−H bond
activation (Figure 1). It is noteworthy to say that the pyridyl
sulfone moiety found widespread application in medicinal and
agricultural chemistry.7 Further, the sulfonylated pyridines also
show interesting biological properties, including anti-inflamma-
tory, antihyperglycemic, and immunosuppressive agents.7d
of halopyridines with sulfonylated sources.7d In the present
reaction, the sulfonylated pyridines are prepared by the C−H
bond functionalization without any prefunctionalized halogen
species. Although the sulfonylation reaction emerged via the C−
H activation strategy, to date only the aromatic C−H bond
activation has succeeded. To the best of our knowledge, this is the
first report where the sulfonylation has been achieved at the
heteroaromatic ring via C−H bond activation. It is important to
notethatthemetaselectivealkylationwasobservedinthereaction
of N-aryl-2-aminopyridines with alkyl bromides.5e In the present
work, the sulfonylation was observed at the remote C5 position of
the pyridine moiety instead of the meta position of the aromatic
moiety.
The reaction of N-phenyl-2-aminopyridine (1a) with 4-
toluenesulfonyl chloride (2a) (3.0 equiv) in the presence of
[{RuCl2(p-cymene)}2] (5.0 mol %) and Li2CO3 (2.0 equiv) in
toluene at 120 °C for 24 h provided sulfonylation at the C5
Received: September 29, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b03051
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 1. Ruthenium-Catalyzed C5 Sulfonylation of 1a
Table 1. Scope of N-Phenyl-2-aminopyridines 1b−o
position of the pyridine group of N-phenyl-2-aminopyridine 3aa
in 65% yield (Scheme 1). Initially, the ruthenium-catalyzed
sulfonylation reaction of 1a with 2a was examined with various
bases or carboxylic acids (2.0 equiv) in toluene at 120 °C for 24 h
(see Supporting Information (SI), Table S1). Various bases such
as K2CO3, Na2CO3, Li2CO3, NaHCO3, KHCO3, NaOAc, KOAc,
K3PO4, Na2HPO4, and NEt3 were examined in the reaction of 1a
with 2a. Among them, Li2CO3 was very effective, providing
product3aain65%yield. Inthereaction, theN-Htosylationof1a,
N-tosyl-N-phenyl-2-aminopyridine, was observed in 6% yield.
Na2CO3, NaHCO3, KHCO3, and Na2HPO4 were also equally
effective, giving product 3aa in 45−59% yields, respectively.
Remaining bases such as K2CO3, NaOAc, KOAc, K3PO4, and
NEt3 were less effective, affording product 3aa in 12−32% yields,
respectively. Organic acids such as 1-Adm-COOH and
mesitylenic acid were also partially effective, giving product 3aa
in 54% and 43% yields, respectively. In these reactions also, N-
tosyl-N-phenyl-2-aminopyridine was observed in 11−15% yields.
The sulfonylation reaction was further examined with various
solvents such as CH3COOH, benzene, toluene, 1,2-dichlor-
obenzene, THF, ClCH2CH2Cl (DCE), CH3CN, MeOH, 1,4-
dioxane, DMSO, DMF, and MeOCH2CH2MeO (DME). Among
them, toluene was very effective, providing 3aa in 65% yield. 1,2-
Dichlorobenzene and 1,4-dioxane were also equally effective,
giving product 3aa in 62% and 60% yields, respectively. Benzene,
THF, DME, and DCE were less effective, yielding 3aa in 40%,
53%, 43%, and 30% yields, respectively. Remaining solvents were
not effective. The reaction was examined with 1.2 and 2.2 equiv of
TsCl. In the reaction, product 3aa was observed in 35% and 50%
yields, respectively. Thesulfonylationreactionwasexamined with
N-methyl-N-phenyl-2-aminopyridine and N-phenyl-2-pyrimi-
dine under the optimized reaction conditions. However, no
expected sulfonylation or N-sulfonylation product was observed
and starting material was recovered.
a
All reactions were carried out using 1b−o (75 mg), 2a (3.0 equiv),
[{RuCl2(p-cymene)}2] (5 mol %), Li2CO3 (2.0 equiv) in toluene (3.0
b
mL) under N2 at 120 °C for 24 h. Isolated yield.
providingsulfonylationproducts3kaand3lainexcellent75%and
72% yields, respectively (entries 10 and 11). ortho Methyl 1m and
bromo 1n substituted N-phenyl-2-aminopyridine provided
products 3ma and 3na in 56% and 66% yields, respectively
(entries 12 and 13). 2-Pyridyl naphthylamine 1o effectively
participated in the reaction, affording product 3oa in 70% yield
(entry 14). The structure of compounds 3ca and 3da were
confirmed by single crystal X-ray diffraction (see Supporting
Information, pp S11−S12). It isalso important tonote that the N-
tosylation of 1, N-tosyl-N-phenyl-2-aminopyridine, was observed
in 6−18% yields.
The remote C−H sulfonylation reaction was examined with
substituted aromatic sulfonyl chlorides 2b−h (Scheme 2). Phenyl
sulfonyl chloride (2b), 4-tert-butyl phenyl sulfonyl chloride (2c),
and 4-methoxy phenyl sulfonyl chloride (2d) reacted with 1l,
yielding sulfonylated products 3lb−ld in 62%, 76%, and 63%
yields, respectively. Halogenated 4-bromo 2e and 4-fluoro 2f
phenyl sulfonyl chlorides reacted with 1l, providing 3le and 3lf in
73% and 79% yields, respectively. meta Methyl phenyl sulfonyl
chloride (2g) provided 3lg in 41% yield. 1-Naphthyl sulfonyl
chloride (2h) was also effectively involved in the reaction,
providing product 3lh in 65% yield.
The scope of the remote sulfonylation reaction was examined
with substituted N-phenyl-2-aminopyridine (Table 1). The
reaction of electron-donating OMe 1b, Me 1c, and Et 1d
substituents at the para position of N-phenyl-2-aminopyridine
with 2a provided sulfonylated products 3ba−da in 61%, 68%, and
50% yields, respectively (entries 1−3). Halogen groups such as Br
1e, Cl 1f, and F 1g at the para position of N-phenyl-2-
aminopyridine reacted with 2a, affording products 3ea−ga in
55%, 76%, and 61% yields, respectively (entries 4−6). However,
the electron-withdrawing CF3 substituent at the para position of
N-phenyl-2-aminopyridine 1h provided product 3ha in a very
reduced 25% yield. This resultclearly reveals the ortho C−H bond
activation as a key step in the reaction. Meanwhile, electron-
donating OMe 1i and Me 1j substituents at the meta position of
N-phenyl-2-aminopyridine afforded sulfonylation products 3ia
and 3ja in 57% and 45% yields, respectively (entries 8−9).
Interestingly, halogen Br 1k and Cl 1l substituents at the meta
position of N-phenyl-2-aminopyridine reacted efficiently with 2a,
To know more about the key intermediate in the sulfonylation
reaction, the following studies were done (Scheme 3). The
B
DOI: 10.1021/acs.orglett.7b03051
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Scope of Phenyl Sulfonyl Chlorides
Scheme 4. Proposed Mechanism
affords ruthenacycle intermediate 6. The remote C−H
sulfonylation at the C5 position of intermediate 6 via electrophilic
substitution which was induced by the NH group of 6 provides
intermediate 7 and HX. Later, protonation of the C−Ru bond of
intermediate 7 with HX provides product 3aa and regenerates the
active ruthenium catalyst.
To support the proposed mechanism, we have tried to isolate
the key intermediates 5 and 6 (Scheme 5). When 1a was treated
Scheme 5. Mechanistic Studies
Scheme 3. Deuterium Labelling Studies
with a stoichiometric amount of [{RuCl2(p-cymene)}2] (1.0
equiv) in THF solvent at 60 °C for 5 h, ruthenium complex 5 was
observed in 85% yield. Complex 5 was clearly confirmed by NMR
and mass spectrometry. Later, intermediate 5 was treated with
Li2CO3 (2.0 equiv) in toluene at 120 °C for 16 h, providing
ruthenametallacycle intermediate 6. Intermediate 6 was tenta-
1
tively assigned by H NMR and mass spectrometry. Further,
intermediate 5 was treated with 2a in the presence of Li2CO3 (2.0
equiv) in toluene at 120 °C for 16 h, giving 3aa in 69% yield.
Similarly, intermediate 6 was reacted with 2a in the presence of
Li2CO3 (2.0 equiv) in toluene at 120 °C for 16 h, providing
product 3aa in 62% yield. This clearly reveals that intermediates 5
and 6 are formed in the reaction.
reaction of N-methyl-2-aminopyridine (1p)with 2a under similar
reaction conditions provided N-tosylated pyridine 4b in 35%
yield. In the reaction, no sulfonylation at the C5 position of 2-
aminopyridine was observed. This result clearly reveals that the
arylgroupisneededforthesulfonylationreaction. Further, 1ewas
treated with CD3COOD under similar reaction conditions
without 2a. In the reaction, 30% of deuterium incorporation
was observed at both ortho C−H bonds of product D-1e.
Meanwhile, the reaction of 1b with 2a in the presence of
CD3COODprovided theexpected product D-3bain45%yieldin
which40%ofdeuteriumincorporationwasobservedatbothortho
C−H bonds of the phenyl group. These results also clearly reveal
C−H bond activation as a key step in the reaction as well as its
reversibility. The sulfonylation reaction of 1a with 2a was done in
the presence of the TEMPO radical scavenger. Product 3aa was
observed in 61% yield which says that the radical intermediate
may not be formed in the reaction.
In most of the reported Ru-catalyzed meta functionalization
reactions, sulfonylation, alkylation, bromination, and nitration
selectively takes place at the meta position of substituted
aromatics. In the present reaction, sulfonylation selectively
takes place at the C5 position of the pyridyl group of N-aryl-2-
aminopyridines. In intermediate 6, the NH group of aniline pulls
more electron density toward the pyridine instead of the phenyl
group. Thus, the C5 position of 2-aminopyridine has more
nucleophilic character as compared with other carbons in
intermediate 6, and thus sulfonylation takes place selectively at
the C5 position. To know more about the charge distribution, the
natural population analysis (NPA) has been carried out for
intermediate 6 by using the hybrid density functional theory
(B3LYP) (Figure 2). The NPA analysis clearly reveals that the C5
position of 2-aminopyridine of intermediate 6 carries more
negative charge (−0.304) as compared with other carbons,
including the meta carbon of the phenyl ring (−0.24) in complex
6.
A possible reaction mechanism for the remote C−H
sulfonylation of 1 is proposed in Scheme 4. The lone pair of the
nitrogen atom of the pyridine of 1a coordinates with the
[{RuCl2(p-cymene)}2] complex giving pyridyl-Ru adduct 5.
Base-mediated deprotonation at the ortho C−H of complex 5
C
DOI: 10.1021/acs.orglett.7b03051
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Delord, J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740.
(j) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed.
2009, 48, 5094. (k) Gandeepan, P.; Cheng, C.-H. Chem. - Asian J. 2015,
10, 824. (l) Das, S.; Incarvito, C. D.; Crabtree, R. H.; Brudvig, G. W.
Science 2006, 312, 1941.
(2) Selected recent reviews: (a) Yang, L.; Huang, H. Chem. Rev. 2015,
115, 3468. (b) Petrone, D. A.; Ye, J.; Lautens, M. Chem. Rev. 2016, 116,
8003. (c) Kim, D. S.; Park, W. J.; Jun, C.-H. Chem. Rev. 2017, 117, 8977.
(d) Gensch, T.; Hopkinson, M. N.; Glorius, F.; Wencel-Delord, J. Chem.
Soc. Rev. 2016, 45, 2900. (e)Zhang, F.;Spring, D.R. Chem. Soc. Rev. 2014,
43, 6906. (f) Park, Y.; Kim, Y.; Chang, S. Chem. Rev. 2017, 117, 9247.
(3) Selected ruthenium papers: (a) Nareddy, P.; Jordan, F.; Szostak, M.
ACS Catal. 2017, 7, 5721. (b) Manikandan, R.; Jeganmohan, M. Chem.
Commun. 2017, 53, 8931. (c) Flegeau, E. F.; Bruneau, C.; Dixneuf, P. H.;
Jutand, A. J. Am. Chem. Soc. 2011, 133, 10161. (d) Ueyama, T.; Mochida,
S.; Fukutani, T.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2011, 13, 706.
(e) Ackermann, L.; Wang, L.; Wolfram, R.; Lygin, A. V. Org. Lett. 2012,
14, 728. (f) Arockiam, P. B.; Fischmeister, C.; Bruneau, C.; Dixneuf, P. H.
Green Chem. 2011, 13, 3075. (g) Parthasarathy, K.; Senthilkumar, N.;
Jayakumar, J.; Cheng, C.-H. Org. Lett. 2012, 14, 3478. (h) Manikandan,
R.; Madasamy, P.; Jeganmohan, M. ACS Catal. 2016, 6, 230. (i) Reddy,
M. C.; Jeganmohan, M. Chem. Sci. 2017, 8, 4130. (j) Mehta, V. P.; García-
Figure 2. Charge distribution of intermediate 6.
In conclusion, we have demonstrated a ruthenium-catalyzed
remote sulfonylation at the C5 position of the pyridyl group of N-
aryl-2-aminopyridines with aromatic sulfonyl chlorides. The
reaction provides substituted pyridyl sulfone derivatives in good
to moderate yields. The deuterium labeling studies and
mechanistic investigation proves that the ruthenametallacycle is
a key intermediate in the reaction which forms via the C−H bond
activation. The DFT calculation clearly supports that the C3
position of the pyridyl group is more nucleophilic as compared
with other carbons of the ruthenametallacycle intermediate.
́
Lopez, J. A.; Greaney, M. F. Angew. Chem., Int. Ed. 2014, 53, 1529.
(k) Nareddy, P.; Jordan, F.; Szostak, M. Chem. Sci. 2017, 8, 3204.
(l)Hashimoto, Y.;Hirano, K.;Satoh, T.;Kakiuchi, F.;Miura,M. Org.Lett.
2012,14,2058. (m)Muralirajan, K.;Parthasarathy, K.;Cheng, C.-H. Org.
Lett. 2012, 14, 4262. (n) Nareddy, P.; Jordan, F.; Brenner-Moyer, S. E.;
Szostak, M. ACS Catal. 2016, 6, 4755.
(4) Selected earlier examples: (a) Tang, R.-Y.; Li, G.; Yu, J.-Q. Nature
2014, 507, 215. (b) Leow, D.; Li, G.; Mei, T.-S.; Yu, J.-Q. Nature 2012,
486, 518. (c) Deng, Y.; Yu, J.-Q. Angew. Chem., Int. Ed. 2015, 54, 888.
(d) Bera, M.; Modak, A.; Patra, T.; Maji, A.; Maiti, D. Org. Lett. 2014, 16,
5760. (e) Bera, M.; Maji, A.; Sahoo, S. K.; Maiti, D. Angew. Chem., Int. Ed.
2015, 54, 8515. (f) Wang, X.-C.; Gong, W.; Fang, L.-Z.; Zhu, R.-Y.; Li, S.;
Engle, K. M.; Yu, J.-Q. Nature 2015, 519, 334 and references therein.
(g) Dong, Z.; Wang, J.; Dong, G. J. Am. Chem. Soc. 2015, 137, 5887 and
references therein.
ASSOCIATED CONTENT
* Supporting Information
■
S
TheSupportingInformationisavailablefreeofchargeontheACS
Publications website at DOI: 10.1021/acs.orglett.7b03051.
(5) (a) Saidi, O.; Marafie, J.; Ledger, A. E. W.; Liu, P. M.; Mahon, M. F.;
Kociok-Kohn, G.; Whittlesey, M. K.; Frost, C. G. J. Am. Chem. Soc. 2011,
̈
General experimental procedure, characterization details,
and X-ray analysis information (PDF)
Crystallographic data for 3ca (CIF)
133,19298. (b)Chinnagolla, R.K.;Pimparkar, S.;Jeganmohan, M.Chem.
Commun. 2013, 49, 3146. (c) Hofmann, N.; Ackermann, L. J. Am. Chem.
Soc. 2013, 135, 5877. (d) Paterson, A. J.; St. John-Campbell, S.; Mahon,
M. F.; Press, N. J.; Frost, C. G. Chem. Commun. 2015, 51, 12807. (e)Li, J.;
Warratz, S.; Zell, D.; De Sarkar, S.; Ishikawa, E. E.; Ackermann, L. J. Am.
Chem. Soc. 2015, 137, 13894. (f) Teskey, C. J.; Lui, Y. W.; Greaney, M. F.
Angew. Chem., Int. Ed. 2015, 54, 11677. (g) Yu, Q.; Hu, L.; Wang, Y.;
Zheng, S.; Huang, J. Angew. Chem., Int. Ed. 2015, 54, 15284. (h) Fan, Z.;
Ni, J.; Zhang, A. J. Am. Chem. Soc. 2016, 138, 8470. (i) Warratz, S.; Burns,
D. J.; Zhu, C.; Korvorapun, K.; Rogge, T.; Scholz, J.; Jooss, C.; Gelman,
D.; Ackermann, L. Angew. Chem., Int. Ed. 2017, 56, 1557. (j) Ruan, Z.;
Zhang, S.-K.; Zhu, C.; Ruth, P. N.; Stalke, D.; Ackermann, L. Angew.
Chem., Int. Ed. 2017, 56, 2045. (k) Li, G.; Ma, X.; Jia, C.; Han, Q.; Wang,
Y.; Wang, J.; Yu, L.; Yang, S. Chem. Commun. 2017, 53, 1261. (l) Li, G.;
Lv, X.; Guo, K.; Wang, Y.; Yang, S.; Yu, L.; Yu, Y.; Wang, J. Org. Chem.
Front. 2017,4,1145. (m)Yuan,C.C.;Chen, X.L.;Zhang,J. Y.;Zhao,Y.S.
Org. Chem. Front. 2017, 4, 1867. (n) Li, J.; Korvorapun, K.; De Sarkar, S.;
Rogge, T.; Burns, D. J.; Warratz, S.; Ackermann, L. Nat. Commun. 2017,
8, 15430. (o) Fan, Z.; Ni, J.; Zhang, A. J. Am. Chem. Soc. 2016, 138, 8470.
(p) Fan, Z.; Li, J.; Wang, D.−Y.; Wang, C.; Uchiyama, M.; Zhang, A. Org.
Lett. 2017, 19, 3199. (q) Li, G.;Zhu, B.; Ma, X.; Jia, C.; Wang, J.;Zhao, F.;
Lv, Y.; Yang, S. Org. Lett. 2017, 19, 5166.
Crystallographic data for 3da (CIF)
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: mjeganmohan@iitm.ac.in; mjeganmohan@iiserpune.
ac.in.
ORCID
Masilamani Jeganmohan: 0000-0002-7835-3928
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the DST-SERB (EMR/2014/000978), India for the
support of this research. B.R. thanks the CSIR for a fellowship.
■
REFERENCES
■
(6) Leitch, J. A.; McMullin, C. L.; Mahon, M. F.; Bhonoah, Y.; Frost, C.
G. ACS Catal. 2017, 7, 2616.
(7) C−S:(a) Beletskaya, I.; Ananikov, V. P. Chem. Rev. 2011, 111, 1596.
(b)Shaaban, S.;Liang,S.;Liu,N.-W.;Manolikakes, G. Org.Biomol.Chem.
(1) Selected reviews: (a) Miura, M.; Nomura, M. Top. Curr. Chem.
2002, 219, 211. (b) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002, 35, 826.
(c) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731.
(d) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147.
(e) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev. 2012, 112,
5879. (f) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215.
(g) Ackermann, L. Chem. Rev. 2011, 111, 1315. (h) Colby, D. A.;
Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (i) Wencel-
́
2017, 15, 1947. (c) Zhao, X.; Dimitrijevic, E.; Dong, V. M. J. Am. Chem.
Soc. 2009, 131, 3466. (d)Maloney, K. M.;Kuethe, J. T.;Linn, K. Org. Lett.
2011, 13, 102 and references therein. (e) Su, Y.; Zhou, X.; He, C.; Zhang,
W.; Ling, X.; Xiao, X. J. Org. Chem. 2016, 81, 4981.
D
DOI: 10.1021/acs.orglett.7b03051
Org. Lett. XXXX, XXX, XXX−XXX