Palladium-Catalyzed Benzylic C-H Arylation of Azaarylmethylamines

Article abstract of DOI:10.1021/acs.orglett.5b02898

A direct C-H functionalization approach to produce aryl(azaaryl)methylamines from azaarylmethylamines without directing groups is described. Under conditions where the azaarylmethylamines' C-H is reversibly deprotonated, a Pd(OAc)₂/NIXANTPHOS-b

Full text of DOI:10.1021/acs.orglett.5b02898

Letter
pubs.acs.org/OrgLett
Palladium-Catalyzed Benzylic C−H Arylation of Azaarylmethylamines
Byeong-Seon Kim,†,∥ Jacqueline Jimenez,†,‡,∥ Feng Gao,†,§ and Patrick J. Walsh*,†
́
†Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States
‡Facultad de Ciencias Químicas, Benemer
́ ́
ita Universidad Autonoma de Puebla, Puebla 72570, Mexico
§Department of Medicinal Plants, Agronomy College, Sichuan Agricultural University, 211 Huimin Roadd, Wenjiang Region,
Chengdu 611130, PR China
S
* Supporting Information
ABSTRACT: A direct C−H functionalization approach to
produce aryl(azaaryl)methylamines from azaarylmethylamines
without directing groups is described. Under conditions where
the azaarylmethylamines’ C−H is reversibly deprotonated, a
Pd(OAc)2/NIXANTPHOS-based catalyst couples the result-
ing carbanions with various aryl halides to provide aryl-
(azaaryl)methylamines. This umpolung strategy directly
provides tertiary amines without protecting or activating groups.
yridine and quinoline derivatives are important hetero-
direct C−H functionalization of amino alkyl moieties
Pcycles that are present in a broad range of biologically (R′CH2NR2), however, is challenging.9 Therefore, activated
substrates, such as Boc-protected amines, ketimines, and (η6-
active natural products and pharmaceutically relevant com-
pounds.1 Aryl(azaaryl)methylamines are prominent in bio-
benzylamine)Cr(CO)3 complexes, have been employed to
logically active small molecules, exhibiting antitumor,2 anti-
virus,3 anti-HIV,4 and antihistamine activities5 (Figure 1).
Furthermore, recent statistical studies indicate that the
prominence of heteroaromatic rings in marketed oral drugs is
increasing.6
facilitate deprotonation of C−H bonds adjacent to nitrogen
(Figure 2).10 The activating groups necessary in Figure 2 to
Figure 2. Representative synthetic intermediates with directing groups
(A, B) and activating groups (C−F) employed in metal-catalyzed C−
H functionalization adjacent to nitrogen.
increase reactivity are often subsequently transformed into the
desired functional groups or excised from the product entirely,
decreasing the synthetic efficiency.
Considering the importance of aryl(azaaryl)methylamines,
the development of in situ deprotonation/arylation strategies
for their synthesis that do not employ activating groups would
be valuable. Based on our experience in deprotonative cross-
coupling reactions10c−f,11 with weakly acidic substrates, we
hypothesized that the reversible deprotonation of (amino-
methyl)pyridines in the presence of a palladium catalyst should
be possible.
Figure 1. Selected pharmacologically active compounds containing
aryl(azaaryl)methylamines.
Conventional approaches to the synthesis of 1,1-diary-
lmethylamine derivatives7 include substitution reactions with
amine nucleophiles, addition of aryl or azaaryl organometallic
reagents to imines, and reduction of imines.8 Despite the
popularity of these methods, they involve prefunctionalized
electrophiles or nucleophiles. Transition-metal-catalyzed cross-
coupling reactions also represent an attractive approach.7d The
Received: October 6, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b02898
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 1. Selected Optimization of Pd-Catalyzed C(sp3)−H
Arylation of 1a with 2a
Herein, we report a practical method to prepare aryl-
(azaaryl)methylamines from (aminomethyl)pyridines and aryl
halides using a Pd−NIXANTPHOS-based catalyst (Scheme 1).
Scheme 1. Palladium-Catalyzed Benzylic C−H Arylation
with Azaarylmethylamines
a
b
entry
base
1a/2a/base
solvent
THF
yield (%)
1
LiO-t-Bu
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:2
1:1.2:2
1:1:1.5
1:1.2:2
0
2
NaO-t-Bu
THF
THF
THF
THF
THF
DME
CPME
0
3
KO-t-Bu
0
4
LiN(SiMe3)2
NaN(SiMe3)2
KN(SiMe3)2
LiN(SiMe3)2
LiN(SiMe3)2
LiN(SiMe3)2
LiN(SiMe3)2
LiN(SiMe3)2
LiN(SiMe3)2
LiN(SiMe3)2
87
80
83
82
85
90
92
5
This approach affords single-step access to aryl(azaaryl)-
methylamines from simple starting materials. Notably, to the
best of our knowledge, the direct functionalization of
aminomethyl azaarenes has not been successfully achieved
prior to this work.
6
7
8
9
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
10
11
12
13
We anticipated two challenges to advancing a successful
deprotonative cross-coupling process (DCCP) with
(aminomethyl)pyridine derivatives: (1) introduction of con-
ditions for the in situ deprotonation of the weakly acidic C−H’s
of the substrate and (2) identification of a catalyst capable of
promoting coupling of the resulting organolithium, -sodium, or
-potassium derivatives with aryl halides. In the latter case, we
have found that palladium complexes of van Leeuwen’s
NIXANTPHOS ligand12 outperform other Pd−phosphine
complexes in this class of reactions. As such, it has become
our “go to” ligand for new substrate classes. Concerning the
deprotonation step, the pKa of the sp3-hybridized C−H’s of 2-
(aminomethyl)pyridines are unknown, although that of 2-
methylpyridine has been determined to be 34 in THF.13 The
high pKa value of these substrates suggests that alkoxide and
silylamide bases are good starting points. Additionally,
palladium-catalyzed benzylic arylations of pyridine derivatives
have become a powerful method to construct aryl(azaaryl)-
methane derivatives.14
c
98 (92)
d
73
e
64
a
Tetrahydrofuran (THF), 1,2-dimethoxyethane (DME), cyclopentyl
b
methyl ether (CPME), and 1,4-dioxane (dioxane). Yields were
determined by H NMR analysis of unpurified reaction mixtures with
internal standard CH2Br2. Isolated yield. 14% of 1a remained. 2.5
mol % of Pd(OAc)2 and 3.75 mol % of NIXANTPHOS.
1
c
d
e
(Scheme 2). Morpholine, pyrrolidine, and N-methylpiperazine
were coupled with aryl bromides bearing various substituents,
generating aryl(2-pyridyl)methylamines in good to excellent
isolated yields (65−98%). The arylated products 3b−d were
obtained in 78−83% yield with bromobenzene and 1-
bromonaphthalene. Under the same reaction conditions,
chlorobenzene was also a suitable coupling partner, providing
3b in 78% yield. Aryl bromides bearing electron-donating 4-
NMe2 and 4-OMe resulted in coupling products 3e−h in 71−
94% yield. Aryl bromides with electron-withdrawing 4-F and 3-
CF3 groups were well tolerated and provided aryl(2-pyridyl)-
methylamines 3i−k in 71−94% yield. Heterocyclic 3-
bromopyridine was also a suitable coupling partner to generate
dipyridylmethyl morpholine 3l in 65% yield. The reactions with
1 mol % of catalyst generally occurred in good yields (71−75%
yield, 3d, 3g, and 3i). To illustrate the scalability of our method,
we conducted coupling of 2-(morphorinomethyl)pyridine (1a,
10 mmol) with 1-bromo-4-fluorobenzene using 4 mol % of
catalyst. The coupling product 3m was isolated in 96% yield
(2.61 g).
Next, we turned our attention to acyclic amines. The
optimized arylation conditions employed with cyclic amines
were easily transferable to N,N-dimethyl- or -diethylamine
derivatives with a variety of aryl bromides. Thus, aryl bromides
with neutral (4-t-Bu, 3-Me), electron-donating (4-OMe, 4-
NMe2), or electron-withdrawing (4-F, 4-Cl, 3-OMe, 3-CF3)
substituents coupled with 2-(N,N-dialkylaminomethyl)pyridine,
providing the cross-coupling products 4a−o in 60−98% yield
(Scheme 3). The yields with N,N-dimethylamine derivatives are
slightly higher than those with cyclic amines. Several relatively
challenging substrates (1-bromo-4-trifluoromethylbenzene and
5-bromobenzofuran) were also competent coupling partners,
albeit in reduced yields (4i,j, 60−66% yield). While 1-
bromonaphthylene furnished coupling product 4k in 69%
We initially tested the reactions of 2-(morphorinomethyl)-
pyridine (1a) with 1-bromo-4-tert-butylbenzene using Pd-
(OAc)2 (5 mol %) and NIXANTPHOS (7.5 mol %) in THF
at 65 °C. Six bases [LiO-t-Bu, NaO-t-Bu, KO-t-Bu, LiN-
(SiMe3)2, NaN(SiMe3)2, and KN(SiMe3)2] were employed,
and the results are displayed in entries 1−6 of Table 1.
Although MO-t-Bu bases [M = Li, Na, K] did not generate
the desired product 3a (entries 1−3), MN(SiMe3)2 bases (M =
Li, Na, K) were all very promising, affording 80−87% assay
yield (AY) of the cross-coupling product 3a (entries 4−6). The
most promising result was obtained with LiN(SiMe3)2 (87%
1
AY as determined by H NMR, entry 4). We next screened
other ethereal solvents (DME, CPME, 1,4-dioxane) (entries 7−
9). Of these, 1,4-dioxane led to 90% AY of the desired product
(entry 9). Examination of the stoichiometry indicated use of a
1:1.2:2 ratio of pyridylmethylamine (1a)/1-bromo-4-tert-
butylbenzene (2a)/LiN(SiMe3)2 rendered 98% AY of 3a,
leading to 92% isolated yield (entry 11). Use of a stoichiometric
amount of 1-bromo-4-tert-butylbenzene (2a) or lower catalyst
loading [2.5 mol % Pd(OAc)2 and 3.75 mol % of
NIXANTPHOS] resulted in incomplete conversion at 65 °C
after 12 h (entries 12−13). The optimized conditions (entry
11, Table 1) were then used to define the substrate scope.
The scope of the arylation was initially explored with 2-
(cyclic amino)methylpyridines (1) using aryl bromides
B
DOI: 10.1021/acs.orglett.5b02898
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Organic Letters
Letter
Scheme 2. Pd-Catalyzed C(sp3)−H Arylation of 2-
isolated in 66−69% yield. Sterically more hindered 2-(N-
benzyl-N-methylaminomethyl)pyridine did not react (<2%
yield). Similar results were observed in related reactions by
Baudoin and our groups with bulkier substituents on
nitrogen.11o,15
a
Pyridylmethylamines 1 with Aryl Bromides 2
The above results led us to wonder if this method would be
limited to 2-pyridyl derivatives because it requires a directed
metalation for the deprotonation. To answer this question,
other heterocyclic substrates were tested. Although the pKa’s of
4-pyridylmethylamines are not reported, 4-methylpyridine has a
pKa of 32.2 in THF.13 As shown in Scheme 4, 4-pyridylmethyl-
Scheme 4. Benzylic Cross-Coupling of Azaarene Derivatives
a
b
c
Isolated yields. X = Br unless noted. 1 mol % of Pd(OAc)2 and 1.5
a
b
c
mol % of NIXANTPHOS and the yields in parentheses with 5 mol %
Isolated yields. X = Br was used unless noted. 5 mol % of
d
of Pd(OAc)2 and 7.5 mol % of NIXANTPHOS. 5 mol % of
Pd(OAc)2 and 7.5 mol % of NIXANTPHOS and the yields in
parentheses with 1 mol % of Pd(OAc)2 and 1.5 mol % of
NIXANTPHOS. 4 mol % of Pd(OAc)2 and 6 mol % of
NIXANTPHOS.
e
Pd(OAc)2 and 10 mol % of NIXANTPHOS. The reaction was
d
conducted in THF at 110 °C with KN(SiMe3)2 instead of
LiN(SiMe3)2.
Scheme 3. Benzylic Cross-Coupling of 2-
(Dialkylaminomethyl)pyridine 1 with Aryl Bromides 2
a
amine derivatives were excellent substrates, providing coupling
products in 55−92% yield (5a−h) with 1 mol % catalyst
loading. These results indicate that chelation of the base to the
2-pyridyl group is not necessary for the reversible deprotona-
tion step of this DCCP.
Additional heterocycles were also amenable to the DCCP.
Under the conditions used for 2-pyridylamines, a 2-
(aminomethyl)quinoline derivative underwent a direct arylation
reaction in 52% yield (5i). The least acidic substrate tested in
this study was the 3-pyridylmethylamine derivative. The pKa of
3-methylpyridine is 37.7 in THF.13 After extensive optimization
of bases, solvents, and temperature, we were able to achieve
coupling in the presence of 2 equiv of KN(SiMe3)2 in THF at
110 °C, resulting in arylation product 5j in 65% yield.
In summary, we report the first direct palladium-catalyzed
benzylic C(sp3)−H arylation of cyclic and acyclic aminomethyl-
substituted azaarenes with aryl bromides. A variety of
aryl(azaaryl)methylamines were prepared in good to excellent
yields from readily accessible tertiary aminomethyl azaarenes. It
is noteworthy that addition and removal of directing groups
was not necessary with these substrates, facilitating their
streamlined synthesis. This new method enables the rapid
preparation of druglike molecules using straightforward
a
Isolated yields.
yield, the sterically more hindered 2-bromotoluene failed to
provide the desired product (<2% yield). 2-(3-Bromophenyl)-
1,3-dioxolane generated acetal-protected aldehyde product 4l in
60% yield. When the same conditions were applied to 2-(N,N-
diethylaminomethyl)pyridine, the desired products 4m−o were
C
DOI: 10.1021/acs.orglett.5b02898
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(9) Dastbaravardeh, N.; Schnuerch, M.; Mihovilovic, M. D. Org. Lett.
2012, 14, 1930.
techniques that are ideal for applications in medicinal
chemistry.16
(10) (a) Niwa, T.; Yorimitsu, H.; Oshima, K. Org. Lett. 2008, 10,
4689. (b) Niwa, T.; Suehiro, T.; Yorimitsu, H.; Oshima, K.
Tetrahedron 2009, 65, 5125. (c) McGrew, G. I.; Temaismithi, J.;
Carroll, P. J.; Walsh, P. J. Angew. Chem., Int. Ed. 2010, 49, 5541.
(d) McGrew, G. I.; Stanciu, C.; Zhang, J.; Carroll, P. J.; Dreher, S. D.;
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.5b02898.
Walsh, P. J. Angew. Chem., Int. Ed. 2012, 51, 11510. (e) Li, M.; Yucel,
̈
B.; Adrio, J.; Bellomo, A.; Walsh, P. J. Chem. Sci. 2014, 5, 2383. (f) Li,
M.; Berritt, S.; Walsh, P. J. Org. Lett. 2014, 16, 4312. (g) Fernandez-
Salas, J. A.; Marelli, E.; Nolan, S. P. Chem. Sci. 2015, 6, 4973.
Spectroscopic characterization data and procedures for
preparation of all new compounds (PDF)
(11) (a) Zhang, J.; Bellomo, A.; Creamer, A. D.; Dreher, S. D.;
Walsh, P. J. J. Am. Chem. Soc. 2012, 134, 13765. (b) Jia, T.; Bellomo,
A.; El Baina, K.; Dreher, S. D.; Walsh, P. J. J. Am. Chem. Soc. 2013, 135,
3740. (c) Montel, S.; Jia, T.; Walsh, P. J. Org. Lett. 2014, 16, 130.
(d) Zheng, B.; Jia, T.; Walsh, P. J. Org. Lett. 2013, 15, 1690. (e) Zheng,
B.; Jia, T. Z.; Walsh, P. J. Org. Lett. 2013, 15, 4190. (f) Frensch, G.;
Hussain, N.; Marques, F. A.; Walsh, P. J. Adv. Synth. Catal. 2014, 356,
2517. (g) Gao, F.; Kim, B.-S.; Walsh, P. J. Chem. Commun. 2014, 50,
10661. (h) Hussain, N.; Frensch, G.; Zhang, J.; Walsh, P. J. Angew.
Chem., Int. Ed. 2014, 53, 3693. (i) Montel, S.; Raffier, L.; He, Y.;
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: pwalsh@sas.upenn.edu.
Author Contributions
∥B.-S.K. and J.J. contributed equally.
Notes
Walsh, P. J. Org. Lett. 2014, 16, 1446. (j) Yucel, B.; Walsh, P. J. Adv.
̈
Synth. Catal. 2014, 356, 3659. (k) Zheng, B.; Jia, T.; Walsh, P. J. Adv.
Synth. Catal. 2014, 356, 165. (l) Zhang, J.; Bellomo, A.; Trongsiriwat,
N.; Jia, T.; Carroll, P. J.; Dreher, S. D.; Tudge, M. T.; Yin, H.;
Robinson, J. R.; Schelter, E. J.; Walsh, P. J. J. Am. Chem. Soc. 2014, 136,
6276. (m) Mao, J.; Eberle, K.; Zhang, J.; Rodríguez-Escrich, C.; Xi, Z.;
Pericas, M. A.; Walsh, P. J. Tetrahedron Lett. 2015, 56, 3604. (n) Sha,
̀
S.-C.; Zhang, J.; Walsh, P. J. Org. Lett. 2015, 17, 410. (o) Hussain, N.;
Kim, B.-S.; Walsh, P. J. Chem. - Eur. J. 2015, 21, 11010.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support for this work was provided by NIH/NIGMS
(GM 104349). J.J. thanks CONACyT (Mex
́
ico) for fellowships.
F.G. thanks the China Scholarship Counsel for fellowships.
(12) (a) van der Veen, L. A.; Keeven, P. H.; Schoemaker, G. C.;
Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Lutz, M.;
Spek, A. L. Organometallics 2000, 19, 872. (b) Kamer, P. C. J.; van
Leeuwen, P. W. N. M.; Reek, J. N. H. Acc. Chem. Res. 2001, 34, 895.
(13) Fraser, R. R.; Mansour, T. S.; Savard, S. J. Org. Chem. 1985, 50,
3232.
(14) (a) Niwa, T.; Yorimitsu, H.; Oshima, K. Angew. Chem., Int. Ed.
2007, 46, 2643. (b) Niwa, T.; Yorimitsu, H.; Oshima, K. Org. Lett.
2007, 9, 2373. (c) Hlavinka, M. L.; Hagadorn, J. R. Organometallics
2007, 26, 4105. (d) Campeau, L.-C.; Schipper, D. J.; Fagnou, K. J. Am.
REFERENCES
■
(1) (a) Henry, G. D. Tetrahedron 2004, 60, 6043. (b) Michael, J. P.
Nat. Prod. Rep. 2005, 22, 627. (c) Laird, T. Org. Process Res. Dev. 2006,
10, 851. (d) Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; John
Wiley & Sons: Chichester, U.K., 2010. (e) Alexander, F. Pozharskii, A.
S., Katritzky, A. R. Heterocycles in Life and Society: An Introduction to
Heterocyclic Chemistry, Biochemistry and Applications, 2nd ed.; John
Wiley & Sons: Chichester, U.K., 2011. (f) Baumann, M.; Baxendale, I.
R. Beilstein J. Org. Chem. 2013, 9, 2265.
(2) Liu, M.; Bryant, M. S.; Chen, J.; Lee, S.; Yaremko, B.; Li, Z.; Dell,
J.; Lipari, P.; Malkowski, M.; Prioli, N.; Rossman, R. R.; Korfmacher,
W. A.; Nomeir, A. A.; Lin, C. C.; Mallams, A. K.; Doll, R. J.; Catino, J.
J.; Girijavallabhan, V. M.; Kirschmeier, P.; Bishop, W. R. Cancer
Chemother. Pharmacol. 1998, 43, 50.
(3) Chern, J.-H.; Shia, K.-S.; Hsu, T.-A.; Tai, C.-L.; Lee, C.-C.; Lee,
Y.-C.; Chang, C.-S.; Tseng, S.-N.; Shih, S.-R. Bioorg. Med. Chem. Lett.
2004, 14, 2519.
(4) Summa, V.; Petrocchi, A.; Matassa, V. G.; Gardelli, C.; Muraglia,
E.; Rowley, M.; Paz, O. G.; Laufer, R.; Monteagudo, E.; Pace, P. J. Med.
Chem. 2006, 49, 6646.
́
Chem. Soc. 2008, 130, 3266. (e) Mousseau, J. J.; Larivee, A.; Charette,
A. B. Org. Lett. 2008, 10, 1641. (f) Schipper, D. J.; Campeau, L.-C.;
Fagnou, K. Tetrahedron 2009, 65, 3155. (g) Burton, P. M.; Morris, J.
A. Org. Lett. 2010, 12, 5359. (h) Shang, R.; Yang, Z.-W.; Wang, Y.;
Zhang, S.-L.; Liu, L. J. Am. Chem. Soc. 2010, 132, 14391. (i) Duez, S.;
Steib, A. K.; Manolikakes, S. M.; Knochel, P. Angew. Chem., Int. Ed.
2011, 50, 7686. (j) Song, G.; Su, Y.; Gong, X.; Han, K.; Li, X. Org. Lett.
2011, 13, 1968. (k) Zhao, D.; Zhu, M.-X.; Wang, Y.; Shen, Q.; Li, J.-X.
Org. Biomol. Chem. 2013, 11, 6246.
(15) Millet, A.; Dailler, D.; Larini, P.; Baudoin, O. Angew. Chem., Int.
Ed. 2014, 53, 2678.
(5) Anagnostopulos, H.; Bartlett, R. R.; Elben, U.; Stoll, P. Eur. J.
Med. Chem. 1989, 24, 227.
(6) Ritchie, T. J.; Macdonald, S. J. F.; Young, R. J.; Pickett, S. D. Drug
(16) From preliminary experiments screening 37 different
Ni(phosphine)-based catalysts in the coupling of 1a with bromo-
benzene, it was found that the Ni(NIXANTPHOS)-based catalyst
gave the highest product/internal standard ratio; see: Cao, X.; Sha, S.-
C.; Li, M.; Kim, B.-S.; Morgan, C.; Huang, R.; Yang, X.; Walsh, P. J.
Chem. Sci. 2016, DOI: 10.1039/C5SC03704B.
Discovery Today 2011, 16, 164.
(7) (a) Doggrell, S. A.; Liang, L. C. Naunyn-Schmiedeberg's Arch.
Pharmacol. 1998, 357, 126. (b) Plobeck, N.; Delorme, D.; Wei, Z.-Y.;
Yang, H.; Zhou, F.; Schwarz, P.; Gawell, L.; Gagnon, H.; Pelcman, B.;
Schmidt, R.; Yue, S. Y.; Walpole, C.; Brown, W.; Zhou, E.; Labarre, M.;
Payza, K.; St-Onge, S.; Kamassah, A.; Morin, P.-E.; Projean, D.;
Ducharme, J.; Roberts, E. J. Med. Chem. 2000, 43, 3878. (c) Ko, Y.;
Malone, D. C.; Armstrong, E. P. Pharmacotherapy 2006, 26, 1694.
(d) Ameen, D.; Snape, T. J. MedChemComm 2013, 4, 893.
(8) (a) Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99, 1069.
(b) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry: Part B:
Reaction and Synthesis, 5th ed.; Springer: New York, 2007.
(c) Kobayashi, S.; Mori, Y.; Fossey, J. S.; Salter, M. M. Chem. Rev.
2011, 111, 2626. (d) Smith, M. B.; March, J. March’s Advanced Organic
Chemistry: Reactions, Mechanisms, and Structure, 7th ed.; John Wiley &
Sons, Inc.: Hoboken, 2013.
D
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