Reaction of Pyridine-N-Oxides with Tertiary sp2-N-Nucleophiles: An Efficient Synthesis of Precursors for N-(Pyrid-2-yl)-Substituted N-Heterocyclic Carbenes

Article abstract of DOI:10.1002/adsc.202001063

N-(Pyrid-2-yl)-substituted azolium and pyridinium salts, precursors for hybrid NHC-containing ligands, were obtained with excellent regioselectivity, employing a deoxygenative CH-functionalization of pyridine-N-oxides with substituted imidazoles, thiazoles, and pyridine. Unlike the traditional S_NAr-based methods, this approach provides high yields for substrates bearing substituents of different electronic nature. The utility of azolium and pyridinium salts thus prepared was also highlighted by the synthesis of pyridyl-substituted imidazolyl-2-thione, benzodiazepine as well as 2-aminopyridines.

Full text of DOI:10.1002/adsc.202001063

Title: Reaction of Pyridine-N-Oxides with Tertiary sp2-N-Nucleophiles:
An Efficient Synthesis of Precursors for N-(Pyrid-2-yl)-Substituted
N-Heterocyclic Carbenes
Authors: Dmitry Bugaenko, Marina Yurovskaya, and Alexander V.
Karchava
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.202001063
Link to VoR: https://doi.org/10.1002/adsc.202001063

10.1002/adsc.202001063
Advanced Synthesis & Catalysis
UPDATE
DOI: 10.1002/adsc.202((will be filled in by the editorial staff))
Reaction of Pyridine-N-Oxides with Tertiary sp2-N-
Nucleophiles: An Efficient Synthesis of Precursors for N-(Pyrid-
2-yl)-Substituted N-Heterocyclic Carbenes
Dmitry I. Bugaenko, Marina A. Yurovskaya, Alexander V. Karchava*
Department of Chemistry, Moscow State University, Moscow 119992, Russia
E-mail: karchava@org.chem.msu.ru
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract:
N-(Pyrid-2-yl)-substituted
azolium
and
pyridinium salts, precursors for hybrid NHC-containing
ligands, were obtained with excellent regioselectivity,
employing
a
deoxygenative CH-functionalization of
pyridine-N-oxides with substituted imidazoles, thiazoles,
and pyridine. Unlike the traditional SNAr-based methods,
this approach provides high yields for substrates bearing
substituents of different electronic nature. The utility of
azolium and pyridinium salts thus prepared was also
highlighted by the synthesis of pyridyl-substituted
imidazolyl-2-thione, benzodiazepine as well as 2-
aminopyridines.
Keywords: Pyridine N-oxide; N-Heterocyclic carbenes;
Nitrogen Heterocycles; Amination; C-H functionalization
Figure 1. Traditional and our ways for synthesis of
precursors for pyridyl-substituted N-heterocyclic carbenes.
N-Heterocyclic carbenes (NHCs) featuring high σ-
donating and weak π-accepting abilities[1] are an
important class of compounds that found numerous
applications in organocatalysis[2] and as ligands for
transition metal and main group elements.[3]
Transition-metal complexes containing NHC ligands
are widely used as active catalysts for fundamental
organic transformations including olefin metathesis,
hydrogenation transfer, various C-C bond-forming
processes, etc.[4] Among others, multidentate NHCs
with an appended pyrid-2-yl-type moiety bearing the
donating nitrogen atom have attracted particular
attention. The chelate complexes with such hybrid
ligands have found wide applications due to their
improved catalyst stability and their potential
hemilability, which provides ease of generation of
vacant coordination site and catalytically active
species.[5] Besides their catalytic applications,
complexes of transition metals with pyrid-2-yl-
substituted NHCs have demonstrated anticancer,
antimalarial, antiplasmodial, and other activities.[6]
Moreover, these complexes possess unique
photophysical properties and have found application in
materials chemistry.[7]
Pyrid-2-yl-substituted NHCs are readily generated
from the corresponding N-substituted azolium or
pyridinium salts by deprotonation.[8] In turn, the N-
pyridyl-substituted azolium and pyridinium salts are
traditionally prepared from 2-halopyridines via a
nucleophilic substitution (SNAr) with N-substituted
azoles and pyridine and often in low yields.[8b] The
SNAr-reactions in 2-halopyridines require high
temperature (>160 °C) for substrates without strong
electron-withdrawing groups, which results in a
restricted functional group compatibility. At the same
time, the variation of substituents on the NHC ligand
would produce changes in the electronic and steric
properties of the carbene moiety, providing an
effective tool for fine-tuning the catalytic properties of
the whole NHC-metal complex. Moreover, substituted
2-halopyridines and quinolines are difficult to prepare
from the parent heterocyles as issues of poor
regioselectivity and over-halogenation often arise.[9]
As a result, the incorporation of halogens onto
pyridines in a selective manner commonly requires
multiple synthetic steps. Given wide applicability of
pyridyl-substituted NHCs in catalysis, medicinal and
materials chemistry, there exists a need in developing
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.202001063
Advanced Synthesis & Catalysis
of an alternative synthetic method toward their
precursors, which would enable a broader substrate
scope and greater functional group tolerance.
A
site-selective
deoxygenative
CH-
functionalization of pyridine-N-oxides arguably
represents a powerful strategy to access diverse
pyridine structures and is recognized as an expedient
and efficient alternative to nucleophilic substitution in
2-halopiridines and their transition-metal catalyzed
reactions.[10] In contrast to 2-halopyridines, pyridine-
N-oxides are straightforward to prepare from widely
accessible parent pyridines via a simple oxidation
process.[10a,11] Generally, electrophilically pre-
activated N-oxides readily react with a wide range of
nucleophiles under relatively mild and eco-friendly
reaction conditions, yielding pyridines with a new
substituent at either the C2 (predominantly) or C4
position.[10] In particular, the N-oxide-based strategy
has been widely used for the installation of the amine
functionalities into pyridines and fused pyridines,
using variety of 1°, 2°, and 3° sp3-amines as the
nucleophilic agents.[12] Meanwhile, reactions of
Table 1. Selected Results of Reaction Optimization.[a]
entry
1
2a:Tf2O
solvent
MeCN
time (h) yield (%)
2:1.5
4
2
4
4
4
4
6
99
67
62
55
74
19
48
2
3
4
5
6
7
2:1.5
1.5:1.5
2:1.5
2:1.5
2:1.5
2:1.5
MeCN
MeCN
DCM
preactivated
pyridine-N-oxides
with
sp2-N-
nucleophiles have received much less attention.[12b,m,n]
Moreover, there have been no reports on the reactions
with N-substituted imidazoles and the related
compounds. If developed effectively, such reactions
would provide a robust and efficient route to
precursors for valuable pyridyl-substituted NHCs.
Herein, we present our study of these novel C–N-bond
forming reactions utilizing pyridine-N-oxides.
We initiated our study by examining the reaction
between 2,2’-bipyridine N-oxide (1a) and 1-
methylimidazole (2a) under different conditions. The
highest yield of the imidazolium salt 3aa was obtained
when the reaction was performed in MeCN with 2
equiv of 1-methylimidazole (2a) and 1.5 equiv of
trifluoromethanesulfonic anhydride (Tf2O) as the
activating agent at ambient temperature (Table 1, entry
1). Employing other typical activating agents (TFAA,
Ac2O, TsCl, MsCl, Ts2O) and performing the reaction
in other solvents (entries 4-6) resulted in decreasing
yields. The ratio of reagents is also crucial for the
reaction to proceed in high efficiency (entries 1 vs 3).
Importantly, this transformation is highly site-
selective at the C2 position and the regioisomeric 4-
substituted product was not detected in the crude
reaction mixture.
Next, the optimized reaction conditions (Table 1,
entry 1) were applied to a variety of N-oxides bearing
substituents of different electronic nature. N-Oxides of
a variety of pyridines and quinolines with both
electron-donating and electron-accepting groups were
equally effective substrates, affording the imidazolium
salts 3 in good to excellent yields (Scheme 1A).
Remarkably, in all cases the product 3 was isolated as
a single regioisomers at the C2 position, including the
salt 3bb obtained from unsubstituted pyridine-N-oxide.
While the N-oxide-based strategy toward the
preparation of functionalized pyridines often suffers
from low 2/4-regioselectivity that limiting its
toluene
THF
EtOAc
[a]
The reaction was performed on 0.2 mmol (1 equiv) of 2,2’-
bipyridine N-oxide (1a) in 2 mL of a solvent at rt. For more
information, see the Supporting Information. Yields were
determined with 1H NMR using 1,4-dibromo-2,5-dimethylbenzene
as an internal standard.
applicability,[8,12b,d] our reaction leads exclusively to
the formation of 2-regioisomers regardless of the
electronic nature of substituents incorporated on the
pyridine ring. Moreover, no products were obtained
with starting materials being almost quantitatively
recovered when N-oxides of 2,6-dimethylpyridine,
2,6-dibromopyridine, and 2-phenylquinoline were
used as the substrates under the optimized reaction
conditions. However, when 3-substituted N-oxides
derived from ethyl isonicotynate and 3,4-lutidine were
employed in the transformation, mixtures of the C2
and C6 regioisomers were formed. While the C2-
regioisomers are the major products in both cases, the
C2/C6 proportion considerably depends on the
electronic nature of the C3-substituent (3gb vs 3hb).
We also explored a variety of substituted imidazoles,
thiazoles and their benzannulated derivatives in the
reaction (Scheme 1B). The expected azolium salts
were obtained in good to high yields, in all cases,
except one. Remarkably, the reaction is perfectly
compatible with a 2-susbstituted imidazole (salt 3mc)
and an imidazole bearing the electron-withdrawing
substituent (salt 3me). It should be noted that
derivatives of histidine were also compatible with the
developed reaction conditions as demonstrated by the
preparation of salts 3ld and 3me in good yields.
Benzothiazole, however, was unreactive due its poor
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.202001063
Advanced Synthesis & Catalysis
nucleophilicity; only the starting N-oxide was almost
fully recovered. Many sensitive functional groups
substituent (salt 3me). It should be noted that
derivatives of histidine were also compatible with the
developed reaction conditions as demonstrated by the
preparation of salts 3ld and 3me in good yields.
Benzothiazole, however, was unreactive due its poor
nucleophilicity; only the starting N-oxide was almost
fully recovered. Many sensitive functional groups
remained intact under the mild reaction conditions
employed, including challenging urethane (3ld),
carbamide (3me) groups and a chlorine atom at the
positions activated to SNAr-reactions (3db, 3pb).
Thus, azolium salts 3aa-ml were obtained using an
operationally simple procedure and, in contrast to
halogenides and trifluoroacetates, were readily
isolated from the reaction mixture in high purity after
an aqueous workup and recrystallization. Importantly,
this protocol provides access to pyridyl-substituted
azolium salts which are impossible or difficult to
obtain through current methods based on the SNAr
chemistry.
To further demonstrate the applicability of the
protocol, we examined reactions of differently
substituted pyridine-N-oxides with pyridine to afford
the
corresponding
N-(pyrid-2-yl)-substituted
pyridinium triflates. In contrast to the imidazole-based
NHC complexes, their pyridine-based counterparts
(pyridylidenes) are less common. However, NHCs
derived by deprotonation of pyridinium salts, being
stabilized by only one nitrogen atom, are particularly
interested as stronger σ-donors and better π-acceptors
than azol-2-ylidenes.[13] Pyridinium salts 4a-k bearing
both electron-donating and electron-withdrawing
substituents on the pyridine ring were isolated in good
to excellent yields employing the above-developed
reaction conditions, thus demonstrating the general
applicability of the method (Scheme 2). Here again,
the transformation exhibits good functional group
compatibility and proceeds with exceptional
regiosectivity at the C2-position.
Besides their application as NHC precursors, N-
pyridyl-substituted azolium and pyridinium salts can
be used as useful reagents in organic synthesis. To
demonstrate this feature, we performed several
synthetic transformations (Scheme 3). First, the
reaction of imidazolium triflate 3aa, derived from 2,2'-
bipyridine (1a) and 1-methylimidazole (2a), with
elemental sulfur under basis conditions resulted in the
formation of a tridentate ligand 5, comprising the
imidazolyl-2-thione moiety (Scheme 3A). Ligands of
this type are widely used to produce metal complexes,
possessing unique catalytic and redox properties.[14]
Next, the quinolyl-substituted benzimidazolium salt
3mf, obtained from quinoline-N-oxide (1l) and 1-
propylbenzimidazole (2f), was readily transformed
into the benzodiazepine derivative 6, employing a
recently developed ring opening/ring closure
protocol.[15] Overall, the complex heterocyclic
compound 6, containing a structural motive of several
marketed pharmaceuticals,[15,16] was obtained in two
simple steps starting from two commercially available
Scheme 1. Scope of N-oxides and azoles.a
Reactions were performed on 0.5 mmol of N-oxides. Yields and
2/6-regioisomeric ratios are reported for the isolated compounds.
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.202001063
Advanced Synthesis & Catalysis
Scheme 2. Reaction of azine N-oxides with pyridine.a
aReactions were performed on 0.5 mmol of N-oxides. Yields are
reported for the isolated compounds.
compounds via
a
selective two-fold CH-
functionalization of the quinoline ring (Scheme 3B).
Finally, we used pyridinium salts 4 for the
preparation
of
2-aminopyridines
and
2-
aminoquinolines 7 (Scheme 3C). The 2-aminopyridine
structural motif is an important pharmacophore found
across many known therapeutic agents.[17] While
several methods to introduce the NH2-functionality
into the pyridine ring have been disclosed to date, none
of them could be considered as a general approach.[12a-
substituents and can accommodate many useful
functional groups such as (activated) halogens, ethers,
c,k,17b,18]
The known methods suffer from significant
Scheme 3. Synthetic aplication.
limitations such as narrow scope, limited functional
group compatibility, harsh reaction conditions, using
either operationally complicated procedures or
sophisticated reagent or sometimes both. Hence, our
two step-one pot procedure, combining a pyridinium
salt formation followed by the Zincke aminolysis,[18]
to furnish 2-aminopyridines 7 represents a highly
attractive alternative for the previously reported
methods. Employing a site-selective deoxygenative
CH-functionalization of N-oxides, we prepared an
amino derivative of Quinoxyfen, an active ingredient
nitriles, carbonyls, esters, and NH-amides. While
azolium and pyridinium salts thus prepared serve as
precursors for valuable N-(pyrid-2-yl)-substituted N-
heterocyclic carbenes, they are also useful starting
materials for the synthesis of ligands and medicinally
relevant compounds.
of many fungicides: amine 7d was obtained in 62% Experimental Section
yield starting from Quinoxyfen.
General Procedure I: Synthesis of Precursors for
In conclusion, the reaction of preactivated with
Tf2O pyridine- and quinoline-N-oxides with tertiary
sp2-N-nucleophiles (imidazoles, benzimidazoles,
thiazoles, and pyridines) enables to obtain the
corresponding azolium and pyridinium salts in a
regioselective manner under mild conditions. The
process is equally effective for substrates, containing
Pyridyl-Substituted N-Heterocyclic Carbenes (3aa-ml,
4a-k)
To a stirred solution of N-oxide (1 equiv) in MeCN (0.2 M)
an azole or pyridine (2 equiv) was added in one portion. The
mixture was cooled to 0 °C and Tf2O (1.5 equiv) was added
dropwise. The resulting mixture was stirred for 15 min at
0°C and 8 h at rt. The reaction mixture was concentrated
under reduced pressure, diluted with CH2Cl2, and washed
with water, the aqueous layers were combined and extracted
with CH2Cl2. The combined organic extracts were dried
electron-withdrawing
and
electron-donating
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.202001063
Advanced Synthesis & Catalysis
with Na2SO4, and concentrated under reduced pressure to
afford the product, which was purified by recrystallization
from a CH2Cl2/Et2O mixture.
J.-M. Augereau, H. Gornitzka, F. Benoit-Vicalab,
Bioorg. Med. Chem. 2016, 24, 3075-3082
[7] a) R Visbal, M. C. Gimeno, Chem. Soc. Rev. 2014, 43,
3551-3574; b) C. A. Smith, M. R. Narouz, P. A.
Lummis, I. Singh, A. Nazemi, C.-H. Li, C. M. Crudden,
Chem. Rev. 2019, 119, 4986−5056; c) S. Liu, S. Xu, J.
Wang, F. Zhao, H. Xia, Y. Wang, J. Coord. Chem.
2017, 70, 584-599; d) H.-S. Chen, W.-C. Chang, C. Su,
T.-Y. Li, N.-M. Hsu, Y. S. Tingare, C.-Y. Li, J.-H.
Shie, W.-R. Li. Dalton Trans. 2011, 40, 6765-6770; e)
G. J. Barbante, P. S. Francis, C. F. Hogan, P. R.
Kheradmand, D. J. D. Wilson, P. J. Barnard, Inorg.
Chem. 2013, 52, 7448-7459.
General Procedure II: One-pot Synthesis of 2-
Aminopyridines and 2-Aminoquinolines from N-
Heterocyclic Carbenes
To a stirred solution of N-oxide (1 equiv) in MeCN [0.2 M]
pyridine (2 equiv) was added in one portion. The mixture
was cooled to 0 °C and Tf2O (1.5 equiv) was added dropwise.
The resulting mixture was stirred for 15 min at 0°C and 8 h
at rt. Then, piperidine (10 equiv) was added dropwise at rt
and stirring was continued for 6 h at the same temperature.
The reaction mixture was concentrated under reduced
pressure and the crude product was purified by flash column
chromatography on silica gel using gradient mixtures of
CH2Cl2 and MeOH (50:1 to 10:1) as eluents.
[8] S. E. Wengryniuk, A. Weickgenannt, C. Reiher, N. A.
Strotman, K. Chen, M. D. Eastgate, P. S. Baran, Org.
Lett. 2013, 15, 792-795
Acknowledgements
[9] a) V. Khlebnikov, A. Meduri, H. Mueller-Bunz, B.
Milani, M. Albrecht, New J. Chem. 2012, 36, 1552-
1555; b) T. Simler, A. A. Danopoulos, P. Braunstein,
Dalton Trans. 2017, 46, 5955-5964.
D.I.B and A.V.K thank RFBR for the partial financial support
(project number 19-33-90280) M.A.Y. thanks RFBR for partial
financial support (project number 20-03-00456).
[10] a) Y. Wang, L. Zhang, Synthesis 2015 47, 389-305; b)
A. R. Katritzky, J. N. Lam, Heterocycles 1992, 33,
1011-1049; c) D. L. Comins, S. O’Connor, Adv.
Heterocycl. Chem. 1988, 44, 199-267.
References
[1] H. V. Huynh, Chem. Rev. 2018, 118, 9457-9492.
[2] a) O. Hollóczki, Chem. Eur. J. 2020, 26, 4885-4894.
b) D. M. Flanigan, F. Romanov-Michailidis, N. A.
White, T. Rovis, Chem. Rev. 2015, 115, 9307-9387.
[11] a) C. Copéret, H. Adolfsson, T.-A. V. Khuong, A. K.
Yudin, K. B. Sharpless. Org. Chem. 1998, 63, 1740-
1741; b) O. V. Larionov, D. Stephens, A. M. Mfuh, H.
D. Arman, A. S. Naumova, G. Chavez, B. Skenderi,
Org. Biomol. Chem., 2014, 12, 3026-3036.
[3] a) A. Doddi, M. Peters, M. Tamm, Chem. Rev. 2019,
119, 6994-7112; b) V. Nesterov, D. Reiter, P. Bag, P.
Frisch, R. Holzner, A. Porzelt, S. Inoue, Chem. Rev.
2018, 118, 9678-9842.
[12] a) D. I. Bugaenko, A. V. Karchava, M. A. Yurovskaya,
Russ. Chem. Rev. 2018, 87, 272-301 and references
therein; b) A. T.Londregan, S. Jennings, L. Wei, Org.
Lett. 2010, 12, 5254-5257; c) J. Yin, B. Xiang, M. A.
Huffman, C. E. Raab, I. W. Davies, J. Org. Chem.
2007, 72, 4554-4557; d) D. I. Bugaenko, M. A.
Yurovskaya, A. V. Karchava, J. Org. Chem. 2017, 82,
2136-2149; e) J. M. Keith, J. Org. Chem. 2008, 73,
327-330; f) A. T. Londregan, S. Jennings, L. Wei, Org.
Lett. 2011, 13, 1840-1843; g) P. J. Manley, M. T.
Bilodeau, Org. Lett. 2002, 4, 3127-3129; h) J. W.
Medley, M. Movassaghi, J. Org. Chem. 2009, 74,
1341-1344; i) L. Zhao, L. Hao, Y. Fu, Y. Cheng, G.
Pan, L. Désaubry, P. Yu, D. Wang, Adv. Synth. Cat.
2020, 362, 3841-3845; i) L.‐ Y. Xie, S. Peng, F. Liu,
J.‐ Y. Yi, M. Wang, Z. Tang, X. Xu, W.‐ M. He, Adv.
Synth. Cat. 2020, 360, 4259-4264; k) R. P. Farrell, M.
V. S. Elipe, M. D. Bartberger, J. S. Tedrow, F.
Vounatsos, Org. Lett. 2013, 15, 168-171; l) Y.Nanaji,
S. Kirar, S.V. Pawar, A. K. Yadav, RSC Adv. 2020,10,
7628-7634; m) H. Xiong, A. T. Hoye, K.-H. Fan, X.
Li, J. Clemens, C. L. Horchler, N. C. Lim, G. Attardo,
Org. Lett. 2015, 17, 3726-3729; n) J. M. Keith, J. Org.
Chem. 2010, 75, 2722–2725.
[4] a) A. A. Danopoulos, T. Simler, P. Braunstein, Chem.
Rev. 2019, 119, 3730-3961; b) Q. Zhao, G. Meng, S. P.
Nolan, M. Szostak, Chem. Rev. 2020, 120, 1981-2048;
c) W. A. Herrmann Angew. Chem. Int. Ed. 2002, 41,
1290-1309; d) F. A. Glorius, Top. Organomet. Chem.
2007, 21, 1-20; e) F. E. Hahn, Angew. Chem. 2006, 118,
1374-1378; Angew. Chem. Int. Ed. 2006, 45, 1348-
1352; f) H. Ohmiya, ACS Catal. 2020, 10, 6862-6869.
[5] a) Y.-B. Wang, B.-Y. Liu, Q. Bu, B. Dai, N. Liu, Adv.
Synth. Catal. 2020, 326, 2930-2940; b) E. Peris, R. H.
Crabtree, Coord. Chem. Rev. 2004, 248, 2239-2246; c)
V. M. Chernyshev, E. A. Denisova, D. B. Eremin, V.
P. Ananikov, Chem. Sci. 2020, 11, 6957-6977; c) B. R.
M. Lake, C. E. Willans, Organometallics 2014, 33,
2027-2038; d) U. J. Scheele, M. John, S. Dechert, F.
Meyer, Eur. J. Inorg. Chem. 2008, 373-377; e) V.
Khlebnikov, A. Meduri, H. Mueller-Bunz, B. Milani,
M. Albrecht, New. J. Chem. 2012, 36, 1552-1555.
[6] a) W. Liu, R. Gust, Coord. Chem. Rev. 2016, 329, 191-
213; b) C. Hemmert, A. Fabié, A. Fabre, F. Benoit-
Vical, H. Gornitzka, Eur. J. Med. Chem. 2013, 60, 64-
75; c) M. Mora, M. C. Gimeno, R. Visba, Chem. Soc.
Rev. 2019, 48, 447-462; d) B. K. Rana, A. Nandy, V.
Bertolasi, C. W. Bielawski, K. Das Saha, J. Dinda,
Organometallics 2014, 33, 2544-2548; e) C. Hemmert,
A. P. Ramadani, L. Boselli, Á. F. Álvarez, L. Paloque,
[13] a) H. G. Raubenheimer, S. Cronje, Dalton Trans. 2008,
1265-1272; b) J. A. Cabeza, I. del Ro, E. Prez-Carreno,
M. G. Sánchez-Vega, D. Vázquez-Garca, Angew.
Chem. Int. Ed. 2009, 48, 555-558; c) G. Song, Y.
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.202001063
Advanced Synthesis & Catalysis
Zhang, Y. Su, W. Deng, K. Han, X. Li,
Organometallics 2008, 27, 6193-6201.
[16] E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem.
2014, 57, 10257-10274.
[14] a) J. C. Bayón, C. Claver, A. M. Masdeu-Bultó, Coord.
Chem. Rev. 1999, 193–195, 73-145; b) C. G. Young, J.
Inorg. Biochem. 2007, 101, 1562-1585; c) D. Plaza-
Lozano, D. Morales-Martínez, F. J. González, J.
Olguín, Eur. J. Inorg. Chem. 2020, 1562-1573.
[17] a) M. Marinescu, Int. J. Pharma Bio Sci. 2017, 8,
338−335; b) P. S. Fier, S. Kim, R. D. Cohen, J. Am.
Chem. Soc. 2020, 142, 8614-8618.
[18] A. E. Chichibabin, O. A. Zeide, J. Russ. Phys. Chem.
Soc. 1914, 46, 1216-1236.
[15] S. Tao, Q. Bu, Q. Shi, D. Wei, B. Dai, N. Liu. Chem.
Eur. J., 2020, 26, 3252-3258.
[19] M. Y. Yakovlev, A. V. Kadushkin, N. P. Solov'eva, O.
S. Anisimova, V. G. Granik. Tetrahedron, 1998, 54,
5775-5780.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.202001063
Advanced Synthesis & Catalysis
UPDATE
Reaction of Pyridine-N-Oxides with Tertiary sp2-N-
Nucleophiles: An Efficient Synthesis of Precursors
for N-(Pyrid-2-yl)-Substituted N-Heterocyclic
Carbenes
Adv. Synth. Catal. Year, Volume, Page – Page
Dmitry I. Bugaenko, Marina A. Yurovskaya,
Alexander V. Karchava*
7
This article is protected by copyright. All rights reserved.