Transition-Metal-Free [3 + 2] Cycloaddition of Nitroolefins and Diazoacetonitrile: A Facile Access to Multisubstituted Cyanopyrazoles

Article abstract of DOI:10.1021/acs.orglett.8b00729

A transition-metal-free [3 + 2] cycloaddition reaction between nitroolefins and diazoacetonitrile (N₂CHCN) is described. This protocol exhibits several merits including simple starting materials, mild reaction conditions, broad substrate scope, good yields, and regioselectivities. The one-pot three-component reaction of nitroolefins with diazoacetonitrile (N₂CHCN) and alkyl halides is also developed, thus delivering a series of multisubstituted cyanopyrazoles in good to high yields.

Full text of DOI:10.1021/acs.orglett.8b00729

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Transition-Metal-Free [3 + 2] Cycloaddition of Nitroolefins and
Diazoacetonitrile: A Facile Access to Multisubstituted
Cyanopyrazoles
Zhen Chen,† Yue Zhang,† Jing Nie, and Jun-An Ma*
Department of Chemistry, Tianjin Key Laboratory of Molecular Optoelectronic Sciences, and Tianjin Collaborative Innovation
Center of Chemical Science & Engineering, Tianjin University, Tianjin 300072, P. R. of China
S
* Supporting Information
ABSTRACT: A transition-metal-free [3 + 2] cycloaddition reaction between nitroolefins and diazoacetonitrile (N2CHCN) is
described. This protocol exhibits several merits including simple starting materials, mild reaction conditions, broad substrate
scope, good yields, and regioselectivities. The one-pot three-component reaction of nitroolefins with diazoacetonitrile
(N2CHCN) and alkyl halides is also developed, thus delivering a series of multisubstituted cyanopyrazoles in good to high yields.
ultisubstituted cyanopyrazoles are well represented
throughout pharmaceuticals, agrochemicals, and related
Traditional approaches to multisubstituted cyanopyrazoles
involve direct cyanation of pyrazole derivatives3 followed by
late elaboration of the resulting cyanopyrazoles,3c the Thorpe−
Ziegler cyclization4 of dicyanohydrazones with activated
methylene reagents,5 three-component reaction of aldehydes
with the Bestmann−Ohira reagent and malononitrile,6,7 and
copper-catalyzed tandem haloalkylation/cyclization of alde-
hyde-derived hydrazones with trichloroacetonitrile.8 However,
these methods usually suffered from several disadvantages, such
as a tedious synthetic procedure for starting materials, limited
substrate scope, release of a toxic byproduct, and/or need for a
precious transition metal. Therefore, it is highly desirable to
develop a direct and general method for the construction of
diverse cyanopyrazole species.
M
candidates.1 Among them are Fipronil, Pyriprole, Pyrafluprole,
and Ethiprole (insectiside),1c,d Zaleplon (sedative-hypnotic),1e
and Lorlatinib (ALK/ROS1 Inhibitor)1f,g (Figure 1). In
Over the past decades, the cycloaddition reactions of small
and reactive diazo compounds with alkenes or alkynes have
emerged as a powerful tool to forge a series of pyrazoles.9
Compared with the well-known 2,2,2-trifluorodiazoethane
(CF3CHN2),9,10 the similar reagent diazoacetonitrile
(N2CHCN) has been rarely investigated.11 Only one report
by Mykhailiuk has addressed the cycloaddition of N2CHCN
with electron-deficient alkynes to afford 5-substituted-3-
cyanopyrazoles (Scheme 1a).12 To the best of our knowledge,
no direct one-step synthesis of 4-substituted-3-cyanopyrazoles
as well as multisubstituted cyanopyrazoles starting from simple
and readily available olefins has been presented to date. As part
of our ongoing interest in the cycloaddition reactions of diazo
compounds,9 we decided to investigate the cycloaddition
reactivity of nitroolefins with N2CHCN to assemble structurally
diverse cyanopyrazoles, wherein the nitro group serves as a
Figure 1. Multisubstituted cyanopyrazole based bioactive compounds.
addition to being prevalent in a series of bioactive molecules,
the cyano group can also serve as an excellent synthetic handle
to forge derivatives of aryl acid, ketones, imines, aldehydes,
amines, amides, and even tetrazoles,2 thus providing a facile
access to structurally diverse pyrazoles. Due to the immense
usefulness of multisubstituted cyanopyrazoles, efficient con-
struction of these coveted frameworks has gained intensive
attention in the fields of synthetic and medicinal chemistry.
Received: March 5, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b00729
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
investigated the effects of several bases, and Cs2CO3 was found
to be optimal with the yield improved to 87% (entries 3−8).
Further solvent screening demonstrated that besides THF,
DMF also promoted this transformation, whereas the use of
MeCN, toluene, or DCM led to significantly lower yields
(entries 9−12). Reducing the amount of Cs2CO3 or N2CHCN
led to lower yields (entries 13−15). Inspired by the elegant
work from Mykhailiuk,12c we then examined the feasibility of in
situ generation of N2CHCN and its one-pot reaction with
nitrostyrene 1a. In aqueous media, the desired product 2a was
obtained in 42% yield when using 2.0 equiv of 2-amino-
acetonitrile hydrochloride (entry 16). Increasing the amount of
2-aminoacetonitrile hydrochloride significantly generated pos-
itive results, and 4.0 equiv proved the best to give 2a in 76%
yield (entries 17 and 18). While this yield is still lower than that
when using pure N2CHCN, this one-pot method represents a
safe and routine application for the construction of 4-
substituted 3-cyanopyrazoles given the potential risk of
explosion of N2CHCN.
Scheme 1. Cycloaddition Reactions of N2CHCN for the
Synthesis of Cyanopyrazoles
traceless activating and directing group (TADG) to effect
regioselective incorporation of alkenes and can be in situ
eliminated (Scheme 1b and 1c).
We embarked on our studies by probing the reaction of
nitrostyrene 1a with N2CHCN in the presence of 1.5 equiv of
Ag2O and 1.5 equiv of Na3PO4 in THF (Table 1), which
Having developed the optimal conditions for the [3 + 2]
cycloaddition reaction, its scope was then investigated with
various nitroolefins 1 (Scheme 2). In the case of nitrostyrenes,
the cycloaddition reaction tolerated diverse substitution
patterns and a broad spectrum of substituents on the phenyl
ring such as methyl (2b), methoxy (2c, 2j, and 2k),
dimethylamino (2d), halo (2e−g and 2l), trifluoromethyl
a
Table 1. Optimization of Reaction Conditions
b
entry
additive (equiv)
solvent
THF
yield (%)
Scheme 2. Substrate Scope of the [3 + 2] Cycloaddition
1
Ag2O (1.5)/Na3PO4 (1.5)
Na3PO4 (1.5)
Na2CO3 (1.5)
K3CO3 (1.5)
0
a b
,
Reactions of Nitroolefins 1 with N2CHCN
2
THF
70
82
84
85
87
80
72
73
32
trace
trace
83
64
52
42
62
76
3
THF
4
THF
5
K3PO4 (1.5)
THF
6
Cs2CO3 (1.5)
Et3N (1.5)
THF
7
THF
8
DABCO (1.5)
Cs2CO3 (1.5)
Cs2CO3 (1.5)
Cs2CO3 (1.5)
Cs2CO3 (1.5)
Cs2CO3 (1.0)
Cs2CO3 (0.5)
Cs2CO3 (1.5)
Cs2CO3 (2.5)
Cs2CO3 (2.5)
Cs2CO3 (2.5)
THF
9
DMF
10
11
12
13
14
MeCN
toluene
DCM
THF
THF
c
15
THF
de
,
16
17
18
THF/H2O
THF/H2O
THF/H2O
df
,
dg
,
a
General reaction conditions: 1a (0.5 mmol), N2CHCN (0.75 mmol),
b
base (x equiv) in 5 mL of solvent under Ar at rt for 3 h. Isolated yield.
c
d
N2CHCN (0.6 mmol). Reaction conditions: a mixture of 2-
aminoacetonitrile hydrochloride and sodium nitrite were stirred at 0
°C in water (0.5 mL) for 1 h. Then, 1a (0.5 mmol), Cs2CO3 (1.25
mmol), and THF (5 mL) were added, and the mixture was stirred at rt
e
for 3 h. 2-Aminoacetonitrile hydrochloride (1.0 mmol) and sodium
f
nitrite (1.1 mmol). 2-Aminoacetonitrile hydrochloride (1.5 mmol),
g
sodium nitrite (1.6 mmol). 2-Aminoacetonitrile hydrochloride (2.0
mmol), sodium nitrite (2.1 mmol).
successfully promoted the [3 + 2] cycloaddition of nitroolefins
with CF3CHN2.9m Unfortunately, no desired cycloadduct was
observed under these reaction conditions, and nitrostyrene 1a
was recovered in quantitative yield (entry 1). To our delight, in
the absence of Ag2O, the desired 4-phenyl-3-cyanopyrazole 2a
could be obtained in 70% yield with excellent regioselectivity
(entry 2). Having this promising result, we subsequently
a
b
Isolated yield. The values in parentheses refer to the isolated yields
under the one-pot reaction conditions.
B
DOI: 10.1021/acs.orglett.8b00729
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(2h), and cyano (2i), thus delivering the desired 4-phenyl-3-
cyanopyrazoles in good to excellent yields (64−96%). The
system was not sensitive to the steric environment, as
demonstrated by the good yields achieved for ortho-substituted
nitrostyrenes (2k and 2l). The reaction could be conducted
with nitroolefins containing a polycyclic group including 1-
naphthyl (2m), 2-naphthyl (2n), and 9-anthracenyl (2o).
Substrates with the furanyl (2p) and thienyl (2q) heterocycles
underwent this transformation smoothly to provide the
expected products in 90% and 92% yields, respectively. Most
notable were the examples of several nitrodienes (2t−v) and
nitroeneyne (2w), which successfully reacted with N2CHCN to
afford the corresponding 3-cyanopyrazoles with excellent
chemo- and regioselectivities. To our excitement, trisubstituted
and alkyl-substituted nitroolefins also proved to be good
substrates under the same reaction conditions, and several 4,5-
disubstituted 3-cyanopyrazoles 2r, 2s, and 4-alkyl-3-cyanopyr-
azoles 2x−a′ were attained in 55−86% yields. In addition, the
reactivity of ethyl (E)-3-nitroacrylate was examined to afford
ethyl 3-cyano-1H-pyrazole-4-carboxylate 2b′ in 55% yield. As
illustrated in the examples of 2a, 2b, 2g, 2h, 2k, and 2w, the in
situ generation of N2CHCN was successfully applied in the
one-pot reaction with nitroolefins, but the yields tended to be
somewhat decreased.
proceeded to forge the desired 1-methyl-4-phenyl-3-cyanopyr-
azole 3a in 73% yield, together with 18% of the isomeric 1-
methyl-4-phenyl-5-cyanopyrazole 3a′. We then explored the
substrate scope of nitroolefins 1 in this multicomponent
reaction. As depicted in Scheme 3, nitroolefins bearing β-
substituents including phenyl (3a−e, 3a′−e′), naphthyl (3f,
3f′), furanyl (3g, 3g′), thienyl (3h, 3h′), and alkyl (3i, 3i′) all
proved to be good partners, assembling a diverse collection of
trisubstituted cyanopyrazoles in good to high yields (79−93%)
with moderate regioselectivities (3:1−4:1). The structures of
3b, 3g, and 3g′ were verified by means of X-ray crystallographic
analysis (Scheme 3). The synthesis of tetrasubstituted
cyanopyrazoles, which is challenging via traditional approaches,
was also successfully accomplished. Products 3j and 3k together
with their isomers 3j′ and 3k′ were isolated in good yields,
albeit with low regioselectivities. Apart from MeI, benzyl
bromide was also a competent alkylating reagent, giving rise to
3l and 3l′ in 77% total yield with 6.7:1 regioselectivity.
The synthetic utility of the cyano group in the generated
pyrazole derivatives was further defined by the transformation
of 3a. As shown in Scheme 4, treating 3a with diisobutylalu-
Scheme 4. Transformation of the Cyano Group of
Cyanopyrazole 3a
To further showcase the repertoire, the feasibility of
translating this [3 + 2] cycloaddition reaction into a three-
component reaction of nitroolefin 1a with N2CHCN and
methyl iodide was investigated (Scheme 3). In the presence of
2.5 equiv of Cs2CO3, this three-component reaction readily
Scheme 3. Substrate Scope of Three-Component
a b c
, ,
Reactions
minum hydride (DIBAL-H) or lithium aluminum hydride
(LiAlH4) readily gave the corresponding aldehyde 4 and amine
5 in 60% and 87% yields, respectively. The pyrazole-3-
carboxamide 6 could also be isolated in 99% yield by reacting
3a with potassium tert-butoxide in toluene at 80 °C.
In summary, we have successfully developed a base-
promoted transition-metal-free [3 + 2] cycloaddition reaction
of N2CHCN with various nitroolefins. Under mild conditions, a
broad range of 4-substituted and 4,5-disubstituted 3-cyanopyr-
azoles were obtained in good to high yields with excellent
regioselectivities. In addition, a one-pot three-component
reaction of nitroolefins with N2CHCN and alkyl halides was
also demonstrated, thereby delivering a diverse collection of
multisubstituted 3-cyanopyrazoles together with 5-cyanopyr-
azoles in good to excellent yields with moderate regioselectiv-
ities. The practical potential of this methodology was
highlighted by transformation of the cycloadducts into
pyrazole-containing aldehydes, amines, and amides. Mecha-
nistic studies and further transformations of the cycloadducts
are underway in our laboratory.
ASSOCIATED CONTENT
* Supporting Information
■
S
a
Reaction conditions: 1 (0.5 mmol), N2CHCN (1.0 mmol), alkyl
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b00729.
halide (0.75 mmol), and Cs2CO3 (1.25 mmol) in THF (5 mL) at rt
for 1−3 h. Isolated yield. The values in parentheses refer to the
isolated yields for minor regioisomer.
b
c
C
DOI: 10.1021/acs.orglett.8b00729
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
1
Proenca
̧
, M. F. R. P.; Griffiths, J.; Maia, H. L. S.; Kaja, M.; Hrdina, R. J.
Experimental procedures, characterization data, and H,
19F, and 13C NMR spectra for new compounds (PDF)
Chem. Res. 2004, 2004, 115. (c) Fevig, J. M.; Cacciola, J.; Buriak, J.;
Rossi, K. A.; Knabb, R. M.; Luettgen, J. M.; Wong, P. C.; Bai, S. A.;
Wexler, R. R.; Lam, P. Y. S. Bioorg. Med. Chem. Lett. 2006, 16, 3755.
Accession Codes
́
(d) Wu, M.-H.; Hu, J.-H.; Shen, D.-S.; Bremond, P.; Guo, H.
CCDC 1523275 and 1813396−1813397 contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/
cif, or by emailing 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.
Tetrahedron 2010, 66, 5112. (e) Corre, L. L.; Tak-Tak, L.; Guillard, A.;
Prestat, G.; Gravier-Pelletier, C.; Busca, P. Org. Biomol. Chem. 2015,
13, 409.
(6) Luvino, D.; Amalric, C.; Smietana, M.; Vasseur, J.-J. Synlett 2007,
2007, 3037.
(7) Mohanan, K.; Martin, A. R.; Toupet, L.; Smietana, M.; Vasseur,
J.-J. Angew. Chem., Int. Ed. 2010, 49, 3196.
AUTHOR INFORMATION
(8) Prieto, A.; Bouyssi, D.; Monteiro, N. ACS Catal. 2016, 6, 7197.
(9) (a) Xie, J.-W.; Wang, Z.; Yang, W.-J.; Kong, L.-C.; Xu, D.-C. Org.
Biomol. Chem. 2009, 7, 4352. (b) Muruganantham, R.; Mobin, S. M.;
Namboothiri, I. N. N. Org. Lett. 2007, 9, 1125. (c) Muruganantham,
R.; Namboothiri, I. J. Org. Chem. 2010, 75, 2197. (d) Artamonov, O.
S.; Slobodyanyuk, E. Y.; Shishkin, O. V.; Komarov, I. V.; Mykhailiuk, P.
K. Synthesis 2013, 45, 225. (e) Li, F.; Nie, J.; Sun, L.; Zheng, Y.; Ma, J.-
A. Angew. Chem., Int. Ed. 2013, 52, 6255. (f) Li, T.-R.; Duan, S.-W.;
Ding, W.; Liu, Y.-Y.; Chen, J.-R.; Lu, L.-Q.; Xiao, W.-J. J. Org. Chem.
2014, 79, 2296. (g) Slobodyanyuk, E. Y.; Artamonov, O. S.; Shishkin,
O. V.; Mykhailiuk, P. K. Eur. J. Org. Chem. 2014, 2014, 2487.
(h) Zhang, F.-G.; Wei, Y.; Yi, Y.-P.; Nie, J.; Ma, J.-A. Org. Lett. 2014,
16, 3122. (i) Mykhailiuk, P. K. Org. Biomol. Chem. 2015, 13, 3438.
(j) Pieber, B.; Kappe, C. O. Org. Lett. 2016, 18, 1076. (k) Hock, K. J.;
Mertens, L.; Metze, F. K.; Schmittmann, C.; Koenigs, R. M. Green
Chem. 2017, 19, 905. (l) Li, F.; Wang, J.; Pei, W.; Li, H.; Zhang, H.;
Song, M.; Guo, L.; Zhang, A.; Liu, L. Tetrahedron Lett. 2017, 58, 4344.
(m) Chen, Z.; Zheng, Y.; Ma, J.-A. Angew. Chem., Int. Ed. 2017, 56,
4569. (n) Qin, S.; Zheng, Y.; Zhang, F.-G.; Ma, J.-A. Org. Lett. 2017,
19, 3406. (o) Mykhailiuk, P. K. Angew. Chem., Int. Ed. 2015, 54, 6558.
(p) Mykhailiuk, P. K.; Ishchenko, A. Y.; Stepanenko, V.; Cossy, J. Eur.
J. Org. Chem. 2016, 2016, 5485. (q) Lebed, P. S.; Fenneteau, J.; Wu,
Y.; Cossy, J.; Mykhailiuk, P. K. Eur. J. Org. Chem. 2017, 2017, 6114.
(r) Li, J.; Yu, X.-L.; Cossy, J.; Lv, S.-Y.; Zhang, H.-L.; Su, F.;
Mykhailiuk, P. K.; Wu, Y. Eur. J. Org. Chem. 2017, 2017, 266.
(s) Mykhailiuk, P. K. Org. Biomol. Chem. 2017, 15, 7296. (t) Audubert,
C.; Marin, O. J. G.; Lebel, H. Angew. Chem., Int. Ed. 2017, 56, 6294.
(u) Britton, J.; Jamison, T. F. Angew. Chem., Int. Ed. 2017, 56, 8823.
(10) (a) Mykhailiuk, P. K.; Afonin, S.; Palamarchuk, G. V.; Shishkin,
O. V.; Ulrich, A. S.; Komarov, I. V. Angew. Chem., Int. Ed. 2008, 47,
5765. (b) Morandi, B.; Carreira, E. M. Angew. Chem., Int. Ed. 2010, 49,
4294. (c) Morandi, B.; Carreira, E. M. Angew. Chem., Int. Ed. 2010, 49,
938. (d) Grygorenko, O. O.; Artamonov, O. S.; Komarov, I. V.;
Mykhailiuk, P. K. Tetrahedron 2011, 67, 803. (e) Morandi, B.; Carreira,
E. M. Angew. Chem., Int. Ed. 2011, 50, 9085. (f) Morandi, B.;
Mariampillai, B.; Carreira, E. M. Angew. Chem., Int. Ed. 2011, 50, 1101.
(g) Chai, Z.; Bouillon, J.-P.; Cahard, D. Chem. Commun. 2012, 48,
9471. (h) Liu, C.-B.; Meng, W.; Li, F.; Wang, S.; Nie, J.; Ma, J.-A.
Angew. Chem., Int. Ed. 2012, 51, 6227. (i) Argintaru, O. A.; Ryu, D.;
Aron, I.; Molander, G. A. Angew. Chem., Int. Ed. 2013, 52, 13656.
(j) Molander, G. A.; Cavalcanti, L. N. Org. Lett. 2013, 15, 3166.
(k) Artamonov, O. S.; Slobodyanyuk, E. Y.; Volochnyuk, D. M.;
Komarov, I. V.; Tolmachev, A. A.; Mykhailiuk, P. K. Eur. J. Org. Chem.
2014, 2014, 3592. (l) Mao, H.; Lin, A.; Tang, Z.; Hu, H.; Zhu, C.;
Cheng, Y. Chem. - Eur. J. 2014, 20, 2454. (m) Molander, G. A.; Ryu, D.
Angew. Chem., Int. Ed. 2014, 53, 14181. (n) Wu, G.; Deng, Y.; Wu, C.;
Wang, X.; Zhang, Y.; Wang, J. Eur. J. Org. Chem. 2014, 2014, 4477.
(o) Xiong, H.-Y.; Yang, Z.-Y.; Chen, Z.; Zeng, J.-L.; Nie, J.; Ma, J.-A.
Chem. - Eur. J. 2014, 20, 8325. (p) Luo, H.; Wu, G.; Zhang, Y.; Wang,
J. Angew. Chem., Int. Ed. 2015, 54, 14503. (q) Hyde, S.; Veliks, J.;
■
Corresponding Author
*E-mail: majun_an68@tju.edu.cn.
ORCID
Jun-An Ma: 0000-0002-3902-6799
Author Contributions
†Z.C. and Y.Z. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Natural Science
Foundation of China (Nos. 21225208, 21472137, and
21532008) and the National Basic Research Program of
China (973 Program, 2014CB745100).
REFERENCES
■
(1) (a) Crocetti, L.; Schepetkin, I. A.; Cilibrizzi, A.; Graziano, A.;
Vergelli, C.; Giomi, D.; Khlebnikov, A. I.; Quinn, M. T.; Giovannoni,
M. P. J. Med. Chem. 2013, 56, 6259. (b) Mizuhara, T.; Kato, T.; Hirai,
A.; Kurihara, H.; Shimada, Y.; Taniguchi, M.; Maeta, H.; Togami, H.;
Shimura, K.; Matsuoka, M.; Okazaki, S.; Takeuchi, T.; Ohno, H.;
Oishi, S.; Fujii, N. Bioorg. Med. Chem. Lett. 2013, 23, 4557. (c) Caboni,
P.; Sammelson, R. E.; Casida, J. E. J. Agric. Food Chem. 2003, 51, 7055.
(d) Sammelson, R. E.; Caboni, P.; Durkin, K. A.; Casida, J. E. Bioorg.
Med. Chem. 2004, 12, 3345. (e) Elie, R.; Ruther, E.; Farr, I.; Emilien,
G.; Salinas, E. J. Clin. Psychiatry 1999, 60, 536. (f) Johnson, T. W.;
Richardson, P. F.; Bailey, S.; Brooun, A.; Burke, B. J.; Collins, M. R.;
Cui, J. J.; Deal, J. G.; Deng, Y.-L.; Dinh, D.; Engstrom, L. D.; He, M.;
Hoffman, J.; Hoffman, R. L.; Huang, Q.; Kania, R. S.; Kath, J. C.; Lam,
H.; Lam, J. L.; Le, P. T.; Lingardo, L.; Liu, W.; McTigue, M.; Palmer,
C. L.; Sach, N. W.; Smeal, T.; Smith, G. L.; Stewart, A. E.;
Timofeevski, S.; Zhu, H.; Zhu, J.; Zou, H. Y.; Edwards, M. P. J. Med.
Chem. 2014, 57, 4720. (g) Elleraas, J.; Ewanicki, J.; Johnson, T. W.;
Sach, N. W.; Collins, M. R.; Richardson, P. F. Angew. Chem., Int. Ed.
2016, 55, 3590.
(2) (a) Hyland, C. J.; O’Connor, C. J. J. Chem. Soc., Perkin Trans. 2
1973, 2, 223. (b) Swain, C. G. J. Am. Chem. Soc. 1947, 69, 2306.
(c) Finholt, A. E.; Jacobson, E. C.; Ogard, A. E.; Thompson, P. J. Am.
Chem. Soc. 1955, 77, 4163. (d) Das, B.; Reddy, C.; Kumar, D.;
Krishnaiah, M.; Narender, R. Synlett 2010, 2010, 391.
(3) (a) Senecal, T. D.; Shu, W.; Buchwald, S. L. Angew. Chem., Int. Ed.
2013, 52, 10035. (b) Pawar, A. B.; Chang, S. Chem. Commun. 2014,
50, 448. (c) Dishington, A.; Feron, J. L.; Gill, K.; Graham, M. A.;
Hollingsworth, I.; Pink, J. H.; Roberts, A.; Simpson, I.; Tatton, M. Org.
Lett. 2014, 16, 6120. (d) Cohen, D. T.; Buchwald, S. L. Org. Lett.
2015, 17, 202. (e) Dutta, U.; Lupton, D. W.; Maiti, D. Org. Lett. 2016,
18, 860. (f) Burg, F.; Egger, J.; Deutsch, J.; Guimond, N. Org. Process
Res. Dev. 2016, 20, 1540.
́
Liegault, B.; Grassi, D.; Taillefer, M.; Gouverneur, V. Angew. Chem.,
Int. Ed. 2016, 55, 3785. (r) Mertens, L.; Hock, K. J.; Koenigs, R. M.
Chem. - Eur. J. 2016, 22, 9542. (s) Qiu, D.; Qiu, M.; Ma, R.; Zhang, Y.;
Wang, J. Huaxue Xuebao 2016, 74, 472. (t) Peng, S.-Q.; Zhang, X.-W.;
Zhang, L.; Hu, X.-G. Org. Lett. 2017, 19, 5689. (u) Zhang, X.-W.; Hu,
W.-L.; Chen, S.; Hu, X.-G. Org. Lett. 2018, 20, 860.
(4) Granik, V. G.; Kadushkin, A. V.; Liebscher, J. Adv. Heterocycl.
Chem. 1998, 72, 79.
(5) (a) Gewald, K.; Calderon, O. Monatsh. Chem. 1977, 108, 611.
(b) Gonca̧ lves, M. S. T.; Oliveira-Campos, A. M. F.; Rodrigues, L. M.;
D
DOI: 10.1021/acs.orglett.8b00729
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Letter
(11) (a) Hooz, J.; Linke, S. J. Am. Chem. Soc. 1968, 90, 6891.
(b) Dowd, P.; Kaufman, C.; Paik, Y. H. Tetrahedron Lett. 1985, 26,
2283. (c) Felpin, F.-X.; Doris, E.; Wagner, A.; Valleix, A.; Rousseau, B.;
Mioskowski, C. J. Org. Chem. 2001, 66, 305. (d) Ferrand, Y.; Le Maux,
P.; Simonneaux, G. Tetrahedron: Asymmetry 2005, 16, 3829.
(e) Galliford, C. V.; Scheidt, K. A. J. Org. Chem. 2007, 72, 1811.
(f) Ikuma, N.; Susami, Y.; Oshima, T. Org. Biomol. Chem. 2010, 8,
1394. (g) Wu, G.; Deng, Y.; Wu, C.; Zhang, Y.; Wang, J. Angew. Chem.,
Int. Ed. 2014, 53, 10510. (h) Yang, Z.; Son, K.-I.; Li, S.; Zhou, B.; Xu,
J. Eur. J. Org. Chem. 2014, 2014, 6380. (i) Hock, K. J.; Spitzner, R.;
Koenigs, R. M. Green Chem. 2017, 19, 2118.
(12) (a) Weis, C. D. J. Org. Chem. 1962, 27, 3695. (b) Markusson,
́
H.; Beranger, S.; Johansson, P.; Armand, M.; Jacobsson, P. J. Phys.
Chem. A 2003, 107, 10177. (c) Mykhailiuk, P. K. Eur. J. Org. Chem.
2015, 2015, 7235.
E
DOI: 10.1021/acs.orglett.8b00729
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