Stereoselective Michael Halogenation Initiated Ring Closure (MHIRC) Synthesis of Spirocyclopropanes from Benzylidenemalononitriles and 3-Arylisoxazol-5(4H)-ones

Article abstract of DOI:10.1055/s-0035-1562690

The new chemical cascade reaction was found: the direct formation of substituted 4-oxo-2,7-diaryl-5-oxa-6-azaspiro[2.4]hept-6-ene-1,1-dicarbonitriles from benzylidenemalononitriles and 3-aryl-2-isoxazol-5(4H)-ones. The action of bromine on the equimolar mixture of benzylidenemalononitrile and 3-aryl-2-isoxazol-5(4H)-one in the basic alcohol solution results in stereoselective formation of spirobicycle containing the 2-isoxazolin-5-one and the cyclopropane fragments in 53-92% yields. Thus, the new simple and efficient ‘one-pot’ approach to substituted (2R*,3R*)-4-oxo-2,7-diaryl-5-oxa-6-azaspiro[2.4]hept-6-ene-1,1-dicarbonitriles was found directly from simple and reasonable starting compounds as benzylidenemalonitriles and 3-aryl-2-isoxazol-5(4H)-ones.

Full text of DOI:10.1055/s-0035-1562690

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Georg Thieme Verlag Stuttgart · New York
2016, 27, A–E
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Synlett
A. N. Vereshchagin et al.
Letter
Stereoselective Michael Halogenation Initiated Ring Closure
MHIRC) Synthesis of Spirocyclopropanes from Benzylidenemalo-
(
nonitriles and 3-Arylisoxazol-5(4H)-ones
Anatoly N. Vereshchagin*a
Michail N. Elinsona
Alexander D. Korshunova
Yuliya E. Anisinaa
Roman A. Novikova
Alexander S. Goloveshkinb
Ivan S. Bushmarinovb
Sergey G. Zlotina
Mikhail P. Egorova
a
N. D. Zelinsky Institute of Organic Chemistry,
Leninsky pr. 47, Moscow, 119991,
Russian Federation
vereshchagin@ioc.ac.ru
A. N. Nesmeyanov Institute of Organoelement
b
Compounds, Vavilova str. 28, Moscow, 119991,
Russian Federation
Received: 18.04.2016
Accepted after revision: 22.06.2016
Published online: 19.07.2016
shown moderate inhibition of fungal growth in the case of
spores of Leptosphaeia nodorum and Blumeria graminis in
appropriate specific conditions of incubation.3b Hashimoto
et al. have determined that some 2-isoxazol-5(4H)-one-
containing structures demonstrate promising antagonistic
antiandrogen activity on human prostate tumor LNCaP
cells.3c
DOI: 10.1055/s-0035-1562690; Art ID: st-2016-b0259-l
Abstract The new chemical cascade reaction was found: the direct
formation of substituted 4-oxo-2,7-diaryl-5-oxa-6-azaspiro[2.4]hept-6-
ene-1,1-dicarbonitriles from benzylidenemalononitriles and 3-aryl-2-
isoxazol-5(4H)-ones. The action of bromine on the equimolar mixture
of benzylidenemalononitrile and 3-aryl-2-isoxazol-5(4H)-one in the ba-
sic alcohol solution results in stereoselective formation of spirobicycle
containing the 2-isoxazolin-5-one and the cyclopropane fragments in
Cl
53–92% yields. Thus, the new simple and efficient ‘one-pot’ approach
CN
to substituted (2R*,3R*)-4-oxo-2,7-diaryl-5-oxa-6-azaspiro[2.4]hept-6-
ene-1,1-dicarbonitriles was found directly from simple and reasonable
starting compounds as benzylidenemalonitriles and 3-aryl-2-isoxazol-
NC
NC
RGS inhibitor
CN
NC
NC
CN
CN
5(4H)-ones.
inhibitor of
protein autosplicing
Key words MHIRC reaction, cyclopropane formation, 3-aryl-2-isoxaz-
olin-5(4H)-ones, benzylidenemalononitriles, 5-oxa-6-azaspiro[2.4]hept-
F
R1
6-enes
R2
N
S
N
Nitrogen-containing heterocycles are among the most
O
N
O
O
O
represented skeletons in complicated natural products and
inhibition of fungal growth
anti-androgen activity
1
bioactive molecules. Isoxazole is a heterocyclic privileged
Figure 1 Bioactive benzylideneisoxazolones and tetracyanocyclopro-
scaffold with a broad spectrum of interesting biological ac-
panes
2
tivities. It has been found that some of the 2-isoxazol-
5(4H)-one-containing compounds demonstrate inhibitory
activities against E. coli and Y. pestis CDP-ME kinases with
The cyclopropyl group is a vital structural unit in many
synthetic and naturally occurring compounds, exhibiting a
wide spectrum of biological properties ranging from en-
zyme inhibition to herbicidal, antibiotic, antitumour, anti-
viral, and antidopamine activities.4 It has been found that
3a
notably low IC50 values. Another beneficial feature of izox-
azolin-5-ones has been approved during a series of experi-
ments revealing fungicidal properties of the following scaf-
fold. For example, benzylideneisoxazolones (Figure 1) have
,5
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Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

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A. N. Vereshchagin et al.
Letter
cyano-substituted cyclopropanes inhibit RGS proteins (reg-
ulators of G-protein signaling)6a and protein autosplicing
and used for the treatment of tuberculosis.
isoxazol-5(4H)-one (2a) into 4-oxo-2,7-diphenyl-5-oxa-6-
azaspiro[2.4]hept-6-ene-1,1-dicarbonitrile (3a) was carried
out (Table 1).
6b
During the course of our studies on cascade and multi-
component reactions, we suggested new approaches to the
cyano-substituted cyclopropanes: chemical and electro-
Excellent conversions of starting compounds and 72%
yield of cyclopropane 3a were obtained when the reaction
was carried out in ethanol by the action of bromine in the
presence of 1.2 equivalents of EtONa in two hours (Table 1,
entry 6). The increase of EtONa quantity (Table 1, entry 7)
or replaced by the more active EtOK (Table 1, entry 12) re-
sulted in decrease of the reaction yield that may be con-
nected with the activation of undesired base-induced oligo-
merization.11 In the absence of bromine (Table 1, entry 10)
or base (Table 1, entry 11) 3a was not detected.
7
a,b
chemical transformations of C–H acids,
and C–H acids,
activated olefins
7c–f
carbonyl compounds and C–H acids.7g–i
Among a plethora of cyclopropane fragment types, a
spirocyclopropyl configuration assembled with variety of
heterocyclic substructures has received proper attention
owing to its notable synthetic applicability combined with
a considerable amount of beneficial physiological activi-
8
ties. In particular, spirocyclopropyl pyrrolidines have been
recognized as α-L-fucosidase inhibitors;8 spirocyclopropyl
a
Table 1 Optimization of the Reaction Conditions for the Synthesis of
8b
a
β-lactams, as inhibitors of serine β-lactamase; spirocyclo-
propyl oxindoles, as HIV-1 non-nucleoside reverse tran-
scriptase inhibitors and as diagnostic markers for the early
3a
Entry ROH
Base (equiv)
Halogen Time (h) Yield of 3a (%)b
8
c,d
detection of colorectal and hepatocellular cancers.
1
2
MeOH
KOH (1.0)
KOH (1.0)
KOH (1.0)
NaOH (1.0)
EtONa (1.0)
EtONa (1.2)
EtONa (1.5)
EtONa (1.2)
EtONa (1.2)
EtONa (1.2)
–
I
2
2
2
2
2
2
2
2
1
3
2
2
2
28
42
47
35
59
72
52
57
60
n.d.
n.d.
67
Our recent research focuses on the synthesis of spirocy-
clopropanes containing heterocyclic counterparts: barbi-
MeOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
Br
Br
Br
2
2
2
9a–c
9d–g
3
turic
and pyrazolinone.
One of the new approaches to
4
cyclopropanes of this type is the Michael halogenation ini-
9
a,10
tiated ring closure (MHIRC) reaction.
In this reaction,
5
Br2
halogenation of a C–H acid is followed by a Michael addi-
tion step. In a continuation of these studies we report our
results on the direct one-pot cascade transformation of
benzylidenemalononitriles 1 and 3-aryl-2-isoxazol-5(4H)-
6
Br
Br
Br
Br
–
2
2
2
2
7
8
9
ones
2
into substituted 4-oxo-2,7-diaryl-5-oxa-6-
azaspiro[2.4]hept-6-ene-1,1-dicarbonitriles 3 (Scheme 1).
10
11
Br
2
2
R1
12
EtOK (1.2)
Br
O
a
base, EtOH
Hal2
O
Reaction conditions: 4 mmol of 1a, 4 mmol of 2a, 20 mL of alcohol, 1.0–1.5
O
N
equiv of base, 4 mmol of halogen, room temperature.
CN
NC
NC
b
Isolated yields; n.d. = not detected.
R1
+
O
CN
r.t., 2 h
N
Hal = Br, I
Under the optimal conditions found, namely bromine as
halogen, 1.2 equivalents of EtONa as base, and ethanol as
solvent, substituted benzylidenemalononitriles 1a–e and 3-
aryl-2-isoxazol-5(4H)-ones 2a–d were transformed into the
R2
1
a–e
2a–d
3a–j
R2
a R1 = H
b R = 4-Cl
c R = 3-Br
d R = 4-NO2
a R2 = H
b R = F
c R = Cl
d R = Br
a R1 = R2 = H
1
2
1
2
b R = 4-Cl, R = H
corresponding 4-oxo-2,7-diaryl-5-oxa-6-azaspiro[2.4]hept-
1
2
1
2
c R = 3-Br, R = H
12
6-ene-1,1-dicarbonitriles 3a–j in 53–92% yields (Table 2).
1
2
d R = 4-NO2, R2 = H
1
In the NMR spectra of compounds 3a–j only a single set
of signals were identified assuming the stereoselective for-
mation of an individual diastereoisomer. The 2R*,3R* con-
1
e R = 3-Br, R2 = F
1
e R = 4-t-Bu
f R1 = 4-NO2, R2 = F
g R = 4-t-Bu, R2 = Cl
h R = 3-Br, R2 = Cl
i R = 4-NO2, R2 = Cl
j R = 3-Br, R2 = Br
1
1
figuration of 3i was unambiguously assigned based on the
1
CH of cyclopropane ring/aryl ring 1H NOESY correlation
1
(Figure 2).
Scheme 1 Stereoselective synthesis of 4-oxo-2,7-diaryl-5-oxa-6-
azaspiro[2.4]hept-6-ene-1,1-dicarbonitriles
The X-ray powder diffraction (XRD) data unambiguous-
ly support the 2R*,3R* configuration of 3f (Figure 3).
13
Taking into consideration the data obtained and our
previous results on the transformation of benzylidene-
malononitriles and malononitrile into substituted tetracya-
nocyclopropanes7f or benzylidenemalononitriles and barbi-
First, to evaluate the synthetic potential of the proce-
dure proposed and to optimize the conditions, the transfor-
mation of benzylidenemalononitrile (1a) and 3-phenyl-2-
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

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A. N. Vereshchagin et al.
Letter
Table 2 Stereoselective Synthesis of 4-Oxo-2,7-diaryl-5-oxa-6-
azaspiro[2.4]hept-6-ene-1,1-dicarbonitriles 3
turic acids into spirosubstituted barbiturates9a the following
scheme for the transformation of benzylidenemalononi-
triles 1a–e and 3-aryl-2-isoxazol-5(4H)-ones 2a–d into
substituted 4-oxo-2,7-diaryl-5-oxa-6-azaspiro[2.4]hept-6-
ene-1,1-dicarbonitriles 3a–j is proposed (Scheme 2).
a
Entry
1 R1
1a H
2 R2
2a H
3
Yield of 3 (%)b
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
72
60
63
75
67
73
53
78
92
83
1b 4-Cl
1c 3-Br
1d 4-NO
1c 3-Br
1d 4-NO
2a H
O
O
Ar1
2a H
EtO–
CN
CN
O
N
Br2
Ar1
O
+
–
2
2
2a H
– Br–
–
EtOH
N
CN
CN
2b 4-F
2b 4-F
2c 4-Cl
2c 4-Cl
2c 4-Cl
2d 4-Br
Ar2
Ar2
1
2
A
1e 4-t-Bu
1c 3-Br
3g
3h
3i
O
Ar1
O
Ar1
CN
CN
CN
Br
CN
EtO–
– EtOH, – Br–
O
O
N
1d 4-NO
1c 3-Br
2
N
10
3j
Ar2
Ar2
a
4
Reaction conditions: 4 mmol of 1, 4 mmol of 2, 20 mL of alcohol, 4.8
3
(2R*,3R*)
mmol of EtONa, 4 mmol of bromine, room temperature, 2 h.
b
Isolated yields.
Scheme 2 Proposed mechanism for the formation of (2R*,3R*)-4-oxo-
2,7-diaryl-5-oxa-6-azaspiro[2.4]hept-6-ene-1,1-dicarbonitriles 3
O
CN
NO2
The first step of the cascade process is the Michael addi-
O
tion of 3-aryl-2-isoxazol-5(4H)-ones 2 to benzylidenemalo-
nonitriles 1 in the presence of the base with the formation
of anion A. Subsequent bromination of anion A by the ac-
tion of bromine leads to bromo[(5-oxo-3-aryl-4,5-dihy-
droisoxazol-4-yl)(aryl)methyl]malononitrile (4). Next,
deprotonation of 4 and cyclization under least steric hin-
drance stereoselectively give rise to the final spirocyclopro-
pane 3.
N
CN
H
H
H
Cl
Figure 2 NOESY interaction for 3i
Thus, a new type of the MHIRC reaction was found,
namely the direct stereoselective formation of spirocyclo-
propane structures from benzylidenemalononitriles and 3-
aryl-2-isoxazol-5(4H)-ones. The action of bromine on equal
amounts of benzylidenemalononitrile and 3-aryl-2-isoxaz-
ol-5(4H)-one in basic ethanol solution results in the formation
of (2R*,3R*)-4-oxo-2,7-diaryl-5-oxa-6-azaspiro[2.4]hept-6-
ene-1,1-dicarbonitriles in 53–92% yields. This new simple
and efficient ‘one-pot’ approach to substituted (2R*,3R*)-4-
oxo-2,7-diaryl-5-oxa-6-azaspiro[2.4]hept-6-ene-1,1-dicar-
bonitriles uses simple and reasonable starting compounds:
benzylidenemalonitriles and 3-aryl-2-isoxazol-5(4H)-ones.
The procedure utilizes inexpensive reagents, is easily car-
ried out, and the workup is not complicated. (2R*,3R*)-4-
Oxo-2,7-diaryl-5-oxa-6-azaspiro[2.4]hept-6-ene-1,1-dicar-
bonitriles are crystallized directly from the reaction mix-
ture; consequently, the isolation includes only filtration.
The 5-oxa-6-azaspiro[2.4]hept-6-ene system appears to be
of interest because it incorporates a cyclopropane and an
izoxazolone heterocyclic ring, a structure that is promising
with respect to biological responses.
Figure 3 Molecular structure of 3f (crystal). Atoms are represented by
spheres indicating their isotropic thermal displacements (ρ = 50%).
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Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

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A. N. Vereshchagin et al.
Letter
Acknowledgment
A. Y.; Nikishin, G. I. Tetrahedron 2009, 65, 6057.
(i) Vereshchagin, A. N.; Elinson, M. N.; Egorov, M. P. RSC Adv.
This research was supported by the Russian Science Foundation
grant no. 14-50-00126). A. S. Goloveshkin and I. S. Bushmarinov also
2
015, 5, 98522.
(
(
8) (a) Laroche, C.; Behr, J.-B.; Szymoniak, J.; Bertus, P.; Schutz, C.;
thank the RF President’s grant (no. MK-7267.2015.3) for supporting
the XRD study.
Vogel, P.; Plantier-Royon, R. Bioorg. Med. Chem. 2006, 14, 4047.
(b) Sandanayaka, V. P.; Prashad, A. S.; Yang, Y.; Williamson, R. T.;
Lin, Y. I.; Mansour, T. S. J. Med. Chem. 2003, 46, 2569. (c) Jiang,
T.; Kuhen, K. L.; Wolff, K.; Yin, H.; Bieza, K.; Caldwell, J.;
Bursulaya, B.; Wub, T. Y.-H.; He, Y. Bioorg. Med. Chem. Lett. 2006,
Supporting Information
1
6, 2105. (d) Jiang, T.; Kuhen, K. L.; Wolff, K.; Yin, H.; Bieza, K.;
Supporting information for this article is available online at
Caldwell, J.; Bursulaya, B.; Tuntland, T.; Zhang, K.; Karanewsky,
D.; He, Y. Bioorg. Med. Chem. Lett. 2006, 16, 2109.
http://dx.doi.org/10.1055/s-0035-1562690.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
(
9) (a) Elinson, M. N.; Vereshchagin, A. N.; Stepanov, N. O.;
Zaimovskaya, T. A.; Merkulova, V. M.; Vorontsov, A. Y.; Nikishin,
G. I. Tetrahedron Lett. 2010, 51, 428. (b) Dorofeeva, E. O.; Elinson,
M. N.; Vereshchagin, A. N.; Stepanov, N. O.; Bushmarinov, I. S.;
Belyakov, P. A.; Sokolova, O. O.; Nikishin, G. I. RSC Adv. 2012, 2,
References and Notes
(
1) (a) Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V. Comprehensive
Heterocyclic Chemistry II; Pergamon Press: Oxford, 1996.
b) Katritzky, A. R.; Ramsden, C. A.; Scriven, E. F. V.; Taylor, R. J.
4
444. (c) Vereshchagin, A. N.; Elinson, M. N.; Dorofeeva, E. O.;
Stepanov, N. O.; Zaimovskaya, T. A.; Nikishin, G. I. Tetrahedron
013, 69, 1945. (d) Elinson, M. N.; Vereshchagin, A. N.;
Tretyakova, E. O.; Bushmarinov, I. S.; Nikishin, G. I. Synthesis
011, 3015. (e) Elinson, M. N.; Dorofeeva, E. O.; Vereshchagin, A.
N.; Nasybullin, R. F.; Egorov, M. P. Catal. Sci. Technol. 2015, 5,
384. (f) Vereshchagin, A. N.; Elinson, M. N.; Dorofeeva, E. O.;
(
K. Comprehensive Heterocyclic Chemistry III; Pergamon Press:
Oxford, 2008.
2
(
2) (a) Lakhvich, E. V. K. F. A.; Akhrem, A. A. Chem. Heterocycl.
Compd. 1989, 25, 359. (b) Sperry, J. B.; Wright, D. L. Curr. Opin.
Drug Discovery Dev. 2005, 8, 723.
2
2
(
3) (a) Tang, M.; Odejinmi, S. I.; Alette, Y. M.; Vankayalapati, H.; Lai,
K. Bioorg. Med. Chem. 2011, 19, 5886. (b) Hallenbach, W.; Guth,
O.; Seitz, T.; Wroblowsky, H.-J.; Desbordes, P.; Wachendorff-
Neumann, U.; Dahmen, P.; Voerste, A.; Lösel, P.; Malsam, O.;
Rama, R.; Hadano, H. US 20120100989, 2012. (c) Ishioka, T.;
Tanatani, A.; Nagasawa, K.; Hashimoto, Y. Bioorg. Med. Chem.
Lett. 2003, 13, 2655.
Nasybullin, R. F.; Bushmarinov, I. S.; Goloveshkin, A. S.; Egorov,
M. P. Electrochim. Acta 2015, 165, 116. (g) Elinson, M. N.;
Dorofeeva, E. O.; Vereshchagin, A. N.; Korshunov, A. D.; Egorov,
M. P. Res. Chem. Intermed. 2016, 42, 2191.
(
10) (a) Vereshchagin, A. N.; Elinson, M. N.; Korshunov, A. D.;
Korolev, V. A.; Egorov, M. P. Heterocycl. Commun. 2015, 21, 355.
(b) Vereshchagin, A. N.; Elinson, M. N.; Korshunov, A. D.; Egorov,
(4) For reviews, see: (a) Donaldson, W. A. Tetrahedron 2001, 57,
M. P. Mendeleev Commun. 2016, 26, 19.
8
(
2
589. (b) Brandt, W.; Thiemann, T. Chem. Rev. 2003, 103, 1625.
c) Chen, D. Y.-K.; Pouwerb, R. H.; Richard, J.-A. Chem. Soc. Rev.
012, 41, 4631.
(
11) (a) Campaigne, F.; Sohneller, S. W. Synthesis 1976, 705.
(b) Freeman, F. Chem. Rev. 1980, 80, 329.
(
12) 4-Oxo-2,7-diaryl-5-oxa-6-azaspiro[2.4]hept-6-ene-1,1-dicar-
bonitriles 3a-j; General Procedure
(
5) (a) Graham, D. W.; Ashton, W. T.; Barash, L.; Brown, J. E.; Brown,
R. D.; Canning, L. F.; Chen, A.; Springer, J. P.; Rogers, E. F. J. Med.
Chem. 1987, 30, 1074. (b) Salaün, J.; Baird, M. S. Curr. Med. Chem.
To a 15 mL EtOH suspension of benzylidenemalononitrile 1 (4
mmol) and 3-aryl-2-isoxazol-5(4H)-one 2 (4 mmol) in a 50 mL
beaker, sodium ethylate (4.8 mmol) in alcohol (5 mL) was
poured. Then bromine (4 mmol) was added without cooling.
The mixture was magnetically stirred at room temperature for 2
h. Then reaction mixture was cooled to –10 °C for 2 h, filtered
out, and dried under reduced pressure to give pure 3.
1995, 2, 511. (c) Boger, D. L.; Hughes, T. V.; Hedrick, M. P. J. Org.
Chem. 2001, 66, 2207. (d) Yamaguchi, K.; Kazuta, Y.; Hirano, K.;
Yamada, S.; Matsuda, A.; Shuto, S. Bioorg. Med. Chem. 2008, 16,
8875.
(6) (a) Roman, D. L.; Talbot, J. N.; Roof, R. A.; Sunahara, R. K.;
Traynor, J. R.; Neubig, R. R. Mol. Pharmacol. 2007, 71, 169.
(2R*,3R*)-4-Oxo-2,7-diphenyl-5-oxa-6-azaspiro[2.4]hept-6-
(b) Henry, P. (Boston Biomedical Research Institute) WO
ene-1,1-dicarbonitrile (3a)
2006079057, 2006.
White solid; yield 0.90 g (72%); mp 188–190 °C. IR (KBr): 3052,
(7) (a) Elinson, M. N.; Lizunova, T. L.; Dekaprilevich, M. O.;
–1 1
2
324, 2248, 1804, 1448, 1132, 872, 764, 700, 612 cm . H NMR
Struchkov, Y. T.; Nikishin, G. I. Mendeleev Commun. 1993, 192.
(
300.1 MHz, DMSO-d ): δ = 5.00 (s, 1 H, CH), 7.40–7.47 (m, 3 H,
6
(b) Vereshchagin, A. N.; Elinson, M. N.; Dorofeeva, E. O.;
13
Ph), 7.50–7.66 (m, 5 H, Ph), 7.69–7.75 (m, 2 H, Ph). C NMR
75.5 MHz, DMSO-d ): δ = 22.4, 40.6, 44.2, 109.1, 110.7, 125.8,
Demchuk, D. V.; Bushmarinov, I. S.; Goloveshkin, A. S.; Nikishin,
G. I. Tetrahedron 2013, 69, 5234. (c) Elinson, M. N.; Feducovich,
S. K.; Vereshchagin, A. N.; Dorofeev, A. S.; Dmitriev, D. E.;
Nikishin, G. I. Russ. Chem. Bull. Int. Ed. 2003, 52, 2235.
(
6
1
26.5, 128.4 (2 C), 128.8 (2 C), 129.0 (2 C), 129.1 (2 C), 130.0,
+
131.6, 163.1, 168.4. MS (EI, 70 eV): m/z (%) = 313 (3) [M ], 268
(11), 191 (10), 179 (54), 166 (60), 139 (44), 129 (75), 103 (18),
(d) Elinson, M. N.; Feducovich, S. K.; Zaimovskaya, T. A.;
7
7 (100), 51 (87). Anal. Calcd for C19H11N O : C, 72.84; H, 3.54;
3
2
Vereshchagin, A. N.; Gorbunov, S. V.; Nikishin, G. I. Russ. Chem.
Bull. Int. Ed. 2005, 54, 1593. (e) Elinson, M. N.; Feducovich, S. K.;
Starikova, Z. A.; Vereshchagin, A. N.; Belyakov, P. A.; Nikishin, G.
I. Tetrahedron 2006, 62, 3989. (f) Vereshchagin, A. N.; Elinson, M.
N.; Stepanov, N. O.; Nikishin, G. I. Mendeleev Commun. 2009, 19,
N, 13.41. Found: C, 72.78; H, 3.64; N, 13.46.
2R*,3R*)-2-(4-Nitrophenyl)-4-oxo-7-phenyl-5-oxa-6-
(
azaspiro[2.4]hept-6-ene-1,1-dicarbonitrile (3d)
White solid; yield 1.07 g (75%); mp 175–177 °C. IR (KBr): 2924,
1
2
340, 2252, 1804, 1520, 1352, 1136, 872, 764, 692 cm–1
.
H
324. (g) Vereshchagin, A. N.; Elinson, M. N.; Zaimovskaya, T. A.;
NMR (300.1 MHz, DMSO-d ): δ = 5.19 (s, 1 H, CH), 7.50–7.66 (m,
6
Nikishin, G. I. Tetrahedron 2008, 64, 9766. (h) Elinson, M. N.;
Vereshchagin, A. N.; Stepanov, N. O.; Ilovaisky, A. I.; Vorontsov,
3
H, Ph), 7.68–7.74 (m, 2 H, Ph), 8.23 (d, J = 8.6 Hz, 2 H, Ar), 8.37
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

E
Synlett
A. N. Vereshchagin et al.
Letter
(
d, J = 8.6 Hz, 2 H, Ar). 13C NMR (75.5 MHz, DMSO-d ): δ = 22.6,
99 (28), 75 (54), 44 (76), 30 (100). Anal. Calcd for C19H ClN O :
6
9
4
4
3
9.5, 40.0, 108.9, 110.3, 123.2 (2 С), 125.8, 128.8 (2 С), 129.0 (2
C, 58.10; H, 2.31; Cl, 9.03; N, 14.27. Found: C, 58.08; H, 2.36; Cl,
9.06; N, 14.22.
С), 131.7, 131.9 (2 С), 134.1, 147.8, 162.9, 168.8. MS (EI, 70 eV):
m/z (%) = 358 (1) [M ], 267 (4), 207 (31), 179 (91), 165 (16), 129
+
(13) Crystal Data for 3f
(84), 103 (82), 77 (100), 51 (83). Anal. Calcd for C19H10N O : C,
C19H FN O (M = 376.30 g·mol–1): monoclinic, space group
4
4
9
4
4
7
2.84; H, 3.54; N, 13.41. Found: C, 63.77; H, 2.75; 15.70.
P21/n (no. 14), a = 15.47733(19) Å, b = 9.22402(10) Å, c =
3
(2R*,3R*)-7-(4-Chlorophenyl)-2-(4-nitrophenyl)-4-oxo-5-
12.46236(14) Å, β = 89.9765(10)°, V = 1779.17(4) Å , Z = 4, T =
–1
–3
oxa-6-azaspiro[2.4]hept-6-ene-1,1-dicarbonitrile (3i)
298 K, μ(Cu Kα ) = 0.926 mm , Dcalc = 1.405 g·cm . At average
1
White solid; yield 1.44 g (92%); mp 189–191 °C. IR (KBr): 3048,
Δd of 0.01 Å (K = 44) the refinement converged to Rp/R ′/ RWP/
RWP′/RBragg values of 3.384/7.663/4.545/8.187/1.514% with
Rexp/Rexp′ of 0.856/1.543%, GOF = 5.307.
1
P
–1 1
2336, 2250, 1796, 1576, 1524, 1356, 1088, 852, 740 cm
.
H
NMR (300.1 MHz, DMSO-d ): δ = 5.31 (s, 1 H, CH), 7.65 (d, J = 8.4
6
Hz, 2 H, Ar), 7.76 (d, J = 8.4 Hz, 2 H, Ar), 7.98 (d, J = 8.3 Hz, 2 H,
CCDC 1454070 contains the supplementary crystallographic
data for compound 3f. The data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/getstructures.
13
Ar), 8.30 (d, J = 8.3 Hz, 2 H, Ar). C NMR (75.5 MHz, DMSO-d ):
6
δ = 22.6, 23.4, 39.9, 108.8, 110.8, 123.2 (2 C), 124.7, 129.0 (2 C),
1
30.6 (2 C), 131.0, 131.5 (2 C), 162.2, 168.7. MS (EI, 70 eV): m/z
+
(%) = 392 (1) [M ], 302 (2), 267 (2), 213 (43), 163 (27), 137 (44),
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E