Chemistry of unsaturated arenetricarbonylchromium compounds: 2. Synthesis of new isoxazolidine complexes by 1,3-dipolar cycloaddition reaction of nitrone (η6-arene)tricarbonylchromium derivatives with acrylonitrile

Article abstract of DOI:10.1007/s11172-015-0956-9

1,3-Dipolar cycloaddition reactions of nitrones of a general formula RCH=N⁺(O-)R, where R = Ph, Ph[Cr(CO)₃], R = Me, Ph, Bu^t, with acrylonitrile were studied. The isoxazolidines obtained by these reactions were isolated an

Full text of DOI:10.1007/s11172-015-0956-9

Russian Chemical Bulletin, International Edition, Vol. 64, No. 4, pp. 923—929, April, 2015
923
Chemistry of unsaturated arenetricarbonylchromium compounds
2.* Synthesis of new isoxazolidine complexes by 1,3ꢀdipolar cycloaddition reaction
of nitrone (6ꢀarene)tricarbonylchromium derivatives with acrylonitrile
N. Yu. Zarovkina,a E. V. Sazonova,a A. N. Artemov,a and G. K. Fukina,b
aN. I. Lobachevsky State University of Nizhny Novgorod,
5 korp., 23 prosp. Gagarina, 603950 Nizhny Novgorod, Russian Federation.
Fax: +7 (831) 465 8162. Eꢀmail: zarovkinan@mail.ru
bG. A. Razuvaev Institute of Organometallic Chemistry, Russian Academy of Sciences,
49 ul. Tropinina, 603950 Nizhny Novgorod, Russian Federation.
Fax: +7 (831) 462 7497. Eꢀmail: gera@iomc.ras.ru
1,3ꢀDipolar cycloaddition reactions of nitrones of a general formula RCH=N+(O–)R´,
where R = Ph, Ph[Cr(CO)3], R´ = Me, Ph, But, with acrylonitrile were studied. The isoxazoꢀ
lidines obtained by these reactions were isolated and identified. The introduction in the nitrone
molecule of a tricarbonylchromium group led to the increase in the regioꢀ and stereoselectivity
of cycloaddition. The influence of deuterated solvents on chemical shifts of protons in the
isoxazolidine ring was studied.
6
Key words: nitrone, ( ꢀarene)tricarbonylchromium, isoxazolidine, 1,3ꢀdipolar cycloaddiꢀ
tion, acrylonitrile.
Nowadays, unsaturated (6ꢀarene)tricarbonylchromiꢀ
Scheme 1
um complexes are widely used in different fields of chemꢀ
istry. The presence of the electronꢀwithdrawing tricarboꢀ
nylchromium group in the aromatic compound molecule
considerably affects properties of the substrate, which reꢀ
sults in the high selectivity of metallation reactions, the
tendency of the coordinated arene to nucleophilic addiꢀ
tion. Besides, the bulky chromiumꢀcontaining fragment,
which stabilizes both the negative and the positive charge
in a transition state, also facilitates the stereoselective proꢀ
ceeding of a wide range of reactions.2—6 One of the promꢀ
ising fields of application of arenetricarbonylchromium
complexes as the selectivity increasing agents is a 1,3ꢀdiꢀ
polar cycloaddition of nitrones to functional alkenes,
which is widely used for the design of fiveꢀmembered
heterocyclic compounds.7—10
Earlier, it was found that, in contrast to the reactions
1
a
b
c
R1
Me
But
Ph
R2
Ph
Ph
Ph
1
d
e
f
R1
Me
But
Ph
R2
of free nitrones 1a—c with styrene leading as a rule to
mixtures of stereoisomers,11,12 the cycloaddition of a conꢀ
jugated alkene 2 to nitrone (6ꢀarene)tricarbonylchromiꢀ
um complexes 1d—f proceeds stereoselectively with the
formation of the corresponding cisꢀC(5)ꢀsubstituted isoxꢀ
azolidine as the only product13,14 (Scheme 1, Table 1).
The reactions of free nitrones with electronꢀdeficient
monosubstituted dipolarophiles containing such functional
groups as —CN, —CO2R, —NO2, etc., frequently give
Ph[Cr(CO)3]
Ph[Cr(CO)3]
Ph[Cr(CO)3]
2: R3 = Ph (a); CN (b)
3
a
b
c
d
e
f
R1
Me
But
Ph
R2
Ph
Ph
Ph
R3
Ph
Ph
Ph
Ph
Ph
Ph
3
g
h
i
j
k
l
R1
Me
But
Ph
Me
But
Ph
R2
Ph
Ph
Ph
R3
CN
CN
CN
Me Ph[Cr(CO)3]
But Ph[Cr(CO)3]
Ph Ph[Cr(CO)3]
Ph[Cr(CO)3] CN
Ph[Cr(CO)3] CN
Ph[Cr(CO)3] CN
* For Part 1, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 0923—0929, April, 2015.
1066ꢀ5285/15/6404ꢀ0923 © 2015 Springer Science+Business Media, Inc.

924
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 4, April, 2015
Zarovkina et al.
Table 1. Ratios of isomers* of isoxazolidines 3a—l and 4a—l in the
reactions of nitrones 1a—f with styrene (2a) and acrylonitrile (2b)
ical shifts of the protons at carbon atom C(4) in cisꢀisoꢀ
mers is considerably larger than the corresponding values
for transꢀproducts (~0.28—0.44 ppm).14,19—21 In the
1H NMR spectrum of isoxazolidine cisꢀ3i recorded in deuꢀ
teroacetone, the protons at atom C(4) are found as two
separate signals with the difference in the chemical shift
values of 0.71 ppm (see Experimental), whereas the spinꢀ
spin coupling constants of the upfield proton ( 2.66,
J = 12.9 Hz, J = 5.5 Hz, J = 3.9 Hz) are smaller than
similar constants of the proton with chemical shift at  3.37
(J = 12.9 Hz, J = 9.0 Hz), that indicates a cisꢀstructure of
this compound. A predominant formation in this reacꢀ
tion of C(5)ꢀsubstituted isoxazolidines can be explained
both within the theory based on the consideration of muꢀ
tual arrangement of boundary orbitals of reacting comꢀ
pounds22—25 and by the approach considering charge disꢀ
tribution on the atoms of the nitrone and alkene moleꢀ
cules (Fig. 1, a).
Cꢀ(6ꢀPhenyltricarbonylchromium)ꢀNꢀphenylnitrone
(1f) reacts with acrylonitrile (2b) similarly to give isoxazolꢀ
idines containing a cyano group at carbon atom C(5) of
the heterocyclic ring. The reaction proceeds in toluene at
80 C and already within 3 min leads to the formation of
C(5)ꢀsubstituted stereoisomers in the ratio of 93 : 7 (see
Table 1) in 96% total yield. The absence of C(4)ꢀsubstiꢀ
tuted isoxazolidines in this case is mainly explained by the
steric factor arisen from the bulkiness of the nitrone triꢀ
carbonylchromium group and is confirmed by the charge
distribution in the reagent molecules (see Fig. 1, b). The
high stereoselectivity of cycloaddition, probably, is related
to the formation of the intermediate complex between the
Starting
compounds
Products
Ratio of products
cisꢀ3 transꢀ3 cisꢀ4 transꢀ4
1a
1b
1c
1d
1e
1f
1a
1b
1c
1d
1e
1f
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
3a, 4a
3b, 4b
3c, 4c
3d, 4d
3e, 4e
3f, 4f
3g, 4g
3h, 4h
3i, 4i
67
100
90
100
100
100
23
50
81
100
100
93
33
0
10
0
0
0
77
50
10
0
0
7
0
0
0
0
0
0
0
0
3
0
0
0
0
0
0
0
0
0
0
0
6
0
0
0
3j, 4j
3k, 4k
3l, 4l
* The data for isoxazolidines 3a—g and 4i were taken from the
literature: 3a,11 3b,12 3c,11 3d,13 3e,f,14 3g,15 4i.16
mixtures of regioꢀ and stereoisomeric products9 (see
Scheme 1). Increasing the selectivity of such reactions is
a very actual direction in the chemistry of heterocyclic
compounds, natural and physiologically active comꢀ
pounds.7—14 The purpose of the present work is the synꢀ
thesis of new isoxazolidine (6ꢀarene)tricarbonylchromiꢀ
um complexes by the 1,3ꢀdipolar cycloaddition of acryloꢀ
nitrile to coordinated nitrones 1d—f and the establishꢀ
ment of the structure of the heterocycles formed.
Results and Discussion
In the syntheses to be studied, the free C,Nꢀdisubstiꢀ
tuted nitrones13,17,18 (1a—c) with transꢀconfiguration13,15
and their coordinated analogs13,14 (1d—f) were used as the
dipoles, while acrylonitrile as a dipolarophile. The reacꢀ
tions were carried out in sealed degassed tubes at 80 C in
excess acrylonitrile.
a
The reaction of free C,Nꢀdiphenylnitrone (1c) with
acrylonitrile is known16 to proceed with the formation of
all four possible isoxazolidines, with the content of C(4)ꢀ
substituted stereoisomers cisꢀ, transꢀ4i in the mixture of
products being 9% (3 and 6%, respectively) and that of
C(5)ꢀsubstituted products cisꢀ, transꢀ3i being 91%. Since
the authors of the work16 did not report the ratio of cisꢀ,
transꢀ3i stereoisomers, we used HPLC to show that isoxꢀ
azolidine cisꢀ3i is the major reaction product (81%) (see
Table 1). Compound cisꢀ3i was isolated from the reaction
mixture by column chromatography, and its structure was
b
1
confirmed by UV, IR, and H NMR spectroscopy and
mass spectrometry. The cisꢀarrangement of substituents
at carbon atoms C(3) and C(5) of the heterocyclic ring in
compound cisꢀ3i was established by 1H NMR spectroscopy.
It is known that the ~0.7—0.9 ppm difference in the chemꢀ
Fig. 1. Charge distribution in C,Nꢀdiphenylnitrone (1c) (a),
Cꢀ( ꢀphenyltricarbonylchromium)ꢀNꢀphenylnitrone (1f) (b),
and acrylonitrile (2a) and direction of their reactions (the
B3LYP/LanL2DZ calculations).
6

6ꢀArene)tricarbonylchromium isoxazolidines
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 4, April, 2015
925
C(13)
N(2)
molecules of coordinated nitrone and substituted alkene
stabilized by the stacking interaction of the phenyltriꢀ
carbonylchromium substituent on the dipole and the cyano
group of acrylonitrile (transition state A), which predoꢀ
minates over transition state of type B.12—14,17 Such
a structural arrangement of substituents at atoms C(3) and
C(5) is preserved in the final product, that was confirmed
by Xꢀray diffraction study of complex 3k (Fig. 2).
C(12)
C(11)
O(4)
C(4)
C(9)
C(5)
C(10)
N(1)
C(6)
C(14)
C(8)
O(1)
C(7)
Cr(1)
C(1)
C(3)
C(2)
O(3)
O(2)
Fig. 2. Molecular structure of isoxazolidine 3k (hydrogen atoms
are omitted). Thermal ellipsoids are given with 30% probability.
R = Me (3j), But (3k), Ph (3l)
compound 3k was also studied by singleꢀcrystal Xꢀray difꢀ
fraction (Fig. 2, Table 2).
To sum up, using the reactions of free nitrone 1c and
its arenetricarbonylchromium analog 1f as examples we
showed that the introduction of the Cr(CO)3 group in the
dipole molecule led to the increase in both regioꢀ and
stereoselectivity of cycloaddition.
The literature data,15,16 as well as our studies, show
that free nitrones 1a and 1b regioselectively react with
acrylonitrile (2b) with the formation of mixtures of two
C(5)ꢀsubstituted cisꢀ and transꢀisomers in the ratio 23 : 77
and 50 : 50, respectively (see Table 1). The reactions of
similar coordinated nitrones 1d,f with acrylonitrile proꢀ
ceed more stereoselectively with the formation of only
C(5)ꢀsubstituted isoxazolidines 3k,l having the cisꢀconꢀ
figuration. The products 3k,l isolated from the reaction
mixtures by column chromatography are yellow crystalꢀ
line compounds with sharp melting points, they are charꢀ
acterized by different physicochemical analytical methods,
The Xꢀray diffraction study of isoxazolidine 3k showed
that the heterocyclic ring in 3k has an envelope conformaꢀ
tion. Atoms O(4)N(1)C(10)C(11) lie virtually in one plane
(the mean deviation from it is 0.002 Å), whereas atom
C(12) deviates from it by 0.575 Å. In isoxazolidine and
isoxazoline arenetricarbonylchromium complexes syntheꢀ
sized earlier, the envelope conformation of the fiveꢀmemꢀ
bered ring was formed by the deviation of the nitrogen
atom from the plane of the ring.1,12,14 It should be noted
that atom N(2) of the cyano group is located above the
ꢀsystem of the benzene substituent. The torsion angle
C(9)C(10)C(12)N(2) is 11.1, the angle N(2)—benzene
ring center—C(9) is 65.5, whereas the distance N(2)—
benzene ring center is 4.003 Å. Thus, the phenyltriꢀ
carbonylchromium and the cyano groups are placed on
one side of the heterocyclic ring, that confirms the
Table 2. Principal bond distances (d) and bond angles () in the sructure of complex 3k
Bond
d/Å
Bond
d/Å
Angle
/deg
N(1)—O(4)
O(4)—C(12)
C(10)—C(11)
C(11)—C(12)
N(1)—C(10)
Cr(1)—C(1)
Cr(1)—C(2)
Cr(1)—C(3)
Cr(1)—C(4)
Cr(1)—C(5)
Cr(1)—C(6)
1.4916(14)
1.4041(17)
1.5403(16)
1.5179(19)
1.4871(16)
1.8429(15)
1.8481(14)
1.8427(13)
2.2075(12)
2.1989(13)
2.2174(14)
Cr(1)—C(7)
Cr(1)—C(8)
Cr(1)—C(9)
C(4)—C(5)
C(5)—C(6)
C(6)—C(7)
C(7)—C(8)
C(8)—C(9)
C(4)—C(9)
C(12)—C(13)
C(13)—N(2)
2.2165(12)
2.2403(12)
2.2570(11)
1.4060(2)
1.4130(19)
1.3959(18)
1.4221(17)
1.4016(17)
1.4260(16)
1.4948(18)
1.1390(2)
C(12)—C(11)—C(10) 101.23(10)
N(1)—C(10)—C(11)
C(10)—N(1)—O(4)
O(4)—C(12)—C(11)
C(12)—O(4)—N(1)
C(12)—С(13)—N(2)
C(10)—N(1)—C(14)
O(4)—N(1)—C(14)
105.56(9)
106.15(9)
104.77(11)
105.54(9)
179.47(17)
116.02(10)
105.43(9)

926
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 4, April, 2015
Zarovkina et al.
Table 3. The differences in the chemical shifts for the
protons at C(4) carbon atom of isoxazolidines 3h—l
Deuterobenzene exerts an anisotropic influence also
on the signals for the protons at carbon atoms C(3) and
C(5), as well as the protons of the aryl substituents in
isoxazolidines: their chemical shift values displace toward
the high field on going from deuteroacetone to deuteroꢀ
benzene (see Table 4 and Experimental). In a number of
cases, the difference in chemical shifts for the protons
() whose signals are recorded in two different solvents is
more than 1 ppm. Such an essential discrepancy in the
signal chemical shifts can be due to the ASISꢀeffects*
caused by deuterobenzene,29,30 as well as to the formation
of molecular complexes between the coordinated substitꢀ
uent in isoxazolidine and the solvent molecule.31—33
In conclusion, based on the experimental data obtained
it was found that the introduction of the tricarbonylchroꢀ
mium group in the molecules of C,Nꢀdisubstituted nitrones
can considerably increase the diastereoselectivity of 1,3ꢀdiꢀ
polar cycloaddition of nitrones to acrylonitrile, as well as
the regioselectivity of the process.
Compound

H
Acetoneꢀd6
Benzeneꢀd6
cisꢀ3h
transꢀ3h
сisꢀ3i
0.82
0.23
0.71
—
—
0
cisꢀ3j
сisꢀ3k
cisꢀ3l
~0.80
0.60
~0.41
~0.21
~0.19
0
cisꢀstructure of the compound. As in the recently reported
2ꢀtertꢀbutylꢀ4ꢀmethylcarboxyꢀ3ꢀ(6ꢀphenyltricarbonylꢀ
chromium)ꢀ5ꢀphenylꢀ4ꢀisoxazoline,1 in compound 3k the
carbonyl groups are in the staggered orientation relative to
the aryl ring. The distances Cr—6ꢀC and Cr—C(CO) are
2.1989(13)—2.2570(11) Å and 1.8427(13)—1.8481(14) Å,
respectively. The aryl ring is characterized by a pronounced
alternation of the C—C bonds (see Table 2). Note that the
CO groups are located under the longer C—C bonds. The
characteristics of the (6ꢀC6H5)Cr(CO)3 fragment in comꢀ
pound 3k listed above are similar to those in unsubstituted
6ꢀ(benzene)tricarbonylchromium.26—29
The cisꢀstructure of compounds 3k,l is also consistent
with the 1H NMR spectroscopic data, since the difference
in chemical shifts of the protons at carbon atom C(4) of
the heterocycle in deuteroacetone is ~0.8 and 0.6 ppm for
compounds 3k and 3l, respectively (Table 3), while transꢀ
isoxazolidines are characterized by considerably smaller
difference in the chemical shift values, which in many
cases leads to the collapse of the signals for the C(4)H2
protons (see Refs 14 and 19—21). Note that this pattern,
clearly exhibited in the spectra recorded in deuteroaceꢀ
tone and deuterochloroform, is absent when aromatic
C6D6 is used as the solvent, when even in cisꢀisomers the
signals for the protons at carbon atom C(4) become conꢀ
siderably closer or collapse, with their chemical shifts driftꢀ
ing upfield (see Tables 3 and 4).
Experimental
Solvents were distilled over metallic sodium at atmospheric
pressure. Ethyl acetate was dried with calcium chloride and
distilled.34 NꢀPhenylꢀ and Nꢀtertꢀbutylhydroxylamines were
obtained by the reduction of the corresponding nitro comꢀ
pounds.17,35 NꢀMethylhydroxylamine hydrochloride from Sigꢀ
maꢀAldrich was used for the synthesis of CꢀphenylꢀNꢀmethylꢀ
nitrone (1a). Benzaldehyde and triethyl orthoformate were puriꢀ
fied by distillation at reduced pressure, the reaction of these
compounds gave benzaldehyde diethyl acetal.36 The reaction
between benzaldehyde diethyl acetal and chromium hexacarboꢀ
6
nyl led to  ꢀ(benzaldehyde diethyl acetal)tricarbonylchromium,
6
which was hydrolyzed to  ꢀ(benzaldehyde)tricarbonylchromiꢀ
um.37 C,NꢀDisubstituted nitrones 1a—f were obtained by the
condensation of the corresponding hydroxylamine derivatives
6
with benzaldehyde13,17,18 or  ꢀ(benzaldehyde)tricarbonylꢀ
chromium.13,14 Acrylonitrile was purified by distillation at atmoꢀ
spheric pressure.
* Aromatic solvent induced shifts.
Table 4. Chemical shifts () for the protons at C(3), C(4), and C(5) carbon atoms of isoxazolidines cisꢀ3i—l and the difference of these
values (, ppm) for the spectra recorded in deuteroacetone and deuterobenzene
Com
Solvent






C(5)H
C(3)H
C(3)H
C(4)H
C(4)H
C(5)H
pound
сisꢀ3i
сisꢀ3j
сisꢀ3k
сisꢀ3l
Acetoneꢀd6
Benzeneꢀd6
Acetoneꢀd6
Benzeneꢀd6
Acetoneꢀd6
Benzeneꢀd6
Acetoneꢀd6
Benzeneꢀd6
4.69
3.82—3.93
3.51—3.67
2.33—2.49
4.45
3.35
4.88—5.15
3.82
~0.82
~0.82
~1.18
~1.18
1.10
1.10
~1.20
~1.20
2.66 (1 H); 3.37 (1 H)
1.94—2.10 (2 H)
~0.64; ~1.35
~0.64; ~1.35
~0.77; ~1.36
~0.77; ~1.36
~0.81; ~1.24
~0.81; ~1.24
~1.05; ~1.46
~1.05; ~1.46
5.37
3.82—3.93
5.08—5.22
3.68
5.20
3.69
5.22—5.47
3.90
~1.50
~1.50
~1.47
~1.47
~1.51
~1.51
~1.45
~1.45
2.48—2.64 (1 H); 3.28—3.43 (1 H)
1.73—1.86 (1 H); 2.00 (1 H)
2.67 (1 H); 3.21—3.37 (1 H)
1.78—1.95 (1 H); 1.96—2.14 (1 H)
2.64—2.95 (1 H); 3.07—3.34 (1 H)
1.69—1.81 (2 H)

6ꢀArene)tricarbonylchromium isoxazolidines
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 4, April, 2015
927
6
Products were isolated and purified by column chromatoꢀ
graphy using Acros silica gel (SG) (0.035—0.070 mm) under
argon, eluent hexane—ethyl acetate (5 : 1); HPLC was carried
out on a Knauer Smartline 5000 chromatograph with a S 2600
UV diode matrix detector, a Diasferꢀ110ꢀC16 column, 5 m,
4.6×250 mm, eluent was a mixture of acetonitrile—water
(84 : 16); UV spectra of eluates were recorded in the 200—500 nm
range. IR spectra were recorded on a Infralyum FTꢀ801 spectroꢀ
5ꢀCyanoꢀ2ꢀmethylꢀ3ꢀ( ꢀphenyl)tricarbonylchromiumisoxꢀ
azolidine (cisꢀ3j). The yield was 90%, m.p. 112—113 C. MS
(MALDI MS), m/z (Irel (%)): 363.0 [M + K]+ (100), 279.1
[M + K – 3 CO]+ (38), 227.1 [M + K – Cr(CO)3]+ (19). IR
(KBr), v/cm–1: 2966, 2920, 2835 ((C—H)); 1964, 1875 ((CO));
1
1531, 1458 ((C—CAr)); 829, 790 ((CAr—H)). H NMR (aceꢀ
toneꢀd6), : 2.48—2.64 (m, 1 H, HC(4)); 2.79 (s, 3 H, NMe);
3.28—3.43, 3.51—3.67, 5.08—5.22 (all m, 1 H each, HC(4),
HC(3), HC(5)); 5.53—6.38 (m, 5 H, PhCr). 1H NMR (benzeneꢀd6),
: 1.73—1.86 (m, 1 H, HC(4)); 2.00 (dd, 1 H, HC(4), J = 21.5 Hz,
J = 9.4 Hz); 2.27 (s, 3 H, NMe); 2.33—2.49 (m, 1 H, HC(3));
3.68 (d, 1 H, HC(5), J = 7.8 Hz); 4.13—4.35 (m, 3 H, C(3)PhCr);
4.61 (br.s, 2 H, C(3)PhCr).
1
meter in the 480—4600 cm–1 range in KBr pellets. H NMR
spectra were recorded on an Agilent DD2 NMR 400NB spectroꢀ
meter (400 MHz) in acetoneꢀd6 or benzeneꢀd6. Electron impact
(70 eV) mass spectrometric studies were carried out on a Trace
DSQII instrument in the 70—500 m/z range, the temperature
was programmed from 50 to 450 C at the rate of heating
100 deg min–1, matrixꢀactivated laser desorption/ionization
timeꢀofꢀflight mass spectra (MALDI MS) were recorded on
a Bruker Microflex LT instrument.
6
2ꢀtertꢀButylꢀ5ꢀcyanoꢀ3ꢀ( ꢀphenyl)tricarbonylchromiumꢀ
isoxazolidine (cisꢀ3k). The yield was 81%, m.p. 120—121 C. MS
(MALDI MS), m/z (Irel (%)): 405.1 [M + K]+ (100), 321.2 [M +
+ K – 3 CO]+ (42), 269.3 [M + K – Cr(CO)3]+ (16). IR (KBr),
v/cm–1: 2918, 2851 ((C—H)); 1969, 1886, 1871 ((CO)); 1645,
1575 (C—CAr)); 830, 663 ((CAr—H)). 1H NMR (acetoneꢀd6),
: 1.15 (s, 9 H, NBut); 2.67 (d, 1 H, C(4), J = 13.7 Hz); 3.21—3.37
(m, 1 H, HC(4)); 4.45 (dd, 1 H, HC(3), J = 8.0 Hz, J = 4.0);
5.20 (br.d, 1 H, HC(5), J = 7.4 Hz); 5.56 (t, 1 H, PhCr, J = 6.3 Hz);
5.65 (t, 1 H, PhCr, J = 6.3 Hz); 5.73 (t, 1 H, PhCr, J = 5.9 Hz);
6.01 (d, 1 H, PhCr, J = 6.3 Hz); 6.14 (d, 1 H, PhCr, J = 5.9 Hz).
1H NMR (benzeneꢀd6), : 0.81 (s, 9 H, NBut); 1.78—1.95,
1.96—2.14 (both m, 1 H each, C(4)); 3.35 (br.s, 1 H, HC(3));
3.69 (d, 1 H, C(5), J = 5.1 Hz); 4.08—4.48 (m, 3 H, PhCr); 5.03,
5.12 (both s, 1 H each, PhCr).
6
The isolation of nitrone and isoxazolidine ( ꢀarene)triꢀ
carbonylchromium complexes were carried out under argon.
Synthesis of isoxazolidines 3h—l (general procedure).
A corresponding nitrone 1b—f (1.8 mmol), freshly distilled acryꢀ
lonitrile (2b) (3 mL), and pyrocatechol (0.02 mmol) were placed
into a 5ꢀmL glass tube. The tube was degassed and sealed
in vacuo. The reaction mixture was heated in an oil bath at 80 C.
In the case of complexed nitrones 1d—f, the heating was continꢀ
ued until the color of the reaction mixture turned from bright red
to yellow. The heating time for the reactions involving nitrones
1b,e was 50 min, 1c,f 3 min, 1d 25 min. Then, the tubes were
unsealed, the excess of acrylonitrile was evaporated in vacuo.
A dense residue was subjected to column chromatography to
isolate the reaction products, which were purified by recrystalliꢀ
zation from a mixture of hexane—ethyl acetate (10 : 3).
6
5ꢀCyanoꢀ3ꢀ( ꢀphenyltricarbonylchromium)ꢀ2ꢀphenylisoxꢀ
azolidine (cisꢀ3l). The yield was 89%, m.p. 119—120 C. MS
(MALDI MS), m/z (Irel (%)): 425.0 [M + K]+ (100), 341.1 [M +
+ K – 3 CO]+ (29), 289.1 [M + K – Cr(CO)3]+ (36). IR (KBr),
v/cm–1: 2997, 2954, 2927 ((C—H)); 1954, 1893, 1872 ((CO));
1596, 1488, 1451 ((C—CAr)); 834, 807, 771, 663 ((CAr—H)).
1H NMR (acetoneꢀd6), : 2.64—2.95, 3.07—3.34, 4.88—5.15,
5.22—5.47 (all m, 1 H each, HC(4), HC(3), HC(5)); 5.53—6.72,
6.90—7.70 (both m, 5 H, PhCr, NPh). 1H NMR (benzeneꢀd6),
: 1.69—1.81 (m, 2 H, H2C(4)); 3.82 (dd, 1 H, HC(3), J = 8.6 Hz,
J = 4.7 Hz); 3.90 (dd, 1 H, HC(5), J = 7.0 Hz, J = 3.5 Hz);
4.19—4.26 (m, 1 H, oꢀC(3)PhCr); 4.33 (ddd, 2 H, mꢀHCr,
J = 6.3 Hz); 5.11 (d, 1 H, pꢀC(3)PhCr, J = 6.7 Hz); 6.81 (t, 1 H,
pꢀNPh, J = 7.4 Hz); 6.87 (d, 2 H, NPh, J = 7.8 Hz); 7.00 (t, 2 H,
NPh, J = 7.8 Hz).
Quantum chemical calculations. Charge distribution in niꢀ
trones 1c,f and acrylonitrile (2a) was evaluated by different
quantum chemical methods of simulation. The initial geoꢀ
metry of compounds under study was optimized using the
HyperChem 8.0 program within the PM3 semiempirical
method.18 The calculated structures were used as the starting
ones for the optimization of geometry within the density funcꢀ
tional theory38,39 using the B3LYP hybrid gradient funcꢀ
tional22,23 and a basis set with the LanL2DZ pseudoꢀcore potenꢀ
tial.24 The stationary points found were characterized by
the calculation of vibration frequencies. The calculations within
the density functional theory were carried out using the Gaussꢀ
ian 09 program.40
2ꢀtertꢀButylꢀ5ꢀcyanoꢀ3ꢀphenylisoxazolidine (cisꢀ, transꢀ3h).
The yield was 62%. 1H NMR (acetoneꢀd6), : 1.03, 1.08 (both s,
9 H each, NBut); 2.35 (ddd, 1 H, cisꢀHC(4), J = 12.5 Hz,
J = 5.9 Hz, J = 3.1 Hz); 2.68 (dt, 1 H, transꢀHC(4)), J = 12.5 Hz,
J = 7.8 Hz); 2.91 (ddd, 1 H, transꢀHC(4), J = 12.5 Hz, J = 7.8 Hz,
J = 4.7 Hz); 3.17 (dt, 1 H, cisꢀHC(4)), J = 9.0 Hz, J = 5.9 Hz);
4.26 (dd, 1 H, cisꢀHC(3), J = 12.5 Hz, J = 9.8 Hz); 4.58 (t, 1 H,
transꢀHC(3)), J = 7.8 Hz); 4.98 (dd, 1 H, transꢀHC(5), J = 7.8 Hz,
J = 5.1 Hz); 5.09 (dd, 1 H, cisꢀHC(5), J = 9.0 Hz, J = 3.1 Hz);
7.22—7.29, 7.30—7.41 (both m, 3 H each, transꢀPh, cisꢀPh);
7.48—7.54, 7.55—7.61 (both m, 2 H each, transꢀPh, cisꢀPh).
5ꢀCyanoꢀ2,3ꢀdiphenylisoxazolidine (cisꢀ3i). The yield was
84%, m.p. 60—61 C. IR (KBr), v/cm–1: 3063, 3031 ((CAr—H));
2981, 2925, 2877 ((C—H)); 1598, 1489, 1425 ((C—CAr)); 758,
697 ((CAr—H)). MS (EI, 70 eV), m/z (Irel (%)): 250.1 [M]+
(100), 180.1 [M – 2 with – CN – O – 4 H]+ (14), 143.1 [M –
–NPh – O]+ (32), 142.0 [M – NPh – O – H] (40), 115.0
[M – NPh – O – CN – 2 H]+ (28), 91.0 [NPh]+ (53), 77.0
[Ph]+ (29). 1H NMR (acetoneꢀd6, 400 MHz), : 2.66 (ddd, 1 H,
HC(4), J = 12.9 Hz, J = 5.5 Hz, J = 3.9 Hz); 3.37 (dt, 1 H,
HC(4), J = 12.9 Hz, J = 9.0 Hz); 4.69 (dd, 1 H, HC(3), J = 9.0 Hz,
J = 5.5 Hz); 5.37 (dd, 1 H, HC(5), J = 9.0 Hz, J = 3.5 Hz);
7.00—7.06 (m, 3 H, Ph); 7.25 (t, 2 H, Ph, J = 7.4 Hz); 7.35 (t, 1 H,
Ph, J = 7.4 Hz); 7.43 (t, 2 H, Ph, J = 7.4 Hz); 7.60 (d, 2 H, Ph,
1
J = 7.4 Hz). H NMR (benzeneꢀd6, 400 MHz), : 1.94—2.10,
Xꢀray diffraction studies of complex cisꢀ3k. The crystals
(C17H18N2O4Cr, M = 366.33) are orthorhombic, space group
3.82—3.93 (both m, 2 H each, C(4), HC(3), HC(5)); 6.76
(t, 1 H, J = 7.0 Hz); 6.85—7.08 (m, 7 H, Ph); 7.27 (d, 2 H, Ph,
J =7.4 Hz).
Pca2(1), a = 13.9300(8), b = 9.9790(6), c = 11.7793(7) Å,  =  =
=  = 90, V = 1637.41(17) Å , Z = 4, dcalc = 1.486 mg m–3
,
3

928
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 4, April, 2015
Zarovkina et al.
 = 7.22 cm–1; obtained by crystallization from a mixture of hexꢀ
ane—ethyl acetate. Intensities of 22640 reflections (4631 indepꢀ
endent reflections, Rint = 0.0190) were measured on a Smart Apex
diffractometer (graphite monochromator,  (MoꢀK) = 0.71073 Å,
temperature 100 К). Absorption was included using the SADABS
program.41 The structure was solved by a direct method and
14. A. N. Artemov, E. V. Sazonova, N. Yu. Zarovkina, Russ.
Chem. Bull. (Int. Ed.), 2013, 62, 1382 [Izv. Akad. Nauk, Ser.
Khim., 2013, 1382].
15. A. Padwa, L. Fisera, K. F. Koehler, A. Rodriguez, G. S. K.
Wong, J. Org. Chem., 1984, 49, 276.
16. Sk. A. Ali, P. A. Senaratne, C. R. Illig, H. Meckler, J. Tufaꢀ
riello, Tetrahedron Lett., 1979, 20, 4167.
refined by the fullꢀmatrix least squares method on F2 with
hkl
anisotropic thermal parameters for all the nonhydrogen atoms.
Hydrogen atoms were placed in geometrically calculated posiꢀ
tions and refined using a riding model. The final divergence
17. K. Heusler, P. Wieland, Ch. Meystre, Org. Synth., 1973,
5, 1124.
18. H. Feuer, in Nitrile oxides, nitrones and nitronates in organic
synthesis (Novel strategies in synthesis), Hoboken Inc., New
Jersey, 2008.
19. E. CoutouliꢀArgyropoulou, P. Lianis, M. Mitakou, A. Gianꢀ
noulis, J. Nowak, Tetrahedron, 2006, 62, 1494.
20. E. CoutouliꢀArgyropoulou, P. Sarridis, P. Gkizis, Green
Chem., 2009, 11, 1906.
21. E. CoutouliꢀArgyropoulou, S. Trakossas, Tetrahedron, 2011,
67, 1915.
factors: R1 = 0.0266 (I > 2(I)), wR2 = 0.0712 (refined on F2
hkl
for all the independent reflections), S(F2) = 1.076, 
=
max/min
= 0.693/–0.197 e Å–3, the absolute structural parameter
–0.009(12). All the calculations were performed on a personal
computer using the SHELXTL software package.42 The strucꢀ
ture was deposited with the Cambridge Crystallographic Data
Center (CCDC 1024600).
The authors are grateful to I. D. Grishin (N. I. Lobaꢀ
chevsky State University of Nizhny Novgorod) for carryꢀ
ing out mass spectrometric studies.
22. A. D. Becke, Phys. Rev. A, 1988, 38, 3098.
23. C. Lee, W. Yang, R. G. Parr, Phys. Rev. B, 1988, 37, 785.
24. P. J. Hay, W. R. Wadt, J. Chem. Phys., 1985, 82, 270.
25. N. Yu. Zarovkina, E. V. Sazonova, A. N. Artemov, Russ. J.
Org. Chem. (Engl. Transl.), 2014, 50, 1028 [Zh. Org. Khim.,
2014, 50, 1044].
26. B. Rees, P. Coppens, Acta Crystallogr., Sect. B., 1973, 9, 2515.
27. L. J. Farrugia, C. Evans, D. Lentz, M. Roemer, J. Am. Chem.
Soc., 2009, 131, 1251.
28. Y. Wang, K. Angermund, R. Goddard, C. Kruger, J. Am.
Chem. Soc., 1987, 109, 587.
29. N. A. Ustynyuk, L. N. Novikova, V. K. Bel´skii, J. Organoꢀ
met. Chem., 1985, 294, 31.
This work was financially supported by the Ministry
of Education and Science of the Russian Federation
(State Assignment, Project No. 736) and partially fiꢀ
nancially supported by the Ministry of Education and
Science of the Russian Federation and the N. I. Lobaꢀ
chevsky State University of Nizhny Novgorod
(Joint Grant, Agreement No. 02.B.49.21.0003 dated by
August 27, 2013).
30. N. M. Sergeev, Spektroskopiya YaMR (dlya khimikovꢀorganiꢀ
kov) [NMR Spectroscopy (for Organic Chemists)], MSU Publ.,
Moscow, 1981, 279 pp. (in Russian).
References
1. N. Yu. Zarovkina, E. V. Sazonova, A. N. Artemov, G. K.
Fukin, Russ. Chem. Bull. (Int. Ed.), 2014, 63, 970 [Izv. Akad.
Nauk, Ser. Khim., 2014, 970].
2. A. Berger, J. P. Djukic, Ch. Michon, Coord. Chem. Rev.,
2002, 225, 215.
3. M. F. Semmelhack, in Comprehensive Organometallic Chemꢀ
istry II, Eds E. W. Abel, F. G. A. Stone, G. Wilkinson, Perꢀ
gamon Press, Oxford, UK, 1995, 12, 1017.
4. P. J. Dickens, J. P. Gilday, J. T. Negri, D. A. Widdowson,
Pure Appl. Chem., 1990, 62, 575.
31. G. Huttner, E. O. Fischer, R. D. Carter, A. T. McPhaiI,
G. A. Sim, J. Organometal. Chem., 1966, 6, 288.
32. H. Kobayashi, K. Kobayashi, Y. Kaizu, Inorg. Chem., 1981,
20, 4135.
33. W. J. Bland, R. Davis, J. L. A. Durrant, J. Organomet. Chem.,
1982, 234, C20.
34. A. Weissberger, E. Proskauer, J. A. Riddick, E. E. Toops Jr.,
Organic Solvents; Physical Properties and Methods of Puriꢀ
fication, Intersci. Publ. Inc., New York—London, 1955,
552 pp.
5. S. E. Gibson, H. Ibrahim, Chem. Commun., 2002, 21, 2465.
6. M. Rosillo, G. Domínguez, J. PerezꢀCastells, Chem. Soc.
Rev., 2007, 36, 1589.
35. C. Weygand, Organisch Chemische Experimentierkunst,
2 Auflage, Johann Ambrosius Barth, Leipzig, 1948, 824.
36. H. W. Post, J. Org. Chem., 1940, 5, 244.
7. K. V. Gothelf, K. A. Jorgensen, Chem. Rev., 1998, 98, 863.
8. K. V. Gothelf, K. A. Jorgensen, Chem. Commun., 2000,
16, 1449.
9. P. N. Confalone, E. M. Huie, Org. React., 1988, 36, 1.
10. T. B. Nguyen, A. Martel, R. Dhal, G. Dujardin, J. Org.
Chem., 2008, 73, 2621.
11. R. Huisgen, R. Grashey, H. Hawk, H. Seidl, Chem. Ber.,
1968, 101, 2548.
12. A. N. Artemov, E. V. Sazonova, E. A. Mavrina, N. Yu.
Zarovkina, Russ. Chem. Bull. (Int. Ed.), 2012, 61, 2076 [Izv.
Akad. Nauk, Ser. Khim., 2012, 2059].
37. G. Drehfahl, H. H. Horhold, K. Kuhne, Chem. Ber., 1965,
98, 1826.
38. P. Hohenberg, W. Kohn, Phys. Rev. B, 1964, 136, 864.
39. W. Kohn, L. J. Sham, Phys. Rev. A, 1965, 140, 1133.
40. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone,
B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato,
X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng,
J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuꢀ
da, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda,
O. Kitao, H. Nakai, T. Vreven, Jr. Montgomery, J. E. Peralta,
F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N.
Kudin, V. N. Staroverov, R. Kobayashi, J. Normand,
13. C. Mukai, I. J. Kim, W. J. Cho, M. Kido, M. Hanaoka,
J. Chem. Soc., Perkin Trans. 1, 1993, 2495.

6ꢀArene)tricarbonylchromium isoxazolidines
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 4, April, 2015
929
K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar,
J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klen, J. E.
Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo,
R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin,
R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin,
K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador,
D. J. Fox, GAUSSIAN 09., 2009, Revision A.1, Gaussian
Inc. Wallingford CT.
41. G. M. Sheldrick, SADABS, 1997, Bruker AXS, Inc., Madiꢀ
son (WI), USA.
42. G. M. Sheldrick, Acta Crystallogr., Sect. A, Found. Crystalꢀ
logr., 2008, 64, 112.
Received September 24, 2014;
in revised form November 5, 2014