Synthesis of new η6-(arene) chromium tricarbonyl complexes of isoxazolidines by 1,3-dipolar cycloaddition

Article abstract of DOI:10.1007/s11172-012-0290-4

The 1,3-dipolar cycloaddition products of C,N-disubstituted nitrones and different in situ prepared mono-N-substituted nitrones to η⁶- (styrene) chromium tricarbonyl and η⁶-(ethyl cynnamate) chromium tricarbonyl were synthesized and

Full text of DOI:10.1007/s11172-012-0290-4

Russian Chemical Bulletin, International Edition, Vol. 61, No. 11, pp. 2076—2081, November, 2012
2076
Synthesis of new 6ꢀ(arene) chromium tricarbonyl complexes of isoxazolidines
by 1,3ꢀdipolar cycloaddition
A. N. Artemov, E. V. Sazonova, E. A. Mavrina, and N. Yu. Zarovkina
Research Institute of Chemistry, N. I. Lobachevsky Nizhny Novgorod State University,
5 Build., 23 prosp. Gagarina, 603950 Nizhny Novgorod, Russian Federation.
Fax: +7 (831) 465 8162. Eꢀmail: zarovkinan@mail.ru
The 1,3ꢀdipolar cycloaddition products of C,Nꢀdisubstituted nitrones and different in situ
6
6
prepared monoꢀNꢀsubstituted nitrones to  ꢀ(styrene) chromium tricarbonyl and  ꢀ(ethyl
cynnamate) chromium tricarbonyl were synthesized and characterized by HPLC, IR, 1Н NMR
spectroscopy, and mass spectrometry. The resulted isoxazolidines were produced with a full
regioselectivity and high stereoselectivity reached 100% in most cases.
6
Key words: nitrone,  ꢀ(arene) chromium tricarbonyl, isoxazolidine, 1,3ꢀdipolar cycloꢀ
addition.
Scheme 1
It is known that the 1,3ꢀdipolar cycloaddition reacꢀ
tions are universal methods for the synthesis of various
fiveꢀmembered heterocyclic compounds.1—3 For example,
the reactions of nitrones with substituted alkenes result in
the formation of a wide variety of isoxazolidines, which
are fiveꢀmembered heterocycles containing the N—O
bond.4—6 Isoxazolidines are starting compounds in the synꢀ
thesis of many natural compounds, such as alkaloids,4,7—9
amino acids,10—12 and amino sugars.13,14 Depending on
the nature of reagents, cycloaddition of nitrones to diffeꢀ
rent dipolarophiles can proceed both regioselectively and
nonꢀregioselectively,6 which often affords a mixture of
C(4)ꢀ and C(5)ꢀsubstituted isoxazolidines. For this reaꢀ
son, the one of the main research problems is to improve
the selectivity of 1,3ꢀdipolar cycloaddition, i.e., to achieve
the predominant formation of any given isomer. From
this viewpoint, unsaturated arene chromium tricarbonyl
complexes seem to be very attractive, wherein the chromiꢀ
um tricarbonyl groups can influence significantly the
changes in the electronic properties of the substrate and
the structures of the products formed.15,16 The important
factor is the ability of the chromium tricarbonyl moiety to
block one side of the arene ligand, which can be used in
the diastereoselective syntheses of various compounds.17,18
Since isoxazolidines are synthesized under relatively
mild conditions suitable for the preparations of arene chromiꢀ
um tricarbonyl complexes, we decided to study the 1,3ꢀdiꢀ
polar cycloaddition of different nitrones to substituted
alkenes containing arene chromium tricarbonyl groups.
1: R1 = H, R2 = Ph (a), But (b), Me (c),
R
1 = Ph, R2 = Me (d), Ph (e), But (f)
2: R3 = H, R4 = Ph (a), Ph[Cr(CO)3] (b),
R3 = CO2Et, R3 = Ph[Cr(CO)3] (c)
3
a
b
c
d
e
f
g
h
i
j
k
l
m
n
R1
H
H
H
H
R2
Ph
But
Me
Ph
R3
H
H
H
R4
Ph[Cr(CO)3]
Ph[Cr(CO)3]
Ph[Cr(CO)3]
Ph
H
H
H
But
Me
Me
Ph
H
H
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
But
Me
Ph
Ph
Ph[Cr(CO)3]
Ph[Cr(CO)3]
Ph[Cr(CO)3]
Ph[Cr(CO)3]
Ph[Cr(CO)3]
But
Ph
But
H
CO2Et
CO2Et
Results and Discussion
A series of simple monoꢀNꢀsubstituted nitrones 1a—c
were used as dipoles in the performed syntheses (Scheme 1),
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2059—2064, November, 2012.
1066ꢀ5285/12/6111ꢀ2076 © 2012 Springer Science+Business Media, Inc.

6ꢀ(Arene) chromium tricarbonyl isoxazolidines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 11, November, 2012 2077
which were impossible to isolate in pure form due to their
instability; therefore, these substances were obtained in situ
from formaldehyde and Nꢀsubstituted hydroxylamine.19
The stable C,Nꢀdisubstituted nitrones20—22 1d—f were
served as the dipole components. Styrene 2a, 6ꢀ(styrene)
chromium tricarbonyl23 (2b), and 6ꢀ(ethyl cinnamate)
chromium tricarbonyl24 (2c) acted as dipolarophiles in
the reactions.
isoxazolidines. The increase in the yield of the C(5)ꢀsubꢀ
stituted products can be explained by either an increase in
the HOMO energies or a decrease in the LUMO energies
of reacting substances.27
The reaction products of nitrones 1b and 1с with
6ꢀ(styrene) chromium tricarbonyl 2b are isoxazolidines
3b and 3c, respectively. For their nonꢀcoordinated anaꢀ
logs 3e,f, 1,3ꢀdipolar cycloaddition also results in the exꢀ
clusive formation of the C(5)ꢀsubstituted products, which
suggests that the regioselectivity remains unchanged upon
introduction of the chromium tricarbonyl group to the
dipolarophile molecule.
The interesting feature of the IR spectra of all prepared
isoxazolidines containing the phenyl chromium tricarbonyl
group at the C(5) atom of the heterocyclic ring is consiꢀ
derable band splitting (E) of degenerate carbonyl vibraꢀ
tions (СО). This splitting appears to be caused by the С3v
symmetry violation, which is caused by the spatial interꢀ
action of the Cr(CO)3 group with the oxygen atom at the
ꢀposition relative to the 6ꢀ(arene) chromium tricarboꢀ
nyl fragment. We have observed such splitting earlier by
the example of 6ꢀ(1ꢀphenylethanol) chromium tricarboꢀ
nyl28 (Fig. 2).
Thus, we showed that the reaction of monoꢀNꢀsubstiꢀ
tuted nitrones with coordinated dipolarophiles affords the
6ꢀ(arene) chromium tricarbonyl complexes of isoxazoꢀ
lidines, the high regioselectivity of the reaction remaining
unchanged upon introduction of the chromium tricarbonꢀ
yl group to the alkene molecule.
The effect of the Cr(CO)3 group on the stereoselectivꢀ
ity of 1,3ꢀdipolar cycloadditon, namely, on the yield of
the cis and trans isomers, was studied by the example of
the reaction of stable С,Nꢀdisubstituted nitrones 1d—f with
the ,ꢀunsaturated arene chromium tricarbonyl complexꢀ
es 2a—c (see Scheme 1). According to the studies of Gerꢀ
man scientists,29 the reaction of CꢀphenylꢀNꢀmethyl
nitrone (1d) with styrene 2a results in a mixture of
the C(5)ꢀsubstituted cis and trans isomers in a ratio of
cisꢀ3g : transꢀ3g = 67 : 33, while cycloaddition of
C,Nꢀdiphenylnitrone (1e) to styrene 2a affords a mixꢀ
ture of adducts cisꢀ3h and transꢀ3h in the ratio of 90 : 10
(Table 2).
All isoxazolidines obtained were isolated in pure form
and characterized by the physicochemical analysis meꢀ
thods; their main characteristics are given in Table 1.
In all cases, the 1,3ꢀdipolar cycloaddition between
nitrones and dipolarophiles, including coordinated ones,
yielded isoxazolidines containing either phenyl group or
phenylchromium tricarbonyl group at the C(5) carbon
atom of the heterocyclic ring, which evidences a high reꢀ
gioselectivity of the processes. For example, the reaction
of nitrone 1a with 6ꢀ(styrene) chromium tricarbonyl 2b
afforded the C(5)ꢀsubstituted isoxazolidine 3a. The sigꢀ
1
nals in the H NMR spectrum of this compound, viz.,
doublet of doublets of doublets (1 H, 2.35—2.45), multiꢀ
plet (1 H, 2.62—2.77), triplet (1 H, 3.70), and doublet of
doublets (2 H, 4.95), suggest that the phenyl chromium
tricarbonyl group is located at the C(5) carbon atom (Fig. 1).
The spectrum of the corresponding C(4)ꢀsubstituted isoꢀ
mer would display two doublets of doublets for the meꢀ
thylene protons at the C(3) and C(5) carbon atoms due to
their spinꢀspin coupling with the proton at C(4) and one
multiplet for the proton at С(4) resulting from the couꢀ
pling with the protons at C(3) and C(5).
Such a high regioselectivity of the 1,3ꢀdipolar cycloadꢀ
dition can be explained by two major factors. The first
factor is based on the consideration of polarities of 1,3ꢀdiꢀ
pole and dipolarophile and the second one is related to the
calculation of electron populations of the HOMO and
LUMO of reacting molecules. It is assiumed that the closer
the frontier orbitals are arranged to each other by the enerꢀ
gy and orbital symmetry, the stronger the interaction of
reacting components and the higher the process regioꢀ
selectivity.25,26 The quantum chemical calculation data
for a series of the 1,3ꢀdipolar cycloaddition reactions sugꢀ
gest the predominant formation of the C(5)ꢀsubstituted
2.18
1.33
0.98
0.95
5.0
4.5
4.0
3.5
3.0
2.5

Fig. 1. A fragment of the 1H NMR spectrum of complex 3a (in the spectrum, the integral intensities of the signals are given).

2078
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 11, November, 2012
Artemov et al.
(СО)/cm–1
Table 1. Some characteristics* of isoxazolidines 3a—d
Dipole
(nitrone) 1
Dipolaroꢀ
Isoxazolꢀ
R1
R2
R3
R4
M.p./C
Yield
(%)
phile 2
idine 3
1a
1b
1c
1a
1b
1c
1d
1d
1e
1e
1f
1d
1d
1e
1f
1e
1f
2b
2b
2b
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2c
2c
3a
3b
3c
3d
3e
H
H
H
H
H
Ph
But
Me
Ph
But
Me
Me
Me
Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph[Cr(CO)3]
Ph[Cr(CO)3]
Ph[Cr(CO)3]
115—116
103—105
Oil
61—62
Oil
Oil
Oil
Oil
99—100
—
57—58
90—92
112—113
111—113
103—105
91—93
82—84
45
47
44
69
72
41
64
31
85.5
9.5
80
66
14
45
47
5
1950, 1886, 1865
1963, 1888, 1864
1962, 1878, 1866
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
—
—
—
—
3f
H
cisꢀ3g
transꢀ3g
cisꢀ3h
transꢀ3h
cisꢀ3i
cisꢀ3j
transꢀ3j
cisꢀ3k
cisꢀ3l
cisꢀ3m
cisꢀ3n
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
—
Ph
But
Me
Me
Ph
—
Ph[Cr(CO)3]
Ph[Cr(CO)3]
Ph[Cr(CO)3]
Ph[Cr(CO)3]
1953, 1887, 1876
1956, 1895, 1878
1973, 1904, 1858
1960, 1890, 1873
1970, 1910, 1884
1962, 1910, 1878
But
Ph
But
CO2Et Ph[Cr(CO)3]
CO2Et Ph[Cr(CO)3]
21
* Data for isoxazolidines cisꢀ3g, transꢀ3g, cisꢀ3h, and transꢀ3h are taken from Ref. 29.
The conducted reactions between nitrones and coordiꢀ
nated dipolarophiles revealed that introduction of chromiꢀ
um tricarbonyl group into the alkene molecule favors an
increase in the process stereoselectivity. For example, the
reaction of CꢀphenylꢀNꢀmethyl nitrone 1d with 6ꢀ(styꢀ
rene) chromium tricarbonyl 2b afforded a mixture of isoꢀ
mers cisꢀ3j and transꢀ3j, which were separated by column
chromatography. The ratio of cisꢀ3j : transꢀ3j was found
to be 83 : 17, while the ratio of cisꢀ3g : transꢀ3g was 67 : 33.
The structure of complex cisꢀ3j was proved by Xꢀray difꢀ
fraction study: the coordinated and free phenyl substituꢀ
ents are on the same side from the fiveꢀmembered ring
(Fig. 3, Table 3). The structures of isomers cisꢀ3j and
transꢀ3j were confirmed by comparison of their 1H NMR
spectra with those of the nonꢀcoordinated analogs.29
The reactions of C,Nꢀdiphenylnitrone (1e) and Cꢀphenꢀ
ylꢀNꢀtertꢀbutylnitrone (1f) with the coordinated dipolaroꢀ
philes result in the formation of only cisꢀisomers (see
Table 2). One of the reasons of so high stereoselectivity is
strengthening of the interaction between the free and coorꢀ
dinated phenyl rings.15 This conception is confirmed by
the fact that a chargeꢀtransfer complex can form as shown
in Ref. 30 (see Fig. 4, a).
In summary, based on the experimental data obtained
one can conclude that the 1,3ꢀdipolar cycloaddition reacꢀ
tions between nitrones and different alkenes containing
the phenyl chromium tricarbonyl group proceed under
sufficiently mild conditions to form the corresponding
C(5)ꢀsubstituted isoxazolidines, which evidences high reꢀ
gioselectivities of the reactions. It was established that
introduction of the chromium tricarbonyl group to the
dipolarophile molecules increases considerably the stereoꢀ
selectiviy of 1,3ꢀdipolar cycloaddition, which, in some
cases, reached 100%, which can be used in various diasteꢀ
reoselective syntheses.16—18
Table 2. Ratio of the cisꢀ and transꢀisomers of isoxazolꢀ
idines 3g—n in the 1,3ꢀdipolar cycloaddition reactions
Nitrone
(dipole)
Dipolaroꢀ
phile
Product
Cisꢀ3 : transꢀ3
ratio
1d
1e
1f
1d
1e
1f
2а
2а
2а
2b
2b
2b
2с
2с
3g
3h
3i
3j
3k
3l
167 : 33*
190 : 10*
100 : 0
183 : 17
100 : 0
100 : 0
100 : 0
100 : 0
1e
1f
3m
3n
Fig. 2. Intramolecular interaction of the Cr(CO)3 group with the
6
oxygen atoms in the molecules of compound 3b (a) and  ꢀ(1ꢀ
phenylethanol) chromium tricarbonyl (b).
* Data from Ref. 29.

6ꢀ(Arene) chromium tricarbonyl isoxazolidines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 11, November, 2012 2079
Table 3. Selected bond lengths and bond angles in the structure of complex cisꢀ3j
Bond
d/Å
Bond
d/Å
Angle
/deg
N(1)—O(4)
N(1)—C(12)
C(11)—C(12)
C(10)—C(11)
O(4)—C(10)
Cr(1)—C(2)
Cr(1)—C(1)
1.4786(18)
1.472(2)
1.534(2)
1.544(2)
1.436(2)
Cr(1)—C(3)
Cr(1)—C(7)
Cr(1)—C(8)
Cr(1)—C(5)
Cr(1)—C(6)
Cr(1)—C(9)
Cr(1)—C(4)
1.8454(18)
2.2137(18)
2.2172(17)
2.2210(17)
2.2225(17)
2.2286(16)
2.2295(16)
N(1)—C(12)—C(11)
C(12)—C(11)—C(10)
O(4)—C(10)—C(11)
C(10)—O(4)—N(1)
C(12)—N(1)—O(4)
C(2)—Cr(1)—C(1)
C(2)—Cr(1)—C(3)
C(1)—Cr(1)—C(3)
101.62(13)
102.98(14)
105.79(13)
104.02(12)
101.29(12)
87.59(8)
1.8375(18)
1.8402(19)
87.82(8)
89.64(9)
sized according to the published procedures.23,24 2ꢀMethylꢀ5ꢀ
phenylisoxazolidine (3f) was prepared from styrene, formalꢀ
dehyde, and Nꢀmethylhydroxylamine according to a known proꢀ
cedure.19
To remove the stabilizer, styrene was washed with a 10%
aqueous solution of sodium hydroxide and water, dried, and
distilled (b.p. 48—49 С (10 Torr)). Ethyl cinnamate was syntheꢀ
sized according to a known procedure.32 The products were isoꢀ
lated and purified by column chromatography on silica gel
(Acros, 0.035—0.070 mm). Highꢀperformance liquid chromatoꢀ
graphy was performed on a Knauer Smartline 5000 chromatoꢀ
graph with a S 2600 PDA detector, Diaspherꢀ110ꢀС16 column,
5 m, 4.6×250 mm, the eluent was acetonitrile—water (84 : 16).
The UV spectra of eluates were recorded in the range of
200—500 nm. IR spectra were recorded on a Infralum FTꢀ801
spectrometer in the range of 480—4600 cm–1 in suspension with
KBr or in films on ZnSe glass plates. 1H NMR spectra were
recorded on Bruker DPX 200 and Bruker Avance DPX 400
spectrometers (200 and 400 MHz, respectively) in acetoneꢀd6.
Mass spectrometric studies were performed on a Trace GC
Metra/PS QII instrument in the positive ion mode, electron
impact ionization (70 eV), m/z range of 28—500, TR5MS capilꢀ
lary column (60000×0.25 mm), the flow rate of helium was
1 mL min–1, temperature programming from 60 to 300 С at the
heating rate of 15 deg min–1, and on a Bruker Microflex LT
instrument by matrixꢀassisted laser desorption/ionization timeꢀ
ofꢀflight mass spectrometry (MALDI MS).
C(14)
C(12)
N(1)
C(11)
C(8)
C(7)
C(6)
C(10)
C(9)
C(5)
C(1)
O(1)
C(4)
Cr(1)
O(4)
C(13)
C(3)
O(3)
C(2)
O(2)
Fig. 3. Molecular structure of complex cisꢀ3j (the hydrogen atoms
are not shown).
The synthesis and isolation of 2,5ꢀdisubstituted (3a—c), as
6
well as isolation of 2,3,5ꢀtrisubstituted (3j—n)  ꢀ(arene) chromiꢀ
um tricarbonyl complexes were performed under an argon atꢀ
mosphere.
Fig. 4. Transition states of the 1,3ꢀdipolar cycloaddition reacꢀ
tions leading to the formation of the isoxazolidine cisꢀ (a) and
transꢀisomers (b).
Synthesis of the 2,5ꢀdisubstituted isoxazolidines 3a—f (generꢀ
al procedure).19 To a mixture of the corresponding dipolarophile
2а,b (0.014 mol), 37% aqueous formaldehyde (0.020 mol), and
dioxane (15 mL), a solution of the Nꢀsubstituted hydroxylamine
(0.012 mol) in dioxane (5 mL) was added dropwise with vigorous
stirring at room temperature. The reaction mixture was kept for
16 h, concentrated, and extracted with ethyl acetate, the organic
layer was dried with calcium chloride. The solvent was removed
under reduced pressure. The target products were isolated by
column chromatography of a viscous residue and subsequent
recrystallization from a hexane—ethyl acetate mixture.
Experimental
All solvents were distilled over sodium metal under atmoꢀ
30
spheric pressure
.
NꢀPhenylꢀ and Nꢀtertꢀbutylhydroxylamines
were prepared by reduction of the corresponding nitro comꢀ
pounds.20,31 For the synthesis of CꢀphenylꢀNꢀmethylnitrone (1d),
Nꢀmethylhydroxylamine hydrochloride (Sigma—Aldrich) was
used. C,NꢀDisubstituted nitrones 1d—f were synthesized by
condensation of benzaldehyde with the corresponding hydrꢀ
oxylamines.20—22  ꢀ(Styrene) chromium tricarbonyl (2b) and
 ꢀ(ethyl cinnamate) chromium tricarbonyl (2c) were syntheꢀ
6
 ꢀ(5ꢀPhenyl chromium tricarbonyl)ꢀ2ꢀphenylisoxazolidine
(3a). The yield was 45%, m.p. 115—116 С. Found (%): Сr,
13.97. С18H15NO4Cr. Calculated (%): Cr, 14.40. MS (MALDI
MS), m/z (Irel (%)): 399.9 [M + K]+ (30), 333.0 [M – CO]+
(25), 277.1 [M – 3 CO]+ (35), 221.1 [M – Cr(CO)3 – 4 H]+
6
6

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Russ.Chem.Bull., Int.Ed., Vol. 61, No. 11, November, 2012
Artemov et al.
(100). IR (KBr), /cm–1: 1950, 1886, 1865 ((СО)); 1177,
1036 ((N—O, C—O)); 763, 664, 633 ((CAr—H)). 1H NMR
(200 MHz), : 2.35 (ddd, 1 H, H2C(4), J = 12.6 Hz, J = 6.4 Hz,
J = 6.2 Hz); 2.62—2.77 (m, 1 H, H2C(4)); 3.70 (t, 1 H, HC(5),
J = 7.1 Hz); 4.95 (dd, 2 H, H2C(3), J = 7.8 Hz, J = 6.2 Hz);
5.49—5.90 (m, 5 H, C(5)PhCr); 6.95 (t, 1 H, pꢀPhN, J = 7.1 Hz);
7.12 (d, 2 H, mꢀPhN, J = 7.7 Hz); 7.26 (d, 2 H, oꢀPhN,
J = 7.3 Hz).
5.13 (dd, 1 H, HC(5), J = 5.0 Hz, J = 10.0 Hz); 7.16—7.52
(m, 10 H, Ph).
6
 ꢀ(5ꢀPhenyl chromium tricarbonyl)ꢀ2ꢀmethylꢀ3ꢀphenylisoxꢀ
azolidine (transꢀ3j and cisꢀ3j) were synthesized at 80 C (bath
temperature).
Isomer cisꢀ3j. The yield was 66%, m.p. 90—92 C. IR (KBr),
/cm–1: 1953, 1887, 1876 ((C—O)); 1384 ((C—C)); 1292, 1150
((N—O, C—O)); 1011 ((C—N)); 761, 662, 633 ((CAr—H)).
1H NMR (400 MHz), : 2.29 (ddd, 1 H, HC(4), J = 12.6 Hz,
J = 9.5 Hz, J = 6.3 Hz); 2.57 (s, 3 H, CH3N); 3.22—3.29 (m, 1 H,
HC(4)); 3.71 (t, 1 H, HC(3), J = 8.2 Hz); 4.98 (dd, 1 H, HC(5),
J = 8.5 Hz, J = 6.3 Hz); 5.52—5.59 (m, 1 H, C(5)ꢀmꢀPhCr);
5.66 (d, 2 H, C(5)ꢀoꢀPhCr, J = 3.8 Hz); 5.71 (t, 1 H, C(5)ꢀmꢀ
PhCr, J = 6.4 Hz); 5.95 (d, 1 H, C(5)ꢀpꢀPhCr, J = 6.3 Hz); 7.29
(d, 1 H, pꢀPhC(3), J = 7.0 Hz); 7.34 (t, 2 H, mꢀPhC(3), J = 7.3 Hz);
7.39 (d, 2 H, oꢀPhC(3), J = 7.3 Hz).
6
 ꢀ(5ꢀPhenyl chromium tircarbonyl)ꢀ2ꢀtertꢀbutylisoxazolidine
(3b) was synthesized at 55 C (bath temperature). The yield was
47%, m.p. 103—105 С. Found (%): C, 56.80; H, 5.81; Сr, 14.93.
C16H19NO4Cr. Calculated (%): C, 56.30; H, 5.57; Cr, 15.25.
MS (MALDI MS), m/z (Irel (%)): 379.9 [M + K]+ (100), 352.0
[M + K – CO]+, 313.1 [M – CO]+ (28), 257.1 [M – 3 CO]+
(39). IR (KBr), /cm–1: 3155, 2976, 2927 ((C—H)); 1963, 1888,
1864 ((CO)); 1457 ((C—C)); 1233, 1031 ((N—O, C—O));
814, 662, 633 ((CAr—H)).
Isomer transꢀ3j. The yield was 14%, m.p. 112—113 C. IR
(KBr), /cm–1: 1956, 1895, 1878 ((CO)); 1384 ((C—C));
1290, 1150 ((N—O, C—O)); 1037((C—N)); 706, 661, 633
((CAr—H)). 1H NMR (400 MHz), : 2.59 (s, 3 H, NCH3);
2.62—2.69 (m, 1 H, HC(4)); 2.74 (d, 1 H, HC(4), J = 9.5 Hz);
3.13 (d, 1 H, HC(3), J = 5.3 Hz); 4.93 (t, 1 H, HC(5), J = 7.2 Hz);
5.57—5.71 (m, 3 H, C(5)PhCr); 5.73—5.83 (m, 2 H, C(5)PhCr);
7.30 (d, 1 H, oꢀPhC(3), J = 7.0 Hz); 7.36—7.52 (m, 4 H, oꢀ, mꢀ,
pꢀPhC(3)).
6
 ꢀ(5ꢀPhenyl chromium tricarbonyl)ꢀ2ꢀmethylisoxazolidine
(3c) was synthesized at 55 C (bath temperature). The yield was
44%. MS (MALDI MS), m/z (Irel (%)): 337.9 [M + K]+ (100),
309.9 [M + K – CO]+ (17), 270.9 [M – CO]+ (22). IR, /cm–1
:
2959, 2916, 2849 ((C—H)); 1962, 1878, 1866 ((CO)); 1457,
1424 ((C—C)); 1290, 1026 ((N—O, C—O)); 819, 662, 631
1
((CAr—H)). H NMR (400 MHz), : 2.21 (m, 1 H, H2C(4));
2.62 (br.s, 1 H, H2C(4)); 2.67 (br.s, 3 H, NCH3); 2.84 (br.s, 1 H,
H2C(3)); 3.21—3.43 (m, 1 H, H2C(3)); 4.90 (br.s, 1 H, HC(5));
5.45—5.79 (m, 5 H, C(5)PhCr).
6
 ꢀ(5ꢀPhenyl chromium tricarbonyl)ꢀ2,3ꢀdiphenylisoxazoꢀ
lidine (3k). The yield was 42%, m.p. 111—113 C. IR (KBr),
/cm–1: 2987, 2923, 2893 ((C—H)); 1973, 1904, 1858 ((CO);
1650 ((C—CAr)); 1489 ((C—C)); 1261, 1127 ((N—O, C—O));
1027 ((C—N)); 802, 664 ((CAr—H)). 1H NMR (400 MHz),
: 2.37 (td, 1 H, HC(4), J = 7.2 Hz, J = 8.8 Hz, J = 12.4 Hz); 3.37
(td, 1 H, HC(4), J = 7.2 Hz, J = 6.0 Hz, J = 15.0 Hz); 5.00
(t, 2 H, HC(3)Ph,HC(5)Ph, J = 7.0); 5.50—5.80 (m, 4 H, oꢀ, mꢀ,
pꢀC(5)PhCr); 5.85 (d, 1 H, oꢀC(5)PhCr, J = 6.0 Hz); 6.94 (t, 1 H,
pꢀPhN, J = 7.2 Hz); 7.11 (d, 2 H, oꢀPhN, J = 3.8 Hz); 7.26
(m, 3 H, mꢀPhN, pꢀPhC(3)); 7.40 (m, 2 H, mꢀPhC(3)); 7.58 (d, 2 H,
oꢀPhC(3), J = 7.4 Hz).
2,5ꢀDiphenylisoxazolidine (3d). The yield was 69%, m.p.
61—62 C. IR (КВr), /cm–1: 2985, 2959, 2917 ((C—H)); 1596
((C—CAr)); 1284, 1176 ((N—O, C—O)); 1024 ((C—N)); 761,
698, 669 ((CAr—H)). 1H NMR (200 MHz), : 2.45—2.10
(m, 1 H, H2C(4)); 2.68 (ddd, 1 H, H2C(4), J = 14.8 Hz, J= 12.1 Hz,
J = 7.9 Hz); 3.93—3.52 (m, 2 H, H2C(3)N); 5.18 (t, 1 H,
HC(5)Ph, J = 7.5 Hz); 6.99 (t, 1 H, pꢀPhN, J = 7.2 Hz); 7.13
(d, 2 H, oꢀPhN, J = 7.7 Hz); 7.19—7.66 (m, 7 H, Ph).
2ꢀtertꢀButylꢀ5ꢀphenylisoxazolidine (3e). The yield was 72%.
Found (%): C, 76.62; H, 9.60. C13H19NO. Calculated (%):
C, 76.10; H, 9.27. MS (EI, 70 eV), m/z (Irel (%)): 205.0 [M]+ (20),
190.0 [M – CH3]+ (50), 117.2 [PhC2O]+ (100), 104.0
[PhCHCH2]+ (68), 77.2 [Ph]+ (28), 57.0 [But]+ (26). IR (KBr),
/cm–1: 2971, 2925, 2855 ((C—H)); 1604 ((C—CAr)); 1361,
1232 ((N—O, C—O)); 830, 757, 698 ((CAr—H)).
Synthesis of 2,3,5ꢀtrisubstituted isoxazolidines 3i—n (genꢀ
eral procedure). The corresponding C,Nꢀdisubstituted nitrone
1d—f (0.002 mol), dipolarophile 2a—c (0.002 mol) and toluene
(3 mL) were placed into a 20 mL glass tube. The tube was deꢀ
gassed and sealed in vacuo. The reaction mixture was heated for
40 h at 105 C. The tube was opened, the content was filtered
through a glass filter, the filtration residue was washed with
toluene, and the solvent was evaporated in vacuo. The reaciton
products were isolated from a viscous residue by column chromꢀ
atography and recrystallized from hexane to yield the target
products.
2ꢀtertꢀButylꢀ3,5ꢀdiphenylisoxazolidine (3i). The yield was
80%, m.p. 57—58 C. Found (%): C, 80.97; H, 8.30. C19H23NO.
Calculated (%): C, 81.14; H, 8.19. IR (KBr), /cm–1: 3055,
2977, 2926 ((C—H)); 1579 ((C—CAr)); 1447 ((C—C)); 1222,
1193 ((N—O, C—O)); 1028 ((C—N)); 842, 753, 699 ((CAr—H)).
1H NMR (200 MHz), : 1.12 (s, 9 H, But); 2.35 (dt, 1 H, HC(4),
J = 10.0 Hz, J = 12.0 Hz); 2.94 (dt, 1 H, HC(4), J = 6.0 Hz,
J = 12.0 Hz); 4.46 (dd, 1 H, HC(3), J = 7.0 Hz, J = 10.0 Hz);
6
 ꢀ(5ꢀPhenyl chromium tricarbonyl)ꢀ2ꢀtertꢀbutylꢀ3ꢀphenylꢀ
isoxazolidine (3l). The yield was 47%, m.p. 103—105 C. IR
(KBr), /cm–1: 2961, 2925, 2855 ((C—H)); 1960, 1890, 1873
((CO)); 1632 ((C—CAr)); 1458 ((C—C)); 1261, 1120 ((N—O,
C—O)); 1091 ((C—N)); 802, 662 ((CAr—H)). 1H NMR
(400 MHz), : 1.08 (s, 9 H, But); 2.19 (dt, 1 H, HC(4), J = 9.0 Hz,
J = 12.0 Hz); 3.16 (dt, 1 H, HC(4), J = 7.0 Hz, J = 12.0 Hz);
4.49 (dd, 1 H, HC(3), J = 6.0 Hz, J = 9.0 Hz); 4.88 (dd, 1 H,
HC(5), J = 7.0 Hz, J = 9.0 Hz); 5.58 (m, 2 H, mꢀC(5)PhCr);
5.63 (d, 1 H, oꢀC(5)PhCr, J = 4.0 Hz); 5.71 (t, 1 H, pꢀC(5)PhCr,
J = 6.0 Hz); 5.99 (d, 1 H, oꢀC(5)PhCr, J = 6.0 Hz); 7.32 (m, 3 H,
mꢀ, pꢀPhC(3)); 7.48 (d, 2 H, oꢀPhC(3), J = 7.0 Hz).
6
 ꢀ(5ꢀPhenyl chromium tricarbonyl)ꢀ2,3ꢀdiphenylꢀ4ꢀethylꢀ
carboxyisoxazolidine (3m). The yield was 5%, m.p. 91—93 C.
IR (KBr), /cm–1: 2958, 2919, 2852 ((C—H)); 1970, 1910,
1884 ((CO)); 1734 ((C=O)); 1649, 1457 ((C—CAr)); 1261,
1172 ((N—O, C—O)); 1089 ((C—N)); 801, 664, 631 ((CAr—H)).
6
 ꢀ(5ꢀPhenyl chromium tricarbonyl)ꢀ2ꢀtertꢀbutylꢀ3ꢀphenylꢀ
4ꢀethylcarboxyisoxazolidine (3n). The yield was 21%, m.p.
82—84 C. IR (KBr), /cm–1: 2967, 2922, 2874 ((C—H)); 1962,
1910, 1878 ((CO)); 1733 ((C=O)); 1650, 1456 ((C—CAr));
1269 ((N—O, C—O)); 1092 ((C—N)); 799, 662, 631
1
((CAr—H)). H NMR (400 MHz), : 1.09 (s, 9 H, But); 1.19
(t, 3 H, OCH2CH3, J = 7.0 Hz); 3.36 (dd, 1 H, HC(4), J = 7.0 Hz,

6ꢀ(Arene) chromium tricarbonyl isoxazolidines
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 11, November, 2012 2081
J = 9.0 Hz); 4.16 (s, 2 H, OCH2CH3, J = 7.0 Hz); 4.62 (d, 1 H,
HC(3), J = 9.0 Hz); 5.15 (d, 1 H, C(5)H, J = 7.0 Hz); 5.63
(m, 3 H, oꢀ, mꢀC(5)PhCr); 5,75 (t, 1 H, pꢀC(5)PhCr, J = 6.0 Hz);
6.11 (d, 1 H, oꢀC(5)PhCr, J = 6.0 Hz); 7.30 (m, 3 H, pꢀ, mꢀPh);
7.47 (dd, 2 H, oꢀPh, J = 2.0 Hz, J = 8.0 Hz).
11. D. Kiers, D. Moffat, K. Overton, R. J. Tomanek, Chem.
Soc., Perkin Trans. 1, 1991, 1041.
12. C. M. Tice, B. Ganem, J. Org. Chem., 1983, 48, 5048.
13. A. Vasella, R. Voeffray, J. Chem. Soc., Chem. Commun.,
1981, 97.
Xꢀray diffraction study of complex cisꢀ3j. The crystals
(С19H17NO4Cr, M = 375.34) are monoclinic (space group Р2(1)/c,
at 100 К: a = 10.3424(7), b = 7.1473(5), c = 23.9375(16) Å,
 = 90,  = 95.692(10),  = 90, V = 1760.7(2) Å3, Z = 4,
dcalc = 1.416 g cm–3,  = 6.72 cm–1) and were obtained by crysꢀ
tallization from hexane. The intensities of 19 268 reflections
(3458 independent reflections, Rint = 0.0243) were measured
on a Smart Apex diffractometer (graphite monochromator,
(MoꢀK) = 0.71073 Å, 100 K). The account of absorption was
performed by the SADABS program.33 The structure were solved
by the direct method and refined by the fullꢀmatrix leastꢀsquares
14. A. Vasella, R. Voeffray, Helv. Chim. Acta, 1982, 65, 1134.
15. C. Mukai, I. J. Kim, W. J. Cho, M. Hanaoka, Tetrahedron
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D. Astruc, WillyꢀVCH, 2003, p. 368.
18. S. E. Gibson, H. Ibrahim, Chem. Commun., 2002, 21, 2465.
19. E. J. Fornefeld, A. J. Pike, J. Org. Chem., 1979, 44, 835.
20. K. Heusler, P. Wieland, Ch. Meystre, Org. Synth., 1973,
5, 1124.
21. C. Mukai, I. J Kim, W. J. Cho, M. Kido, M. Hanaoka,
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method over F2 with the anisotropic thermal parameters for
hkl
all nonꢀhydrogen atoms. The hydrogen atoms were placed into
the geometrically calculated positions and refined in the riding
model. The final divergence factors were R1 = 0.0300 (I > 2(I)),
2
wR2 = 0.0805 (refinement over Fhkl for all independent refꢀ
lections). All calculations were performed on PC using the
SHELXTL software.34 The full tables of atomic coordinates,
bond lengths and angles, and anisotropic thermal parameters are
deposited in the Cambridge Crystallographic Data Center
(CCDC 913412).
24. N. B. Valetova, A. N. Artemov, D. F. Grishin, Izv. Vyssh.
Uchebn. Zaved., Khimiya and Khim. Tekhnologiya, 2007, 50,
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1968, 101, 2548.
The authors are grateful to G. K. Fukin for Xꢀray difꢀ
fraction study.
This work was financially supported by the Ministry of
Education and Science of the Russian Federation (Federal
Target Program "Scientific and ScientificꢀPedagogical
Personnel of the Innovative Russia" for 2009—2013).
30. W. J. Bland, R. Davis, J. L. A. Durrant, J. Organomet. Chem.,
1982, 234, C20.
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Received August 30, 2012;
in revised form October 8, 2012