On the reaction of sterically hindered α,β-unsaturated ketones with hydroxylamine: Preparation of 5-hydroxy derivatives of isoxazolidine and 4,5-dihydroisoxazole

Article abstract of DOI:10.1007/s11172-012-0088-4

A reaction of hydroxylamine with α,β-unsaturated ketones containing a tertiary carbon atom α to the keto group leads to 5-hydroxyisoxazolidine and 5-hydroxy-Δ²-isoxazoline derivatives.

Full text of DOI:10.1007/s11172-012-0088-4

Russian Chemical Bulletin, International Edition, Vol. 61, No. 3, pp. 606—615, March, 2012
606
On the reaction of sterically hindered ,ꢀunsaturated ketones
with hydroxylamine: preparation of 5ꢀhydroxy derivatives of
isoxazolidine and 4,5ꢀdihydroisoxazole
M. V. Mavrov and S. I. Firgang
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (495) 137 2944. Eꢀmail: nig@ioc.ac.ru
A reaction of hydroxylamine with ,ꢀunsaturated ketones containing a tertiary carbon
2
atom  to the keto group leads to 5ꢀhydroxyisoxazolidine and 5ꢀhydroxyꢀ ꢀisoxazoline deꢀ
rivatives.
Key words: isoxazolidinꢀ5ꢀols, isoxazolinꢀ5ꢀols, ,ꢀenones, hydroxylamine.
,ꢀUnsaturated ketones 1 are important synthons for
amino group is bonded to the nitrogen heterocycles.6d—f,10
The well known [3+2] cycloaddition reactions of nitrones
to olefins allow one to synthesize such isoxazolidinols in
two steps, using Pd catalysts and pressure (see, for examꢀ
ple, reviews11).
We studied regioselectivity of reactions of hydroxylꢀ
amine with ,ꢀenones containing bulky tertꢀalkyl or hydrꢀ
oxydialkyl groups at the ꢀposition to the keto group
in the assumption that they would block approach of
a nucleophile to the carbon atom of the keto group, thereꢀ
by directing the process predominantly toward the 1,4ꢀadꢀ
dition.
In fact, the reaction of enones 2a,b, 3a—h, 4a,b, and
5a,b with hydroxylamine hydrochloride in aqueous methꢀ
anol in the presence of NaOH (Scheme 2) leads predoꢀ
minantly to hydroxy derivatives of isoxazolidine 6—9 and
2ꢀisoxazoline 10—12 (according to the 1H NMR spectroꢀ
scopic data, the content of the products in the reaction
mixture was 45—80%). An increase in the amount of hydrꢀ
oxylamine to 2.5—3 equiv. virtually does not affect the
the preparation of various heterocyclic systems.1,2 In parꢀ
ticular, their reactions with hydroxylamine derivatives lead
to isoxazoline and isoxazolidine derivatives,2 which are
used in the synthesis of steroids,3 nucleosides and peptiꢀ
domimetics,4 alkaloids (cocaine, biotin, cedridin, etc.).5a
In addition, they possess useful biological properties,3,5,6
including antibacterial and antifungal,5b,6a antiinflamꢀ
matory,3b antiviral,6b herbicide and fungicide,6c—f neuroꢀ
tropic and antitumor,6g they are mediators of various bioꢀ
chemical processes and enzyme inhibitors, as well.6h—l
In the reactions indicated, hydroxylamine can funcꢀ
tion as both the Nꢀ and the Oꢀnucleophile.2a—c Moreover,
products of either 1,2ꢀ (oximes A) or 1,4ꢀaddition (hydrꢀ
oxylamines B, C) can be obtained depending on the strucꢀ
ture of ,ꢀenone 1, as well as products of their subseꢀ
quent transformations D—F (Scheme 1).2a,d,7,8
5ꢀHydroxyisoxazolidines F are formed only in the reꢀ
actions with mesityl oxide,8a fluorineꢀcontaining enones 1
(R1 = CF3),2d,9 and some ꢀaminoenones, in which the
Scheme 1
X = O (B), NOH (C)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 604—612, March, 2012.
1066ꢀ5285/12/6103ꢀ606 © 2012 Springer Science+Business Media, Inc.

Reactions of ,ꢀunsaturated ketones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
607
yields of compounds 6—12. In the presence of other bases
(Et3N, Py, AcOK, K2CO3), the products of oximation A
and conjugate addition B, C are mainly formed.
the 1H and 13C NMR spectra and confirmed by the dehyꢀ
dration of compound 10a to the corresponding isoxazole
16 (Scheme 3).
Scheme 2
Scheme 3
i. NH2OH.
i. H2NOH•HCl, NaOH, MeOH—H2O (4 : 1), 28—45 C.
13: X = O (a), NOH (b)
2—10: R1 = Ph (a), 4ꢀMeOC6H4 (b), 3,4ꢀ(MeO)2C6H3 (c),
3,4,5ꢀ(MeO)3C6H2 (d), 4ꢀMe2NC6H4 (e), furanꢀ2ꢀyl (f),
Me2CH (g), 4ꢀMeC6H4 (h);
Compounds 10—12, which earlier have not been conꢀ
sidered among the reaction products of ,ꢀenones with
hydroxylamine (see reviews2,11), are apparently formed by
the oxidation of isoxazolidinols 6, 8, and 9 in alcoholic
medium upon the action of atmospheric oxygen.
2, 4, 6, 8, 11: R2 = Me;
3, 5, 7, 9, 12: R2 + R2 = (CH2)5
Besides the major products, some byꢀproducts are
formed in all the cases (15—35% of total amount). Some
of them were successfully isolated and characterized. Thus,
the oximation of ꢀhydroxyenones, for example 2a,b and
3a, leads to the isolation of 3ꢀketotetrahydrofuran oximes
13 and 14, which are the products of Oꢀheterocyclization
characteristic of conjugated hydroxyenones,12a,b and oxime
of ,ꢀenone 2a, i.e., compound 15.
Moreover, after a prolonged standing (2—4 months) of
the mother liquors from the reactions with involvement of
enones 2a, 4a, and 5a, we successfully isolated ꢀisꢀ
oxazolines 10a,b, 11, and 12 in 8—15% yields. The strucꢀ
ture of obtained 2ꢀisoxazolines 10—12 was inferred from
The structure of compounds obtained was inferred from
1
the H and 13C NMR spectroscopic and mass spectroꢀ
metric data and confirmed by elemental analysis. Comꢀ
parison of the 1H (an ABX spectrum typical of rings) and
13C NMR spectra of the compounds synthesized with
the spectra of similar compounds reported in the literaꢀ
ture,2a,6f,9 as well as studies of their reactivity (see below),
gave us a reason to believe that the cyclic derivatives 6—9
have the structure of 1,2ꢀisoxazolidine containing a hetꢀ
erocycle with the hemiacetal fragment (O—C—Oꢀsurꢀ
rounding).
1
The H NMR spectra of substituted 5ꢀhydroxyisoxꢀ
azolidines containing an additional vicinal hydroxyl group

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Mavrov and Firgang
Table 1. Influence of solvents on the ratio of diastereomers of
isoxazolidinol 6aa
as a substituent (compounds 6a,b and 7a—h) showed the
presence of two sets of signals assigned to cisꢀ/transꢀdiaꢀ
stereomers with respect to the orientation of substituents
at positions 3 and 5 of the isoxazolidine ring (for example,
in the case of 6b the ratio cis : trans  2 : 1).
Solvent
CDCl3

Ratio
cis : trans
H(3)
(J/Hz)
To confirm the structure of isoxazolidinol 6b, we carꢀ
4.47 (t, J = 8.1);
4.73 (partial t,
J = 7.0)
62 : 38
1
ried out a detailed analysis using 2D H NMR spectroꢀ
scopy (HSQC, HMBC, and NOESY). The presence in
the predominant isomer of the contact of the Me group at
 1.41 with the protons of the aryl fragment H(3´) or
H(5´), as well as nonequivalence of the Me groups (two
singlets) caused by the absence of free rotation, speak in
favor of its cisꢀstructure (Fig. 1). In addition, a large spinꢀ
spin coupling constant JHN—H(3) = 11.7 Hz was observed
for the cisꢀisomer, while for the transꢀisomer, the signal
for the proton H(3) was found in the lower field than that
for the cisꢀisomer, with the spinꢀspin coupling constant
being nonexistent.
CDCl3—DMSOꢀd6 4.30 (t, J = 8.1);
58 : 42
58 : 42
(4 : 1)
4.58 (t, J = 7.1)
4.24 (dd, J = 8.9,
J = 7.7);
CCl4—DMSOꢀd6
(4 : 1)
4.56 (dd, J = 8.9,
J = 7.8)
DMSOꢀd6
CD3OD
4.22 (m);
4.56 (dd, J = 8.7,
J = 7.9)
4.40 (t, J = 8.1);
4.69 (dd, J = 8.6,
J = 7.9)
55 : 45
42 : 58
A predominance of cisꢀisomer can be explained if
a coordinating effect of the hydroxyl group is allowed for
(formation of hydrogen bonds between the hydroxyl and
the keto groups of hydroxyenones 2 and 3). A similar picꢀ
ture is observed in the NMR spectra of isoxazolidinols
7a—h, other representatives of this group of compounds.
The ratio of signal intensities for the indicative protons
C(3)H of isoxazolidinols varies depending on the reaction
conditions, however, a cisꢀisomer is usually the major
product. Moreover, the ratio of isomers depends on the
nature of the solvent and the aggregate state. Thus, the
content of the transꢀisomer increases as the low polar
CDCl3 is exchanged for the polar solvents (Table 1). Reꢀ
crystallization is accompanied by the loss in the major
compound and appearance in the 1H NMR spectra of
additional signals, which were absent in the spectra of
crude products. Compounds 6—9 in chloroform are enꢀ
tirely in the isoxazolidine form, however, in DMSOꢀd6,
according to the IR and 13C NMR spectroscopic data,
these compounds (or, most likely, one of the diastereꢀ
omers) due to the ringꢀchain tautomerism13 are subject to
noticeble isomeric transformation into the linear structure
of the type B (see Scheme 1).
b
CD3COCD3
—
—
a Before recording the 1H NMR spectra (300 MHz), the preꢀ
prepared samples were kept for 8—10 h at 20 C.
b Isoxazolidinol 6a converted to ,ꢀenone 2a (25%) and oxime
15 (75%).
cycle appear as an ABX system in the region  2.2—3.2
(JAB = 16.7—17.2 Hz), with their chemical shift for
cisꢀisomer being different (  0.5 ppm). At the same
time, both protons of transꢀisomer have close (or the same)
chemical shifts, with their geminal constants slightly
differing.
Unlike hydroxyꢀcontaining isoxazolidinols considered
above, three sets of signals for the proton of the CHN
1
group of unequal intensity are present in the H NMR
spectra of isoxazolidinols 8a,b and 9a,b having a methyl
(not coordinated with the keto group) substituent, with
the transꢀisomer becoming predominant. This was demꢀ
onstrated for compounds 8a,b using NOESY spectra. From
the three signals for the tertꢀbutyl group, only the most
highꢀfield (shifted by 0.07 and 0.1 ppm for compounds 8a
and 8b, respectively) broad singlet has contacts with the
oꢀaryl protons. Such a change in the chemical shift is typical
of substituents placed inside the conical magnetic field of
the aryl fragment and is indicative. The absence of the
crossꢀlines from interactions of the protons indicated, apꢀ
parently, suggests a transꢀisomerism of the latter. We supꢀ
pose that the appearance of additional transꢀisomers is
caused by the presence or absence of hydrogen bonding
between the hydroxyl and NH groups or by steric reasons.
Thus, the minor transꢀisomer 8b, judging from the intenꢀ
sities of analogous signals for the protons of the CHN
cycle, became the major for 9a,b.
In the 1H NMR spectrum of compound 6b and in the
spectra of other isoxazolidinols 6a, 7a—h, the signals for
the two geminal protons at position 4 of the heteroꢀ
The hemiacetal structure of compounds 6—9 was adꢀ
ditionally confirmed by the N,Oꢀacylation reactions. For
Fig. 1. Configuration of cisꢀisomer of isoxazolidinol 6b.

Reactions of ,ꢀunsaturated ketones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
609
Compounds 2a,b,12a 3a,b,12b 4a,b,14 and earlier undescribed
3c—h and 5a,b were obtained by the reaction of R methyl keꢀ
tones RCOMe (R = 2ꢀhydroxypropꢀ2ꢀyl, 1ꢀhydroxycyclohexyl,
1ꢀmethylcyclohexyl,15 and tertꢀbutyl) with the methylideneꢀ
forming components: aromatic aldehydes R´ArCHO (R´ = H,
4ꢀMe, 4ꢀMeO, 3,4ꢀ(MeO)2, 3,4,5ꢀ(MeO)3, 4ꢀMe2N), furfurol
and isobutyraldehyde.
instance, their treatment with Ac2O leads to the isolation
of linear ketoamides 17a,b, as well as acetates of the corꢀ
responding hydroxyenones 18a—d as the side products.
The action of AcCl in pyridine (0—5 C) leads to the
formation of individual Nꢀacetyl derivatives 19a,b (the
only isomer) and 20 (a mixture of isomers).
,ꢀEnones 2—5 (general procedure). A 50% aqueous KOH
(6 mL) was added dropwise to a solution of stoichiometric amount
of a ketone and an aldehyde (10 mmol each) in EtOH (10—15 mL)
over 10—15 min with stirring. The mixture was heated for
12—15 h at 45—50 C, then diluted with water (10 mL), and
neutralized with 2 M HCl. The organic layer was extracted with
benzene, dried with Na2SO4, and concentrated. The residue was
distilled from a collar flask in vacuo. The crystallizing oils were
filtered off to obtain compounds 2a,b, 3a,b,g, 4a, and 5a,b. In
the synthesis of compounds 3c—f,h, a solid product precipitated
from the reaction mixture was filtered off, washed with water,
and recrystallized from the corresponding solvent.
1ꢀ(1ꢀHydroxycyclohexyl)ꢀ3ꢀphenylpropꢀ2ꢀenꢀ1ꢀone (3a).
The yield was 62%, m.p. 61—62 C (from hexane) (cf. Ref. 12b:
liquid compound ). UV, max/nm (): 295 (26300). The 1H NMR
and IR spectra are consistent with those described in the work.12b
1ꢀ(1ꢀHydroxycyclohexyl)ꢀ3ꢀ(3,4ꢀdimethoxyphenyl)propꢀ2ꢀ
enꢀ1ꢀone (3c). The yield was 44%, m.p. 140—142 C (from light
petroleum—AcOEt). Found (%): C, 70.24; H, 7.47. C17H22O4.
Calculated (%): C, 70.32; H, 7.64. UV, max/nm (): 241 (10200),
341 (20200). IR, /cm–1: 3512 (OH), 1676 (C=O). 1H NMR
(300 MHz, CDCl3), : 1.34 (m, 1 H, CH2); 1.54 (m, 2 H, CH2);
1.66—1.86 (m, 7 H, CH2); 3.77 (s, OH); 3.92, 3.96 (both s,
3 H each, MeO); 6.89 (dd, 1 H, Ar, J = 8.0 Hz, J = 1.0 Hz);
6.99, 7.80 (both d, 1 H each, CH=CH, J = 16.0 Hz); 7.11 (d, 1 H,
Ar, J = 1.0 Hz); 7.22 (dd, 1 H, Ar, J = 8.0 Hz, J = 1.0 Hz).
1ꢀ(1ꢀHydroxycyclohexyl)ꢀ3ꢀ(3,4,5ꢀtrimethoxyphenyl)propꢀ
2ꢀenꢀ1ꢀone (3d). The yield was 32%, m.p. 122—123 C (from
light petroleum—AcOEt). Found (%): C, 67.32; H, 7.37. C18H24O5.
Calculated (%): C, 67.48; H, 7.35. UV, max/nm (): 240 (14000),
325 (28700). IR, /cm–1: 3456 (OH), 1668 (C=O). 1H NMR
(300 MHz, CDCl3), : 1.36 (m, 1 H, CH2); 1.56 (m, 2 H, CH2);
1.68—1.86 (m, 7 H, CH2); 3.72 (s, OH); 3.81 (s, 3 H, OMe);
3.83 (s, 6 H, OMe); 6.82 (s, 2 H, Ar); 7.02, 7.72 (both d, 1 H each,
CH=CH, J = 16.0 Hz).
R1 = Me (a, c), R1 + R1 = (CH2)5 (b, d)
R
2 = H (a, b), OMe (c, d)
Formation of a mixture of diastereomeric acetates 20
1
can be concluded from the H NMR spectroscopic data,
namely, from the presence (a downꢀfield shift of the signal
for the OH group) or the absence of hydrogen bonding in
the case of synꢀ or antiꢀarrangement of the OH and C=O
groups.
In conclusion, the reaction of ,ꢀenones containing
a tertiary C atom ´ to the keto group with hydroxylamine
leads to 5ꢀhydroxyisoxazolidine derivatives as the major
products. It was unexpectedly found that 5ꢀhydroxyisꢀ
oxazolidines are oxidized to 5ꢀhydroxyꢀ2ꢀisoxazolines
upon the action of atmospheric oxygen.
Experimental
1ꢀ(1ꢀHydroxycyclohexyl)ꢀ3ꢀ(4ꢀdimethylaminophenyl)propꢀ
2ꢀenꢀ1ꢀone (3e). The yield was 32%, m.p. 134—136 C
(from EtOH—AcOEt). Found (%): C, 74.37; H, 8.49; N, 4.95.
C17H23NO2. Calculated (%): C, 74.62; H, 8.48; N, 5.12. UV,
1
H and 13C NMR spectra were recorded on Bruker DRXꢀ500
(500.13 MHz) and Bruker AMꢀ300 (300 (1H) and 75.5 (13C)
MHz) spectrometers for solutions in CDCl3 and DMSOꢀd6, with
Me4Si as an internal standard. Standard procedures from Bruker
were used for the studies of 2D spectra. UV spectra were recordꢀ
ed on a Specord Mꢀ40 spectrometer (Carl Zeiss Jena) for soluꢀ
tions in EtOH. Mass spectra were recorded on a Kratos MSꢀ30
instrument (70 eV). IR spectra were recorded on a Specord Mꢀ80
spectrometer (oily products as neat samples, solid compounds in
KBr pellets). Melting points were measured on a Boetius heating
stage (Germany) and were not corrected. Reaction progress was
monitored by TLC on Silufol plates (UVꢀ254), with visualizaꢀ
tion in iodine vapors. Silica gel 60 purchased from Merck was
used for chromatography, with ethyl acetate—hexane (CH2Cl2)
as an eluent.

max/nm (): 253 (5500), 400 (10800). IR, /cm–1: 3452, 3428
(OH), 1656 (C=O). 1H NMR (300 MHz, DMSOꢀd6), :
1.24 (m, 1 H, CH2); 1.48 (m, 4 H, CH2); 1.48—1.70 (m, 5 H,
CH2); 2.99 (s, 6 H, Me2N); 5.0 (s, OH); 6.73, 7.54 (both d,
2 H each, Ar, J = 8.0 Hz); 7.26, 7.49 (both d, 1 H each, CH=CH,
J = 15.9 Hz).
1ꢀ(1ꢀHydroxycyclohexyl)ꢀ3ꢀ(furanꢀ2ꢀyl)propꢀ2ꢀenꢀ1ꢀone
(3f). The yield was 43%, m.p. 144—145 C (from light petroꢀ
leum). Found (%): C, 70.61; H, 7.23. C13H16O3. Calculated (%):
C, 70.89; H, 7.32. UV, max/nm (): 324 (28000). IR, /cm–1
:
3464 (OH), 1672 (C=O). 1H NMR (300 MHz, CDCl3), :
1.23—1.41 (m, 1 H, CH2); 1.44—1.54 (m, 2 H, CH2); 1.58—1.88
(m, 7 H, CH2); 3.82 (s, 1 H, OH); 6.50 (t, 1 H, furyl, J = 2.8 Hz);
6.72 (d, 1 H, furyl, J = 2.8 Hz); 6.98, 7.56 (both d, 1 H each,
CH=CH, J = 16.0 Hz); 7.51 (d, 1 H, furyl, J = 3.6 Hz).
Reactants of the homeꢀcountry (Khimmed) and foreign
(Aldrich, Lancaster) production were used without additional
purification.

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Mavrov and Firgang
1ꢀ(1ꢀHydroxycyclohexyl)ꢀ4ꢀmethylpentꢀ2ꢀenꢀ1ꢀone (3g).
gave unsatisfactory results: the processes were accompanied by
losses in the major compound (~20—30%) and changes in the
diastereomeric composition.
Method A was used for obtaining compounds 6a,b and 7a—h.
B. A reaction mixture was diluted with water (10—15 mL),
the solvent was partially evaporated. A slowly forming precipiꢀ
tate was filtered off, compounds 8a,b and 9a,b were isolated
after washing with solvents and drying similarly to the manner
described in method A.
The yield was 27%, a heterogeneous liquid (the product purity
~80%), b.p. 91—96 C (20 Torr), nD20 1.4860. UV, max/nm ():
232 (9400). IR, /cm–1: 3440 (OH), 1670 (C=O). 1H NMR
(300 MHz, CDCl3), : 1.08 (d, 6 H, Me, J = 6.8 Hz); 1.18
(m, 1 H, CH2); 1.44 (m, 2 H, CH2); 1.56—1.82 (m, 7 H, CH2);
2.51 (octet, 1 H, CHMe2, J = 6.8 Hz); 3.84 (s, 1 H, OH); 6.45
(d, 1 H, CH=, J = 16.0 Hz); 7.10 (dd, 1 H, =CHCH, J = 16.0 Hz,
J = 6.8 Hz).
1ꢀ(1ꢀHydroxycyclohexyl)ꢀ3ꢀ(4ꢀmethylphenyl)propꢀ2ꢀenꢀ1ꢀone
(3h). The yield was 41%, m.p. 98 C (from AcOEt). Found (%):
C, 78.39; H, 8.18. C16H20O2. Calculated (%): C, 78.65; H, 8.25.
UV, max/nm (): 293 (25700). IR, /cm–1: 3442 (OH), 1674
(C=O). 1H NMR (300 MHz, DMSOꢀd6), : 1.18—1.31 (m, 1 H,
CH2); 1.44—1.91 (m, 9 H, CH2); 2.35 (s, 3 H, Me); 5.08 (s, 1 H,
OH); 7.25, 7.61 (both d, 2 H each, Ar, J = 8.0 Hz); 7.47, 7.53
(both d, 1 H each, CH=CH, J = 16.0 Hz).
C. The filtrates left after isolation of the solid precipitates of
isoxazolidines 6—9 (mainly in the series a,b) and, according to
the 1H NMR spectroscopic data, containing mixtures of miꢀ
nor products A—D (see Scheme 1) were allowed to stand for
3—4 months at ~20 C. A solid precipitate formed was filtered
off, washed with water and a mixture of light petroleum—AcOEt
and dried to obtain nearly individual ꢀisoxazolines 10a, 11,
2
and 12 or a mixture of  ꢀisoxazoline 10b (82—92%) with the
1ꢀ(1ꢀMethylcyclohexyl)ꢀ3ꢀphenylpropꢀ2ꢀenꢀ1ꢀone (5a). The
yield was 39%, a crystallizing oil, m.p. 36—37 C (from penꢀ
tane). Found (%): C, 84.23; H, 8.80. C16H20O. Calculated (%):
corresponding isoxazolidine.
D. The mother liquor, obtained after isolation of the correꢀ
sponding azolidines from the products of the reactions of hyꢀ
droxyenones 2b, 3a, was concentrated, the residue was diluted
with light petroleum (25 mL) and refluxed for 5 min. The soluble
minor products were decanted without analysis, the mother liquor
was extracted with a mixture of AcOEt—C6H6 (~1 : 1, 2×10 mL),
repeatedly washed with water and brine, and dried. Oxime 15
and the corresponding tetrahydrofuranone oximes 13 and 14
were isolated after purification by column chromatography (SiO2,
eluent a mixture of CH2Cl2—AcOEt (from 20 : 1 to 10 : 1)).
The mother liquors obtained in the reactions of hydroxylꢀ
amine with other enones were not analyzed.
5ꢀHydroxyꢀ5ꢀ(2ꢀhydroxypropꢀ2ꢀyl)ꢀ3ꢀphenylisoxazolidine
(6a). Method A gave a chemically homogeneous (~94%) mixꢀ
ture of cisꢀ and transꢀisomers in the ratio ~2 : 1 (0.96 g, 43%),
m.p. 155 C (from EtOH).* Found (%): C, 64.22; H, 7.79; N, 6.41.
C12H17NO3. Calculated (%): C, 64.55; H, 7.68; N, 6.27. IR,
/cm–1: 3464, 3180—3300, 3104. 1H NMR (500 MHz, CDCl3),
: 1.29, 1.30, 1.38, 1.45 (all s, 6 H, Me); 1.85—2.25 (br.s, 1 H,
OH); 2.31 (dd, 1 H, H(4), J = 13.2 Hz, J = 7.3 Hz); 2.72
(dd, 1 H, H(4), J = 13.2 Hz, J = 9.3 Hz); 4.46 (br.t, 0.63 H,
cisꢀH(3), J = 8.1 Hz); 4.73 (br.t, 0.37 H, transꢀH(3), J = 7.0 Hz);
6.04 (br.s, 1 H, OH); 7.25—7.42 (m, 5 H, Ph). 13C NMR
(300 MHz, DMSOꢀd6), : 24.39, 25.88, 45.15 (C(3)), 64.45,
72.08, 111.04 (C(5)), 112.04 (C(5)), 126.66, 127.39, 127.60,
127.83, 128.18, 128.45; an additional signal was found at 210.7
(C=O). MS, m/z (Irel (%)): 223 [M]+ (~2), 192 (8), 131 (17),
122 (29), 106 (17), 105 (23), 104 (75), 103 (23), 91 (29), 78 (20),
77 (44), 59 (100), 43 (59).
C, 84.16; H, 8.83. UV, max/nm (): 292 (25800). IR, /cm–1
:
1672 (C=O). 1H NMR (CDCl3), : 1.16 (s, 3 H, Me); 1.30—1.68
(m, 8 H, CH2); 2.02—2.15 (m, 2 H, CH2); 7.14, 7.68 (both d,
1 H each, CH=CH, J = 16.0 Hz); 7.38 (m, 3 H, Ph); 7.57
(m, 2 H, Ph).
Ketone 5a semicarbazone. The yield was 40%, m.p. 122—124 C
(from EtOH). Found (%): C, 71.25; H, 8.17; N, 14.41. C17H23N3O.
Calculated (%): C, 71.54; H, 8.12; N, 14.73. 1H NMR (300 MHz,
CDCl3), : 1.12 (s, 3 H, Me); 1.08—1.60 (m, 8 H, CH2);
1.81—1.98 (m, 2 H, CH2); 6.39, 6.71 (both d, 1 H each, CH=CH,
J = 16.0 Hz); 7.31—7.49 (m, 5 H, Ph); 8.02 (br.s, 1 H, NH);
other signals do not appear.
3ꢀ(4ꢀMethoxyphenyl)ꢀ1ꢀ(1ꢀmethylcyclohexyl)propꢀ2ꢀenꢀ1ꢀ
one (5b). The yield was 42%, a crystallizing oil, m.p. 49—50 C
(from hexane). Found (%): C, 79.15; H, 8.64. C17H22O2. Calcuꢀ
lated (%): C, 79.03; H, 8.58. UV, max/nm (): 296 (30900). IR,
/cm–1: 1676 (C=O). 1H NMR (300 MHz, CDCl3), : 1.18
(s, 3 H, Me); 1.28—1.63 (m, 8 H, CH2); 2.02—2.14 (m, 2 H,
CH2); 3.86 (s, 3 H, MeO); 6.91, 7.53 (both d, 2 H each, Ar,
J = 8.0 Hz); 7.02, 7.67 (both d, 1 H each, CH=CH, J = 16.0 Hz).
Reactions of ,ꢀunsaturated ketones 2—5 with hydroxylamine
(general procedure). Sodium hydroxide (0.60 g, 15 mmol) was
added in one portion to a warm (28—32 C) solution of the
corresponding enone 2—5 (10 mmol) and NH2OH•HCl (0.98 g,
14 mmol) in aq. MeOH (45 mL, H2O : MeOH = 1 : 4) with
stirring. The reaction was accompanied by the elevation of temꢀ
perature by 5—8 C. The reaction mixture was kept for 2—4 h at
35—43 C (disappearance of the starting ketone was monitored
by TLC) and workedꢀup according to one of the following methꢀ
ods (A—D).
5ꢀHydroxyꢀ5ꢀ(2ꢀhydroxypropꢀ2ꢀyl)ꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ
isoxazolidine (6b). Method A gave a chemically homogeneous
(~94%) mixture of two diastereomers (~2 : 1) (1.36 g, 54%), m.p.
140—141 C (from AcOEt). Found (%): C, 61.49; H, 7.32; N, 5.47.
A. A plentiful flaky precipitate formed was filtered off, thorꢀ
oughly washed with water, aq. MeOH (H2O : MeOH 2 : 1),
mixtures of AcOEt and light petroleum with MeOH (~4 : 1, v/v),
dried on the filter and in vacuo of a waterꢀjet pump at ~80 C.
Isoxazolidinꢀ5ꢀols 6 and 7 were obtained without recrystallizaꢀ
tion as mixtures of diastereomers in the ratio close ( 10%) to
statistical.
C13H19NO4. Calculated: C, 61.64; H, 7.56; N, 5.53. IR, /cm–1
:
3224 br (NH, OH). MS, m/z (Irel (%)): 253 [M]+ (2), 222 (14),
176 (17), 162 (41), 161 (100), 136 (31), 135 (51), 134 (78),
133 (47), 108 (12), 103 (11), 92 (15), 91 (18), 59 (95).
Compound cisꢀ6b. 1H NMR (500 MHz, CDCl3), : 1.41,
1.50 (both s, 3 H each, Me); 2.20 (br.s, 1 H, CMe2OH); 2.24
Attempts to isolate individual isomers were unsuccessful. Atꢀ
tempted separation of the mixtures by recrystallization from difꢀ
ferent solvents (H2O, MeOH, EtOH, MeCN, EtOAc, BunOAc)
or isolation of a predominant isomer by column chromatography
* The samples obtained by recrystallization from other solvents
(AcOEt, BunOAc, MeCN, EtOH—H2O, EtOH—AcOEt) melt
in the range 130—138 C within 1—2 C.

Reactions of ,ꢀunsaturated ketones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
611
(dd, 1 H, H(4), J = 13.3 Hz, J = 7.3 Hz); 2.67 (dd, 1 H, H(4),
J = 13.3 Hz, J = 9.4 Hz); 3.58 (br.s, 1 H, OH); 3.78 (s, 3 H, OMe);
4.39 (ddd, 1 H, H(3), J = 11.7 Hz, J = 9.4 Hz, J = 7.3 Hz); 6.04
(d, 1 H, NH, J = 11.7 Hz); 6.88 (d, 2 H, H(3´), H(5´), J = 8.7 Hz);
7.37 (d, 2 H, H(2´), H(6´), J = 8.7 Hz). 13C NMR (CDCl3), :
24.59, 43.83, 55.30, 64.61, 73.90, 111.59 (C(5)), 114.16, 128.98,
130.45, 159.60.
2.18—2.47 (m, 0.8 H, transꢀH(4)); 2.82 (dd, 0.6 H, cisꢀH(4),
J = 13.1 Hz, J = 9.0 Hz); 3.69, 3.74, 3.81 (all s, 6 H, MeO); 4.16
(br.q, 0.6 H, cisꢀH(3), J = 7.8 Hz); 4.49 (br.t, 0.4 H, transꢀH(3),
J = 6.7 Hz); 5.52, 6.02 (both br.s, 1 H each, NH or OH);
6.72—7.04 (m, 3 H, Ar). MS, m/z (Irel (%)): 305 (8), 290 (8),
272 (7), 206 (15), 192 (72), 191 (67), 181 (16), 166 (17), 165 (19),
164 (29), 99 (84), 95 (16), 82 (16), 81 (100), 77 (15), 55 (32). No
peak for the molecular ion with m/z 323 was observed in the
mass spectrum.
5ꢀHydroxyꢀ5ꢀ(1ꢀhydroxycyclohexyl)ꢀ3ꢀ(3,4,5ꢀtrimethoxyꢀ
phenyl)isoxazolidine (7d). Method A from enone 3d (5 mmol)
gave a chemically homogeneous (~94%) mixture of diastereoꢀ
mers in the ratio ~58 : 42 (0.68 g, 39%), m.p. 161—163 C (from
EtOH). Found (%): C, 60.92; H, 7.43; N, 4.07. C18H27NO6.
Calculated (%): C, 61.17; H, 7.70; N, 3.96. IR, /cm–1: 3248 br,
3190 sh. 1H NMR (300 MHz, CDCl3—DMSOꢀd6 (4 : 1)), :
1.04 (m, 1 H, CH2); 1.32—1.78 (m, 9 H, CH2); 2.04 (dd, 0.58 H,
cisꢀH(4), J = 13.2 Hz, J = 7.4 Hz); 2.30—2.48 (m, 0.84 H,
transꢀH(4)); 2.81 (dd, 0.58 H, cisꢀH(4), J = 13.2 Hz, J = 9.1 Hz);
3.67, 3.70, 3.74, 3.77 (all s, 9 H, MeO); 4.28 (t, 0.58 H, cisꢀH(3),
J = 7.9 Hz); 4.47 (t, 0.42 transꢀH, H(3), J = 6.8 Hz); 6.54, 6.65
(both s, 1 H each, Ar). MS, m/z (Irel (%)): 353 [M]+ (1), 317 7),
236 (22), 223 (56); 222 (100), 219 (51), 195 (46), 194 (61),
179 (24), 99 (12), 81 (36), 55 (29).
5ꢀHydroxyꢀ5ꢀ(1ꢀhydroxycyclohexyl)ꢀ3ꢀ(4ꢀdimethylaminoꢀ
phenyl)isoxazolidine (7e). Method A from enone 3e (5 mmol)
gave a chemically homogeneous (~94%) mixture of diastereoꢀ
mers in the ratio ~3 : 2 (0.70 g, 26%), m.p. 164—166 C (from
EtOH). Found (%): C, 66.41; H, 8.33; N, 9.27. C17H26N2O3.
Calculated (%): C, 66.64; H, 8.55; N, 9.14. IR, /cm–1: 3424,
3304 br, 3232. 1H NMR without assignment of the isomers
(300 MHz, CDCl3—DMSOꢀd6 (2 : 1)), : 1.00—1.72 (m, 10 H,
CH2); 1.92—2.02 (m, 0.6 H, H(4)); 2.21 (m, 0.4 H, H(4));
2.40—2.60 (m, 1 H, H(4)); 2.98 (br.s, 6 H, NMe2); 4.02 (br.t,
0.6 H, H(3), J = 7.4 Hz); 4.41 (br.t, 0.4 H, H(3), J = 6.6 Hz);
6.70, 7.52 (both br.s, 2 H each, Ar). MS, m/z (Irel (%)): 306 [M]+ (3),
288 (8), 273 (25), 175 (14), 174 (100), 149 (24), 147 (36), 146 (25),
139 (14), 81 (13), 55 (12).
1
Compound transꢀ6b. H NMR (500 MHz, CDCl3), : 1.39
(s, 6 H, Me); 220 (br.s, 1 H, CMe2OH); 2.29 (dd, 1 H, H(4),
J = 13.3 Hz, J = 7.3 Hz); 2.60 (dd, 1 H, H(4), J = 13.3 Hz,
J = 9.4 Hz); 3.58 (br.s, 1 H, OH); 3.70 (s, 3 H, OMe); 4.67 (dd,
1 H, H(3), J = 9.4 Hz, J = 7.3 Hz); 6.90 (d, 2 H, Ar, J = 8.7 Hz);
7.28 (d, 2 H, Ar, J = 8.7 Hz). 13C NMR (CDCl3), : 24.97,
43.83, 55.30. 61.80, 73.90, 110.96 (C(5)), 113.96, 127.41,
128.23, 159.60.
5ꢀHydroxyꢀ5ꢀ(1ꢀhydroxycyclohexyl)ꢀ3ꢀphenylisoxazolidine
(7a). Method A gave a chemically homogeneous (~96%) mixꢀ
ture of cisꢀ and transꢀisomers in the ratio 58 : 42 (1.50 g, 57%),
m.p. 147—148 C (from MeCN). Found (%): C, 68.21; H, 7.78;
N, 5.44. C15H21NO3. Calculated (%): C, 68.41; H, 8.04; N, 5.32.
1
IR, /cm–1: 3208. H NMR (500 MHz, CDCl3), : 1.12—1.80
(m, 8 H, CH2); 1.84—1.96 (m, 2 H, CH2); 2.27 (dd, 0.58 H,
cisꢀH(4), J = 13.2 Hz, J = 7.4 Hz); 2.31 (m, 0.42 H, cisꢀH(4));
2.66 (br.dd, 0.42 H, transꢀH(4), J = 11.2 Hz, J = 9.0 Hz); 2.77
(dd, 0.58 H, cisꢀH(4), J = 13.2 Hz, J = 9.4 Hz); 3.52 (br.s, 1 H,
OH); 4.42 (br.dd, 0.58 H, cisꢀH(3), J = 8.5 Hz, J = 7.7 Hz); 4.71
(br.t, 0.42 H, transꢀH(3), J = 6.7 Hz); 7.34 (t, 1 H, Ph, J = 6.7 Hz);
7.38 (t, 2 H, Ph, J = 6.7 Hz); 7.48 (d, 2 H, Ph, J = 6.7 Hz).
13C NMR (DMSOꢀd6), : 20.62, 20.78, 20.99, 21.04, 25,04,
25.55, 25.62, 30.08, 31.78, 31.84, 32.71, 32.79, 32.91, 45.10,
61.74, 64.47, 72.77, 77.09, 111.36 (O—C—O), 112.45 (O—C—O),
121.23, 126.80, 127.54, 127.91, 128.28, 128.56, 192.02, 142.20,
142.58; an additional signal was found at 214.50 (C=O). MS,
m/z (Irel (%)): 263 [M]+ (<1), 231 (6), 213 (2), 146 (20), 132 (37),
131 (45), 122 (19), 119 (15), 106 (24), 105 (21), 104 (87), 103
(25), 99 (48), 91 (16), 81 (100), 79 (18), 77 (42),69 (10), 55 (54).
5ꢀHydroxyꢀ5ꢀ(1ꢀhydroxycyclohexyl)ꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ
isoxazolidine (7b). Method A gave a chemically homogeneous
(~96%) mixture of cisꢀ and transꢀisomers in the ratio 65 : 35
(1.89 g, 65%), m.p. 150—151 C (from EtOH). Found (%): C, 65.62;
H, 7.79; N, 4.68; C16H23NO4. Calculated (%): C, 65.51; H, 7.90;
N, 4.78. IR, /cm–1: 3220, 3120—3180. 1H NMR (500 MHz,
CDCl3), : 1.16 (m, 1 H, CH2); 1.35 (m, 1 H, CH2); 1.52—1.76
(m, 6 H, CH2); 1.82 (m, 2 H, CH2); 2.24 (dd, 0.65 H, cisꢀH(4),
J = 12.1 Hz, J = 7.2 Hz); 2.28, 2.69 (both br.m, 0.35 H each,
transꢀH(4)); 2.69 (dd, 0.65 H, cisꢀH(4), J = 12.1 Hz, J = 7.8 Hz);
3.52 (br.s, 1 H, OH); 5.82 (br.s, 0.65 H, OH); 4.36 (br.t, 0.65 H,
cisꢀH(3), J = 7.4 Hz); 4.80 (br.m, 0.35 H, transꢀH(3)); 6.89 (d, 2 H,
Ar, J = 8.2 Hz); 7.32 (d, 0.70 H, Ar, J = 8.2 Hz); 7.40 (d, 1.3 H,
Ar, J = 8.2 Hz). MS, m/z (Irel (%)): 293 [M]+ (2), 261 (14),
162 (34), 161 (35), 152 (14), 151 (19), 149 (15), 136 (23), 135 (59),
134 (100), 133 (18), 99 (88), 91 (17), 81 (85), 79 (19), 77 (24),
65 (16), 55 (49), 41 (44).
3ꢀ(Furanꢀ2ꢀyl)ꢀ5ꢀhydroxyꢀ5ꢀ(1ꢀhydroxycyclohexyl)isoxazolꢀ
idine (7f). Method A gave a chemically homogeneous (~94%)
mixture of cisꢀ and transꢀisomers in the ratio 1 : 1 (0.98 g, 39%),
m.p. 144—145 C (from BunOAc). Found (%): C, 61.40; H, 7.50;
N, 5.31. C13H19NO4. Calculated (%): C, 61.64; H, 7.56; N, 5.53.
1
IR, /cm–1: 3200. H NMR (500 MHz, CDCl3), : 1.12—1.94
(m, 10 H, CH2); 2.34 (dd, 0.5 H, cisꢀH(4), J = 13.2 Hz,
J = 7.5 Hz); 2.47 (dd, 0.5 H, transꢀH(4), J = 12.9 Hz, J = 8.4 Hz);
2.57 (dd, 0.5 H, transꢀH(4), J = 12.9 Hz, J = 5.1 Hz); 2.67 (dd,
0.5 H, cisꢀH(4), J = 13.2 Hz, J = 9.4 Hz); 3.20—3.70 (br.s, 2 H,
NH or OH); 4.47 (t, 0.5 H, cisꢀH(3), J = 8.4 Hz); 4.71 (br.t,
0.5 H, transꢀH(3), J = 6.8 Hz); 6.28, 6.32 (both br.s, 0.5 H each,
furyl); 6.37 (br.s, 1 H, furyl); 7.39, 7.41 (both s, 0.5 H each,
+
furyl). MS, m/z (Irel (%)): 253 [M] (3), 221 (25), 122 (15),
121 (35), 112 (25), 111 (21), 109 (36), 99 (80), 96 (19), 95 (40),
94 (100), 81 (65), 55 (17).
5ꢀHydroxyꢀ5ꢀ(1ꢀhydroxycyclohexyl)ꢀ3ꢀ(3,4ꢀdimethoxyphenyl)ꢀ
isoxazolidine (7c). Method A from enone 3c (5 mmol) gave
a chemically homogeneous (~94%) mixture of diastereomers in
the ratio ~3 : 2 (0.70 g, 44%), m.p. 169—170 C (from EtOH).
Found (%): C, 63.01; H, 7.84; N, 4.05. C17H25NO5. Calculatꢀ
ed (%): C, 63.14; H, 7.79; N, 4.33. IR, /cm–1: 3450 sh, 3184 br.
1H NMR (300 MHz, CDCl3—DMSOꢀd6 (4 : 1)), : 1.0—1.72
(m, 10 H, CH2); 1.98 (dd, 0.6 H, cisꢀH(4), J = 13.1 Hz, J = 7.2 Hz);
5ꢀHydroxyꢀ5ꢀ(1ꢀhydroxycyclohexyl)ꢀ3ꢀ(propꢀ2ꢀyl)isoxazolꢀ
idine (7g). Method A from enone 3g (5 mmol) gave a chemically
homogeneous (~94%) mixture of cisꢀ and transꢀisomers in the
ratio ~3 : 2 (0.37 g, 32%), m.p. 158—159 C (from AcOEt—EtOH).
Found (%): N, 5.92. C12H23NO3. Calculated (%): N, 6.11. IR,
/cm–1: 3288. 1H NMR (500 MHz, DMSOꢀd6), : 0.91, 0.97,
0.99, 1.02 (all d, 6 H, Me, J = 6.7 Hz); 1.15 (m, 1 H, CH2); 1.34

612
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
Mavrov and Firgang
(m, 1 H, CH2); 1.44—1.84 (m, 9 H, CH2, CHMe2); 1.86 (dd,
0.6 H, H(4), J = 13.1 Hz, J = 8.0 Hz); 1.98 (m, 0.4 H, H(4));
2.17 (dd, 0.4 H, H(4), J = 12.4 Hz, J = 7.9 Hz); 2.39 (dd, 0.6 H,
H(4), J = 13.1 Hz, J = 8.6 Hz); 3.04 (q, 0.6 H, H(3), J = 8.3 Hz);
3.19 (q, 0.4 H, H(3), J = 7.6 Hz). MS, m/z (Irel (%)): 229 [M]+
(1), 168 (22), 109 (20), 99 (55), 88 (26), 86 (28), 81 (80), 70 (43),
69 (15), 60 (23), 57 (15), 55 (56), 43 (100), 41 (87).
0.52 H, H(4), J = 13.1 Hz, J = 7.6 Hz); 2.83 (overlaps, 0.24 H,
H(4)); 2.93 (dd, 0.52 H, H(4), J = 13.1 Hz, J = 6.0 Hz); 4.13
(br.q, 0.24 H, H(3), J 8.0 Hz); 4.27 (t, 0.52 H, H(3), J = 7.1 Hz);
4.51 (m, 0.24 H, H(3)); 5.0, 5.2, 6.1, 6.4 (all br.s, 2 H, NH, OH);
7.19—7.46 (m, 5 H, Ph). 13C NMR (DMSOꢀd6), : 17.85, 18.16,
21.38, 22.27, 22.49, 23.95, 25.35, 25.87, 25.95, 30.99, 31.15,
31.32, 33.82, 33.90, 40.68, 45.34, 46.0, 47.56, 60.25, 61.97, 64.42,
111.93 (O—C—O), 113.5 (O—C—O), 126.22, 126.83, 127.63,
127.79, 127.88, 128.09, 128.88, 142.48. MS, m/z (Irel (%)): 261
[M]+ (1), 230 (15), 146 (38), 131 (75), 122 (35), 106 (59), 104
(25), 97 (100), 91 (22), 77 (27), 55 (92).
5ꢀHydroxyꢀ5ꢀ(1ꢀhydroxycyclohexyl)ꢀ3ꢀ(4ꢀmethylphenyl)ꢀ
isoxazolidine (7h). Method A from enone 3h (5 mmol) gave
a chemically homogeneous (~94%) mixture of diastereomers
in the ratio ~4 : 3 (0.42 g, 40%), m.p. 168—170 C (from
AcOEt—EtOH). Found (%): N, 5.21. C16H23NO3. Calculated (%):
5ꢀHydroxyꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀ(1ꢀmethylcyclohexyl)ꢀ
isoxazolidine (9b) was obtained by method A, the yield was 2.2 g
(76%), a mixture of three isomers in the ratio ~2 : 2 : 1, m.p.
120—121 C (from AcOEt). Found (%): C, 69.92; H, 8.70;
N, 4.60. C17H25NO3. Calculated (%): C, 70.07; H, 8.65;
N, 4.81. IR, /cm–1: 3264, 3192, 3136. 1H NMR (500 MHz,
CDCl3), : 0.99, 1.02, 1.09 (all s, in the ratio ~2 : 1 : 2, 3 H, Me);
1.10—1.70 (m, 8 H, CH2); 1.63—1.92 (m, 2 H, CH2); 2.13 (dd,
~0.4 H, H(4), J = 13.3 Hz, J = 7.8 Hz); 2.28 (dd, ~0.2 H, H(4),
J = 12.2 Hz, J = 6.5 Hz); 2.52 (br.s, 0.2 H, H(4)); 2.68, 5.40,
5.90 (all br.s, not assigned, NH, OH); 2.74 (dd, 0.4 H, H(4),
J = 13.3 Hz, J = 9.2 Hz); 2.83 (dd, 0.4 H, J = 16.7 Hz,
J = 5.3 Hz); 2.96 (dd, 0.4 H, H(4), J = 17.3 Hz, J = 7.8 Hz);
3.78, 3.79, 3.80 (all s, in the ratio ~2 : 1 : 2, 3 H, MeO); 4.30
(br.d, 0.4 H, H(3), J = 7.8 Hz); 4.42 (dd, 0.4 H, H(3), J = 7.6 Hz,
J = 5.3 Hz); 4.62 (br.s, 0.2 H, H(3)); 6.85, 6.88, 7.27, 7.38 (all d,
1 H each, Ar, J = 8.6 Hz). 13C NMR (DMSOꢀd6), : 17.77,
18.10, 21.28. 22.17, 22.40, 23.83, 25.27. 25.79, 25.86, 30.93,
31.24, 33.75. 33.84, 40.60, 45.15, 47.46, 54.92, 55.05, 61.28,
6.83, 111.85 (O—C—O), 113.20, 113.41, 113.84, 114.26, 127.27,
128.75, 130.30, 134.17, 158.16, 158.80, an additional signal was
found at 213.06 (C=O). MS, m/z (Irel (%)): 291 [M]+ (0.5),
177 (12), 161 (47), 137 (52), 136 (16), 134 (31), 131 (26), 122 (11),
97 (100), 91 (16), 55 (56).
1
N, 5.05. IR, /cm–1: 3264 br. H NMR without assignement of
the isomers (300 MHz, CDCl3—DMSOꢀd6 (1 : 2)), : 1.02 (m, 1 H,
CH2); 1.28—1.78 (m, 9 H, CH2); 1.98 (br.t, 1 H, H(4), J = 6.0 Hz);
2.24, 2.25 (both s, 3 H, Me); 2.80 (br.t, 1 H, H(4), J = 9.0 Hz);
3.69, 5.38, 5.93, 5.97 (all br.s, 2 H, NH, OH); 4.17, 4.47
(both br.m, in the ratio ~4 : 3, 1 H, H (3)); 7.05, 7.07 (both d,
2 H, Ar, J = 8.4 Hz); 7.18, 7.25 (both d, 2 H, Ar, J = 6.0 Hz).
5ꢀtertꢀButylꢀ5ꢀhydroxyꢀ3ꢀphenylisoxazolidine (8a). Method
A gave a mixture of transꢀ, transꢀ, and cisꢀisomers in the ratio
~3 : 1 : 3 (0.90 g, 41 %), m.p. 100—101 C (from hexane—AcOEt).
Found (%): C, 70.47; H, 8.39; N, 6.04. C13H19NO2. Calculatꢀ
ed (%): C, 70.55; H, 8.65; N, 6.33. IR, /cm–1: 3240 br. 1H NMR
(500 MHz, DMSOꢀd6), : 0.88, 0.95, 1.00 (all s, in the ratio
~3 : 1 : 3, 9 H, Me); 1.96 (dd, 0.43 H, transꢀH(4), J = 13.1 Hz,
J = 8.9 Hz); 2.17 (dd, 0.43 H, cisꢀH(4), J = 12.8 Hz, J = 5.4 Hz);
2.50 (q, 0.43 H, cisꢀH(4), J = 1.8 Hz); 2.81 (dd, 0.43 H,
transꢀH(4), J = 13.1 Hz, J = 8.4 Hz); 2.82 (overlaps, 0.14 H,
transꢀH(4)); 2.94 (dd, 0.14 H, transꢀH(4), J = 13.0 Hz, J = 9.0 Hz);
4.16 (dd, 0.43 H, transꢀH(3), J = 8.5 Hz, J = 6.4 Hz); 4.24 (br.t,
0.14 H, transꢀH(3), J = 6.4 Hz); 4.58 (br.q, 0.43 H, cisꢀH(3),
J = 5.5 Hz); 5.09, 5.18, 5.26 (all br.s, in the ratio ~3 : 1 : 3,
1 H, OH); 6.22, 6.84, 7.18 (all br.s, 1 H, NH); 7.16—7.48
(m, 5 H, Ph).
5ꢀtertꢀButylꢀ5ꢀhydroxyꢀ3ꢀ(4ꢀmethoxyphenyl)isoxazolidine
(8b) was obtained by method A and from the mother liquor by
method B, the overall yield was 1.3 g (52%), a mixture of transꢀ,
transꢀ, and cisꢀisomers in the ratio ~6 : 1 : 3, m.p. 102 C (from
hexane—AcOEt). Found (%): C, 66.72; H, 8.15; N, 5.39.
C14H21NO3. Calculated (%): C, 66.90; H, 8.42; N, 5.57. IR,
/cm–1: 3224, 3144 br. 1H NMR (500 MHz, CDCl3), : 0.92,
1.02, 1.03 (all s, in the ratio 3 : 1 : 6, 9 H, But); 2.17 (dd, 0.6 H,
transꢀH(4), J = 13.2 Hz, J = 7.7 Hz); 2.29 (dd, 0.3 H, cisꢀH(4),
J = 12.6 Hz, J = 6.1 Hz); 2.38 (br.s, 1 H, OH); 2.56 (dd, 0.3 H,
cisꢀH(4), J = 12.6 Hz, J = 8.4 Hz); 2.73 (dd, 0.6 H, transꢀH(4),
J = 13.2 Hz, J = 9.2 Hz); 2.86, 3.02 (both br.d, 0.1 H each,
cisꢀH(4), J 8.0 Hz); 3.67, 3.68, 3.70 (all s, 3 H, OMe); 4.38
(t, 0.6 H, transꢀH(3), J = 8.4 Hz); 4.42 (br.t, 0.1 H, transꢀH(3),
J = 7.2 Hz); 4.64 (br.t, 0.3 H, cisꢀH(3), J = 7.4 Hz); 5.90 (br.s,
1 H, NH); 6.61, 6.87, 7.42 (all d, 3 H, Ar, J 8.4 Hz); 7.28 (t, 1 H,
Ar, J 8.4 Hz).
2
5ꢀHydroxyꢀ5ꢀ(2ꢀhydroxypropꢀ2ꢀyl)ꢀ3ꢀphenylꢀ ꢀisoxazoline
(10a) was obtained by method B, the yield was 230 mg (~7%),
m.p. 158—159 C (from EtOH). Found (%): C, 65.02; H, 6.89;
N, 6.04. C12H15NO3. Calculated (%): C, 65.14; H, 6.89; N, 6.33.
IR, /cm–1: 3250 br, 1668, 1652. 1H NMR (500 MHz,
DMSOꢀd6), : 1.20, 1.26 (both s, 6 H, Me); 3.01, 3.65 (both d,
1 H each, AB system, CH2, J = 17.6 Hz); 4.56, 4.72 (both br.s,
1 H each, OH); 7.36 (br.t, 3 H, Ph, J = 6.8 Hz); 7.70 (br.s, 2 H,
Ph). 13C NMR (DMSOꢀd6), : 23.87, 25.90, 40.94, 71.75,
112.26 (O—C—O), 126.28, 127.54, 128.53, 129.79, 130.21,
156.21 (C=N).
2
5ꢀtertꢀButylꢀ5ꢀhydroxyꢀ3ꢀ(4ꢀmethoxyphenyl)ꢀ ꢀisoxazoline
(10b) was obtained by method B, the yield was 230 mg (~8%),
contains an admixture (~8%) of isomers of compound 6b, m.p.
128—130 C (from AcOEt—hexane). Found (%): N, 5.42.
C13H17NO4. Calculated (%): N, 5.57. IR, /cm—1: 3240 br, 1656.
1H NMR (300 MHz, CDCl3—DMSOꢀd6 (4 : 1)), : 1.27, 1.32
(both s, 3 H each, Me); 3.02, 3.56 (both d, AB system, 1 H each,
CH2, J = 17.4 Hz); 3.76 (s, 3 H, MeO); 6.84, 7.53 (both d,
2 H each, Ar, J = 7.8 Hz); other signals do not appear.
5ꢀHydroxyꢀ5ꢀ(1ꢀmethylcyclohexyl)ꢀ3ꢀphenylisoxazolidine
(9a) was obtained by method A, the yield was 1.1 g (42%),
a mixture of three isomers in the ratio ~1 : 2.2 : 1, m.p. 119—120 C
(from AcOEt—EtOH). Found (%): C, 73.50; H, 8.96; N, 5.04.
C16H23NO2. Calculated (%): C, 73.53; H, 8.87; N, 5.36. IR,
/cm–1: 3224, 3216—3190. 1H NMR (500 MHz, DMSOꢀd6), :
0.85, 1.01, 1.12 (all s, 3 H, Me); 1.02—1.72 (m, 10 H, CH2); 1.94
(dd, 0.24 H, H(4), J = 13.1 Hz, J = 8.3 Hz); 2.17 (dd, 0.24 H,
H(4), J = 12.8 Hz, J = 5.6 Hz); 2.43 (m, 0.24 H, H(4)); 2.83 (dd,
2
5ꢀtertꢀButylꢀ5ꢀhydroxyꢀ3ꢀphenylꢀ ꢀisoxazoline (11) was
obtained by method C, the yield was 243 mg (~11%), m.p.
~140 C (from AcOEt). Found (%): C, 70.94; H, 7.61; N, 6.08.
C13H17NO2. Calculated (%): C, 71.20; H, 7.82; N, 6.30. IR,
1
/cm–1: 3277 br, 1680. H NMR (300 MHz, CCl4—DMSOꢀd6
(4 : 1)), : 1.04 (s, 9 H, Me); 3.02, 3.42 (both d, 1 H each, CH2,

Reactions of ,ꢀunsaturated ketones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
613
J = 17.6 Hz); 6.36 (br.s, 1 H, OH); 7.42 (m, 3 H, Ph); 7.68
(m, 2 H, Ph). MS, m/z (Irel (%)): 219 [M]+ (13), 162 (84), 146
(28), 144 (45), 120 (78), 118 (48), 117 (49), 104 (53), 103 (100),
95 (73), 93 (80), 91 (58), 85 (64), 78 (56), 77 [Ph]+ (96), 76 (65),
75 (26), 67 (37), 65 (24), 63 (25), 57 [But]+ (57), 55 (28), 51 (38).
diethyl ether, washed with aq. NaHCO3 and brine. The residue
was twice subjected to chromatography on SiO2 (eluent light
petroleum—AcOEt (2—8%)) to obtain isoxazole 16 (120 mg,
~12%) as an oil. In the work,17 compound 16 was obtained by
[3+2] cycloaddition of benzaldoxime to 2ꢀmethylbutꢀ3ꢀynꢀ2ꢀol,
no physicochemical data were reported. IR, /cm–1: 3240, 1852.
1H NMR (300 MHz, CDCl3), : 1.39 (s, 6 H, Me); 1.54 (s, 1 H,
OH); 5.92 (s, 1 H, CH=); 7.42 (m, 3 H, Ph); 7.68 (d, 2 H, Ph,
J = 8.1 Hz).
N,OꢀAcylation of isoxazolidinols and hydroxyꢀ,ꢀenones. E.
A mixture of isoxazolidinol 6 or 7 (3 mmol), anhydrous CH2Cl2
(20 mL), acetic anhydride (1.2 mL), triethylamine (5 mL), and
4ꢀdimethylaminopyridine (DMAP) (10 mg) was allowed to stand
for 2 days at 20—25 C, suspended in aq. NaHCO3 cooled to
0 C, and extracted with a mixture of benzene—ethyl acetate.
The organic layer was washed with saturated aq. NaHCO3 and
brine, dried with Na2SO4, and subjected to chromatography on
SiO2 (eluent CH2Cl2—AcOEt (2—10%)) to obtain N,Oꢀacylꢀ
ated compounds 17a,b.
2
5ꢀHydroxyꢀ5ꢀ(1ꢀmethylcyclohexyl)ꢀ3ꢀphenylꢀ ꢀisoxazoline
(12) was obtained by method C, the yield was 340 mg (~14%),
m.p. 139—140 C (from AcOEt). Found (%): C, 73.89; H, 8.28;
N, 5.21. C16H21NO2. Calculated (%): C, 74.10; H, 8.16; N, 5.40.
IR, /cm–1: 3224, 1684, 1652. 1H NMR (500 MHz, DMSOꢀd6),
: 0.99 (s, 3 H, Me); 1.34 (m, 1 H, CH2); 1.64 (m, 9 H, CH2);
2.96, 3.53 (both d, AB system, 1 H each, CH2, J = 18.2 Hz); 6.51
(s, 1 H, OH); 7.45 (m, 3 H, Ph); 7.67 (m, 2 H, Ph). 13C NMR
(DMSOꢀd6), : 17.55, 21.32, 24.64, 25.84, 29.31, 30.68, 41.0,
113.31 (O—C—O), 121.41, 126.29, 128.71, 129.73, 130.17,
155.95 (C=N). MS, m/z (Irel (%)): 259 [M]+ (6), 162 (37), 146
(35), 144 (21), 120 (57), 117 (92), 105 (17), 104 (37), 103 (48), 98
(55), 93 (40), 91 (50), 81 (54), 77 (100), 55 (37).
5ꢀ(4ꢀMethoxyphenyl)ꢀ2,2ꢀdimethyltetrahydrofuranꢀ3ꢀone
oxime (13b). A solution of ketone 13a (1.97 g, 8.3 mmol) (obꢀ
tained by cyclization of hydroxyenone 2b (20 mmol) upon treatꢀ
ment with H3PO4 (d = 1.7 g cm–3) under conditions given in
work12a at 100 C in 22% yield), NH2OH•HCl (1.81 g, 26 mmol),
and NaOAc (3.5 g, 26 mmol) in a mixture of H2O (10 mL) and
EtOH (10 mL) was refluxed for 5 h and cooled. After usual
workꢀup, a colorless liquid was isolated (2.1 g). Crystallization
from aq. EtOH gave oxime 13b (1.5 g, 63%), m.p. 136 C (from
EtOH). Found (%): C, 66.18; H, 7.14; N, 5.78. C13H17NO3.
Calculated (%): C, 66.36; H, 7.28; N, 5.95. IR, /cm–1: 3260 br,
1652. 1H NMR (500 MHz, DMSOꢀd6), : 1.32, 1.38 (both s,
3 H each, Me); 2.45 (dd, 1 H, H(4), J = 17.6 Hz, J = 9.6 Hz);
3.12 (dd, 1 H, H(4), J = 17.6 Hz, J = 6.2 Hz); 3.75 (s, 3 H,
OMe); 4.99 (dd, 1 H, H(5), J = 9.6 Hz, J = 6.2 Hz); 6.91, 7.22
(both d, 2 H each, Ar, J = 8.6 Hz); 10.14, 10.32 (both s, in the
ratio 1 : 24, NOH). MS, m/z (Irel (%)): 235 (22), 137 (76), 43 (100).
Method D and column chromatography on SiO2 (CH2Cl2—
AcOEt) gave oxime 13b (95 mg, ~4%), whose spectral characꢀ
teristics are in accord with those of an authentic sample.
2ꢀPhenylꢀ1ꢀoxaspiro[4,5]decenꢀ4ꢀone oxime (14). Method D
and column chromatography on SiO2 (eluent CH2Cl2—AcOEt)
gave a mixture of synꢀ and antiꢀisomers in the ratio 10 : 1 (withꢀ
out assignement) (110 mg, ~4%), m.p. 126—128 C (from AcOEt).
Found (%): C, 73.37; H, 7.62; N, 5.70. C15H19NO2. Calculatꢀ
ed (%): C, 73.44; H, 7.81; N, 5.71. IR, /cm–1: 3344, 1672.
1H NMR (500 MHz, CDCl3—DMSOꢀd6 (4 : 1)), : 1.21 (m, 1 H,
CH2); 1.37—1.90 (m, 9 H, CH2); 2.47 (m, 1 H, H(4)); 3.17 (dd,
1 H, H(4), J = 17.2 Hz, J = 9.2 Hz); 4.94 (dd, 1 H, H(5), J = 9.2 Hz,
J = 5.6 Hz); 7.12—7.37 (m, 5 H, Ph), 9.43, 10.09 (both br.s,
in the ratio 1 : 10, NOH).
F. A solution of hydroxyenone 2 or 3 (3 mmol), anhydrous
CH2Cl2 (20 mL), acetic anhydride (0.22 mL), triethylamine
(1 mL), and a catalytic amount of DMAP was kept for 10—12 h
at 20—25 C, workedꢀup similarly to method E, and passed
through a short layer of SiO2 to obtain acetates 18a—c.
G. A solution of AcCl (0.4 g, 4 mmol) in diethyl ether
(0.5 mL) was added dropwise to a solution of isoxazolidinols 6—9
(3 mmol) and anhydrous pyridine (0.4 g, 4 mmol) in diethyl
ether (20 mL) at 0—5 C. A turbid precipitate formed was filꢀ
tered off and the mixture was allowed to stand for 12—15 h at
20—25 C, poured into aq. NaHCO3 cooled to 0 C, and exꢀ
tracted with a mixture of benzene—ethyl acetate. After drying
with Na2SO4, the residue was passed through a short layer of
SiO2 to obtain Nꢀacetamides 19a,b and 20.
2ꢀAcetoxyꢀ2ꢀmethylꢀ5ꢀ(NꢀacetylꢀNꢀacetoxy)aminoꢀ5ꢀphenylꢀ
pentanꢀ3ꢀone (17a) was obtained by method E through the acylaꢀ
tion of compound 6a, the yield of an oily product was (0.46 g,
44%). Found (%): N, 3.69. C18H23NO6. Calculated (%): N, 4.01.
IR, /cm–1: 3460 br, 1800, 1728, 1684 (NC=O). 1H NMR
(300 MHz, CDCl3), : 1.42, 1.48 (both s, 3 H each, Me); 2.06
(s, 6 H, MeC=O); 2.09 (s, 3 H, MeC=O); 3.19, 3.37 (both dd,
ABX system, CH2, JAB = 12.8 Hz, JAX = 8.1 Hz, JBX = 7.4 Hz);
5.87 (br.t, 1 H, NCH, J = 7.8 Hz); 7.34—7.48 (m, 5 H, Ph).
1ꢀ(1ꢀAcetoxycyclohexyl)ꢀ3ꢀ(NꢀacetylꢀNꢀacetoxy)aminoꢀ3ꢀ
phenylpropanꢀ1ꢀone (17b) was obtained by method E through
the acylation of compound 7a, a light crystallizing oil, the yield
was 0.22 g (38%), m.p. 169—170 C. Found (%): C, 64.47;
H, 6.79; N, 3.30. C21H27NO6. Calculated (%): C, 64.76; H, 6.99;
N, 3.60. IR, /cm–1: 1796, 1764, 1736 (C=O, ester), 1704
(C=O), 1676 (C=O, amide). 1H NMR (300 MHz, CDCl3), :
1.06—1.72 (m, 10 H, CH2); 2.08, 2.12 (both s, in the ratio ~2 : 1,
9 H, MeC=O); 3.12, 3.31 (both dd, ABX system, 1 H each,
CH2, JAB = 12.6 Hz, JAX = 8.0 Hz, JBX = 7.2 Hz); 5.84 (br.t, 1 H,
NCH, J = 6.4 Hz); 7.22—7.38 (m, 5 H, Ph). 13C NMR (CDCl3),
: 18.07, 20.95, 23.40, 24.75, 30.55, 30.76, 37.83, 57.85, 83.31,
85.12, 118.77, 127.64, 128.04, 128.36, 128.71, 130.34, 137.38,
143.93, 167.72, 170.20, 205.33 (C=O). MS, m/z (Irel (%)): 389
[M]+ (6), 331 (13), 330 (12), 288 (31), 270 (47), 256 (63), 249 (51),
229 (32), 214 (43), 212 (47), 174 (38), 164 (148), 163 (66),
161 (41), 146 (42), 141 (68), 131 (100), 124 (37), 122 (49),
109 (83), 104 (97), 103 (66), 99 (93), 91 (37), 81 (93), 67 (53),
57 (64), 51 (68).
1ꢀ(2ꢀHydroxypropꢀ2ꢀyl)ꢀ3ꢀphenylpropꢀ2ꢀenꢀ1ꢀone oxime
(15) was obtained by method D, the yield was ~5%, m.p.
122—123 C (from AcOEt) (cf. Ref. 16: m.p. 136 C). Found (%):
N, 6.54. C12H15NO2. Calculated (%): N, 6.82. IR, /cm–1: 3240,
1620. 1H NMR (300 MHz, DMSOꢀd6), : 1.39 (s, 6 H, Me);
4.84 (br.s, 1 H, OH); 7.06, 7.74 (both d, 1 H each, CH=CH,
J = 16.0 Hz); 7.21—7.39 (m, 3 H, Ph); 7.49 (d, 2 H, Ph,
J = 8.0 Hz); 10.88 (s, 1 H, N—OH).
5ꢀ(2ꢀHydroxypropꢀ2ꢀyl)ꢀ3ꢀphenylisoxazole (16). A mixture
of isoxazoline 10a (1.1 g, 5 mmol), TsOH (10 mg), and anhyꢀ
drous sodium sulfate (0.5 g) in benzene (8 mL) was refluxed for
1 h with stirring. After cooling to ~20 C, it was diluted with

614
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 3, March, 2012
Mavrov and Firgang
2ꢀAcetoxyꢀ2ꢀmethylꢀ5ꢀphenylpentꢀ4ꢀenꢀ3ꢀone (18a) was obꢀ
ane). Found (%): C, 66.71; H, 7.40; N, 4.42. C17H23NO4. Calꢀ
culated (%): C, 66.86; H, 7.59; N, 4.59. IR, /cm–1: 3460 br,
1662 (NC=O). 1H NMR (500 MHz, CDCl3), : 0.91—1.89
(m, 10 H, CH2); 2.16 (s, 3 H, MeC=O); 2.44 (dd, 1 H, H(4),
J = 12.1 Hz, J = 6.9 Hz); 2.70 (dd, 1 H, H(4), J = 12.1 Hz,
J = 9.3 Hz); 3.40, 5.24 (both br.s, 1 H each, OH); 5.61 (br.t, 1 H,
H(3), J = 7.8 Hz); 7.29—7.35 (m, 5 H, Ph). 13C NMR (CDCl3),
: 20.86, 20.98, 21.13. 25.15, 25.39, 31.01, 31.58, 43.77, 59.60,
73.92, 110.28 (O—C—O), 125.79, 127.33, 128.70, 141.61, 174.55
(NC=O). MS, m/z (Irel (%)): 305 [M]+ (50), 231 (55), 214 (29),
213 (57), 206 (48), 179 (83), 173 (52), 164 (77), 163 (84), 140 (42),
133 (57), 132 (86), 131 (85), 122 (43), 129 (47), 109 (43), 105 (87),
104 (95), 103 (81), 91 (49), 81 (74), 77 (92), 69 (47), 55 (100).
NꢀAcetylꢀ5ꢀhydroxyꢀ5ꢀ(1ꢀmethylcyclohexyl)ꢀ3ꢀphenylisoxꢀ
azolidine (20) was obtained by method G through the acylation of
isoxazolidine 9a, the yield was 0.51 g (46%), a mixture of two
isomers (~2 : 1), m.p. 138—139 C (from ethyl acetate—hexꢀ
ane). Found (%): C, 71.01; H, 8.22; N, 4.29. C18H25NO3. Calꢀ
culated (%): C, 71.25; H, 8.31; N, 4.62. IR, /cm–1: 3224, 1648
(NC=O). 1H NMR (500 MHz, DMSOꢀd6), : 0.99, 1.01 (both s,
3 H, Me); 1.02—1.59 (m, 8 H, CH2); 1.80—1.91 (both m, 2 H,
CH2); 1.95, 2.06 (both br.s, in the ratio ~2 : 1, 3 H, MeCO); 2.23
(dd, 0.33 H, H(4), J = 12.7 Hz, J = 7.5 Hz); 2.57 (dd, 0.33 H,
H(4), J = 12.7 Hz, J = 6.2 Hz); 3.09, 3.22 (both m, 0.67 H each,
H(4)); 5.38 (t, 0.33 H, H(3), J = 7.8 Hz); 5.88 (br.s, 0.67 H,
H(3)); 6.21 (s, 0.33 H, OH); 7.22—7.38 (m, 5 H, Ph); 9.58 (br.s,
0.67 H, OH). 13C NMR (DMSOꢀd6), : 17.86, 20.65, 21.00,
21.11, 22.21, 22.40. 22.30, 24.02. 25.29. 25.63, 30.82, 30.89,
33.86, 43.58, 47.45, 53.79, 59.03, 111.02 (O—C—O), 122.02,
125.73, 126.87, 127.11, 127.48, 128.06, 140.14, 142.68, an addiꢀ
tional signal was found at 211.50 (C=O).
tained by method F through the acetylation of alcohol 2a, the
yield was 81%, m.p. 82—83 C (cf. Ref. 18: m.p. 83—84 C). IR,
/cm–1: 1728 (OC=O), 1688 (C=O). 1H NMR (300 MHz,
CDCl3), : 1.57 (s, 6 H, Me); 2.12 (s, 3 H, MeC=O); 6.96, 7.78
(both d, 1 H each, CH=CH, J = 16.0 Hz); 7.38 (m, 3 H, Ph);
7.56 (m, 2 H, Ph).
Compound 18a was also synthesized according to method E
by acetylation of isoxazolidine 6a, the yield was 12%. The
1H NMR spectra of the samples obtained by methods E and F are
identical.
1ꢀ(1ꢀAcetoxycyclohexyl)ꢀ3ꢀphenylpropꢀ2ꢀenꢀ1ꢀone (18b) was
obtained by method E through the acylation of isoxazolidine 7a,
the yield was 16%, m.p. 68—70 C (from hexane—AcOEt). UV,

max/nm (): 240 (24700). IR, /cm–1: 1724 (OC=O), 1696
1
(C=O). H NMR (300 MHz, CDCl3), : 1.31 (m, 1 H, CH2);
1.49—1.84 (m, 9 H, CH2); 2.12 (s, 3 H, Me); 6.96, 7.76 (both d,
1 H each, CH=CH, J = 16.0 Hz); 7.36 (m, 3 H, Ph); 7.55
(m, 2 H, Ph).
2ꢀAcetoxyꢀ5ꢀ(4ꢀmethoxyphenyl)ꢀ2ꢀmethylpentꢀ4ꢀenꢀ3ꢀone
(18c) was obtained by method E through the acetylation of
isoxazolidine 6b, the yield was 17%, m.p. 75—76 C (from hexꢀ
ane). UV, max/nm (): 325 (36500). IR, /cm–1: 1730 (OC=O),
1686 (C=O). 1H NMR (300 MHz, CDCl3), : 1.52 (s, 6 H, Me);
2.09 (s, 3 H, MeC=O); 3.83 (s, 3 H, OMe); 6.84, 7.73 (both d,
1 H each, CH=CH, J = 16.0 Hz); 6.89, 7.49 (both d, 2 H each,
Ar, J = 8.0 Hz).
Compound 18c was also synthesized according to method F
by acetylation of alcohol 3a, the yield was 82%. The spectral
characteristics of the samples obtained by methods E and F are
identical.
1ꢀ(1ꢀAcetoxycyclohexyl)ꢀ3ꢀ(4ꢀmethoxyphenyl)propꢀ2ꢀenꢀ1ꢀ
one (18d) was obtained by method G through the acetylation of
isoxazolidine 7b, the yield was 43%, m.p. 85—86 C (from hexꢀ
ane—AcOEt). UV, max/nm (): 325 (24500). IR, /cm–1: 1736
(OC=O), 1680 (C=O). 1H NMR (300 MHz, DMSOꢀd6), : 1.32
(m, 1 H, CH2); 1.42—1.78 (m, 7 H, CH2); 1.96—2.10 (m, 2 H,
CH2); 2.12 (s, 3 H, MeC=O); 3.82 (s, 3 H, MeO); 6.92, 7.54
(both d, 1 H each, CH=CH, J = 16.0 Hz); 7.56 (m, 2 H, Ar);
7.62 (d, 2 H, Ar, J = 8.0 Hz).
References
1. (a) P. Perlmutter, Conjugate Addition Reaction in Organic
Synthesis, Pergamon Press, Oxford, 1992, p. 114; (b) L. W. Xu,
C. Y. Xia, Eur. J. Org. Chem., 2005, 633; (c) S. M. Desenko,
V. D. Orlov, Azageterotsikly na osnove aromaticheskikh neꢀ
predel´nykh ketonov [Azaheterocycles Derived from Aromatic Unꢀ
saturated Ketones], Folio, Khar´kov, 1998, 148 pp. (in Russian);
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Hydroxyenone 3b was also isolated as a side product in
20% yield.
NꢀAcetylꢀ5ꢀhydroxyꢀ5ꢀ(2ꢀhydroxypropꢀ2ꢀyl)ꢀ3ꢀphenylisoxꢀ
azolidine (19a) was obtained by method G from isoxazolidine 6a,
the yield was 0.33 g (41%), m.p. 142—144 C (from AcOEt—light
petroleum). Found (%): C, 63.08; H, 7.12; N, 4.99. C14H19NO4.
Calculated (%): C, 63.38; H, 7.22; N, 5.28. IR, /cm–1: 3436,
1
3376, 1648 (NC=O). H NMR (300 MHz, CDCl3—DMSOꢀd6
(4 : 1)), : 1.21, 1.29 (both s, 3 H each, Me); 2.11 (s, 3 H,
MeC=O); 2.41—2.64 (m, 2 H, H(4)); 4.32, 6.07 (both br.s,
1 H each, OH); 5.41 (t, 1 H, H(3), J = 7.6 Hz); 7.10—7.40
(m, 5 H, Ph). 13C NMR (CDCl3), : 20.97, 24.36, 25.0, 44.02,
59.74, 72.98, 110.16, 125.76, 126.0, 127.38, 128.72, 141.45,
174.52 (N—C=O). MS, m/z (Irel (%)): 265 [M]+ (17), 248 (14),
223 (22), 207 (16), 206 (31), 191 (76), 193 (30), 179 (31), 164
(18), 163 (43), 162 (32), 147 (32), 145 (39), 133 (32), 132 (41),
131 (72), 106 (57), 104 (100), 103 (58), 91 (32), 77 (38), 69 (43),
59 (91), 51 (67), 42 (53).
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NꢀAcetylꢀ5ꢀhydroxyꢀ5ꢀ(1ꢀhydroxycyclohexyl)ꢀ3ꢀphenylisoxꢀ
azolidine (19b) was obtained by method G from isoxazolidine 7a,
the yield was 0.36 g (39%), m.p. 123—124 C (from AcOEt—hexꢀ

Reactions of ,ꢀunsaturated ketones
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Received April 19, 2011;
in revised form January 10, 2012