Characteristic features of reduction with i-Bu2AlH of products of ring opening with (-)-α-Methylbenzylamine of (3aS,4R,7R,7aS)-3a,4,7,7a- Tetrahydro-4,7-epoxy-2-benzofuran-1,3-dione

Article abstract of DOI:10.1134/S1070428011050101

A special procedure of synthesis was developed for amidoaminals of atypical topology through a reduction with i-Bu2AlH of primary products of thermodynamical opening of (3aS,4R,7R,7aS)-3a,4,7,7a-tetrahydro-4,7-epoxy-2- benzofuran-1,3-dione at treating with (-)-α-methylbenzylamine. Characteristic spectral criteria are described for assignment of diastereomeric compounds; possible routes of reaction stages are considered. Pleiades Publishing, Ltd., 2011.

Full text of DOI:10.1134/S1070428011050101

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 5, pp. 714−721. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.V. Loza, N.S. Vostrikov, M.R. Talipov, M.S. Miftakhov, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 5,
pp. 710−716.
Characteristic Features of Reduction with i-Bu2AlH of Products
of Ring Opening with (–)-α-Methylbenzylamine
of (3aS,4R,7R,7aS)-3a,4,7,7a-Tetrahydro-4,7-epoxy-
2-benzofuran-1,3-dione
V. V. Loza, N. S. Vostrikov, M. R. Talipov, and M. S. Miftakhov
Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, Ufa, 450054 Russia
e-mail: bioreg@anrb.ru
Received June 16, 2009
Abstract—A special procedure of synthesis was developed for amidoaminals of atypical topology through a
reduction with i-Bu2AlH of primary products of thermodynamical opening of (3aS,4R,7R,7aS)-3a,4,7,7a-tetrahydro-
4,7-epoxy-2-benzofuran-1,3-dione at treating with (–)-α-methylbenzylamine. Characteristic spectral criteria are
described for assignment of diastereomeric compounds; possible routes of reaction stages are considered.
DOI: 10.1134/S1070428011050101
The desymmetrization of prochiral meso-anhydrides
with chiral nucleophiles under the conditions of kinetic
control is a convenient and efficient synthetic procedure
for the preparation of optically active compounds. This
approach was applied to the synthesis of chiral di- and he-
miesters, amidoacids, lactones, ketoacids, thioesters [1–5].
Lately [6] we utilized (+)- and (–)-α-methylbenzylamines
for the opening of α,α-dichlorocyclobutane ring of
(±)-7,7-dichlorobicyclo-[3.2.0]hept-2-en-6-one and
demonstrated the ready separation by column chroma-
tography of the mixture of diastereomeric hemiaminals
I into individual diastereomers II and III.
the procedure and to estimate the possibility to separate
diastereomers we planned to design structures V, VI
like compounds II, III from meso-anhydride IV using
(–)-α-methylbenzylamine as an auxiliary chiral substance.
As seen from the structure of diastereomers V, VI, after
the removal of the chiral source (amine) they should
provide the corresponding enantiomeric compounds
(Scheme 2).
To this end we studied the reaction of anhydride IV
with (–)-α-methylbenzylamine. On mixing exo-anhydride
IV with 2 equiv of amine in CH2Cl2 solution the reac-
tion proceeded fast with some self-heating. The workup
provided a crystalline substance. Its spectral character-
In continuation of this research in order to extend
Scheme 1.
O
O
O
SiO2
N
N
N
+
OH
OH
OH
II
III
I
714

CHARACTERISTIC FEATURES OF REDUCTION WITH i-Bu2AlH
715
Scheme 2.
O
O
OH
N
O
O
O
N
+
O
O
OH
O
(±)-IV
V
VI
of α-methylbenzylammonium salts in the materially
istics indicated the formation of a diastereomeric mix-
quantitative yield.
tures of monoamides of acids VIIa, VIIb in the form
O
O
+
_
N
Ph
H3N
Ph
O
H
O
O
H
N
_
+
O
H3N
Ph
Ph
O
O
VIIa
VIIb
We planned to transform amides VIIa, VIIb into dia-
stereomers V and VI in the following sequence: amides
VIIa, VIIb → ester → aldehyde. However in the stage
of methylating amides VIIa, VIIb with diazomethane
or with MeI in the system NaH–THF we observed an
unexpected reaction course. Therewith we obtained in
high yield (>90%) a tricyclic imide as a diastereomeric
mixture VIIIa, VIIIb in the ratio 1 : 1 (Scheme 3).
According to the 1Н NMR spectrum imide VIII is an
equimolar mixture of diastereomers as show the integral
intensities of different singlet signals of bridging СНО
groups at 5.23 and 5.28 ppm. The proton signals of groups
СН3, СНN, CH, and protons at the double bond are iden-
tical in both diastereomers. In the 13С NMR spectrum
of diastereomers VIIIa, VIIIb the signals of all atoms
are different, and the largest difference is observed for
СН3 (16.6, 19.4 ppm) and Сi of the aromatic ring (139.0,
142.5 ppm).
The easy formation of cyclic imides VIIIa, VIIIb un-
der mild conditions of the methylation with diazomethane
(Et2O, 0°C) calls for special attention.
As shown in [7] the reaction of CH2N2 with ammo-
nium salts of organic acids proceeded to form methyl
esters of acids and to liberate a free amine. Therewith
the methylating agent is the protonated diazomethane,
i.e., the intermediate CH3N+≡N [8]. Yet in the reaction
of amide VII with the diazomethane no methyl esters
form and instead occurs an intramolecular cyclization to
imide VIII. For amidoacids А resembling amide VII the
cyclization into imides B required fairly severe conditions
Scheme 3.
O
O
(а) CH2N2 MeOH_H2O
,
O
O
N
VIIa + VIIb
N
+
Ph
Ph
(b) MeI, NaH, THF
O
O
VIIIa
VIIIb
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

LOSA et al.
716
Scheme 4.
Ph
O
O
O
Ph
OH
N
Ac2O_AcONa
100oC, 3 h
H
OAc
N
CO2H
А
B
[9] (Scheme 4).
formed one compound of low polarity and two pairs of
compounds strongly differing in polarity. The low polar
compound proved to be identical to previously isolated
imide VIII; it formed in 10% yield. Basing on the spectral
characteristics and the quantum-chemical calculations
(see further) two less polar major compounds formed in
the ratio 1:1 with the overall yield 65% were considered
to be tricyclic aminals IXa, IXb, and to the minor (20%)
more polar substances hemiaminal structures Xa, Xb
were assigned (Scheme 6).
Therefore evidently a specific activation occurs of
one among the functional groups of compound VII. In
particular, we believe that in the reaction of diazomethane
with salt VII the latter becomes protonated generating
intermediate C which transforms into a covalently bound
acyloxydiazo derivative D where the carboxy group is
sufficiently activated to undergo the intramolecular cycli-
zation to imide VIII. On the other hand, the formation of
imide VIII at the alkylation with the system NaH–MeI we
ascribe first of all to the possibility of ready deprotonation
of the amide moiety of compound VII followed by the
cyclization of anion E (Scheme 5).
In some experiments attempting to reduce aminals
IXa, IXb with NaBH4 the reagents were boiled in 1,4-di-
oxane–water mixture. Therewith alongside the formation
of strongly polar decomposition products slowly formed
a new compound whose Rf was practically identical to
that of aminal IXa and which also had similar spectral
characteristics. However certain difference also existed.
In the alternative approach with the goal of building up
the structures of cyclic hemiaminals V and VI we studied
the reduction of the salt mixture VIIa, VIIb with 2 equiv
of i-Bu2AlH in CH2Cl2.According to TLC in this reaction
Scheme 5.
O
O
N
Ph
CH N
VII +
2
2
H
H2N
+
O
[
CH3
CH3
N
N
Ph
O
+
]
C
N
N
O
O
O
O
_
N
N
H
Ph
N
P
VIIIа, VIIIb
h
[
]
OH
CH3
N
N
O
N
CH3
OR
O
O
E
D
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

CHARACTERISTIC FEATURES OF REDUCTION WITH i-Bu2AlH
717
Scheme 6.
O
O
N
2 equiv i-Bu2AlH
+
VIIа, VIIb
Ph
VIIIа, VIIIb
CH Cl _78°C
,
2
2
NH
Ph
IXа
O
O
Ph
O
OH
O
N
HN
+
+
+
N
N
Ph
Ph
Ph
O
O
OH
O
Xa
IXb
Xb
Scheme 7.
O
Ph
NH
O
Ph
O
O
O
H
N
_
_
N
N
2H
2H
N
N
N
Ph
HN
Ph
Ph
Ph
O
O
Ph
Ph
XIa
XIc
IXc
IXd
It was clear that the notable distinctions in the spectra
of the new compound may be due to the epimerization
of aminals IXa, IXb in the severe reduction conditions.
Since in aminals IXa, IXb the trans-junction of the pyr-
rolidone ring is unfavorable, it is possible to suggest the
epimerization in the aminal center, probably, through
amidinium intermediates XIa, XIb leading to new dia-
stereomers IXc, IXd respectively (Scheme 7).
pounds IXa, IXb along the pathway: retrodiene decom-
position → reverse Diels–Alder reaction → aminal IXe
(Scheme 8).
In keeping with models (Orbit molecular building sys-
tem, Oxford, UK), in the assignment of α- or β-epimeric
aminals IXа–IXd the signals of the nodal proton Н3а in
the 1Н NMR spectra may be regarded as characteristic.
Here the effect of the side N-substituent at the С3 atom
should be taken into consideration, since it induces the
downfield shift of the trans-vicinal proton [10]. In the case
of α-epimers IXa, IXd due to the syn-coplanar location
of the proton H3a with respect to heteroatom the signal
of this proton should appear upfield relative to the cor-
responding signal of the β-epimers. For instance, in the
1Н NMR spectra of isomers IXa, IXb a strong difference
is observed in the shifts of doublet signals of protons H3а
(1.6 and 2.0 ppm respectively). Besides in the 1H NMR
spectrum of the α-epimer the signals of contiguous groups
As seen from the structures aminals IXc, IXd are
enantiomeric in pairs with respect to aminals IXa, IXb.
Enantiomeric compounds IXa, IXd and aminals IXb,
IXc should have identical spectral characteristics but the
angles of the optical rotation αD of the opposite signs.
However the spectral data and αD of the new product did
not correspond to the data of compounds IXc, IXd. We
presume that the formation of the new diastereomer at
boiling aminals IXa, IXb in the mixture NaBH4–1,4-
dioxane–water proceeds as the isomerization of com-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

LOSA et al.
718
Scheme 8.
O
O
H
O
O
NaBH4
N
N
IXа, IXb
+
H
1,4-dioxane_water, Δ
NH
Ph
NH
IXe
Ph
Ph
Ph
СНО and СН= also are shifted upfield as compared with
the corresponding signals of β-epimeric compound. To
choose two more favorable by energy diastereomers from
aminals IXа–IXd we carried out quantum-chemical cal-
culations of the relative stability of the isomers.
product of the low-temperature reduction of compounds
VIIa, VIIb with i-Bu2AlH, aminoaldehyde F existing
in a cyclic form. It is allowable that in the course of
the reduction free amine is liberated or aminoalanes of
type XI are generated. Further both aminoalane XI and
α-methylbenzylamine may react with aldehyde F and
through imine XII give aminals IXa, IXb (Scheme 9).
The relative energies of conformers of aminals IXа–
IXd possessing low energy were calculated by the method
DFT B3LYP/6-31G(d).
Thus in this research we have demonstrated the pos-
sibility to prepare diastereomeric aminals IXa, IXb by
direct reduction of salts VIIa, VIIb with i-Bu2AlH. Note
also that the easily separable SiO2 aminals IXa, IXb are
masked equivalents of planned in our study compounds
V and VI.
Comd. no.
IXа
IXb
IXc
IXd
Erel, kJ mol−1
9.8
0.0
8.3
17.2
As seen, among the α-aminals IXa is more stable,
and among the β-aminals evidently the more favorable
is aminal IXb possessing the lowest energy. Spectral
data of aminal IXe formed in the reaction of the mixture
IXa, IXb with NaBH4 are slightly different from the data
EXPERIMENTAL
IR spectra were obtained on a spectrophotometer
1
UR-20 from thin films or mulls in mineral oil. H and
1
of compounds IXa, IXb. For instance, in the Н NMR
13С NMR spectra were registered on a spectrometer Bruk-
er AM-300 [operating frequencies 300 (1Н), 75.47 MHz
(13С)], internal reference TMS. Rotation angles were
measured on an instrument Perkin Elmer-341. Mass
spectra were taken on an instrument MKh-1320, ionizing
electrons energy 70 eV, ionizing chamber temperature
60–90°С, direct admission of the sample into the ion
source. TLC analyses were carried out on Sorbfil plates.
spectrum of aminal IXe the nodal proton Н3а gives rise to
a triplet signal at 1.97 ppm with J 8 Hz, thus indicating its
trans-antiperiplanar orientation with respect to nitrogen
atom. Compared to isomers IXa, IXb in the 13С NMR
spectrum of compound IXe because of strong sterical
strain in the fragment NC3C3aC4 the signals of atoms С3,
С3а, С4 are shifted upfield.
The next after compounds IXa, IXb pair of sub-
stances, minor and more polar in keeping with TLC, are
α- and β-diastereomeric hemiacetals Xa, Xb, evidently
genetically related to the pair IXa, IXb. In the 1Н NMR
spectrum of more polar hemiaminal the nodal protons
resonate as doublets at 2.22 and 2.62 ppm, J 7.3 Hz, olefin
protons, as a singlet at 6.45 ppm. These data testify to
the β-hemiaminal structure of compound Xb. Less polar
hemiaminal Xa have the characteristic signals of the nodal
protons H3а and H7а at 2.56 and 1.60 ppm respectively.
(S)-1-Phenylethylammonium (±)-3-{[(1S)-1-
phenyl-ethyl]aminocarbonyl}-7-oxabicyclo[2.2.1]
hept-5-ene-2-carboxylate (VII). To a solution of 2 g
(12.02 mmol) of anhydride IV in 10 ml of CH2Cl2 was
added at stirring a solution of 2.44 g (24 mmol) of (S)-
phenylethylamine in 5 ml of CH2Cl2. The reaction mix-
ture slightly self-heated. After stirring for 30 min to the
reaction mixture 3 ml of 10% HCl was added. The organic
layer was separated, the water layer was extracted with
CH2Cl2 (2 × 5 ml).The combined organic solutions were
washed with the saturated solution of NaHCO3, with wa-
ter and with brine. On evaporating the solvent we obtained
The formation of hemiaminals Xa, Xb apparently pro-
ceeds through the stage of the formation of the presumed
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

CHARACTERISTIC FEATURES OF REDUCTION WITH i-Bu2AlH
719
Scheme 9.
O
O
N
Ph
H
+
VIIа, VIIb
H3N
Ph
_
O
-i
OAl-Bu2
i-Bu2Al
N
H
Ph
XI
O
O
N
Ph
+
_
+
H
i-Bu2AlO H3N
Ph
O
E
i-Bu AlOH H N
+
2
2
Ph
Xа, Xb
O
O
H
N
Ph
F
IXа, IXb
N
Ph
XII
compound VII in the quantitative yield, white amorphous
powder. IR spectrum, ν, cm–1: 3292, 1720 w 1531 s,
1454 s. 1H NMR spectrum (CDCl3), δ, ppm: 1.38 d (3Н,
СН3, J 7 Hz), 1.43 d (3Н, СН3, J 6.9 Hz), 2.62 d (0.5Н,
Н3, J 9 Hz), 2.73 d (1Н, Н3, J 4.9, 6 Hz), 2.84 d (0.5Н,
Н2, J 9 Hz), 4.91 s, 4.94 s, 4.96 s, 5.17s, 5.22 s, 5.30 s
(6Н, 2СНО, СНN, H3N+), 6.25–6.50 m (СН=СН, CНN),
7.0 d (0.5Н, NH, J 6 Hz), 7.15 d (0.5Н, NH, J 6 Hz),
7.20–7.40 m (10Н, 2С6Н5). 13С NMR spectrum (CDCl3),
δ, ppm: 20.4, 21.6, 21.8, 22.05 (СН3), 47.5, 47.6, 48.6,
48.8 (С2, С3), 50.1 (CHN), 51.3 (CHN), 79.78, 79.9, 80.4,
81.0 (С1, С4), 126.1, 126.2, 126.4, 126.9, 127.3, 127.6,
128.4, 128.6, 128.7, 128.9, 129.0, 132.3, 135.3, 135.7,
136.9, 137.2, 138.5, 142.3, 143.3 (2С6Н5, СН=СН), 165.4
and 167.4 (СО), 172.3 and 175.3 (СО2). Mass spectrum,
m/z (Irel, %): 286 [M – H3N – CH(CH3)Ph]+ (74), 218
[M – H3N – CH(CH3)Ph – C4H4O]+ (100).
(±)-2-[(1S)-1-Phenylethyl]-3a,4,7,7a-tetrahydro-
1H-4,7-epoxyisoindole-1,3-diones VIIIа, VIIIb. а.
Into a solution of 0.1 g (0.25 mmol) of salt VII in 4 ml
of anhydrous THF was added 6 mg (0.25 mmol) of NaH
maintaining the temperature of –5°С, and was added at
stirring 35.5 mg (0.25 mmol) of freshly distilled MеI.
The reaction mixture was stirred for ~1 h, then saturated
solution of NH4Cl was added. The solvent was evapo-
rated, the residue was extracted with CH2Cl2 (3 × 5 ml).
Combined extracts were washed with water, with brine,
and evaporated to obtain 60 mg of cyclic amides VIIIа,
VIIIb.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

LOSA et al.
720
b. In 4 ml of a mixture methanol–water, 10 : 1, was dis-
(1Н, С6, J 6 Hz), 7.03 d (1Н, NH, J 9 Hz), 7.16–7.40 m
(10H, 2С6Н5). 13С NMR spectrum (CDCl3), δ, ppm: 16.6
(СН3), 24.7 (СН3), 44.7 (С3а), 49.0 (СНN), 50.1 (СHN),
53.1 (С7a), 73.7 (NCN), 81.1 (С4), 83.0 (С7), 126.7, 127.2,
128.0, 128.5, 141.8, 144.7 (2С6Н5), 135.7 (С5), 136.1
(С6), 173.0 (СО).
solved 0.1 g (0.25 mmol) of compound VII, the solution
was cooled to –5°С, and at stirring an ether solution of
CH2N2 was added till weak yellow color appeared. Excess
CH2N2 was neutralized with АсОН. On evaporation the
residue was extracted with CH2Cl2 (3 × 5 ml), washed
with the saturated solution of NaHCO3, with water and
with brine, dried with Na2SO4, and evaporated. Yield
66 mg (97%) white crystals, mp 138–139°C,
[α]D20 – 36.9° (с 2, СН2Сl2). IR spectrum, ν, cm–1: 1772 w,
1697 s, 1496 w, 1450 w, 1390 s, 1361 s. 1H NMR spec-
trum (CDCl3), δ, ppm: 1.79 d (3Н, СН3, J 00 Hz), 2.77 s
(2Н, Н3а,7а), 5.23 s and 5.28 s (2Н, Н4, Н7), 5.38 q (1Н,
CHN, J 6 Hz), 6.49 s (2Н, Н5, Н6), 7.25–7.40 m (5H,
С6Н5). 13С NMR spectrum (CDCl3), δ, ppm: 16.6 and
19.4 (СН3), 41.2, 41.3 and 50.2, 51.4 (С3а, С7а), 79.0,
79.2 (СНN), 79.5, 79.9 and 81.0, 81.3 (С4, С7), 126.5,
126.8, 127.5, 128.0, 128.3, 128.4, 139.0, 142.5 (С6Н5),
135.0, 135.3 and 138.2, 138.4 (С5, С6).
(3aR,4S,7S,7aR)-2-[(1S)-1-Phenylethyl]-3-{[(1S)-
1-phenylethyl]amino}-2,3,3а,4,7,7а-hexahydro-
1Н-4,7-epoxyisoindole-1-one (IXb). Oily substance,
Rf 0.66 (chloroform–methanol, 10:1), [α]D20 –114.3°
(с 1.2 CHCl3). 1H NMR spectrum (CDCl3), δ, ppm: 1.01 d
(3Н, СН3, J 6 Hz), 1.52 d (3Н, СН3, J 6 Hz), 2.00 d (1Н,
Н3a, J 7 Hz), 2.56 d (1Н, Н7a, J 7 Hz), 3.65 q (1Н, СНN,
J 6 Hz), 4.14 s (1Н, NCHN), 4.67 s (1Н, Н4), 5.12 s (1Н,
Н3), 5.23 q (1Н, СНN, J 6 Hz), 6.30 d (1Н, Н5, J 6 Hz),
6.36 d (1Н, Н6, J 6 Hz), 7.20–7.45 m (11H, 2С6Н5, NH).
13С NMR spectrum (CDCl3), δ, ppm: 18.7 (СН3), 23.0
(СН3), 47.7 (С3a), 49.1 (СНN), 50.7 (СHN), 56.0 (С7a),
75.1 (NCN), 81.0 (С4), 82.7 (С7), 126.5, 127.3, 128.2,
128.6, 139.0, 146.0 (2С6Н5), 135.6 (С5), 136.1 (С6),
171.6 (СО).
Reduction of compound VII with diisobutylalumi-
num hydride. To a solution of 3 g (7.63 mmol) of salt
VII in 10 ml of anhydrous CH2Cl2 at –78°С was added
dropwise 4 ml (19.08 mmol) of 73% hexane solution
of i-Bu2AlH. The mixture was stirred for 2 h at –78°С,
0.5 ml of water was added dropwise, and the reaction
mixture was warmed to 0°С. The solvent was evapo-
rated at a reduced pressure, the dry residue was washed
on a glass frit filter with hot MеОН (3 × 15 ml). On
evaporating MеОН we obtained 3.3 g of orange-yellow
oily substance. According to TLC data the residue was a
mixture of five compounds, one among them, less polar
and appearing as a single spot with Rf 0.9 (chloroform–
methanol, 10:1) was identified as above described imide
VIII; 4 other compounds according to TLC gave two
pairs of spots with strongly differing Rf values. These
compounds were isolated by column chromatography
on SiO2. Yield of imide VIII 10%, overall yields (IXa +
IXb) 65, (Ха + Хb) 20%.
(3aR, 4S, 7R, 7aS)-3-Hydroxy-2-[(1S)-1-
phenylethyl]-2,3,3a,4,7,7a-hexahydro-1H-4,7-epoxy-
inden-1-one (Xа). Oily substance, Rf 0.31 (chloroform–
methanol, 10:1). IR spectrum, ν, cm–1: 1454, 1645, 3300.
1H NMR spectrum (CDCl3–CD3OD), δ, ppm: 1.62 d (3H,
CH3, J 7 Hz), 1.80 d (1Н, Н3а, J 5.8 Hz), 2.74 d (1Н,
Н7а, J 5.8 Hz), 4.97 br.s (1Н, Н3), 5.16 br.s (2Н, 2СНО),
5.35 q (1Н, CHN, J 6 Hz), 6.36 d (1Н, Н7а, J 5.8 Hz),
6.42 d (1H, CH=CH, J 5.7 Hz), 7.20–7.50 m (5Н, С6Н5).
(3aR,4S,7R,7aR)-3-Hydroxy-2-[(1S)-1-
phenylethyl]-2,3,3a,4,7,7a-hexahydro-1H-4,7-epoxy-
inden-1-one (Xb). Rf 0.33 (chloroform–methanol, 10 :
1), white crystals, mp 145–147°С (decomp.), [α]D20 –58.8
(с 1.8, СHCl3–MeOH, 1:1). IR spectrum, ν, cm–1: 1453,
1
1645, 2850, 2951, 3302. H NMR spectrum (CDCl3–
CD3OD), δ, ppm: 1.68 d (3H, CH3, J 7.3 Hz), 2.22 d (1Н,
Н3a, J 7.3 Hz), 2.62 d (1Н, Н7a, J 7.3 Hz), 4.95 br.s (2Н,
Н3,7), 5.02 s (1Н, H4), 5.10 q (1H, CHN, J 9 Hz), 6.45 s
(2Н, H5,6), 7.20–7.50 m (5Н, С6Н5). 13С NMR spectrum
(CDCl3), δ, ppm: 17.4 (CH3), 47.7 (C3a), 48.9 (C7a), 51.7
(CHN), 80.5 (C4), 82.2 (C7), 85.4 (C3), 126.8, 128.1,
135.8, 136.1, 136.6, 146.6 (C6H5), 173.4 (CO).
(3aS,4S,7R,7aS)-2-[(1S)-1-Phenylethyl]-3-{[(1S)-
1-phenylethyl]amino}-2,3,3а,4,7,7а-hexahydro-
1Н-4,7-epoxyisoindole-1-one (IXа). Oily substance,
Rf 0.73 (chloroform–methanol, 10:1), [α]D20 –30.0° (с 2.0,
СНСl3). IR spectrum, ν, cm–1: 3296, 1647, 1448. 1H NMR
spectrum (CDCl3), δ, ppm: 1.18 d (3Н, СН3, J 6 Hz),
1.61 d (1Н, Н3а, J 7.5 Hz), 1.74 d (3Н, СН3, J 6 Hz),
2.56 d (1Н, Н7а, J 7.5 Hz), 3.31 q (1Н, СНN, J 6 Hz),
3.73 s (1Н, NCHN), 3.94 s (1Н, Н4), 5.11 s (1Н, Н7),
5.32 q (1Н, СНN, J 9 Hz), 5.94 d (1Н, С5, J 6 Hz), 6.26 d
(3aR,4S,7R,7aR)-2-[(1S)-1-Phenylethyl]-3-{[(1S)-
1-phenylethyl]amino}-2,3,3a,4,7,7a-hexahydro-1H-
4,7-epoxyisoindole-1-one (IXe). In a solution of 0.3
g (0.79 mmol) of a mixture of compounds IXa, IXb
in 5 ml of a mixture of 1,4-dioxane with water, 4:1, was
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011

CHARACTERISTIC FEATURES OF REDUCTION WITH i-Bu2AlH
721
added 0.13 g (3.4 mmol) of NaBH4 , and the reaction
mixture was boiled for 6 h. The solution was evaporated,
the residue was extracted with СН2Сl2 (3 × 10 ml), the
combined extracts were washed with an NH4Cl solution,
with water and with brine. On evaporating СН2Сl2 we
obtained 0.29 g of viscous oily substance, Rf 0.72 (chlo-
roform–methanol, 10:1), [α]D20 –29.4° (с 4.2, СН2Сl2).
IR spectrum, ν, cm–1: 1423, 1674, 1681, 3138. 1H NMR
spectrum (CDCl3), δ, ppm: 0.92 d (3Н, СН3, J 6 Hz),
1.62 d (3Н, СН3NH, J 9 Hz), 1.97 t (1Н, Н3а, J 8 Hz),
2.44 d (1Н, Н7а, J 8 Hz), 3.34 q (1Н, СНN, J 6 Hz),
4.19 m (1Н, NCHN), 4.74 s (1Н, Н4), 5.02 s (1Н, Н7),
5.23 q (1Н, СНN, J 9 Hz), 6.07 d.d (1Н, Н5, J 1.7, 6 Hz),
6.28 d.d (1Н, Н6, J 1.5, 6 Hz), 6.99 d (1Н, NH, J 6 Hz),
7.06–7.26 m (10H, 2С6Н5). 13С NMR spectrum (CDCl3),
δ, ppm: 18.9 (СН3), 22.7 (СН3), 40.3 (С3a), 50.0 (СНN),
51.0 (СHN), 55.6 (С7a), 70.9 (NCN), 79.7 (С4), 80.1 (С7),
126.5, 127.0, 127.2, 127.4, 127.8, 128.2, 128.4, 128.6,
139.8, 145.6 (2С6Н5), 136.1 (С5), 137.4 (С6), 171.6 (СО).
Mass spectrum, m/z (Irel, %): 375 [M + H]+ (25), 307
[M – C4H4O]+ (100), 254 [M – PhCH(CH3)NH]+ (41).
of the FederalAgency on Science and Innovations (State
contract 02.512.12.2015).
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ACKNOWLEDGMENTS
The study was carried out under the financial support
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 5 2011