Synthesis of new aminocyclitols by selective epoxidation of N-benzyl-N-methyl-2-cyclohepten-1-amine and tert-butyl 4-[benzyl(methyl)amino]- 2,3,4,7-tetrahydro-1H-azepine-1-carboxylate

Article abstract of DOI:10.1134/S1070428014020183

Synthesis of N-benzyl-N-methyl-2-cyclohepten-1-amine and tert-butyl 4-[benzyl(methyl)amino]-2,3,4,7-tetrahydro-1H-azepine-1-carboxylate from cyclic allyl acetates was performed. The features of stereoselective epoxidation of these substrates were investig

Full text of DOI:10.1134/S1070428014020183

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 2, pp. 251−256. © Pleiades Publishing, Ltd., 2014.
Original English Text © E.A. Larin, V.S. Kochubei, Yu.M. Atroshchenko, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 2, pp. 258−263.
Synthesis of New Aminocyclitols by Selective Epoxidation
of N-Benzyl-N-methyl-2-cyclohepten-1-amine
and tert-Butyl 4-[benzyl(methyl)amino]-2,3,4,7-tetrahydro-1H-
azepine-1-carboxylate
E. A. Larina, V. S. Kochubeia, and Yu. M. Atroshchenkob
aJoint Stock Co “New Scientific Technologies,” Moscow, 125480 Russia
bTolstoi Tula State Pedagogical University, Tula, Russia
е-mail: elarin@nnteh.ru
Received February 26, 2013
Abstract—Synthesis of N-benzyl-N-methyl-2-cyclohepten-1-amine and tert-butyl 4-[benzyl(methyl)amino]-
2,3,4,7-tetrahydro-1Н-azepine-1-carboxylate from cyclic allyl acetates was performed. The features of
stereoselective epoxidation of these substrates were investigated. The subsequent epoxide opening with water
led to the formation of new pseudosaccharides, (1RS,2RS,3RS)-3-[benzyl(methyl)amino]-1,2-cycloheptanediol,
(1RS,2RS,3SR)-3-[benzyl(methyl)amino]-1,2-cycloheptanediol, and (3RS,4RS,5RS)-3-[benzyl(methyl)amino]-
4,5-azepanediol.
DOI: 10.1134/S1070428014020183
Aminocyclitols are indispensable part of many natural activity of such compounds [1]. In the case of synthetic
antibiotics underlain by pseudosaccharides a possibility
arises to prepare compounds with preliminary determined
stereochemistry [2, 3].
and synthetic biologically active substances of amino-
glycoside type, antibiotics among them. Nowadays a
considerable attention is attracted to the synthesis of
mimetics of this fragment. This is due to the significant
role played by the presence of a carbocyclic aminoalco-
hol and the stereochemistry in governing the biological
The main starting material for the synthesis of ami-
noglycoside mimetics are cycloalkenes containing in
most cases a priori one or several stereocenters. These
Scheme 1.
Ph
AcO
N
[(n-C H )PdCl] , Fe(C H PPh )
2 2
3
5
2
5
4
HN(Me)CH Ph
2
E-/Z-I
E-/Z-II
AcO
Ph
Ph
[(n-C H )PdCl] , Fe(C H PPh )
2 2
3
5
2
5
4
Boc
N
N
N
+
N
Boc
HN(Me)CH Ph
2
N
Boc
E-/Z-III
E-IV
Z-V
251

LARIN et al.
252
cycloalkanes can be prepared from the corresponding
allyl alcohols and their derivatives. Palladium catalysis is
the most efficient in reactions of allyl alcohols and their
derivatives with various nucleophiles [4]. We showed that
using as catalyst n-allylpalladium(II) chloride dimer and
the ligand 1,1'-bis(diphenylphosphanyl)ferrocene made
it possible to perform the nucleophilic substitution of the
acetate group in 2-cycloheptenyl acetate (I) for N-benzyl-
N-methylamine affording compound II in a relatively
high yield. In the reaction of tert-butyl-4-(acetoxy)-
2,3,4,7-tetrahydro-1Н-azepine-1-carboxylate (III) with
N-benzyl-N-methylamine formed two isomers IV and
V in a ratio 3 : 1, which were successfully separated by
chromatography (Scheme 1).
IV lacks the correlation peak Н5/Н6, consequently, these
atoms are located in the trans-position, and the presence
of the corresponding correlation peak in the spectrum of
compound V indicates the cis-arrangement of the hydro-
gen atoms at the double bond.
In the next stage we carried out the epoxidation of the
obtained allylamines by treating with 3-chloro-perbenzoic
acid under acid conditions [5]. Before analyzing the ste-
reochemistry of epoxides obtained by the oxidation of
heterocyclic allylamines IV and V we first removed the
Вoc-protection in order to obtain narrower signals in the
1Н NMR spectra (Scheme 2).
The epoxidation of compound II in the presence
of toluenesulfonic acid resulted in the formation of a
mixture of syn-epoxide VI and anti-epoxide VII in the
ratio 2 : 1, whereas the oxidation in the presence of
trichloroacetic acid [6] afforded only anti-epoxide VII
in a lower yield, and in trifluoroacetic acid the reaction
did not occur. These facts confirm the assumption on the
significant influence of the nature of the acid used for
the protonation of the nitrogen atom in the allylamine
prior to adding the oxidant into the reaction mixture. The
epoxidation process of cyclohept-2-enol is known to pos-
sess low cis-diastereoselectivity [7] caused by the high
conformational flexibility of the cycloheptene. The high
trans-diastereoselectivity of epoxidation of compound
II in the presence of trichloroacetic acid shows, that in
the transition state the seven-membered ring is in the
chair conformation, and the olefin epoxidation proceeds
from the sterically more accessible side. The formation
of syn-epoxide VI at the use of toluenesulfonic acid
demonstrates that the nature of the acid protonating the
nitrogen not only influences the stability of the transition
state, but also governs the diastereoselectivity of the oxi-
dation process. The presence of the correleation peaks in
the NOESY spectrum at 3.29/2.92 and 3.09/2.92 ppm in-
dicates the coupling of Н2е/Н3а and Н1е/Н3а respectively,
consequently, compound VI is a β-oriented epoxide. The
absence of the cross-peak Н3а/Н1а and the presence of
the cross-peak Н2а/Н1а (3.15/2.48 ppm) in the NOESY
spectrum of compound VII show that it is an α-oriented
1
In the Н NMR spectrum of compound II a charac-
teristic singlet signal is observed at 2.24 ppm belonging
to the methyl group protons, and also an АВ system of
nonequivalent protons of the methylene group of the
benzyl substituent in the region 3.53–3.68 ppm with a
geminal coupling constant of 2J 13.4 Hz.
To prove the structure of IV and V isomers we ana-
lyzed the spectra COSY 1Н-1Н. It was presumed that the
reaction would afford a mixture of two regioisomers: tert-
butyl-4-[benzyl(methyl)amino]-2,3,4,7-tetrahydro-1Н-
azepine-1-carboxylate and tert-butyl-6-[benzyl(methyl)-
amino]-2,3,6,7-tetrahydro-1Н-azepine-1-carboxylate.
However the COSY spectra of the reaction products did
not contain the correlation peaks corresponding to the
coupling of the double bond protons with the protons
bound to С3 indicating the formation of two stereomers
IV and V. Their spatial arrangement was analyzed ap-
plying NOESY spectra. The NOESY spectrum of isomer
Scheme 2.
Ph
+
Ph
N
N
3-ClC H COOOH
6
4
3
O
3
O
2
7
2
7
4
II
4
1
1
5
5
6
6
syn-IV
sin-VI
anti-VII
epoxide. The vicinal constant for syn-epoxide VI 3JН2е 3а
Н
amounts to 5.2 Hz, for anti-epoxide VII, 3JН2а 3а 7.2 Hz
O
Н
(1) 3-ClC H COOOH
6
4
confirming the axial location of the hydrogen atoms at
С2 and С3 in the α-oriented epoxide VII.
5
Ph
4
(2) CF COOH
6
7
3
3
IV
N
2
1
The analysis of the epoxidation products of com-
pounds IV and V showed that the mechanism of this
reaction is significantly influenced by the presence of a
N
H
VIII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 2 2014

SYNTHESIS OF NEW AMINOCYCLITOLS
253
Scheme 3.
_
=/
O
O
Ph
H
O
OCOCCl3
Ph
Ar
N
3-ClC H COOH
+
6
4
Boc
Boc
HO+
N
N
IV
N
A
B
Ph
+
(1) DBU
Boc
Boc
Ph
N
(2) CF COOH
N
N
3
HO
OCOCCl
N
VIII
HO
_
3
Cl COCO
3
D
C
heteroatom in the seven-membered ring. The epoxidation
of isomer IV where the hydrogen atoms at the double
bond are present in the trans-position in trichloroace-
tic acid with subsequent Вос-deprotection leads to the
formation of regioisomer VIII. Thus an intramolecular
rearrangement occurs in the course of the oxidation. The
structure of obtained epoxide VIII was proved by reg-
istering 2D NMR spectra with homonuclear correlation
COSY and NOESY. In the COSY spectrum cross-peaks
were observed corresponding to the spin-spin coupling
of the protons Н6/Н5, Н4/Н3, and Н3/Н2, confirming the
formation of regioisomer VIII. The analysis of the ob-
tained correlations in the NOESY spectrum shows that
in epoxide VIII molecule the NOE-effect is observed
between the protons Н4/Н3 and Н4/Н5, indicating their
close spatial proximity (β-oriented epoxide).
nonselectively providing as a result a complex mixture
of regio- and stereoisomers whose chromatographic
separation seems impossible. The formation of isomer
mixture is confirmed by the presence of two singlets at
2.30 and 2.36 ppm corresponding to the protons of the
methyl groups of isomers.
Further we carried out the oxirane ring opening in
epoxides VI–VIII by treating with water in the presence
of acid (Scheme 4).
Scheme 4.
N
Ph
Ph
OH
H SO
3
2
4
2
7
VI
4
_
THF H O
1
OH
2
5
6
Taking into consideration the above reasoning we
suggested the epoxidation mechanism for this type
compounds (Scheme 3). In the initial stage substrate IV
reacts with 3-chloroperbenzoic acid in the presence of
trichloroacetic acid leading to the formation of transition
state А [5]. Further the protonation of oxygen occurs
(intermediate B). Therewith the nucleophile attacks not
the carbon atoms of the oxirane ring , but the carbon
atom linked to the nitrogen (transition state C) giving
intermediate D.
IX
N
OH
H SO
2
4
3
2
VII
4
5
_
1
THF H O
OH
2
7
6
X
HO
OH
_
At the use of toluenesulfonic acid no corresponding
epoxide is formed. This is due to the occurrence in this
case parallel to the epoxidation the Boc-deprotection of
substrates IV and V resulting in the decomposition of
the initial compounds. Isomer V having the boat confor-
mation under these epoxidation conditions is oxidized
5
4
CF COOH H O
3
2
6
7
3
N
VIII
2
1
N
H
Ph
XI
Ar = 3-ClC6H4.
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LARIN et al.
254
The direction of the opening of the epoxide ring in
(diphenylphosphanyl)ferrocene in 50 mL of toluene was
added at stirring 5.0 mmol of cyclic allyl acetate. The mix-
ture was stirred for 10 min, and then 1.82 g (15.0 mmol)
of N-benzyl-N-methylamine was added. The reaction
mixture was stirred at room temperature for 4 h, then it
was diluted with 50 mL of 5% water solution of sodium
hydroxide, the organic layer was separated, the solvent
was removed in a vacuum. The residue was chromato-
graphed on silica gel (eluent hexane–ethyl acetate, 3 : 1).
Yield 0.94 g (87%). 1Н NMR spectrum (CDCl3), δ, ppm:
1.20–2.08 br.m (8Н, 4СН2), 2.24 s (3Н, NCH3), 3.38 d
(1Н, СН, 2J 7.5 Hz), 3.57 d, 3.64 d (2Н, CH2Ph, 2J 15.0,
2J 13.4 Hz), 5.75–5.95 m (2Н, СН=СН), 7.12–7.42 m
(5Н, Ph). 13C NMR spectrum (CDCl3), δ, ppm: 26.96
(C5), 28.70 (C6), 28.74 (C7), 29.14 (C4), 37.95 (NCH3),
57.89 (CH2Ph), 64.11 (C3), 126.75, 128.27, 128.78
(Carom), 131.02 (C2), 135.40 (C1), 140.30 (Carom). Found,
m/z: 216.27 [M]+ (APCI), 216.1745 [M + H]+ (ESI).
C15H21N. Calculated M 216.1747.
compounds VI–VIII is consistent with the mechanism
of the acid hydrolysis of epoxides [5]. The optimum
condition for carbocyclic epoxides VI and VII is the
application of sulfuric acid in the system THF–water. In
the event of epoxide VIII trifluoroacetic acid should be
used as solvent, and the rate of the epoxide ring opening
is significantly lower than for the carbocyclic substrates.
Therefore longer time of maintenance of the reaction mix-
ture till the complete conversion of epoxide is required
resulting in lower yield of the target compound X due to
the formation of intractable side products.
Therefore we have confirmed that the epoxidation
involving N-benzyl-N-methyl-2-cyclohepten-1-amine
proceeds with a low diastereoselectivity, but we have
succeeded to separate the obtained diastereomers by
chromatography. This provides a possibility to obtain
finally aminocyclitols of diverse spatial arrangement.
The presence of a nitrogen atom in the ring of tert-
butyl-4-[benzyl(methyl)amino]-2,3,4,7-tetrahydro-1Н-
azepine-1-carboxylate is an additional factor affecting the
epoxidation mechanism and its regio- and stereoslectivity.
Along with the conformational flexibility and lability of
the seven-membered carbocycles governing the stere-
oselectivity of the epoxidation process, the possibility of
intermolecular rearrangements should also be taken into
consideration. The results obtained make it possible to
perform a targeted synthesis of diastereomers of amino-
cyclitols for preparing new mimetics of aminoglycosides.
Compounds IV, V were obtained similarly.
tert-Butyl-4-[benzyl(methyl)amino]-(E)-2,3,4,7-
tetrahydro-1Н-azepine-1-carboxylate (IV). Yield
1
0.85 g (54%). Н NMR spectrum (CDCl3), δ, ppm:
1.44 s (9Н, Вoc), 1.76–2.12 m (2Н, 3-CH2), 2.22 s (3Н,
NСН3), 3.39–3.85 m (6Н, 3CH2N), 3.87–4.20 br.m (1Н,
СН), 5.72–5.92 m (2Н, СН=СН), 7.18–7.40 m (5Н, Ph).
13C NMR spectrum (DMSO-d6), δ, ppm: 27.30 (C6),
27.48 (C2), 27.63 [C(CH3)3], 36.99 (NCH3), 45.58 (C7),
56.88 (CH2Ph), 62.13 (C5), 78.08 [C(CH3)3], 126.06,
127.46, 127.69 (Carom), 128.05 (C3), 132.05 (C4), 139.32
(Carom), 153.80 (C=O). Found, m/z: 317.24 [M]+ (APCI),
317.2229 [M + H]+ (ESI). C19H28N2O2. Calculated
M 317.2224.
EXPERIMENTAL
1H (400 MHz) and 13С (100 MHz) NMR spectra were
registered on a spectrometer Varian Mercury Plus 400.
GC-MS spectra were recorded on an instrument Thermo
Fisher Scientific Surveyor MSQ [chemical ionization at
the atmospheric pressure (APCI)]. High resolution mass
spectra were taken on an instrument Bruker Dalton-
ics MicrоTOF II [electrospray ionization (ESI)]. The
reaction progress was monitored and the homogeneity
of compounds obtained was tested by TLC on Sorbfil
plates, development with iodine vapor and 1% solu-
tion in acetone of 2,2-dihydroxyindane-1,3-dione. The
column chromatography was carried out on silica gel
Merck 40-60.
tert-Butyl-4-[benzyl(methyl)amino]-(Z)-2,3,4,7-
tetrahydro-1Н-azepine-1-carboxylate (V). Yield
1
0.29 g (18%). Н NMR spectrum (CDCl3), δ, ppm:
1.41–1.51 m (2Н, 3-CH2), 1.46 s (9Н, Вoc), 2.29 s (3Н,
NСН3), 2.89–3.21 br.m (1Н, СН), 3.42–4.78 br.m (6Н,
3CH2N), 5.74–5.87 m (2Н, СН=СН), 7.17–7.37 m
(5Н, Ph). 13C NMR spectrum (DMSO-d6), δ, ppm:
27.29 (C6), 27.61 [C(CH3)3], 36.87 (NCH3), 44.12 (C2),
44.24 (C7), 56.92 (CH2Ph), 60.38 (C5), 78.02 [C(CH3)3],
126.05, 127.46 (Carom), 127.71 (C3), 127.77 (Carom),
133.74 (C4), 139.31 (Carom), 153.86 (C=O). Found,
m/z: 317.24 [M]+ (APCI), 317.2233 [M + H]+ (ESI).
C19H28N2O2. Calculated M 317.2224.
N-Benzyl-N-methyl-2-cyclohepten-1-amine (II). To
a solution of 18 mg (0.005 mmol) of n-allyl-palladium(II)
chloride dimer and 70 mg (0.125 mmol) of 1,1'-bis-
1,2-Epoxy-3-(N-benzyl-N-methylamino)cyclohep-
tanes VI, VII. To a solution of 0.94 g (4.4 mmol) of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 2 2014

SYNTHESIS OF NEW AMINOCYCLITOLS
255
compound II in 50 mL of dichloromethane was added
at stirring 2.50 g (15.4 mmol) of trichloroacetic acid. The
mixture was stirred for 30 min, then 0.91 g (5.3 mmol)
of m-chloroperbenzoic acid was added by portions. The
reaction mixture was stirred at room temperature for 3 h.
The excess of m-chloroperbenzoic acid was neutralized with
1 mL of saturated water solution of sodium sulfite and the
saturated water solution of sodium hydrogen carbonate was
used to adjust the medium to pH 8.0. The organic layer was
separated and to the solution was added at stirring 0.67 g
(4.4 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene. The
reaction mixture was stirred at room temperature for 1 h,
diluted with water, the organic layer was separated and
dried with sodium sulfate. The solvent was removed at a
reduced pressure, the residue was subjected to chromatog-
raphy on silica gel (eluent hexane–ethyl acetate, 2 : 1).
fonic acid monohydrate. The mixture was stirred for
30 min, then 0.56 g (3.2 mmol) of m-chloroperbenzoic
acid was added by portions. The reaction mixture was
stirred at room temperature for 20 h. The excess of
m-chloroperbenzoic acid was neutralized with 1 mL of
saturated water solution of sodium sulfite and with saturated
water solution of sodium hydrogen carbonate the reaction of
the medium was adjusted to pH 8.0. The organic layer was
separated and at stirring to the solution was added 0.41 g
(2.7 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene. The
stirring was continued for 1 h, the reaction mixture was
washed with water (3 × 50 mL), the organic layer was
separated and dried with sodium sulfate.. To a solution
1.85 g (16.2 mmol) of trifluoroacetic acid was added, the
reaction mixture was stirred at room temperature for 3 h,
then it was neutralized with a saturated water solution of
potassium carbonate. The water layer was separated and
extracted with ethyl acetate (5 × 20 mL), the combined
organic solutions were dried with sodium sulfate. The
solvent was removed at a reduced pressure. Yield 0.30 g
(1RS,2SR,3RS)-1,2-Epoxy-3-(N-benzyl-N-me-
thylamino)cycloheptane (VI). Yield 0.15 g (15%).
1Н NMR spectrum (CDCl3), δ, ppm: 0.70–0.82 m (1Н,
СН2), 1.26–1.60 m (4Н, 2СН2), 1.62–1.70 m (1Н, СН2),
1.71–1.79 m (2Н, СН2), 2.32 s (3Н, NCH3), 2.92 d.d
1
(52%). Н NMR spectrum (CDCl3), δ, ppm: 2.01 d.d.d
(1Н, 6-СН2, 2J 15.9, 3J 12.4, 3J 3.9 Hz), 2.32 d.d.d (1Н,
3
3
(1Н, 1-СН, J 11.5, J 2.3 Hz), 3.08 t (1Н, 3-СН,
3J 5.2 Hz), 3.29 d (1Н, 2-СН, 3J 4.7 Hz), 3.58 d, 3.78 d
2
3
3
6-СН2, J 15.4, J 6.1, J 4.3 Hz), 2.40 s (3Н, NCH3),
2.50 br.s (1Н, NH), 2.63–2.72 m (1Н, СН2NH), 2.77 d.d
(1Н, 2-СН, 3J 12.8, 3J 10.9 Hz), 2.95 d.t (1Н, СН2NH,
2
(2Н, CH2Ph, J 13.5 Hz), 7.14–7.46 m (5Н, Ph).
13C NMR spectrum (CDCl3), δ, ppm: 23.31 (C4), 24.09
(C6), 27.30 (C5), 28.27 (C7), 38.17 (NCH3), 53.00 (C1),
58.14 (CH2Ph), 59.90 (C2), 63.68 (C3), 126.70, 128.09,
128.55 and 135.73 (Carom). Found, m/z: 232.20 [M]+
(APCI), 232.1699 [M + H]+ (ESI). C15H21NO. Calculated
M 232.1696.
3
2
2J 13.6, J 3.5 Hz), 3.12 d.d (1Н, СН2NH, J 12.9,
3J 3.2 Hz), 3.18 d (1Н, 3-СН, J 3.3 Hz), 3.12–3.21 m
(1Н, 5-СН), 3.40 d (1Н, 4-СН, J 4.7 Hz), 3.71 d,
3.84 d (2Н, CH2Ph, J 13.6 Hz), 7.21–7.40 m (5Н,
3
3
2
Ph). 13C NMR spectrum (CDCl3), δ, ppm: 31.22 (C6),
38.64 (NCH3), 44.98 (C7), 45.50 (C2), 52.40 (C5), 58.55
(CH2Ph), 58.74 (C4), 64.86 (C3), 68.86 (C3), 127.00,
128.40, 128.73, 135.78 (Carom). Found, m/z: 233.17 [M]+
(APCI), 233.1643 [M + H]+ (ESI). C14H20N2O. Calculated
M 233.1648.
(1RS,2SR,3SR)-1,2-Epoxy-3-(N-benzyl-N-me-
thylamino)cycloheptane (VII). Yield 0.34 g (33%).
1Н NMR spectrum (CDCl3), δ, ppm: 1.19–1.27 m (1Н,
СН2), 1.30–1.41 m (2Н, СН2), 1.54–1.75 m (2Н, СН2),
1.85–1.98 m (2Н, СН2), 2.23–2.27 m (1Н, СН2), 2.29 s
3
3
3-[Benzyl(methyl)amino]-1,2-cycloheptanediols
IX, X. In 20 mL of a mixture THF–water, 2 : 1, was
dissolved 0.15 g (0.66 mmol) of epoxide, and at stirring
0.20 g (2.0 mmol) of conc. sulfuric acid was added. The
reaction mixture was stirred at 50°С for 2 h. On cooling
the reaction mixture was neutralized with the saturated
water solution of potassium carbonate and diluted with
20 mL of ethyl acetate. The organic layer was dried with
sodium sulfate, the solvent was evaporated in a vacuum,
the residue was chromatographed on silica gel (eluent
ethyl acetate).
(3Н, NCH3), 2.51 d.d (1Н, 3-СН, J 10.4, J 7.2 Hz),
3
2.98–3.06 m (1Н, 1-СН), 3.14 d.d (1Н, 2-СН, J 7.0,
3J 5.0 Hz), 3.66 d, 3.73 d (2Н, CH2Ph, J 13.4 Hz),
2
7.12–7.46 m (5Н, Ph). 13C NMR spectrum (CDCl3),
δ, ppm: 24.11 (C6), 29.17 (C5), 29.75 (C7), 30.87 (C4),
38.30 (NCH3), 53.09 (C1), 55.87 (C2), 58.70 (CH2Ph),
65.88 (C3), 126.80, 128.01, 128.78, 135.85 (Carom).
Found, m/z: 232.20 [M]+ (APCI), 232.1694 [M + H]+
(ESI). C15H21NO. Calculated M 232.1696.
(3RS,4SR,5RS)-4,5-Epoxy-3-(N-benzyl-N-me-
thylamino)azepane (VIII). To a solution of 0.85 g
(2.7 mmol) of compound IV in 50 mLof dichloromethane
was added at stirring 1.03 g (5.4 mmol) of toluenesul-
(1RS,2RS,3RS)-3-[Benzyl(methyl)amino]-1,2-
1
cycloheptanediol (IX). Yield 0.12 g (72%). Н NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 2 2014

LARIN et al.
256
2
spectrum (C6D6), δ, ppm: 1.97 d.d (1Н, СН2, J 23.7,
extracted with ethyl acetate (5 × 20 mL), the combined
organic solutions were dried with sodium sulfate. The
solvent was removed at a reduced pressure. Yield 0.07 g
3J 11.5 Hz), 1.23 d.d (1Н, СН2, J 24.5, J 11.3 Hz),
1.29–1.38 m (1Н, СН2), 1.42–1.51 m (1Н, СН2),
1.52–1.75 m (4Н, 2СН2), 2.05 s (3Н, NCH3), 2.23 s
(1Н, ОH), 2.27 s (1Н, ОH), 2.93 d.t (1Н, 3-СН, 3J 11.9,
3J 6.0 Hz), 3.41 d, 3.51 d (2Н, CH2Ph, J 13.2 Hz),
3.63–3.70 m (1Н, 2-СН), 3.74 t.d (1Н, 1-СН, J 9.1,
3J 2.2 Hz), 7.17–7.37 m (5Н, Ph). 13C NMR spectrum
(C6D6), δ, ppm: 23.78 (C4), 25.65 (C5), 27.37 (C6), 36.46
(C7), 38,62 (NCH3), 60.61 (CH2Ph), 63.27 (C3), 72.94
(C1), 75.38 (C2), 127.98, 128.98, 129.32, 138.84 (Carom).
Found, m/z: 250.16 [M]+ (APCI), 250.1794 [M + H]+
(ESI). C15H23NO2. Calculated M 250.1802.
2
3
1
(41%). Н NMR spectrum (DMSO-d6), δ, ppm: 1.53 d
(1Н, 6-СН2, 2J 14.4 Hz), 1.83 d.d (1Н, 6-СН2, 2J 14.4,
3J 11.0 Hz), 2.18 с (3Н, NCH3), 2.52–2.61 m (1Н, 7-СН2),
2.63–2.73 m (1Н, 7-СН2), 2.82 d.d (1Н, 2-СН2, 2J 12.3,
3J 6.4 Hz), 2.90–3.00 m (1Н, 2-СН2), 3.24 br.s (1Н, NH),
2
3
3
3
3.24 d.d (1Н, 3-СН, J 9.8, J 6.5 Hz), 3.57 d, 3.71 d
(2Н, CH2Ph, 2J 13.9 Hz), 3.78 d (1Н, 5-СН, 3J 5.1 Hz),
4.52 br.s (2Н, 2ОH), 7.09–7.41 m (5Н, Ph). 13C NMR
spectrum (DMSO-d6), δ, ppm: 35.45 (C6), 38.26 (NCH3),
41.10 (C7), 44.93 (C2), 57.42 (CH2Ph), 58.73 (C3), 69.27
(C5), 73.06 (C4), 127.58 (Carom). Found, m/z: 251.16
[M]+ (APCI), 251.1754 [M + H]+ (ESI). C14H22N2O2.
Calculated M 251.1754.
(1RS,2RS,3SR)-3-[Benzyl(methyl)amino]-1,2-
cycloheptanediol (X). Yield 0.10 g (64%). Н NMR
1
spectrum (DMSO-d6), δ, ppm: 0.55–0.64 m (2Н, СН2),
2
0.66–0.71 m (1Н, СН2), 0.79 d.d (1Н, СН2, J 18.9,
REFERENCES
3J 10.0 Hz), 0.84–0.92 m (2Н, СН2), 0.95–1.10 m (2Н,
СН2), 1.39 s (3Н, NCH3), 1.67 t (1Н, 3-СН, 3J 9.4 Hz),
1. Bergmeier, S.C., Tetrahedron, 2000, vol. 56, p. 2561.
2. Busscher, G.F., Rutjes, F.P.G.T, and Delft, F.L., Chem. Rev.,
2005, vol. 105, p. 775.
3. Verhelst, S.H.L., Wennekes, T., van der Marel, G.A., Over-
kleeft, H.S., van Boeckel, C.A.A., and van Boom, J.H.,
Tetrahedron, 2004, vol. 60, p. 2813.
4. Merten, S., Froehlich, R., Kataeva, O., and Metz, P., Adv.
Synth. Catal., 2005, vol. 347, p. 754.
5. Aciro, C., Claridge, T.D.W., Davies, S.G., Roberts, P.M.,
Russell, A.J., and Thompson, J.E., Org. Biomol. Chem.,
2008, vol. 6, p. 3751.
3
3
2.54 d.d (1Н, 2-СН, J 9.2, J 6.7 Hz), 2.59–2.67 m
(1Н, 1-СН), 2.73 d, 2.96 d (2Н, CH2Ph, J 13.3 Hz),
2
3.55 d (1Н, 1-СНОН, 3J 3.2 Hz), 3.78 s (1Н, 1-СНОН),
6.49–6.65 m (5Н, Ph). 13C NMR spectrum (DMSO-d6),
δ, ppm: 20.85 (C4), 21.32 (C5), 24.59 (C6), 30.50 (C7),
35.92 (NCH3), 57.13 (CH2Ph), 64.70 (C3), 74.60 (C1),
76.29 (C2), 126.58, 127.99, 128.50, 139.19 (Carom).
Found, m/z: 250.16 [M]+ (APCI), 250.1795 [M + H]+
(ESI). C15H23NO2. Calculated M 250.1802.
(3RS,4RS,5RS)-3-[Benzyl(methyl)amino]-4,5-
azepanediol (XI). In 20 mL of dichloromethane was
dissolved 0.15 g (0.67 mmol) of compound VIII, and
at stirring 0.76 g (6.7 mmol) of trifluoroacetic acid was
added. The reaction mixture was boiled for 8 h, on cool-
ing it was neutralized with the saturated water solution of
potassium carbonate. The water layer was separated and
6. Brennan, M.B., Claridge, T.D.W., Compton, R.G.,
Davies, S.G., Fletcher, A.M., Henstridge, M.C., Hew-
ings, D.S., Kurosawa, W., Lee, J.A., Roberts, P.M. Schoo-
nen, A.K., and Thompson, J.E., J. Org. Chem., 2012,
vol. 77, p. 7241.
7. Denmark, S.E., Barsanti, P.A., Wong, K.-T., Stavenger, R.A.,
J. Org. Chem., 1998, vol. 63, p. 2428.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 2 2014