Chiral modification of polyformyl compounds of dendrite type with optically active primary and secondary 1,2-aminoalcohols

Article abstract of DOI:10.1134/S107042801002020X

Procedures were developed for preparation of optically active dendrones and dendrimers with terminal 1,2-hydroxylimino, 1,2-hydroxylamino and oxazolidinyl groups containing ether bonds in the branches and ester bonds in the backbone of the macromolecule.

Full text of DOI:10.1134/S107042801002020X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 2, pp. 260−267. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © E.S. Kelbysheva, A.P. Pleshkova, S.E. Lyubimov, S.P. Dolgova, N.M. Loim, 2009, published in Zhurnal Organicheskoi
Khimii, 2010, Vol. 46, No. 2, pp. 265−267.
Chiral Modification of Polyformyl Compounds
of Dendrite Type with Optically Active Primary
and Secondary 1,2-Aminoalcohols
E. S. Kelbysheva, A. P. Pleshkova, S. E. Lyubimov, S. P. Dolgova, and N. M. Loim
Nesmeyanov Institute of Organoelemental Compounds, Russian Academy of Sciences
Moscow,117813 Russia
e-mail: loim@ineos.ac.ru
Received May 6, 2009
Abstract—Procedures were developed for preparation of optically active dendrones and dendrimers with terminal
1,2-hydroxylimino, 1,2-hydroxylamino and oxazolidinyl groups containing ether bonds in the branches and ester
bonds in the backbone of the macromolecule. The compounds described may serve as chiral ligands for asymmetric
metallocomplex catclysis.
DOI: 10.1134/S107042801002020X
The theoretical interest and versatile applications of
dendrimers promote the research in the field of mono-
disperse macromolecular compounds of cascade archi-
tecture [1–10]. A special place among these compounds
belongs to chiral and optically active dendrite molecules
providing new opportunities for creating systems of chiral
recognition and separation of optically active substances,
compounds with nonlinear optic properties, and reagents
for reactions of asymmetric synthesis [11–20]. Recently
by an example of dendrimers with hydrazidothiophosphate
monomer units the promising opportunities were
demonstrated of employing the peripheral formyl groups
for the preparation of optically active dendrite catalysts
[21, 22]. We reported in the previous communication on
the synthesis of formyl-containing dendritc molecules of
Frische type [23]. In this study we performed a chiral
modification of these compounds using optically active
1,2-aminoalcohols leading to the formation of a series of
new chiral polyligands of cascade architecture.
By an example of a model reaction of perfluoro-
benzaldehyde (I) with (–)-(1R,2S)- or (+)-(1S,2R)-
enantiomers of norephedrine we demonstrated that both
in the solid phase without solvent or in the benzene or
chloroform solutions the corresponding Schiff bases II
formed quantitatively. According to the 1H NMR spectra
the latter substances are present in the solution as
Scheme 1.
Ph
O
H
H
H
H
C6F5CHO + H2N
OH
C
C
C6F5 C N
C
C
OH
C6F5
H
CH3 Ph
CH3 Ph
N
CH3
H
I
III
IV
Ph
O
NaBH4
H H
H
C6F5CH2 N C C OH
C6F5
N
CH3 Ph
CH3
H
V
VI
260

CHIRAL MODIFICATION OF POLYFORMYL COMPOUNDS OF DENDRITE TYPE
261
a mixture of three compounds (Scheme 1): proper imine
III (open form) and two diastereomeric oxazolidines IV
and V (closed forms of imine). The spectrum in CDCl3
solution contains, in particular, three doublets of CH3 groups
in the region 0.74–1.38 ppm, three overlapping multiplets
in the region 3.4–3.7 ppm corresponding to the proton
CHMe, and also singlets of protons from the fragment
NCHO of diastereomers IV and V (δ 5.76, 6.28 ppm)
Scheme 2.
H
C
H
C
Ph
H
C
CH3
H
C
Ph
H2N
OH
OC6F4CHO
OC6F4CHO
OC6F4 C N
OH
H
CH3
(S,R)
(S,R)
H3COOC
H3COOC
H
H
OC6F4 C N C C OH
H
CH3 Ph
(S,R)
IX
VII
H
H
C
H
C
H
C
Ph
OCH2C6H4CHO
OCH2C6H4 C N
H
OH
C
H2N
OH
CH3
(S,R)
CH3 Ph
(S,R)
H3COOC
H3COOC
H
H
OCH2C6H4CHO
OCH2C6H4 C N
H
OH
C
C
CH3 Ph
VIII
X
(S,R)
NaBH4
IX
CH3OOCC6H3(OC6F4CH2NHCHMeCHPhOH)2
XI
CHO
OHC
CH2O
COOCH2
CHO
OCH2
CH2OOC
OHC
COOCH2
CHO
COOCH2
CHO
OHC
D0-CHO
COOCH2
CH2OOC
CH2O
OCH2
H2CO
OCH2
CHO
OHC
D1-CHO
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

KELBYSHEVA et al.
262
and of the proton CH=N of imine III (7.97 ppm). The
ratio of the three isomeric forms of the condensation
product III, IV and V is ~1:1:1 and depends neither on
the reaction conditions nor on the conformation of the
initial norephedrine indicating that a fast equilibrium
between the forms exists in the solution.
At the solid-phase synthesis of dendrimers with the
pseudoephedrine in both cases after the completion of
the condensation (the absence of the formyl group signal
in the 1H NMR spectrum) the oxazolidine fragments in
compounds XIII and XVII exist as two diastereomers
1
at the C2 center of the heterocycle. In the H NMR
spectrum of the reaction mixture after 48 h appears
a double set of signals for all groups bound to the
oxazolidine ring. In particular, in the spectrum of XVII
two doublets at δ 0.91 and 1.20 ppm are observed and
two singlets at 2.35 and 2.15 ppm from the methyl groups
in the positions of 4 and 3 of the ring respectively. The
relative intensity of the signals of diastereomers essentially
depends on the time, and after keeping the reaction
mixture over 100 h the thermodynamically less stable
diastereomer completely undergoes epimerization into the
none stable homochiral stereoisomer of the dendrimer
XVII with the chemical shifts of the methyl groups 0.91
and 2.35 ppm. Analogous pattern was observed in the
reaction of formyldendrimers D0-CHO and D1-CHO with
the pseudoephedrine in chloroform as solvent.
The similar modification of the terminal layer of
dendrones VII and VIII with (+)-norephedrine in solution
or in the solid phase also resulted in a quantitative
formation of imines IX and X (Scheme 2) and each among
them in solution was present in the form of three isomers:
the imine and two diastereomeric oxazolidines.
The reduction of 1,2-oxyimines III and IX with sodium
borohydride in methanol furnished the corresponding 1,2-
aminoalcohols VI and XI.
Based on these results we carried out the chiral
modification of the peripheral layer of formyldendrimers
of the zero (D0-CHO) and the first (D1-CHO) genera-
tions [23] using (R)-2-aminobutanol, (1S,2R)-norephedrine,
(S)-isoleucinol, and (1S,2S)-pseudoephedrine both in the
solid phase and in chloroform solution or by boiling the
reagents in ethanol in the presence of sodium sulfate
(Scheme 3). The yields of the target optically active
products in all cases were nearly quantitative (>98%).
The chiral modification of formyldendrimers D0-CHO
and D1-CHO with optically active primary 2-
aminoalcohols completes with the formation of Schiff
Scheme 3.
Ph
CH3
O
(+)-norephedrine
H H
HO C
(+)-pseudoephedrine
D0
C
N C D0
H
N
3
Ph CH3
XII
CH3
3
D0-CHO
XIII
(S)-(+)-isoleucuinol
(R)-2-aminobutanol
H
H
HOH2C C N C D0
H
HOH2C
N C D0
C
H
CH(Me)Et3
3
C2H5
XV
XIV
Ph
CH3
O
(+)-pseudoephedrine
D1
N
CH3
XVII
(+)-norephedrine
6
H H
D1-CHO
HO C
C
N C D1
H
6
Ph CH3
(R)-2-aminobutanol
H
HOH2C C N C D1
H
XVI
6
C2H5
XVIII
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CHIRAL MODIFICATION OF POLYFORMYL COMPOUNDS OF DENDRITE TYPE
263
bases at all aldehyde groups As expected, in solutions
compounds XII, XIV–XVI, XVIII exist in an equilibrium
mixture of the open and two closed (oxazolidine) forms
of 1,2-hydroxyimine terminal groups with a considerable
prevalence of the imine form. In particular, in the
spectrum of compound XII the intensity of proton singlets
of the imine group (δ 8.27 ppm) and of proton signals of
OCHN groups of the oxazolidine rings (δ 6.08 and
5.63 ppm) are in the ratio 5:1:2 (see the figure). Therewith
the 1H NMR spectra in all cases contain only three sets
of signals corresponding to each of the three forms of
the terminal groups. Thus the presence in the dendrimer
of several peripheral fragments of different nature does
not affect the chemical shifts of the terminal groups.
sodium sulfate. In these conditions the quantitative yield
of products was reached already in 2 h although the initial
dendrimers were insoluble in ethanol. Besides by an
example of the reaction between D0-CHO and (1S,2R)-
norephedrine and (S)-isoleucinol we showed that this
procedure made it possible to carry out the reduction of
the dendrimeric iminoalcohols into the aminoalcohols
without their isolation (Scheme 4).
In order to confirm the structure of the above mention-
ed dendrite compounds and to estimate their molecular
weight a comparative investigation was performed of the
mass spectra of the formyldendrimers D0-CHO and D1-
CHO and their derivatives XII–XV, XVII, and XVIII.
The ionization was performed by electron impact (EI) or
matrix-activated laser desorption-ionozation (MALDI).
Although for compounds D0-CHO, XII, XIV, and XV
with the molecular weigh up to 1000 it is possible to obtain
EI spectra, the direct information on the molecular mass
Although the condensation of the reagents in solution
and in the solid phase gave the same results, the most
efficient procedure proved to be the preparation of the
Schiff bases by boiling in ethanol in the presence of
Scheme 4.
COOCH2
CH2NHCHR1CHR2OH
(1) H2NCHR1CHR2OH
(2) NaBH4
D0-CHO
HOCHR2CHR1NHCH2
CH2OOC
COOCH2
CH2NHCHR1CHR2O
H
XIX, XX
R1 = Me, R2 = Ph (XIX), R1 = CH(Me)Et, R2 = H (XX).
1H NMR spectrum oof the isomer mixture of compound XII.
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KELBYSHEVA et al.
264
1H NMR spectra of the samples of reaction mixtures.
For column chromatography silica gel 60 (Merck) was
used. Optically active aminoalcohols were commercial
products of Fluka. Synthesis of compounds VII and VIII
was previously reported [23].
and structure is contained only in the mass spectrum of
D0-CHO, m/z (Irel, %): 564 (10) [M]+, 445 (50) [M –
OCHC6H4CH2]+·, 429 (80) [M – OCHC6H4CH2O]+, and
119 (95) [OCHC6H4CH2]+. In the other EI spectra only
the peaks of fragment ions were observed from the
products of the thermal degradation of the initial
compound. Unlike that, the application of MALDI in all
cases provided informative mass spectra. Therewith
among the three tested matrices [2,5-dihydroxybenzoic,
2-cyano-4-hydroxycinnamic, and trans-3-(indol-3-
yl)acrylic acids] the most generally suitable and efficient
was the latter which provided a highly intense peaks in
the region of molecular masses and a high signal to noise
ratio (≤ 80–102) in the range of masses 700–3000.
Reactions of aldehydes with optically active 1,2-
aminoalcohols. General procedure. a. In the solid
phase without solvent. The equimolar (with respect to
every formyl group) mixture of aldehyde and the chiral
aminoalcohol was thoroughly stirred for 24–48 h till the
formation of a homogeneous viscous or crystalline
substance. The monitoring of the reaction progress was
1
carried out by TLC and by H NMR spectra of the
samples of reaction mixture. On obtaining solid reaction
products they were additionally recrystallized from
a mixture hexane–benzene.
The peaks of ions and clusters observed in the
MALDI spectra unambiguously confirm both the
molecular weight of the dendrite molecules (see
EXPERIMENTAL) and their structure. In particular, the
comparison of spectra of compounds XII, XIV, XV,
XVIII and oxazolidine derivatives XIII and XVII led to
the conclusion that in the solid phase 1,2-oxyimines
evidently existed in the open and not cyclic form which
is registered in the 1H NMR spectra (see above).Actually,
in the spectrum of compound XIII [M]+ of m/z 1005 was
observed, and in the spectrum of compound XVII, a peak
of ion [M – H]+ with m/z 2166, their fragmentation
occurred through the decomposition of the heterocycle
resulting in both cases in the formation of the
corresponding ions [M – PhCHOH]+· and [M –
C10H14N]+·. The pattern in the MALDI spectra of
dendrite Schiff bases is another. The characteristic
feature of these compounds was the presence of ions
[M + 2H]+ (XII, XIV, XV) or [M + H]+· (XVIII), whose
fragmentation involved the cleavage of the N–C bond in
the peripheral substituent with the elimination of a neutral
molecule of the corresponding oxide and with the
formation of ions of dendrite amines.
b. Liquid-phase interaction. A solution of equimolar
(with respect to every formyl group) mixture of aldehyde
and the chiral aminoalcohol in benzene was boiled with
the use of a Dean-Stark trap for 2–4 h or by stirring the
reagents in the chloroform solution at room temperature
for 24 h. The solvent was distilled off in a vacuum, and in
event of obtaining solid products they were additionally
recrystallized from a mixture hexane–benzene.
c. To a dispersion of 3.5 g of anhydrous sodium sulfate
in 25 ml of anhydrous EtOH was added 1.8 mmol of
dendrimer and 4.83 mmol of (S)-aminobutanol or
9.66 mmol of (S)-isoleucinol, and the mixture was boiled
for 2 h with D0-CHO or 12 h with D1-CHO. Then the
reaction mixture was cooled to room temperature, the
Na2SO4 precipitate was filtered off, washed with ethanol,
the solvent was distilled off in a vacuum, the residue was
recrystallized from a mixture hexane–benzene.
2-Perfluorophenylmethylideneamino-1-phenyl-
propanol (III). a. It was obtained from 0.26 g (1.3
mmol) perfluorobenzaldehyde (I) and 0.19 g (1.3 mmol)
of (+)-(1S,2R)- or (–)-(1R,2S)-enantiomer of
norephedrine. Yield 0.43 g (>99%). Oily substance.
1H NMR spectrum of the open form (toluene-d8), δ, ppm:
1.38 d (3H, CH3, J 6.8 Hz), 2.60 br.s (1H, OH), 3.62 m
(1H, CHCH3), 5.20 d (1H, CHOH, J 8.2 Hz), 7.19–
7.40 m (5H, Ph), 7.97 s (1H, CH=N). Found, %: C 58.54;
H 3.65; F 28.92; N 4.22. C16H12FNO. Calculated, %:
C 58.36; H 3.67; F 29.03; N 4.25.
EXPERIMENTAL
1H, 13C (internal reference the solvent, δ from Me4Si),
and 19F NMR spectra were registered on a spectrometer
Bruker WP-200 SY at operating frequencies 200.13,
50.32, and 188.3 MHz respectively. Mass spectra EI were
obtained on an instrument MAT 95X at 70 eV, and MALDI
spectra, on an instrument Bruker AutoFlex IV with
a nitrogen laser, 337 nm. The monitoring of the reaction
progress and checking of the products purity was carried
out by analytic TLC on Silufol UV-245 plates and by
b. It was obtained from 0.52 g (2.6 mmol) of
compound I and 0.39 g (2.6 mmol) of norephedrine in
25 ml of benzene. Yield 0.87 g (>99%). 1H NMR spec-
trum (acetone-d6), δ, ppm: 1.13 d (3H, CH3, J 6.4 Hz),
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CHIRAL MODIFICATION OF POLYFORMYL COMPOUNDS OF DENDRITE TYPE
265
0.78 g of compound VIII and 0.62 g of (+)-norephedrine
1.34 g (>99%).
3.78 m (1H, CHCH3), 5.02 d (1H, CHOH, J 8.5 Hz),
7.2–7.4 m (5H, Ph), 8.29 s (1H, CH=N).
Methyl (3,5-bis[4-(1R,2S)-(2-hydroxy-1-methyl-
2-phenylethylaminomethyl)-2,3,5,6-tetrafluoro-
phenyloxy])benzoate (XI). At reducing 0.41 g
(0.52 mmol) of Schiff base IX with 50 mg (1.24 mmol)
1-Phenyl-2-(perfluorophenylmethylamino)-
propanol (VI). To a solution of 1.26 g (3.8 mmol) of
compound III in 15 ml of MeOH was gradually added
under constant stirring at 0°C 0.14 g (3.8 mmol) of sodium
borohydride. The reaction mixture was stirred in these
conditions for 1 h (TLC monitoring). Then the solvent
was evaporated in a vacuum, the residue was dissolved
in ethyl acetate and washed with water (2×20 ml). The
organic layer was dried with MgSO4, concentrated, the
residue was recrystallized from a mixture hexane–ethyl
acetate. Yield 1.1 g (61%), mp 115.5–116°C. 1H NMR
spectrum (toluene-d8), δ, ppm: 0.91 d (3H, CH3, J 6.7 Hz),
2.79 m (1H, CHCH3), 3.66 s (2H, CH2), 4.76 d (1H,
CHOH, J 7.5 Hz), 7.37–7.48 m (5H, Ph). 19F NMR
spectrum (toluene-d8), δ, ppm: –68.86 m (2F, C6F5),
–79.70 m (1F, C6F5), –86.19...–86.47 m (2F, C6F5). Found,
%: C 58.01; H 4.23; N 4.46. C16H14F5NO. Calculated,
%: C 58.21; H 4.32; N 4.29.
1
of sodium borohydride yield 0.37 g (90%). H NMR
spectrum (toluene-d8), δ, ppm: 1.02 d (6H, CH3, J 6 Hz),
2.86 m (2H, CHCH3), 3.5–3.7 m (4H, CH2), 3.85 s (3H,
CH3O), 4.84 d (2H, CHOH, J 7.5 Hz), 5.96 s (1H, C6H3),
6.36 m (2H, C6H3), 7.19–7.28 m (10H, Ph). 19F NMR
spectrum (toluene-d8), ppm: –63.87...–63.99 m (4F, C6F4),
–75.82...–76.20 m (4F, C6F4). Found, %: C 60.64; H 4.46;
F 19.28; N 3.59. C40H34F8N2O6. Calculated, %: C 60.75;
H 4.34; F 19.22; N 3.54.
1,3,5-Tris[4-(1R,2S)-(2-hydroxy-1-methyl-2-
phenylethyliminomethyl)benzyloxycarbonyl]benzene
(XII) was obtained by method b from 562 mg (1 mmol)
of D0-CHO and 454 mg (3 mmol)of (+)-norephedrine in
50 ml of chloroform. Yield 945 mg (98%), mp 84–85°C
(hexane–benzene), [α]D21 –29° (C 0.842, DMF). 1H NMR
spectrum of predominant open form (CDCl3), δ, ppm:
1.15 d (9H, CH3, J 6.5 Hz), 3.63 m (3H, CHCH3), 4.82 d
(3H, CHOH, J 5.9 Hz), 5.41 s (6H, CH2), 7.2–7.4 m
(15H, Ph), 7.48 d (6H, C6H4, J 7.9 Hz) and 7.72 d (6H,
C6H4, J 7.9 Hz), 8.27 s (3H, CH=N), 8.88 s (3H, C6H3).
Mass spectrum, m/z: 965 [M + 2H]+, 831 [M + 2H
– C9H10O]+. Found, %: C 74.65; H 6.19; N 4.41.
C60H57N3O9. Calculated, %: C 74.75; H 5.99; N 4.36.
Methyl (3,5-bis[4-(2-hydroxy-2-phenyl-1-
methylethyliminomethyl)-2,3,5,6-tetrafluoro-
phenyloxy])benzoate (IX) was obtained from 1.6 g (3.1
mmol) of dialdehyde VII and 0.94 g (6.2 mmol) of (+)-
norephedrine in 50 ml toluene by method b. Yield 2.4 g
(>99%), mp 65.5–66°C. 1H NMR spectrum of imine
form (toluene-d8), δ, ppm: 1.27 d (6H, CH3, J 6.6 Hz),
3.68 m (2H, CHCH3), 3.83 s (3H, CH3O), 4.74 d (2H,
CHOH, J 8.6 Hz), 5.82 m (1H, C6H3), 6.35 m (2H, C6H3),
7.19–7.36 m (10H, Ph), 8.31 s (2H, CH=N). 19 F NMR
spectrum (toluene-d8), δ, ppm: –63.81÷–63.99 m (4F,
C6F4), –75.82÷–76.24 m (4F, C6F4). Found, %: C 60.97;
H 3.86; F 19.32; N 3.52. C40H30F8N2O6. Calculated, %:
C 61.07; H 3.84; F 19.32; N 3.56.
Yield of compound XII by method a from 0.78 g of
D0-CHO and 0.6 g of (+)-norephedrine 1.4 g (98%).
1,3,5-Tris[4-(4S,5S)-(3,4-dimethyl-5-phenyl-1,3-
oxazolidin-2-yl)benzyloxycarbonyl]benzene (XIII)
was obtained by method b from 564 mg (1 mmol) of D0-
CHO and 496 mg (3 mmol) of (+)-pseudoephedrine in
50 ml of chloroform. Yield 987 mg (99%), mp 79–80°C
(hexane–benzene), [α]D21 –107° (C 0.836, DMF).
1H NMR spectrum (CDCl3), δ, ppm: 0.79 d (9H, CH3CH,
J 6.4 Hz), 2.19 s (9H, NCH3), 2.98 m (3H, CHCH3),
4.71 s (3H, NCHO), 5.15 d (3H, CHPh, J 7.7 Hz), 5.44 s
(6H, OCH2), 7.20–7.40 m (15H, Ph), 7.52 d (6H, C6H4,
J 8 Hz), 7.68 d (6H, C6H4, J 8 Hz), 8.92 s (3H, C6H3).
13C NMR spectrum (CDCl3), δ, ppm: 14.45 (CH3), 35.27
(NCH3), 67.19 (CH2), 68.82 (CHN), 86.60 (CHO), 99.19
(NCHO), 136.33–126.72 (Ph), 161.79 (CO). Mass
spectrum, m/z: 1005 [M]+, 898 [M – PhCHOH]+, 857
[M – C10H14N]+. Found, %: C 75.16; H 6.21; N 4.20.
C63H63N3O9. Calculated, %: C 75.20; H 6.31; N 4.18.
Yield by method a 1.12 g (98%).
Methyl (3,5-bis[4-(1R,2S)-(2-hydroxy-1-methyl-
2-phenylethyliminomethyl)benzyloxy])benzoate (X)
was obtained from 0.25 g (0.62 mmol) of compound VIII
and 0.2 g (1.25 mmol) of (+)-norephedrine by method b.
Yield 0.44 g (99%). 1H NMR spectrum of the open imine
form (toluene-d8), δ, ppm: 1.22 d (6H, CH3, J 6.4 Hz),
3.65 m (2H, CHCH3), 3.84 s (3H, CH3OC), 4.45 d (2H,
CHOH, J 8.1 Hz), 5.17 s (4H, OCH2), 6.95 m (1H,
C6H3), 7.14 m (2H, C6H3), 7.23–7.35 m (10H, Ph), 7.51–
7.70 m (8H, C6H4), 8.16 s (2H, CH=N). Found, %:
C 75.38; H 6.04; N 3.98. C42H42N2O6. Calculated, %:
C 75.22; H 6.29; N 4.17.
Yield of compound X obtained by method a from
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KELBYSHEVA et al.
266
Yield of compound XIII in the solid-phase synthesis
by method a from 578 mg of D0-CHO and 509 mg of
(+)-pseudoephedrine 1.09 g (>98%).
b from 398 mg (0.3 mmol) of D1-CHO and 296 mg
(1.83 mmol) of (+)-pseudoephedrine in 50 ml of
chloroform. Yield 650 mg (99%), mp 108–109°C
(hexane–benzene), [α]D21 –14.0° (C 0.678, DMF).
1H NMR spectrum (CDCl3), δ, ppm: 1.20 d (18H, CH3,
J 6.3 Hz), 2.15 s (18H, NCH3), 2.48 m (6H, CHCH3),
4.75 d (6H, CHPh, J 8.3 Hz), 4.92 s (6H, NCHO), 5.01
s (12H, OCH2), 5.27 s (6H, COOCH2), 6.55 br.s (3H,
C6H3), 6.63 br.s (6H, C6H3), 7.20–7.43 m (30H, Ph and
12H, C6H4), 7.55 d (12H, C6H4, J 8 Hz), 8.90 s (3H,
C6H3). Mass spectrum, m/z: 2166 [M – H]+, 2060 [M –
PhCHOH]+, 2019 [M – C10H14N]+. Found, %: C 76.27;
H 6.39; N 3.97. C138H138N6O18. Calculated, %: C 76.42;
H 6.37; N 3.87.
1,3,5-Tris[(S,S)-4-(1-hydroxymethyl-2-methyl-
butyliminomethyl)benzyloxycarbonyl]benzene
(XIV) was obtained by method c from 1 g (1.8 mmol) of
D0-CHO and 0.67 g (5.7 mmol) of (+)-(2S,3S)-isoleucinol
in 25 ml of anhydrous ethanol in the presence of 3 g of
anhydrous Na2SO4. Yield 1.54 g (98%), mp 69–70°C
(hexane–benzene), [α]D21 24° (c 0.804, benzene). 1H
NMR spectrum of main isomer (CDCl3), δ, ppm: 0.86–
0.97 m (18H, CH3), 1.15 m (3H, CH2CH3), 1.26 m (3H,
CH2CH3), 1.72 m [3H, CH(Mε)Et], 2.93 m (3H, CHN),
3.94 m (3H, CH2OH), 4.1 m (3H, CH2OH), 5.42 s (6H,
CH2C6H4), 7.45 d and 7.78 d (12H, C6H4, J 7.7 Hz),
8.25 s (3H, CH=N), 8.88 s (3H, C6H3). Mass spectrum,
m/z: 863 [M + 2H]+, 763 [M + 2H – C6H12O]+. Found,
%: C 71.36; H 7.27; N 5.04. C51H63N3O9. Calculated,
%: C 71.05; H 7.37; N 4.87.
1,3,5-Tris(3,5-bis{4-[1-(S)-hydroxymethylpropyl-
imino]benzyloxy}benzyloxycarbonyl)benzene
(XVIII) was obtained by method c from 642 mg
(0.5 mmol) of D1-CHO and 267 mg (3 mmol) of (S)-2-
aminobutanol in 35 ml of anhydrous ethanol in the
presence of 5 g of anhydrous sodium sulfate. Yield 0.84 g
(98%), mp 142–143°C (hexane–benzene), [α]D21 2.4°
1,3,5-Tris[4-(S)-(1-hydroxymethylpropyl-
imino)benzyloxycarbonyl]benzene (XV) was obtained
by method b from 564 mg (1 mmol) of D0-CHO and
269 mg (3 mmol) of (+)-(S)-2-aminobutanol in 50 ml of
chloroform. Yield 767 mg (98%), mp 119–120°C
1
(C 0.829, DMF). H NMR spectrum of main isomer
(CDCl3), δ, ppm: 0.85 br.t (18H, CH3), 1.15 m (6H,
CH2Me), 1.40 m (6H, CH2Me), 1.73 m (6H, CHN), 3.8–
4.1 m (12H, CH2OH), 5.01 s (12H, OCH2), 5.30 s (6H,
COOCH2), 6.55 s (3H, C6H3), 6.68 m (6H, C6H3), 7.28–
7.63 m (12H, C6H4), 8.51 br.s (6H, CH=N), 9.0 s (3H,
C6H3). Mass spectrum, m/z: 1712 [M + H]+, 1640 [M –
C4H8O]+. Found, %: C 71.48; H 6.60; N 4.79.
C103H114N6O21× H2CO3. Calculated, %: C 71.56; H 6.71;
N 4.91.
(hexane–benzene), [α]D21 18° (C 0.752, DMF). H NMR
1
spectrum of main isomer (CDCl3), δ, ppm: 0.92 br.s (9H,
CH3), 1.28 m (6H, CH2CH3), 1.69 m (3H, CHN), 3.73 m
(6H, CH2OH), 5.48 s (6H, CH2), 7.51–7.81 m (12H,
C6H4), 8.45 s (3H, CH=N), 8.94 s (3H, C6H3). Mass
spectrum, m/z: 779 [M + 2H]+, 707 [M + 2H – C4H8O]+.
Found, %: C 69.36; H 6.67; N 5.41. C45H51N3O9.
Calculated, %: C 69.48; H 6.61; N 5.40.
1,3,5-Tris[4-(1R,2S)-(2-hydroxy-1-methyl-2-
phenylethylaminomethyl)benzyloxycarbonyl]benzene
(XIX). To a dispersion of 3 g of anhydrous sodium sulfate
in 25 ml of anhydrous EtOH was added 566 mg (1 mmol)
of D0-CHO and 456 mg (3 mmol) of (+)-norephedrine,
and the mixture was boiled for 2 h. Then the reaction
mixture was cooled to 0°C, and 40 mg (10 mmol) of
NaBH4 was added by portions, the mixture was
additionally stirred for 1 h and diluted with 100 ml of cold
water. The reaction products were extracted into AcOEt,
the extract was dried with Na2SO4. on filtering the solvent
was removed in a vacuum, the residue was crystallized
from a mixture hexane–benzene. Yield 941 mg (96%),
mp 70–72°C (hexane–benzene), [α]D21 –33° (C 0.880,
1,3,5-Tris{3,5-bis[4-(1R,2S)-(2-hydroxy-1-
methyl-2-phenylethylimino)benzyloxy]benzyl-
oxycarbonyl}benzene (XVI) was obtained by method
b from 797 mg (0.62 mmol) of D1-CHO and 562 mg
(3.72 mmol) of (+)-norephedrine in 50 ml of chloroform.
Yield 1.29 g (98%), mp 111–112°C (hexane–benzene),
[α]D21 2.0° (C 1.61, DMF). 1H NMR spectrum of imine
form (CDCl3), δ, ppm: 1.20 d (18H, CH3, J 7.6 Hz),
2.58 m (6H, CHCH3), 4.77 d (6H, CHOH, J 7.6 Hz),
5.00 s (12H, OCH2), 5.31 s (6H, COOCH2), 6.53 s (3H,
C6H3), 6.66 m (6H, C6H3), 7.23–7.32 m (30H, Ph), 7.36–
7.63 m (24H, C6H4), 8.17 s (6H, CH=N), 8.88 s (3H,
C6H3). Found, %: C 75.98; H 6.32; N 4.12.
C132H126N6O18. Calculated, %: C 76.05; H 6.10; N 4.03.
1
DMF). H NMR spectrum (CDCl3), δ, ppm: 1.09 d (9H,
CH3, J 6.2 Hz), 2.45 m (3H, CHCH3), 4.66 d (3H,
CHOH, J 7.9 Hz), 4.82 br.s (6H, CH2N), 5.35 s (6H,
CH2), 7.27–7.34 m (15H, Ph), 7.36 d (6H, C6H4,
1,3,5-Tris{3,5-bis[4-(4S,5S)-(3,4-dimethyl-5-
phenyl-1,3-oxazolidin-2-yl)benzyloxy]benzyl-
oxycarbonyl}benzene (XVII) was obtained by method
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

CHIRAL MODIFICATION OF POLYFORMYL COMPOUNDS OF DENDRITE TYPE
267
vol. 30, p. 385.
J 7.9 Hz), 7.62 d (6H, C6H4, J 7.9 Hz), 8.84 s (3H, C6H3).
Found, %: C 74.15; H 6.19; N 4.18. C60H63N3O9.
Calculated, %: C 74.28; H 6.55; N 4.33.
7. Astruc, D. and Chardac, F. Chem. Rev., 2001, vol. 101,
p. 2991.
8. Mery, D. andAstruc, D., Coord. Chem. Rev., 2006, vol. 250,
p. 1965.
9. Kabir, A., Hamlet, C., Newkome, G.R., Yoo, K.S., and
Malic,A., J. Chromatography, A, 2004, vol. 1034, p. 1.
10. Breslow, R., Wei, S., and Kenesky, C., Tetrahedron, 2007,
vol. 63, p. 6317.
11. Peerlings, H.W.I., Struijk, M.P., and Meijer, E.W., Chirality,
1998, vol. 10, p. 46.
12. Seebach, D., Rheiner, P. B., Greiveldinger, G., Butz, T., and
Sellner, H., Top. Curr. Chem., 1998, vol. 197, p. 125.
13. Pugh, V.J., Hu, Q.-S., and Pu, L., Angew Chem., Int. Ed.,
2000, vol. 39, p. 3638.
14. Kluger, R. and Zhang, J., J. Am. Chem. Soc., 2003, vol. 125,
p. 6070.
15. Yamagata, M., Kawano, T., Shiba, K., Mori, T., Kataya-
ma, Y., and Niidome, T., Bioorg. Med. Chem. Lett., 2007,
vol. 15, p. 526.
16. Haba, K., Popkov, M., Shamis, M., Lerner, R.A., Bar-
bas, III, C.F., and Shabat, D., Angew. Chem., Int. Ed., 2005,
vol. 44, p. 716.
17. Kollner, C. and Togni, A., Canad. J. Chem., 2001, vol. 79,
p. 1762.
18. Imbos, R., Minnaard,A.J., and Feringa, B.L., J. Chem. Soc.,
Dalton, Trans., 2003, p. 2017.
19. Breinbauer, R. and Jacobsen, E.N., Angew Chem., Int. Ed.,
2000, vol. 41, p. 3123.
20. Tang, W.J., Huang, Y.-Y., He, Y.-M., and Fan, Q.H.,
Tetrahedron Asymmetry, 2006, vol. 17, p. 536.
21. Maraval, V., Pyzowski, J., Caminade, A.-M., and Majo-
ral, J.-P., J. Org. Chem., 2003, vol. 68, p. 6043.
22. Laurent, R., Caminade, A.-M., and Majoral, J.-P.,
Tetrahedron Lett., 2005, vol. 46, p. 6503.
23. Loim, N.M. and Kelbysheva, E.S., Izv. Akad. Nauk, Ser.
Khim., 2004, p. 1995.
1,3,5-Tris[(S,S)-4-(1-hydroxymethyl-2-methyl-
butylaminomethyl)benzyloxycarbonyl]benzene (XX)
was obtained similarly from 1.2 g (1.8 mmol) of D0-
CHO and 0.67 g (5.7 mmol) of (2S,3S)-isoleucinol in 25 ml
of anhydrous ethanol in the presence of 3 g of anhydrous
sodium sulfate. Yield 1.51 g (96%), mp 61–62°C (hexane–
benzene), [α]D21 12° (c 0.784, benzene). H NMR
1
spectrum (CDCl3), δ, ppm: 0.92 t (9H, CH3, J 6.3Hz),
1.05 d (9H, CH3, J 7 Hz), 1.42 m (6H, CH2CH3), 1.92 m
[3H, CH(Mε)Et], 2.83 m (3H, CHN), 3.4 m (3H,
CH2OH), 3.86 m (3H, CH2OH), 4.80 br.s (6H, CH2N),
5.50 s (6H, CH2C6H4), 7.53–7.66 m (12H, C6H4), 8.90 s
(3H, C6H3). Found, %: C 68.97; H 8.00; N 4.52.
C51H69N3O9·H2O. Calculated, %: C 69.13; H 8.08;
N 4.74.
The study was carried out under a financial support
of the Program of Fundamental Research of the
Presidium of the Russian Academy of Sciences
“Development of methods of chemical compounds
preparation and creation of new materials” P-18.
REFERENCES
1. Soto-Castro, D., Evangelisya-Lara, A., and, Guadarra-
ma, P., Tetrahedron, 2006, vol. 62, p. 12116.
2. Gao, C. andYan, D. Prog. Polym. Sci., 2004, vol. 29, p. 183.
3. Beletskaya, I.P. and Chuchuryukin,A.V., Usp. Khim., 2000,
vol. 69, p. 699.
4. Sharma,A., Desai,A.,Ali, R., andTomalia, D., J. Chromato-
graphy. A., 2005, vol. 1081, p. 238.
5. Bystrova,A.V., Parshina, E.V., Tatarinova, E.A., Buzin, M.I.,
Ozerina, P.A., Ozerin, A.N., and Muzafarov, A.M., Ros.
Nanotekhnologii, 2007, vol. 2, p. 83.
6. Liang, C. and Frechet, J.M.J.. Prog. Polym. Sci., 2005,
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