Reactions of glycosylamines with diphenylphosphine oxide and ethyl and phenyl phenylphosphinates

Article abstract of DOI:10.1134/S1070428008080071

A novel procedure has been proposed for the synthesis of chiral α-aminophosphoryl compounds from glycosylamines and PH compounds (diphenylphosphine oxide and ethyl and phenyl phenylphosphonates) under mild conditions. The reaction is accompanied by dehydration of the carbohydrate moiety in unprotected monosaccharides to form furan ring.

Full text of DOI:10.1134/S1070428008080071

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 8, pp. 1150–1156. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © A.A. Bobrikova, M.P. Koroteev, A.I. Stash, V.K. Bel’skii, E.E. Nifant’ev, 2008, published in Zhurnal Organicheskoi Khimii, 2008,
Vol. 44, No. 8, pp. 1164–1170.
Reactions of Glycosylamines with Diphenylphosphine Oxide and
Ethyl and Phenyl Phenylphosphinates
A. A. Bobrikovaa, M. P. Koroteeva, A. I. Stashb, V. K. Bel’skiib, and E. E. Nifant’eva
a Moscow State Pedagogical University, Nesvizhskii per. 3, Moscow, 119021 Russia
e-mail: nastenka-bobrik@yandex.ru
b Karpov Research Physicochemical Institute, Moscow, Russia
Received September 26, 2007
Abstract—A novel procedure has been proposed for the synthesis of chiral α-aminophosphoryl compounds
from glycosylamines and PH compounds (diphenylphosphine oxide and ethyl and phenyl phenylphosphonates)
under mild conditions. The reaction is accompanied by dehydration of the carbohydrate moiety in unprotected
monosaccharides to form furan ring.
DOI: 10.1134/S1070428008080071
The Kabachnik–Fields reaction provides a conven-
ient method for the synthesis of α-aminophosphoryl
compounds that attract interest due to diversity of their
useful properties, including broad spectrum of biolog-
ical activity. Some α-aminophosphoryl derivatives
were shown to act as antibacterial and antiviral agents,
antibiotics, enzyme inhibitors, pesticides, and plant
growth regulators [1].
In the first step of our study, diphenylphosphine
oxide (II) [3] was brought into reactions with
N-(β-D-pentopyranosyl)anilines Ia–Id. As a result, we
obtained N-[(2-furyl)(diphenylphosphoryl)methyl]ani-
line (III) (Scheme 1). N-(β-D-Hexopyranosyl)anilines
IVa–IVc reacted with compound II to give analogous
substituted furan V having a hydroxymethyl group in
the α-position of the furan ring. Presumably, the re-
action involves ring–chain tautomeric transformation
of pyranosylamines I and IV into imino forms A and B
[4] which take up diphenylphosphine oxide to give
adducts C and D, respectively. This step corresponds
to a version of the Kabachnik–Fields reaction [5–7].
Dehydration of adducts C and D leads to stable furan
structures III and V (Scheme 2). It should be em-
phasized that the dehydration of the carbohydrate
moiety occurs under mild conditions (at a temperature
of 25 to 55°C) in 3.5–4 h. The proposed mechanism is
supported by experiments with N-(2,3:5,6-di-O-alkyli-
Nowadays development of new procedures for the
synthesis of α-aminophosphoryl compounds, specifi-
cally from naturally occurring materials such as sugars,
steroids, amino acids, etc., remains an important prob-
lem. N-Glycosides occupy a specific place among car-
bohydrate derivatives capable of being involved in the
Kabachnik–Fields reaction. They are structural frag-
ments of biomolecules and some medicines [2]. With
a view to combine N-glycoside and phosphoryl frag-
ments in a single molecule we examined reactions of
glycosylamines with PH-containing compounds.
Scheme 1.
R7
R5
R6
NHPh
Ph
Ph
O
DMF, pyridine
R3 R1
P
+
Ph2P(O)H
O
R7
O
NHPh
R4 R2
Ia–Id, IVa–IVc
II
III, V
I, R1 = R4 = R5 =H, R2 = R3 = R6 = OH (a); R1 = R3 = R5 = H, R2 = R4 = R6 = OH (b); R2 = R3 = R5 = H, R1 = R4 = R6 = OH (c);
R2 = R4 = R5 = H, R1 = R3 = R6 = OH (d); IV, R1 = R4 = R5 = H, R2 = R3 = R6 = OH (a); R1 = R4 = R6 = H, R2 = R3 = R5 = OH (b);
R2 = R4 = R5 = H, R1 = R3 = R6 = OH (c); I, III, R7 = H; IV, V, R7 = CH2OH.
1150

REACTIONS OF GLYCOSYLAMINES WITH DIPHENYLPHOSPHINE OXIDE
1151
Scheme 2.
O
Ph
Ph
P
NHPh
NPh
Ph2P(O)H
(
)
(
)
n
H
OH
H
OH
OH
n
I, IV
III, V
–3H2O
OH
A, B
C, D
A, C, n = 3; B, D, n = 4.
Scheme 3.
O
O
Ph
Ph
Ph
H
H
N
P
N
P
R'
X
Ph
R'
H
O
H
HO
H
NHR'
H
CHCl3, pyridine
60°C, 23–27 h
O
O
H+, H2O
O
O
H
H
H
HO
H
H
O
O
+
Ph2P(O)H
X
X
OH
O
OH
OH
H
H
H
H
H2C
X
CH2OH
O
VI–VIII
II
IXa–IXc
X
VI, VII, X = isopropylidene; VIII, X = cyclohexylidene; VI, VIII, R′ = Ph; VII, R′ = naphthyl.
dene-β-D-mannofuranosyl)anilines (Scheme 3). Hy-
drolysis of adducts IXa–IXc obtained from com-
pounds VI–VIII and diphenylphosphine oxide (II)
gave 1-deoxy-1-diphenylphosphoryl-1-phenylamino-
D-mannite (X) which can be either isolated as indi-
vidual substance or subjected to dehydration. The
dehydration product of X was identical to substituted
furan V.
ditions, reactions of N-glycosides Ia–Id, IVa–IVc, and
VI–VIII with readily accessible stable ethyl and
phenyl phenylphosphinates XI and XII led to the
formation of compounds XIIIa–XIIId and XIVa–
XIVd. When the reaction was complete, the 31P NMR
spectra of the reaction mixtures contained three sig-
nals, two of which (δP 36–38 ppm) corresponded to the
major products. The third minor signal (δP 11 ppm) in-
dicated partial decomposition of phosphinic acid ester
during the process with formation of free phenylphos-
phinic acid which failed to react with glycosylamines
(presumably because of insufficient electron density on
the phosphorus atom). The presence of two downfield
signals in the 31P NMR spectra is related to chirality of
The structure of the isolated compounds was con-
firmed by polarimetry, NMR spectroscopy, and X-ray
analysis. The products obtained from D-xylose and
D-ribose derivatives were identical to each other
(mp 238–240°C, [α]D20 = 0.0, c = 0.5, DMSO) and were
racemates (Fig. 1). The compounds obtained from
D-arabinose and D-lyxose derivatives were individual
dextrorotatory enantiomers (Fig. 2) having S-config-
uration of the chiral carbon atom (mp 248–250°C,
[α]D20 = +36.4°, c = 0.5, DMSO). We believe that the
above results are determined by the monosaccharide
nature. Insofar as glycosylamines containing D-xylose
or D-ribose differ from those derived from D-arabinose
or D-lyxose by the position of hydroxy group on C2,
just its orientation is likely to be responsible for the
observed stereochemical effect.
O
Ph
H
N
P
R
X
R'
O
H
R'
Ph
O
H
H
H
P
O
R
OH
O
O
NHPh
H2C
X
O
XIIIa–XIIId
XIVa–XIVd
To develop studies in this line, we tried to extend
the proposed approach to another class of PH com-
pounds, phosphinic acid esters. Under analogous con-
XIII, R = H (a, c), HOCH2 (b, d); R′ = OEt (a, b), OPh (c, d);
XIV, X = isopropylidene (a, b, d), cyclohexylidene (c); R =
Ph (a, c), 2-naphthyl (b, d); R′ = OEt (a, b), OPh (c, d).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

BOBRIKOVA et al.
1152
a
0
c
b
Fig. 1. Structure of the molecule and crystal packing of N-[(diphenylphosphoryl)(2-furyl)methyl]aniline (III) obtained from D-xylose
or D-ribose. Different enantiomers are shown; a unit cell contains four molecules III.
C23
C22
O2
a
0
C21
c
C3
C20
C13
C2
C18
C17
C16
C19
C14
O1
C1
C4
C15
C6
N
C5
P
C7
C12
C11
C8
C9
C10
b
Fig. 2. Structure of the molecule and crystal packing of N-[(diphenylphosphoryl)(2-furyl)methyl]aniline (III) obtained from
D-arabinose or D-lyxose. Only one stereoisomer is present; a unit cell contains three molecules III.
the phosphorus atom in the resulting phosphinates. The
major products were characterized by similar chro-
matographic mobilities and were isolated as mixtures
of stereoisomers by column chromatography on silica
gel (benzene–dioxane, 1:3) in 30–35% yield. Their
tra two signals in the region δP 36–38 ppm, and the
difference in the phosphorus chemical shifts for stereo-
1
isomers was ΔδP = 0.3–0.4 ppm. In the H NMR
spectra of XIIIa–XIIId, protons at the carbon atom
attached to phosphorus give rise to two multiplets at
δ 4.19–5.38 ppm due to the presence of geminal chiral
1
structure was confirmed by the H, 13C, and 31P NMR
2
spectra and elemental analyses. Compounds XIIIa–
centers (S*,R*), the coupling constant JHP being 17–
XIIId and XIVa–XIVd showed in the 31P NMR spec-
18 Hz. Signals from the other protons are somewhat
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

REACTIONS OF GLYCOSYLAMINES WITH DIPHENYLPHOSPHINE OXIDE
1153
Parameters of X-ray diffraction experiments and principal
crystallographic data for compound III
broadened and are characterized by double relative
intensity.
To conclude, we have developed a novel method
for the synthesis of chiral α-aminophosphoryl com-
pounds on the basis of glycosylamines and prepared
a series of new phosphinates and tertiary phosphine
oxides, including those containing a carbohydrate resi-
due. The products attract interest as potential biolog-
ically active substances, as well as ligands for metal-
complex catalysis. Our results extend the interdis-
ciplinary research area implying the use of tervalent
phosphorus reagents in the chemistry of carbohydrates
and other natural compounds.
Parameter
Formula
From Ia or Ib From Ic or Id
C23H20NO2P
373.37
293
C23H20NO2P
373.37
293
M
Temperature, K
a, Å
05.777(1)
16.421(3)
20.215(4)
90.91(3)
1917.4(6)
1.293
05.774(1)
16.471(3)
20.176(4)
90
b, Å
c, Å
β, deg
V, Å3
1918.8(6)
1.480
d
calc, g/cm3
Crystal system
Space group
N
Monoclinic
P21/c
Orthorhombic
P212121
4
EXPERIMENTAL*
The 31P NMR spectra of compounds III, V, and
IXa–IXc were recorded on a Bruker WP-80 spectrom-
eter at 32.4 MHz, and the 31P NMR spectra of XIIIa–
XIIId and XIVa–XIVd were measured on a Bruker
Avance-400 instrument at 161.98 MHz; the chemical
shifts were determined relative to 85% H3PO4 as ex-
4
F(000)
784
904
Scan mode
ω/2Θ
ω/2Θ
Total number of
reflections
3783
2001
Number of independent
reflections (Rint)
3417
(0.0276)
2001
(0.0)
1
ternal reference. The H NMR spectra were recorded
on a Bruker H-250 spectrometer (250 MHz) relative to
tetramethylsilane as internal reference. The 13C NMR
spectra were obtained on a Bruker AC-200 spectrom-
eter at 50 MHz using tetramethylsilane as internal
reference. Thin-layer chromatography was performed
on Silufol UV-254 plates; spots were detected by cal-
cination. Silica gel L 40–100 μm was used for column
chromatography (10 mm i.d.; benzene–dioxane, 1:3).
The optical rotations were measured on a Jasco DIP-
360 polarimeter. The elemental compositions were
determined on a Perkin–Elmer 2400 analyzer. X-Ray
analysis was performed on an Enraf–Nonius CAD 4
diffractometer (see table).
Number of refined
parameters
0325
0245
Absorption coefficient,
cm–1
1.6100
1.8200
R1 [I > 2σ(I)]
0.0421
0.1271
0.0260
0.0609
wR2
4J5,3 = 1.2 Hz); aniline fragment: 6.56 t (1H, 4-H,
3J4,3 = 7.3 Hz), 6.92 d (2H, 2-H, 6-H, J2,3 = 7.3 Hz),
3
3
7.01 d.d (2H, 3-H, 5-H, J5,4 = 7.0 Hz); diphenylphos-
phoryl fragment: 7.4–7.5 m (6H, 3-H, 4-H, 5-H), 7.80–
7.98 m (4H, 2-H, 6-H). 13C NMR spectrum
1
(DMSO-d6), δC, ppm: 50.3 d (NCHP, JCP = 81.6 Hz);
Phosphine oxides III and V (general procedure).
A mixture of 5 mmol of compound Ia–Id or IVa–IVc
and 5 mmol of diphenylphosphine oxide (II) in 5 ml of
DMF and 1 ml of pyridine was stirred under argon for
3.5–4 h at 25°C (III) or 55°C (V). The solvent was
removed under reduced pressure, and the residue was
purified by chromatography on silica gel.
furan fragment: 109.5 d (C3, 3JCP = 5.0 Hz), 110.4 (C4),
142.4 (C5), 149.9 (C2); aniline fragment: 113.9 (C2,
C6), 117.5 (C4), 128.6 (C3, C5), 147.1 d (C1, JCP
=
3
10.9 Hz); diphenylphosphoryl fragment: 128.1–128.4 m
(C3, C5), 130.3–133.2 m (C1, C4, C2, C6). 31P NMR
spectrum (DMSO-d6): δP 29.1 ppm. Found, %: C 74.08,
74.06; H 5.45, 5.44; N 3.62, 3.65; P 8.52, 8.51.
C23H20NO2P. Calculated, %: C 73.99; H 5.36; N 3.75;
P 8.32.
N-[(Diphenylphosphoryl)(2-furyl)methyl]aniline
1
(III). Yield 40–45%, Rf 0.64. H NMR spectrum
(DMSO-d6), δ, ppm: 6.00 m (2H, NCHP, NH); furan
{5-[(Diphenylphosphoryl)(phenylamino)methyl]-
3
fragment: 6.21 m (1H, 4-H, J4,3 = 3.0 Hz), 6.30 m
furan-2-yl}methanol (V). Yield 38–45%, Rf 0.70,
3
4
(1H, 3-H, J3,4 = 3.0, JHP = 2.7 Hz), 7.37 m (1H, 5-H,
1
mp 179–181°C. H NMR spectrum (DMSO-d6), δ,
ppm: 5.97–6.04 m (3H, NCHP, NH, 4′-H); furan
* Some experiments were performed with participation of
S.V. Metlitskikh.
3
fragment: 4.11 m (2H, CH2), 5.07 t (1H, OH, JHH
=
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

BOBRIKOVA et al.
1154
6.0 Hz), 6.28 m (1H, 3′-H); aniline fragment: 6.57 t
C36H43NO6P. Calculated, %: C 70.02; H 7.13; N 2.27;
P 5.02.
3
3
(1H, 4-H, J4,3 = 6.4 Hz), 6.93 d (2H, 2-H, 6-H, J2,3
7.6 Hz), 7.02 d.d (2H, 3-H, 5-H, J5,4 = 7.2 Hz);
=
3
1-Deoxy-1-diphenylphosphoryl-2,3:5,6-di-O-iso-
propylidene-1-(2-naphthylamino)-D-mannite (IXc).
Yield 53%, oily substance, Rf 0.73. 13C NMR spectrum
(DMSO-d6), δC, ppm: carbohydrate fragment: 25.8–
diphenylphosphoryl fragment: 7.43–7.50 m (6H, 3-H,
4-H, 5-H), 7.77–8.01 m (4H, 2-H, 6-H). 13C NMR
1
spectrum (DMSO-d6), δC, ppm: 50.2 d (NCHP, JCP
=
82.2 Hz); furan fragment: 55.3 (CH2), 107.3 (C3′),
1
27.6 m (CH3), 55.4 d (C1, JCP = 77.5 Hz), 66.2 (C6),
109.9 d (C4′, JCP = 5.0 Hz), 148.7 (C5′), 154.6 (C2′);
4
3
69.4 (C4), 75.1 d (C3, JCP = 5.3 Hz), 76.1 (C5), 80.0 d
aniline fragment: 113.7 (C2, C6), 117.2 (C4), 128.6 (C3,
2
(C2, JCP = 8.4 Hz), 108.4 (O2CO3), 108.9 (O5CO6);
C5), 146.8 d (C1, JCP = 11.3 Hz); diphenylphosphoryl
3
naphthalene fragment: 105.6 (C1), 118.8 (C3), 122.1
(C6), 125.8 (C8), 126.2 (C7), 127.3 (C5), 127.5 (C10),
fragment: 127.8–128.5 m (C3, C5), 130.6–132.4 m
(C1, C4, C2, C6). 31P NMR spectrum (DMSO-d6):
δP 29.2 ppm. Found, %: C 71.78, 71.75; H 5.49, 5.51;
N 3.68, 3.69; P 7.73, 7.48. C24H22NO3P. Calculated, %:
C 71.47; H 5.46; N 3.47; P 7.69.
3
128.8 (C4), 134.6 (C9), 145.0 d (C2, JCP = 9.8 Hz);
diphenylphosphoryl fragment: 128.3–128.6 m (C3, C5),
130.4–133.1 m (C1, C4, C2, C6). 31P NMR spectrum
(DMSO-d6): δP 33.7 ppm. Found, %: C 69.70, 69.67;
H 6.57, 6.54; N 2.14, 2.19; P 5.45, 5.51. C34H38NO6P.
Calculated, %: C 69.51; H 6.47; N 2.39; P 5.28.
Phosphine oxides IXa–IXc (general procedure).
A solution of 5 mmol of compound VI–VIII and
5 mmol of phosphine oxide II in a mixture of 5 ml of
chloroform and 3 ml of pyridine was stirred for 23–
27 h at 60°C under argon. The solvent was removed
under reduced pressure, and the residue was purified
by chromatography on silica gel.
Phosphinates XIIIa–XIIId (general procedure).
A solution of 1.2 mmol of compound Ia–Id or IVa–
IVc and 1.2 mmol of ethyl or phenyl phenylphos-
phinate XI or XII in 2.5 ml of DMF was stirred for
3.5–4 h at 65°C under argon. The solvent was removed
under reduced pressure, the residue was dissolved in
15 ml of ethanol, 5 g of activated charcoal was added,
the mixture was heated under reflux until clarification
and filtered, the filtrate was concentrated, and the resi-
due was purified by chromatography on silica gel.
1-Deoxy-1-diphenylphosphoryl-2,3:5,6-di-O-iso-
propylidene-1-phenylamino-D-mannite (IXa). Yield
50%, oily substance, Rf 0.66. 13C NMR spectrum
(DMSO-d6), δC, ppm: carbohydrate fragment: 25.3–
1
27.3 m (CH3), 54.7 d (C1, JCP = 77.8 Hz), 66.4 (C6),
3
69.6 (C4), 74.9 d (C3, JCP = 5.4 Hz), 76.0 (C5), 80.2 d
Ethyl [(2-furyl)(phenylamino)methyl]phenyl-
2
(C2, JCP = 8.6 Hz), 108.2 (O2CO3), 108.8 (O5CO6);
phosphinate (XIIIa). Yield 0.13 g (31%), oily sub-
aniline fragment: 112.8 (C2, C6), 116.5 (C4), 128.6 (C3,
1
stance, Rf 0.85. H NMR spectrum (DMSO-d6), δ,
3
C5), 147.3 d (C1, JCP = 3.5 Hz); diphenylphosphoryl
2
ppm: 5.21 [5.32]** m (2H, NCHP, JHP = 17.17 Hz),
fragment: 127.6–128.2 m (C3, C5), 130.6–133.7 m
(C1, C4, C2, C6). 31P NMR spectrum (DMSO-d6):
δP 31.0 ppm. Found, %: C 67.28, 67.29; H 6.57, 6.60;
N 2.54, 2.55; P 5.89, 5.92. C30H36NO6P. Calculated, %:
C 67.16; H 6.53; N 2.62; P 5.78.
5.95 br.s (2H, NH); furan fragment: 6.28 m (2H, 4-H,
3J4,3 = 3.05 Hz), 6.39 m (2H, 3-H, J3,4 = 3.05, 4JHH
=
3
2.7 Hz), 7.44 m (2H, C5); aniline fragment: 6.74 t
3
(2H, 4-H, J4,5 = 7.3 Hz), 6.96 d (4H, 2-H, 6-H, 3J2,3
=
7.31 Hz), 7.02 d.d (4H, 3-H, 5-H, 3J3,4 = 7.0 Hz); phos-
phoryl fragment: 1.21 m (6H, CH3CH2), 4.14 m (8H,
2,3:5,6-Di-O-cyclohexylidene-1-deoxy-1-diphen-
ylphosphoryl-1-phenylamino-D-mannite (IXb).
Yield 60%, oily substance, Rf 0.85. 13C NMR spectrum
3
CH2OP, JHP = 8.04 Hz), 7.48–7.62 m (6H, 3-H, 4-H,
5-H), 7.69–7.8 m (4H, 2-H, 6-H). 13C NMR spectrum
1
(DMSO-d6), δC, ppm: 49.9 d (NCHP, JCP = 80.8 Hz);
(DMSO-d6), δC, ppm: carbohydrate fragment: 21.2–
furan fragment: 107.8 d (C3, 3JCP = 5.2 Hz), 109.7 (C4),
1
24.4 and 34.2–36.1 m (CH2), 54.2 d (C1, JCP
=
=
142.5 (C5), 154.8 (C2); aniline fragment: 113.4 (C2,
3
77.6 Hz), 65.7 (C6), 69.0 (C4), 73.4 d (C3, JCP
3
C6), 117.2 (C4), 129.4 (C3, C5), 146.9 d (C1, JCP
=
3.4 Hz), 78.9 (C5), 79.8 d (C2, JCP = 9.6 Hz), 108.3
2
10.5 Hz); phosphoryl fragment: 16.29 (CH3CH2),
66.38 (CH2O), 128.5 m (C3, C5), 130.5–132.3 m (C1,
C4, C2, C6). 31P NMR spectrum (DMSO-d6), δP, ppm:
35.76, 36.04. Found, %: C 66.89, 66.9; H 5.9, 5.92;
(O2CO3), 108.6 (O5CO6); aniline fragment: 112.2 (C2,
3
C6), 116.0 (C4), 128.2 (C3, C5), 146.7 d (C1, JCP
=
3.1 Hz); diphenylphosphoryl fragment: 127.5–128.7 m
(C3, C5), 130.4–133.5 m (C1, C4, C2, C6). 31P NMR
spectrum (DMSO-d6): δP 30.9 ppm. Found, %: C 70.15,
70.19; H 7.25, 7.22; N 2.13, 2.12; P 5.36, 5.29.
** Hereinafter, the chemical shifts for the second enantiomer are
given in brackets.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

REACTIONS OF GLYCOSYLAMINES WITH DIPHENYLPHOSPHINE OXIDE
1155
3
N 4.02, 4.04; P 9.25, 9.28. C19H20NPO3. Calculated,
%: C 66.86; H 5.86; N 4.11; P 9.09.
7.6 Hz), 7.07 d.d (4H, 3-H, 5-H, J3, 4 = 7.2 Hz);
phosphoryl fragment: 7.51–7.67 m (12H, 3-H, 4-H,
5-H), 7.89–8.03 m (8H, 2-H, 6-H). 31P NMR spectrum
(DMSO-d6), δP, ppm: 36.19, 36.43. Found, %: C 68.80,
68.77; H 5.28, 5.27; N 3.30, 3.29; P 7.32, 7.36.
C24H22NO4P. Calculated, %: C 68.74; H 5.25; N 3.34;
P 7.40.
Ethyl [(5-hydroxymethylfuran-2-yl)(phenyl-
amino)methyl]phenylphosphinate (XIIIb). Yield
1
0.13 g (29%), oily substance, Rf 0.75. H NMR spec-
trum (DMSO-d6), δ, ppm: 5.19 [5.26] m (2H, NCHP,
2JHP = 17.91 Hz), 5.92 br.s (2H, NH); furan fragment:
3
4.19 m (4H, 5-CH2), 6.09 t (2H, OH, JHH = 2.92 Hz),
Phosphinates XIVa–XIVd (general procedure).
A solution of 1.2 mmol of glycosylamine VI–VIII and
1.2 mmol of ethyl or phenyl phenylphosphinate XI or
XII in a mixture of 2 ml of chloroform and 0.5 ml of
pyridine was stirred for 5–6 h at 60°C under argon.
The solvent was removed, and the residue was purified
by chromatography on silica gel.
3
6.24 m (2H, 4-H, J4,3 = 2.75 Hz), 6.41 m (2H, 3-H,
3J3,4 = 2.75 Hz); aniline fragment: 6.54 t (2H, 4-H,
3
3J4,3 = 6.4 Hz), 6.73 d (4H, 2-H, 6-H, J2,3 = 7.6 Hz),
3
7.03 d.d (4H, 3-H, 5-H, J3,4 = 7.2 Hz); phosphoryl
fragment: 1.23 m (6H, CH3CH2), 4.04 m (4H, CH2OP,
3JHP = 8.04 Hz), 7.4–7.6 m (6H, 3-H, 4-H, 5-H),
7.7–7.85 m (4H, 2-H, 6-H). 13C NMR spectrum
1-Deoxy-1-[ethoxy(phenyl)phosphoryl)]-2,3:5,6-
di-O-isopropylidene-1-phenylamino-D-mannite
(XIVa). Yield 0.18 g (30%), oily substance, Rf 0.8.
1
(DMSO-d6), δC, ppm: 55.6 d (NCHP, JCP = 79.8 Hz);
3
furan fragment: 61.12 (CH2OH), 107.9 d (C3, JCP
=
5.0 Hz), 109.8 (C4), 146.2 (C5), 155.1 (C2); aniline
fragment: 113.6 (C2, C6), 117.3 (C4), 128.6 (C3, C5),
1H NMR spectrum (DMSO-d6), δ, ppm: carbohydrate
3
fragment: 1.55 m (12H, CH3), 3.84 m (1H, 4-H, J4,5
=
148.8 d (C1, JCP = 10.9 Hz); phosphoryl fragment:
3
6.26, 3JH,OH = 4.6 Hz), 3.98–4.02 m (2H, 6-H, 6′-H,
16.28 (CH3CH2), 66.36 (CH2OP), 128.3 m (C3, C5),
130.4–133.0 m (C1, C4, C2, C6). 31P NMR spectrum
(DMSO-d6), δP, ppm: 35.89, 36.17. Found, %:
C 64.74, 64.76; H 5.98, 5.96; N 3.73, 3.70; P 8.46,
8.48. C20H22NO4P. Calculated, %: C 64.69; H 5.93;
N 3.77; P 8.36.
3J6,5 = 6.21, 3J6′,5 = 6.58 Hz), 4.3 m (1H, 5-H, J5,6
=
3
6.21, J5,6′ = 6.58, 3J5,4 = 6.26 Hz), 4.4 m (1H, 3-H,
3
3J3,2 = 3.29 Hz), 4.65 m (1H, 2-H, J2,1 = 5.8, J2,3
=
=
3
3
3
2
3.29 Hz), 5.13 m (1H, 1-H, J1, 2 = 5.8, JHP
12.50 Hz); aniline fragment: 5.60 br.s (1H, NH), 6.4–
3
6.6 t (1H, 4-H, J4,3 = 6.4 Hz), 6.76 d (2H, 2-H, 6-H,
3J2,3 = 7.6 Hz), 7.04 d.d (2H, 3-H, 5-H, J3,4 = 7.2 Hz);
3
Phenyl [(2-furyl)(phenylamino)methyl]phenyl-
phosphinate (XIIIc). Yield 0.126 g (27%), oily sub-
phosphoryl fragment: 1.24 m (3H, CH3CH2), 3.9 m
1
3
stance, Rf 0.86. H NMR spectrum (DMSO-d6), δ,
(4H, CH2OP, JHP = 9.04 Hz), 7.46 m (3H, 3-H, 4-H,
2
5-H), 7.75 m (2H, 2-H, 6-H). 31P NMR spectrum
(DMSO-d6), δP, ppm: 37.93, 38.43. Found, %: C 61.80,
61.82; H 7.17, 7.18; N 2.74, 2.75; P 6.30, 6.26.
C26H36NO7P. Calculated, %: C 61.78; H 7.13; N 2.77;
P 6.14.
ppm: 5.47 [5.55] m (2H, NCHP, JHP = 17.37 Hz),
5.65 br.s (2H, NH); furan fragment: 6.28 m (2H, 4-H,
3
3J4,3 = 3.04 Hz), 6.39 m (2H, 3-H, J3,4 = 3.04, 4JHH
=
2.75 Hz), 7.2 m (2H, 5-H); aniline fragment: 6.6 t
(2H, 4-H, 3J4,3 = 7.32 Hz), 6.85 d (4H, 2-H, 6-H, 3J2,3
=
7.3 Hz), 7.08 d.d (4H, 3-H, 5-H, 3J3,4 = 7.1 Hz); phos-
phoryl fragment: 7.5–7.67 m (12H, 3-H, 4-H, 5-H),
7.87–8.00 m (8H, 2-H, 6-H). 31P NMR spectrum
(DMSO-d6), δP, ppm: 36.30, 36.65. Found, %: C 70.98,
71.00; H 5.15, 5.17; N 3.56, 3.57; P 7.86, 7.89.
C23H20NO3P. Calculated, %: C 70.95; H 5.14; N 3.60;
P 7.97.
1-Deoxy-1-[ethoxy(phenyl)phosphoryl)]-2,3:5,6-
di-O-isopropylidene-1-(2-naphthylamino)-D-man-
nite (XIVb). Yield 0.21 g (32%), oily substance,
Rf 0.88. 1H NMR spectrum (DMSO-d6), δ, ppm: carbo-
hydrate fragment: 1.5 m (12H, CH3), 3.89 m (1H, 4-H,
3J4,5 = 6.01, 3JH,OH = 4.6 Hz), 3.98–4.01 m (2H, 6-H,
3
3
6′-H, J6,5 = 6.12, J6′,5 = 6.15 Hz), 4.35 m (1H, 5-H,
3J5,4 = 6.01, J5,6 = 6.12, J5,6′ = 6.15 Hz), 4.43 m (1H,
3
3
Phenyl [(5-hydroxymethylfuran-2-yl)(phenyl-
amino)methyl]phenylphosphinate (XIIId). Yield
0.131 g (26%), oily substance, Rf 0.68. 1H NMR spec-
trum (DMSO-d6), δ, ppm: 5.41 [5.48] m (2H, NCHP,
3
3
3-H, J3,2 = 3.29 Hz), 4.62 m (1H, 2-H, J2,1 = 5.88,
3J2,3 = 3.29 Hz), 5.13 m (1H, 1-H, J1,2 = 5.88, JHP
=
3
2
12.50 Hz); naphthalene fragment: 6.43 br.s (1H, NH),
6.8 m (2H, 1-H, 3-H), 7.00 m (1H, 6-H), 7.1 m (1H,
7-H), 7.3 m (3H, 4-H, 5-H, 8-H); phosphoryl fragment:
2JHP = 17.48 Hz), 5.78 br.s (2H, NH); furan fragment:
3
4.10 m (4H, CH2OH), 6.10 t (2H, OH, JHH
=
3
3
3.94 Hz), 6.22 m (2H, 4-H, J4,3 = 2.74 Hz), 6.32 m
1.29 m (3H, CH3CH2), 4.06 m (4H, CH2OP, JHP
=
3
(2H, 3-H, J3,4 = 2.74 Hz); aniline fragment: 6.45 t
9.34 Hz), 7.5–7.7 m (3H, 3-H, 4-H, 5-H), 7.77–7.95 m
(2H, 4-H, 3J4,3 = 6.4 Hz), 6.82 d (4H, 2-H, 6-H, 3J2,3
=
(2H, 2-H, 6-H). 31P NMR spectrum (DMSO-d6), δP,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

BOBRIKOVA et al.
1156
ppm: 37.87, 38.48. Found, %: C 64.90, 64.89; H 6.86,
6.88; N 2.50, 2.48; P 5.72, 5.69. C30H38NO7P. Calculat-
ed, %: C 64.86; H 6.85; N 2.52; P 5.58.
δC, ppm: carbohydrate fragment: 25.3–26.6 m (CH3),
55.4 d (C1, 1JCP = 77.5 Hz), 65.9 (C6), 73.2 (C4), 79.5 d
3
2
(C3, JCP = 5.3 Hz), 85.5 (C5), 100.5 d (C2, JCP
=
8.4 Hz), 108.4 (O2CO3), 108.9 (O5CO6); naphthalene
fragment: 155.3 (C1), 118.8 (C3), 122.1 (C6), 125.8
(C8), 126.2 (C7), 127.3 (C5), 127.5 (C10), 129.4 (C4),
134.6 (C9), 147.6 (C2); phosphoryl fragment: 128.3–
128.6 m (C3, C5), 130.4–133.1 m (C1, C4, C2, C6).
31P NMR spectrum (DMSO-d6), δP, ppm: 37.09, 37.75.
Found, %: C 67.72, 67.71; H 6.33, 6.34; N 2.30, 2.29;
P 5.23, 5.26. C34H38NO7P. Calculated, %: C 67.67;
H 6.30; N 2.32; P 5.14.
2,3:5,6-Di-O-cyclohexylidene-1-deoxy-1-[phen-
oxy(phenyl)phosphoryl]-1-phenylamino-D-mannite
(XIVc). Yield 0.23 g (30%), oily substance, Rf 0.85.
1H NMR spectrum (DMSO-d6), δ, ppm: carbohydrate
fragment: 1.15–1.53 m (20H, CH2), 3.83 m (1H, 4-H,
3
3J4,5 = 5.5 Hz), 3.98 m (2H, 6-H, 6′-H, J6,5 = 8.4,
3
3
3J6′,5 = 8.6 Hz), 4.24 m (1H, 5-H, J5,4 = 5.5, J5,6 = 8.4,
3J5,6′ = 8.6 Hz), 4.45 m (1H, 3-H, J3,2 = 3.29 Hz),
4.73 m (1H, 2-H, J2,1 = 5.85, J2,3 = 3.29 Hz), 5.15 m
3
3
3
3
2
(1H, 1-H, J1,2 = 5.85, JHP = 12.50 Hz); aniline frag-
This study was performed under financial support
by the President of the Russian Federation (program
for support of leading scientific schools, project
no. NSh-5515.2006.3).
ment: 5.5 br.s (1H, NH), 6.5 t (1H, 4-H, 3J4,3 = 6.4 Hz),
3
6.86 d (2H, 2-H, 6-H, J2,3 = 7.6 Hz), 7.11 d.d (2H,
3-H, 5-H, J3,4 = 7.2 Hz); phosphoryl fragment: 7.5–
3
7.6 m (6H, 3-H, 4-H, 5-H), 7.77 m (4H, 2-H, 6-H).
31P NMR spectrum (DMSO-d6), δP, ppm: 38.85, 39.04.
Found, %: C 68.30, 68.28; H 6.97, 6.98; N 2.12, 2.15;
P 5.02, 5.04. C35H44NO7P. Calculated, %: C 68.25;
H 6.95; N 2.21; P 4.90.
REFERENCES
1. Kafarski, P. and Lejczark, B., Phosphorus, Sulfur Silicon.
Relat. Elem., 1991, vol. 63, p. 193.
2. Bognar, R., Usp. Khim., 1952, vol. 21, p. 734.
3. Nifant’ev, E.E., Metlitskikh, S.V., Koroteev, M.P.,
Stash, A.N., and Bel’skii, V.K., Russ. J. Gen. Chem.,
2006, vol. 76, p. 1005.
4. Kochetkov, N.K., Bochkov, A.F., Dmitriev, B.A.,
Usov, A.I., Chizhov, O.S., and Shibaev, V.N., Khimiya
uglevodov (Chemistry of Carbohydrates), Moscow:
Khimiya, 1967.
5. Kabachnik, M.I. and Medved’, T.Ya., Dokl. Akad. Nauk
SSSR, 1952, vol. 83, p. 689.
6. Fields, E.K., J. Am. Chem. Soc., 1952, vol. 74, p. 1528.
7. Nifant’ev, E.E., Khimiya gidrofosforil’nykh soedinenii
(Chemistry of Hydrophosphoryl Compounds), Moscow:
Nauka, 1983.
8. Reichardt, C., Solvents and Solvent Effects in Organic
Chemistry, Weinheim: VCH, 1988, 2nd ed.
1-Deoxy-2,3:5,6-di-O-isopropylidene-1-[phenoxy-
(phenyl)phosphoryl]-1-(2-naphthylamino)-D-man-
nite (XIVd). Yield 0.24 g (33%), oily substance,
Rf 0.84. 1H NMR spectrum (DMSO-d6), δ, ppm: carbo-
hydrate fragment: 1.25–1.35 m (12H, CH3), 3.84 m
3
3
(1H, 4-H, J4,5 = 6.16, JH,OH = 4.76 Hz), 3.98–4.02 m
3
3
(2H, 6-H, 6′-H, J6,5 = 6.21, J6′,5 = 6.58 Hz), 4.25 m
3
3
3
(1H, 5-H, J5,4 = 6.16, J5,6′ = 6.21, J5,6′ = 6.58 Hz),
3
4.46 m (1H, 3-H, J3,2 = 3.29 Hz), 4.72 m (1H, 2-H,
3J2,1 = 5.85, J2,3 = 3.29 Hz), 5.13 m (1H, 1-H, J1,2
=
3
3
5.85, 2JHP = 12.50 Hz); naphthalene fragment: 6.48 br.s
(1H, NH), 6.74 m (2H, 1-H, 3-H), 7.15 m (1H, 6-H),
7.2 m (1H, 7-H), 7.3 m (3H, 4-H, 5-H, 8-H); phos-
phoryl fragment: 7.53–7.65 m (6H, 3-H, 4-H, 5-H),
7.95 m (4H, 2-H, 6-H). 13C NMR spectrum (DMSO-d6),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008