Asymmetric synthesis of (1S,2R)-(1,2,3-trihydroxypropyl)diphenylphosphine oxide [4]

Full text of DOI:10.1023/B:RUGC.0000042440.21455.23

Russian Journal of General Chemistry, Vol. 74, No. 6, 2004, pp. 965 966. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 6, 2004,
pp. 1045 1046.
Original Russian Text Copyright
2004 by Kolodyazhnaya, Kukhar’, Kolodyazhnyi.
LETTERS
TO THE EDITOR
Asymmetric Synthesis
of (1S,2R)-(1,2,3-Trihydroxypropyl)diphenylphosphine Oxide
A. O. Kolodyazhnaya, V. P. Kukhar’, and O. I. Kolodyazhnyi
Institute of Bioorganic and Oil Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received October 21, 2003
Hydroxyphosphonic acids and organophosphorus
structural analogs of carbohydrates attract great
interest as potentially biologically active compounds
[1]. In the present work we have performed an asym-
metric synthesis of (1S,2R)-(1,2,3-trihydroxypropyl)-
diphenylphosphine oxide (III), a structural analog of
the linear form of erythrose IV.
Addition of diphenyl(trimethylsilyl)phosphine to
acetonide of (R)-glyceraldehyde proceeds stereoselec-
tively to form a diastereomerically enriched [1-hydr-
oxy-2,3-(isopropylidenedioxy)propyl]diphenylphos-
phine (II) in high yield. Subsequent removal of the
acetonide group with hydrochloric acid in dioxane
gave (1,2,3-trihydroxypropyl)diphenylphosphine
oxide (III).
O
H
O
O
O
O
OH
O
O /H2O
(Me3SiO)2O
HCl
Ph2PSiMe2
Ph2P
Ph2P
Ph2P
OH
OH
H
OH
OH
OSiMe3
OH
O
I
II
III
O
O
O
OH
H
Ph2P(O)H
H
II
III
H
IV
Phosphaldol addition (Abramov reaction) of di-
phenylphosphine oxide to acetonide of (R)-glyceral-
dehyde, too, leads to formation of compound II, but
the stereoselectivity of this reaction is lower and
depends on the solvent, temperature, and base catalyst
[2, 3]. The highest stereoselectivity was achieved by
performing the reaction in THF in the presence of a
catalytic amount of alkali (potassium hydroxide, 2
3 mol%) (de 75%). If 1,8-diazabicyclo[5.4.0]undec-
7-ene was used as catalyst ( 3 mol%) the stereoselec-
tivity was 60% in toluene, 50% in benzene, 40%
in diethyl ether, and 30% in methylene chloride.
The anti configuration of the major phosphaldol
3
diastereomer II was assessed by NMR: The high JHH
2
and low JHP constants point to an anti conformation
of the H C1 C2 H and O=P C1 H bonds. The anti
diastereomer [proposed absolute configuration (1S,2R)]
was purified by crystallization from toluene and iso-
lated optically pure. The syn diastereomer was charac-
terized spectroscopically.
[1-Hydroxy-2,3-(isopropylidenedioxy)propyl]di-
phenylphosphine (I). Acetonide of (R-glyceraldehyde
(0.01 mol) was added at 0 C to 0.01 mol of diphenyl-
(trimethylsilyl)phosphine, and the mixture was left to
stand for 1 2 h at this temperature. A colorless liquid
easily oxidized in air was obtained. Yield 80%, [ ]D20
The optical purity of diastereomers I III was
established by means of the 31P {1H} NMR spectra.
1070-3632/04/7406-0965 2004 MAIK Nauka/Interperiodica

966
KOLODYAZHNAYA et al.
7 (c 4, toluene). 1H NMR spectrum (CDCl3), , ppm:
(1,2,3-Trihydroxypropyl)diphenylphosphine
oxide (III). Compound II, 0.5 g, was dissolved in 4
5 ml of dioxane, and 2 ml of concentrated hydrochlo-
ric acid was added to the obtained solution. The mix-
ture was left overnight at room temperature. The sol-
vent was then removed, and the residue was crystal-
lized from chloroform or chloroform hexane. Yield
0.02 s (CH3Si), 1.33 s (CH3), 4.49 m (OCH2CH),
4.72 m (CH2CHO), 4.99 m (PCH), 7.5 m, 7.9 m
(C6H5). 31P NMR spectrum (CHCl3),
10.62 ppm (11:1 ratio).
:
7.69;
P
[1-Hydroxy-2,3-(isopropylidenedioxy)propyl]di-
phenylphosphine oxide (II). a. Compound I was left
for 12 h in air for oxidation. The crystalline product
that formed was crystallized from toluene. Yield 65%,
mp 165 167 C, [ ]2D0 +11 (CHCl3, c 1.5).
50%, mp 151 C. [ ]2D0 +5 (c 2, CHCl3). H NMR
1
spectrum (CDCl3), , ppm (J, Hz): 3.61 d (2H,
CHCH2OH, JHH 1), 3.77 br (1H, CHCH2), 4.48 d (1H,
PCH, JHP 7.5), 4.62 br (3H, OH), 7.48 m (6H, C6H5,
7.84 m (4H, C6H5). 31P NMR spectrum (CHCl3):
b. Diphenylphosphine oxide, 0.01 mol, was dis-
solved in 5 ml of toluene, and 0.011 mol of acetonide
of (R)-glyceraldehyde was added. The resulting mix-
ture was cooled to 0 C and treated with several drops
of 1,8-diazabicyclo[4,5,0]-undec-7-ene. After keeping
for 12 h at 0 C, the solvent was removed in a vacuum,
and the residue was crystallized from toluene.
P
35 ppm. Found, %: P 10.50. C15H17O4P. Calculated,
%: P 10.60.
The experimental conditions are identical to those
described in [3].
anti Diastereomer. Yield 60%. mp 167 C, [ ]D20
The NMR spectra were recorded on a Varian-300
spectrometer against internal TMS (1H, 13C) and 85%
phosphoric acid in D2O (31P). The optical rotations
were measured on a Perkin Elmer polarimeter.
1
+11 (CHCl3, c 2). H NMR spectrum (CDCl3).
,
ppm (J, Hz): 1.17 s (Me2Ca), 1.20 s (Me2Cb), 3.88 d
(CaH2, J 2), 3.90 d (CbH2, J 1.5), 4.39 d.t (OCHCH2,
J 6.5, J 2), 4.59 d.d (PCH, J 5, J 0.9), 4.4 m (OH),
7.8 m (4H), 7.49 m (6H), 31P NMR spectrum (CHCl3):
REFERENCES
30.87 ppm.
P
1. Hilderbrand, R.L., The Role of Phosphonates in Living
Systems, Boca Raton: CRS, 1983.
1
cis Diastereomer. H NMR spectrum (CDCl3), ,
ppm (J, Hz): 1.14 s [(CH3)2Ca], 1.23 s [(CH3)2Cb],
3.99 s, 3.90 s (CH2), 4.39 d.t (OCHCH2, J 6.5, J 2),
4.4 br. (OH), 4.59 d.d (PCH, J 5, JHP 5), 7.8 m (4H),
2. Kolodiazhnyi, O.I., Tetrahedron: Asymmetry, 1998,
vol. 9, no. 8, p. 1279.
7.49 m (6H). 31P NMR spectrum (CHCl3),
P
3. Kolodiazhnyi, O.I., Grishkun, E.V., and Sheiko, S.,
29.45 ppm. Found, %: P 9.55. C18H21O4P. Calculated,
%: P 9.32.
Heteroatom. Chem., 2000, vol. 11, p. 138.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 6 2004