Enantioselective synthesis of α-hydroxyalkylphosphonates

Full text of DOI:10.1007/s11176-005-0386-8

Russian Journal of General Chemistry, Vol. 75, No. 7, 2005, pp. 1161 1162. Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 7, 2005,
pp. 1225 1226.
Original Russian Text Copyright
2005 by Nesterov, Kolodyazhnyi.
LETTERS
TO THE EDITOR
Enantioselective Synthesis of -Hydroxyalkylphosphonates
V. V. Nesterov and O. I. Kolodyazhnyi
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received November 26, 2004
In this communication we report on the synthesis
of optically active -hydroxyalkylphosphonates by
asymmetric reduction of dialkyl arylketophosphonates
II.
O
R
O
R
Py2Cr2O7
Me3SiCl
H
RO
RO
IIa IIc
P
RO
RO
P
(RO)2P(O)H + R CHO
O
OH
(S/R)-Ia Ic
OH
OH
HO2C
NaBH4/
HO2C
NaBH4
O
R
O
R
H
RO
RO
(S)-IVa IVc
P
H
RO
RO
(R)-IIIa
P
OH
OH
R = Et, R = Ph (a); R = (1R,2S,5R)-Mnt, R = Ph (b), C6H4F-2 (c).
Arylketophosphonates II were synthesized by a
two-step one-pot procedure. In the first step, dialkyl
phosphites were reacted with aldehydes to obtain
racemic -hydroxyphosphonates in quantitative yields.
The products without isolation and purification were
oxidized with pyridinium dichromate [1, 2] to form
dketophosphonates II in high yields. The chemical
purity of ketophosphonates II prepared in this way
was 90% or higher. Therefore, they were brought in
further transformations without purification. If
necessary, they could be easily purified by column
chromatography on silica gel.
35% de). The products were purified by crystalliza-
tion from acetonitrile (procedure a).
The stereoselectivity of the hydroborination of
ketophosphonates could be enhanced via generation of
a chiral complex of sodium borohydride with natural
L-(+)-tartaric acid (procedure b). This procedure gave
diethyl
IVa] with the enantiomeric purity 60% ee and
dimenthyl -hydroxy(aryl)methylphosphonates (S)-
-hydroxy(phenyl)methylphosphonate [(S)-
IVb (93% de) and (S)-IVc (80% de). We explain the
high stereoselectivity of the reduction of dimenthyl
arylketophosphonates by the effect of dual asymmetric
induction [3]: In this case, the asymmetric inductions
of the menthyl group and tartaric acid acted in the
same direction. -Hydroxyphosphonates (S)-IVb and
The reduction of dimenthyl ketophosphonates with
sodium borohydride in ethanol affords (R)- -hydr-
oxyphosphonates with a low stereoselectivity (30
1070-3632/05/7507-1161 2005 Pleiades Publishing, Inc.

1162
NESTEROV, KOLODYAZHNYI
(S)-IVc were purified by crystallization from aceto-
nitrile to 100% optical purity.
Diethyl (S)-hydroxy(phenyl)methylphosphonate
(IVa) was prepared similarly to compound IVb. Yield
95%, mp 74 76 C, [ ]2D0 15.4 (c 2.6, CHCl3). 31P
Di-(1R,2S,5R)-( a)-menthyl benzoylphosphonate
(IIb). Chlorotrimethylsilane, 0.6 g (5.5 mmol) was
added to a stirred suspension of 1.68 g (4.47 mmol)
of pyridinium dichromate in 30 ml of methylene
NMR spectrum (CDCl3):
with [4 6].
22.00 ppm, in agreement
P
Di-2-(1R,2S,5R)-( )-menthyl (S)-(2-fluoro-
phenyl)(hydroxyl)methylphosphonate (IVc) was
prepared similarly to compound IVb. Yield 97%, mp
137.5 138.5oC, [ ]2D0 83.7 (c 1.3, CHCl3). 1H NMR
spectrum (CDCl3), , ppm (J, Hz): 0.71 d (3H, CH3,
JHH 6.9); 0.76 d (6H, CH3, JHH 6.9); 0.86 d (6H, CH3,
JHH 6.9); 0.91 d (3H, CH3, JHH 6.9); 1.00 2.25 m
(14H, CH3 and CH); 1.74 m [1H, CH(CH3)2]; 2.0 m
[1H, CH(CH3)2]; 4.04 d (1H, CHP, JHH 22.5); 4.2 m
(2H, OCH); 5.18 br (1H, OH); 6.9 t (3H, JHH 8.2,
ArH); 7.45 m (2H, ArH). 31P NMR spectrum (CDCl3):
chloride at 0°C, after which racemic dimenthyl
-
hydroxyphosphonate (Ib) prepared from 1.75 mol of
dimenthyl phosphite and 1.75 mol of benzaldehyde
was added. The mixture of stirred for 2 4 h, the sol-
vent was evaporated, and the product was isolated as
a colorless liquid. Yield 90%, Rf 0.3 (eluent hexane
ethyl acetate, 4:1), [ ]2D0 62 (c 1.5, CHCl3). 1H NMR
spectrum (CDCl3), , ppm (J, Hz): 0.7 1.0 m (CH3);
1.1 2.2 m (CH2 + CH); 4.15 d.t (OCH, JHH 2.3, JHH
4.1); 7.35 m (C6H5); 7.45 m (C6H5). 31P NMR spec-
trum (CDCl3):
2.3 ppm. Ketophosphonates IIa
and IIc were prPepared similarly.
19.8 ppm.
P
The NMR spectra were measured on a Varian-300
instrument against internal TMS (1H) and external
reference 85% H3PO4 in D2O (31P).
Di-(1R,2S,5R)-(3a)-menthyl (R)-hydroxy(phe-
nyl)methylphosphonate (IIIb). a. Yield 40%, mp
139 C (acetonitrile), [ ]2D0 70 (c 1, toluene). 31P
NMR spectrum (CDCl3):
with [5].
22.4 ppm, in agreement
P
ACKNOWLEDGMENTS
Di-(1R,2S,5R)-( )-menthyl (S)-hydroxy(phe-
nyl)methylphosphonate (IVb). b. L-(+)-Tartaric acid,
4 mmol, was added to 4 mmol of sodium borohydride
in 15 ml of THF, and the reaction mixture was re-
fluxed for 4 h. After cooling to 30°C, 0.99 mol of
ketophosphonate in 5 ml of THF was added, the
mixture was kept for 24 h at 30°C, after which 8 ml
of ethyl acetate was added, and 20 ml of 1 N HCl was
added dropwise. The organic layer was separated, and
the aqueous layer was extracted with ethyl acetate.
The solvent was evaporated in a vacuum, and the
residue was crystallized from acetonitrile. Yield 95%,
The work was financially supported by the State
Foundation for Basic Research of the Ministry of
Education and Science of Ukraine (project no. 03.07/
00047).
REFERENCES
1. Cassio, F.P., Aizpurua, J.M., and Palomo, C., Can. J.
Chem., 1986, no. 2, vol. 64, p. 225.
2. Burke, T.R., Smyth, M.S., Nomixu, M., Otaka, A., and
Roller, P.R., J. Org. Chem., 1993, vol. 58, no. 6,
p. 1336.
mp 112 113, [ ]2D0 87.6 (c 1.3, CHCl3). H NMR
1
3. Kolodiazhnyi, O.I., Tetrahedron, 2003, vol. 59, no. 32,
spectrum (CDCl3), , ppm (J, Hz): 1.01 d (3H, CH3,
JHH 6.9); 1.04 d (3H, CH3, JHH 6.9); 1.08 d (3H, CH3,
JHH 6.9); 1.18 d (3H, CH3, JHH 6.9); 1.20 d (3H, CH3,
JHH 6.9); 1.21 d (3H, CH3, JHH 6.9); 1.40 2.6 m (14H,
CH3 and CH); 2.00 m [1H, CH(CH3)2]; 2.4 m [1H,
CH(CH3)2]; 4.49 m (2H, OCH); 5.2 d (1H, CHP, JHH
10.5); 5.10 br (1H, OH); 7.48 m (3H, ArH); 7.8 m
(2H, ArH). 31P NMR spectrum (CDCl3): P 22.3 ppm.
Found, %: P 6.38. C27H45O4P. Calculated, %: P 6.67.
p. 5923.
4. Kolodiazhnyi, O.I., Sheiko, O. and Grishkun, E.V.,
Heteroatom. Chem., 2000, vol. 11, no. 2, p. 138.
5. Blazis, V.J., Koeller, K.J., and Spilling, C.D., Tetra-
hedron: Asymmetry, 1994, vol. 5, no. 4, p. 499.
6. Blazis, V.J., Koeller, K.J., and Spilling, C.D., J. Org.
Chem., 1995, vol. 60, no. 4, p. 931.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 7 2005