Method of ketone hydrophosphorylation

Full text of DOI:10.1134/S1070363209090229

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 9, pp. 1934–1935. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © O.I. Kolodyazhnyi, 2009, published in Zhurnal Obshchei Khimii, 2009, Vol. 79, No. 9, pp. 1578–1579.
LETTERS
TO THE EDITOR
Method of Ketone Hydrophosphorylation
O. I. Kolodyazhnyi
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine,
Murmanskaya ul. 1, Kiev, 02094 Ukraine
fax: 38(044)573-2555
e-mail: olegkol321@rambler.ru
Received December 8, 2008
DOI: 10.1134/S1070363209090229
Aldehydes and occasionally activated ketones are
readily phosphonylated under the Abramov reaction
condition, the most important method of synthesis of
hydroxyphosphonates. The reaction with non-activated
ketones does not generally proceed [1, 2]. We found a
convenient method of ketone hydroxyphosphonylation
using trialkylphosphite-pyridinium bromide reaction
pair. This method allows a successful hydrophos-
phonylation in high yields both of the simple ketones
Ia and ketones of the complex nature like Ic–Id.
Diethyl 1-hydroxycyclohexylphosphonate (IVa).
A solution of 1g of cyclohexanol, 2.25 g of triethyl-
phosphite, and 1.6 g of pyridinium bromide in 3 ml of
methylene chloride was stirred for 6 h at 40оС. Then
the solvent was removed. The residue was dissolved in
5 ml of ether, filtered off, evaporated, and distilled in a
vacuum. Yield 80%, mp 120оС (0.1 mm Hg). Then the
product was recrystallized from hexane at 0оС.
1
Prismes, mp 61–63ºC. Н NMR spectrum (CDCl3), δ,
ppm: 1.3 t (6H, CH3CH2,J 7.2 Hz), 1.52 m (2H, CH2),
1.66 m (4H, CH2), 1.87 m (4H, CH2), 3.6 br. (1H,
OH), 4.16 d.q (4H, OCH2,J 7 Hz, J 8 Hz). 31Р (CDCl3),
δ, ppm: 26.93. Found, %: C 50.62; H 8.91; P 13.09.
C10H21O4P. Calculated, %: C 50.84; H 8.96; P 13.11.
The reaction was carried out in methylene chloride
solution at room temperature or at slight heating. The
high activity of the reaction pair is due to the easy
deprotonation of the intermediate betaine II with pyri-
dinium bromide. Moreover, the bromine ion readily
dealkylates the phosphonium group in the intermediate
compound II. The scheme given below is conform to
the generally accepted mechanism of phospho-aldol
reaction [2, 3]. Some typical experimental examples
demonstrating the efficiency of this method are cited
below. The more detailed description of this method
and its use for synthesis of analogs of natural
compounds will be reported later.
Diethyl 4-hydroxy(tetrahydro-2,2-dimethyl-2H-
pyran-4-yl)phosphonate (IVc). A mixture of 0.9 g of
ketone Ib, 1.2 g of triethylphosphite, and 1.2 g of
pyridinium bromide was heated at 50–60оС
(temperature of oil bath) overnight. Then the volatile
products were evaporated and the residue was distilled
in a vacuum and recrystallized from cooled (0оС)
hexane. Yield 80%, bp 130–135оС (0.08 mm Hg), mp
1
72–75оС. Н NMR spectrum (CDCl3), δ, ppm: 1.19 s
PyH+Br−
EtO
EtO
R
R
+
+
R
O−
R' Br−
(EtO)3P
O
(EtO)3P
(EtO)3P +
P
R'
−Py
−EtBr
R'
OH
Ia−Id
II
III
OH
O
IVa−IVd
O
O
O
O
O (a),
O (b),
RR'C=O =
O
(c),
(d).
1934

1935
METHOD OF KETONE HYDROPHOSPHORYLATION
(3H, [(CH3)2C], 1.43 s (3H, [CH3)2C], 1.64-19 m (4H,
CH2), 3.65 m (2H CH2O), 3.95 br. (1H, OH), 3.65 m
(1H, CH2), 4.05 m (1H, CH2), 4.15 d. q (4H,
CH3CH2O, J 7 Hz, J 8 Hz). 31Р NMR spectrum
(CDCl3), δ, ppm: +23.6. Found, %: P 11.63. C11 H23 O5 P.
Calculated, %: P 11.63.
ppm: 0.8 m (3H, CH3), 0.9 m (3H, CH3), 1.32 t (6H,
CH3CH2), 1.5 s (3H, CH3), 1.6 s (3H, CH3), 1.4–1.9 m
(13H, CH2), 2.25 d (3H, CH3), 4,17 d.q (4H, CH2O, J 8
Hz, J 8 Hz), 5.7 d. d (1H, J 4.5 Hz, J 16 Hz), 5.9 d. d
(1H, CH=С, J 10.5Hz, J 13.5 Hz), 6.65 d. d. d (1H,
CH=С, J 4.5 Hz, J 10.5 Hz, J 15 Hz). 31Р NMR
spectrum (CDCl3), δ, ppm: +24.5. Found, %: C 66.00;
H 9.55; P 7.41. C22H39O4P. Calculated, %: C 66.30; H
9.86; P 7.77.
Diethyl [1-(3,4-dimethoxyphenyl)-1-hydroxypro-
pyl]phosphonate (IVd) was prepared similarly. The
product was purified by column chromatography,
eluent ethyl acetate-hexane (1:1). Yield 60%, Rf 0.33.
1Н NMR spectrum (CDCl3), δ ppm: 0.77 t (3H, CH3, J
7.2 Hz); 1.15 t (3H, CH3CH2O, J 7.2 Hz), 1.27 t (3H,
CH3CH2O, J 7.2 Hz); 2.13 d. q (1H, J 7 Hz, J 8 Hz),
2.24 d.q (1H, J 7 Hz, J 8 Hz), 3.87 s and 3.89 s (3H,
CH3O), 4.1 m (4H, CH2O), 6.9–7.5 m (3H, C6H3). 31Р
NMR spectrum (CDCl3), δP, ppm: +24.3. Found, %: P
9.32. C15H25O6P. Calculated, %: P 9.32.
The NMR spectra were registered on a Varian-300
device, internal reference TMS (1Н and 13С),external
reference 85% Н3РО4 in D2O (31Р).
REFERENCES
1. Abramov, V.S., Khimiya
i primeneniye fosforor-
ganicheskikh soedinenii (Chemistry and Application of
Organophosphorus Compounds), Moscow, 1957, p. 218.
2. Engel, R., Phosphorus Addition at sp2 Carbon. Organic
Diethyl [(2E,4E)-1-hydroxy-1,5-dimethyl-7-(2,6,6-
trimethyl-1-cyclohexyl)-2,4-heptadienyl]phosphonate
(IVe) was prepared similarly. The product was purified
by column chromatography, eluent ethyl acetate-
Reactions, New York: Wiley, 1988, vol. 50, p. 176.
3. Kolodyazhnyi, O.I., Usp. Khim., 2006, vol. 75, no. 3,
1
p. 254.
hexane (1:1). Rf 0.3. Н NMR spectrum (CDCl3), δ
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 9 2009