PAPER
Hydrophosphonylation of Aldehydes and Ketones in Water
3317
13C NMR (125 MHz, CDCl3): d = 53.7 (d, J = 7.5 Hz), 54.0 (d,
J = 6.7 Hz), 70.6 (d, J = 158.4 Hz), 126.9, 128.1, 128.2 (d,
J = 2.5 Hz), 136.2.
due to the poor solubility of PDA in this solvent. The ad-
vantages of using an organocatalyst would clearly be
higher if the catalyst could be efficiently recovered and re-
used. Thus, the reusability of the catalyst was examined
by treating 3-phenylpropionaldehyde and trimethylphos-
phite in the presence of 10 mol% of the catalyst in aqueous
media for three consecutive runs. The reactions proceeded
smoothly with minimum variation in the yield of the prod-
uct, as shown in the Table 3.
Catalyst Recycling
To investigate the reusability of the catalyst, after completion of the
reaction, the product was extracted with CH2Cl2 (3 × 15 mL) and
the aqueous layer was evaporated under reduced pressure to give
PDA, which was then washed with cool H2O (2 × 2 mL) and Et2O
(2 × 2 mL), successively, and dried at 100 °C for 1 h. The recovered
catalyst was reused consecutively three times with a minimum vari-
ation in the yield of the product. Alternatively, after extraction of
the product with CH2Cl2 (3 × 15 mL), the aqueous layer can be used
directly for subsequent runs.
Table 3 Reusability of the PDA Catalyst
Entry
Number of recycle Time (min)
Yield (%)a
1
2
3
fresh
90
90
95
92
90
Acknowledgment
1
2
Financial support for this work from the Research Council of the
University of Mazandaran is gratefully acknowledged.
100
a Yield of isolated product.
References
(1) For reviews see: (a) Dalko, P. I.; Moisan, L. Angew. Chem.
Int. Ed. 2001, 40, 3726. (b) List, B. Tetrahedron 2002, 58,
5573. (c) Duthaler, R. O. Angew. Chem. Int. Ed. 2003, 42,
975. (d) Dalko, P. I.; Moisan, L. Angew. Chem. Int. Ed.
2004, 116, 5248. (e) List, B. Chem. Commun. 2006, 819.
(f) Marigo, M.; Jørgensen, K. A. Chem. Commun. 2006,
2001. (g) Enders, D.; Grondal, C.; Hüttl, M. R. M. Angew.
Chem. Int. Ed. 2007, 46, 1570. (h) Dondoni, A.; Massi, A.
Angew. Chem. Int. Ed. 2008, 47, 4638. (i) Schreiner, P. R.
Chem. Soc. Rev. 2003, 32, 289. (j) Doyle, A. G.; Jacobsen,
E. N. Chem. Rev. 2007, 107, 5713.
In summary, we have developed a method for the synthe-
sis of a-hydroxy phosphonates by reacting aldehydes and
ketones with trimethylphosphite in the presence of a cata-
lytic amount of PDA as a novel organocatalyst in aqueous
media. The simple experimental procedure, application of
an inexpensive catalyst, short reaction times and high
yields are the notable advantages of the protocol. In many
cases the products crystallize directly out of the reaction
mixture.
(2) (a) Csihony, S.; Beaudette, T. T.; Sentman, C. A.; Nyce, W.
G.; Waymouth, M. R.; Hedrickb, L. J. Adv. Synth. Catal.
2004, 346, 1081. (b) Barbas, C. F. III Angew. Chem. Int. Ed.
2008, 47, 42. (c) List, B.; Lerner, R. A.; Barbas, C. F. III
J. Am. Chem. Soc. 2000, 122, 2395. (d) Bengoa, E. G.;
Linden, A.; López, R.; Mendiola, I. M.; Oiarbide, M.;
Palomo, C. J. Am. Chem. Soc. 2008, 130, 7955.
(e) Wittkopp, A.; Schreiner, P. R. Eur. J. Org. Chem. 2003,
407. (f) Palomo, C.; Oiarbide, M.; Mielgo, A. Angew. Chem.
Int. Ed. 2004, 43, 5442. (g) Ibrahem, I.; Rios, R.; Vesely, J.;
Hammar, P.; Eriksson, L.; Himo, F.; Córdova, A. Angew.
Chem. Int. Ed. 2007, 46, 4507. (h) Carlone, A.; Bartoli, G.;
Bosco, M.; Sambri, L.; Melchiorre, P. Angew. Chem. Int. Ed.
2007, 46, 4504. (i) Maerten, E.; Carbrera, S.; Kjaersgaard,
A.; Jørgensen, K. A. J. Org. Chem. 2007, 72, 8893.
(3) Xu, D. Q.; Wang, L. P.; Luo, S. P.; Wang, Y. F.; Zhang, S.;
Xu, Z. Y. Eur. J. Org. Chem. 2008, 1049.
1H and 13C NMR spectra were recorded on a 500 MHz Bruker spec-
trometer in CDCl3 and DMSO using SiMe4 as an internal standard.
Chemical shifts are reported in ppm. The coupling constants (J val-
ues) are reported in Hz. Reactions were monitored by TLC (Merck)
or GC. Evaporation of solvents was performed at reduced pressure,
using a rotary evaporator. Melting points were measured using the
capillary tube method with a Bamstead Electrothermal 9200 appa-
ratus. IR spectra were recorded from KBr disks on a Bruker Tensor
27 FT-IR spectrophotometer. All solvents and reagents were pur-
chased from Aldrich or Merck with high-grade quality and used
without any purification.
Dimethyl 1-Hydroxy-1-phenylmethylphosphonate; Typical
Procedure
A solution of benzaldehyde (0.106 g, 1 mmol), trimethylphosphite
(0.136 g, 1.1 mmol) and pyridine 2,6-dicarboxylic acid (0.0167 g,
0.1 mmol) in H2O (2 mL) was placed in a round-bottomed flask
equipped with a magnetic stirrer and heated at 50 °C for 1.5 h. After
completion of the reaction as indicated by TLC, the mixture was
cooled to r.t. and the product was extracted with CH2Cl2
(3 × 15 mL). The organic layer was dried over anhydrous Na2SO4
and concentrated to give an oily residue that crystallized to give the
title compound.
(4) (a) Mosse, S.; Alexakis, A. Org. Lett. 2006, 8, 3577.
(b) McCooey, S. H.; Connon, S. J. Org. Lett. 2007, 9, 599.
(c) Zhao, J. F.; He, L.; Jiang, J.; Tang, Z.; Cun, L. F.; Gong,
L. Z. Tetrahedron Lett. 2008, 49, 3372.
(5) Li, C. J. Chem. Rev. 2005, 105, 3095.
(6) Lindstrom, U. M.; Andersson, F. Angew. Chem. Int. Ed.
2006, 45, 548.
(7) Hailes, H. C. Org. Process Res. Dev. 2007, 11, 114.
(8) Patel, D. V.; Rielly-Gauvin, K.; Ryono, D. E. Tetrahedron
Lett. 1990, 31, 5591.
Yield: 0.216 g (95%); white solid; mp 86–87 °C.
IR: 3240 (OH) cm–1.
1H NMR (500 MHz, CDCl3): d = 3.7 (d, J = 10.3 Hz, 3 H), 3.74 (d,
J = 10.3 Hz, 3 H), 4.1 (s, OH), 5.06 (d, J = 13.2 Hz, 1 H), 7.3–7.5
(m, 5 H).
(9) Patel, D. V.; Rielly-Gauvin, K.; Ryono, D. E. Tetrahedron
Lett. 1990, 31, 5587.
Synthesis 2010, No. 19, 3315–3318 © Thieme Stuttgart · New York