S. Peyrottes et al. / Tetrahedron Letters 47 (2006) 7719–7721
7721
the microwave synthesizer. This work was supported
by Association pour la Recherche contre le
Cancer (ARC). F.G. and J.B. are grateful to the CNRS
1
00%
8
6
4
2
0%
0%
0%
0%
&
R e´ gion Languedoc–Roussillon, and La Ligue
contre le Cancer, respectively, for their doctoral
fellowships.
0
%
References and notes
5
15
40
60
reaction time
1
. Leblond, L.; Attardo, G.; Hamelin, B.; Bouffard, D. Y.;
Nguyen-Ba, N.; Gourdeau, H. Mol. Cancer Therapeutics
2002, 1, 737–746.
Graph 3. Ratio of triethylphosphite (grey), side product (white) and
desired phosphonate (black) observed over time (min) at 220 °C,
irradiation power 300 W.
2. Nair, V.; Sharma, P. K. Arkivoc 2003, XV, 10–14.
3
4
. DeClercq, E.; Holy, A. Nature Rev. 2005, 4, 928–940.
. Centrone, C. A.; Lowary, T. L. J. Org. Chem. 2003, 68,
purification. However, the amount of trialkylphosphite
engaged was significantly reduced as illustrated for sub-
strate 2, from 25 to 5 equiv and the reaction time was
shortened to 1 h, or less, instead of a few days. Further-
more, we have shown that the MW conditions were
compatible with various sugar protections, such as iso-
propylidene (compound 1), benzoyl (compound 2) and
benzyl (compound 3) groups. We then decided to apply
the MW conditions to a nucleosidic derivative such as
8
115–8119.
5
. Lidstrom, P.; Tierney, J.; Wathey, B.; Westman, J.
Tetrahedron 2001, 57, 9225–9283.
6
7
. Hayes, B. L. Aldrichim. Acta 2004, 37, 66–77.
. Wu, J.; Wu, H.; Wei, S.; Dai, W. M. Tetrahedron Lett.
2
004, 45, 4401–4404.
8
. Kiddle, J. J. Tetrahedron Lett. 2000, 41, 1339–1341.
9. Kiddle, J. J.; Gurley, A. F. Phosphorus, Sulfur Silicon
Relat. Elem. 2000, 160, 195–205.
10. Sabitha, G.; Reddy, M. M.; Srinavas, D.; Yadov, J. S.
Tetrahedron Lett. 1999, 40, 165–166.
11. Bannister, B.; Kagan, F. J. Am. Chem. Soc. 1960, 82,
3363–3368.
0
0
0
0
the 5 -deoxy-5 -iodo-2 ,3 -O-isopropylidene uridine, 4.
The results were somehow disappointing with this last
1
1
substrate, in both thermal and MW conditions the cor-
1
2
responding phosphonate was isolated in less than 25%
yield. The formation of a dark-coloured reaction mix-
ture and side products were observed in all cases, sug-
gesting a thermal degradation of the substrate.
0
0
1
2. Selected physicochemical data for 5 -deoxy-5 -diethylphos-
0
0
20
D
phono-2 ,3 -O-isopropylidene uridine. ½aꢀ
.06, MeOH). R = 0.5 (CH Cl
NMR (400 MHz, DMSO-d
+34.9 (c
1
1
f
2
2
/MeOH, 9/1, v/v). H
6
, 20 °C): d = 1.20 (m, 6H,
0
POCH CH ), 1.30 (s, 3H, CH ), 2.1–2.4 (m, 2H, H-5 , H-
2
3
3
0
0
0
Microwave irradiation is an effective technique to pro-
mote the Michaelis–Arbuzov reaction with short reac-
tion times and reduces the amount of chemical wastes.
However, the high temperatures required to perform
the reaction under both thermal and MW conditions
are still limiting its application to sensitive substrates.
5 ), 3.97 (m, 4H, POCH CH ), 4.25 (m, 1H, H-4 ), 4.80
(dd, J = 3.6 and 6.4 Hz, 1H, H-3 ), 5.10 (dd, J = 1.9 and
6.5 Hz, 1H, H-2 ), 5.65 (d, 1H, H-5), 5.75 (d, J = 1.8 Hz,
H, H-1 ), 7.80 (d, J = 8.0 Hz, 1H, H-6), 11.45 (sl, 1H
2
3
0
0
0
1
1
3
6
exchangeable, NH) ppm. C NMR (100 MHz, DMSO-d ,
2
2
0 °C): d = 14.7, 14.8 (2d, J = 4.3 Hz, POCH
2 3
CH ), 23.7,
0
5.5 (CH ), 27.9 (C-5 , d, J = 137.9 Hz), 59.6, 59.8 (2d,
3
0
0
J = 4.3 Hz, POCH
3
1
2
CH
3
), 80.8 (C-4 ), 82.1 (C-2 ), 82.7 (C-
0
0
, d, J = 11.1 Hz), 91.6 (C-1 ), 100.4 (C-5), 111.7 (Cq),
Acknowledgements
31
42.0 (C-6), 148.0 (C-2), 161.9 (C-4) ppm. P NMR
(
121 MHz, DMSO-d , 20 °C): d = 27.9 ppm. MS (FAB,
6
+
ꢁ
ꢁ
We thank Professor J. Martinez and Dr. F. Lamaty
GT) 405 (M+H) and 807 (2MꢁH) , 403 (MꢁH) , 111
ꢁ
(
LAPP, University of Montpellier II) for the access to
(B) . UV (EtOH 95°) kmax = 256 nm (emax = 10200).