A. Dondoni, A. Massi / Tetrahedron Letters 42 (2001) 7975–7978
7977
(Scheme 1).19 The whole synthesis–purification
procedure20 was tested with the above model reaction
(Table 1, entry 1) which in fact afforded 5a in good
yield and high purity. A wide range of b-dicarbonyl
compounds 121 and aromatic aldehydes 221 were cou-
pled with urea by the optimized protocol to produce
the corresponding dihydropyrimidinones 5–12 in good
yield and purity.22 The results are listed in Table 1. All
compounds were characterized by MS analysis and
8. (a) Ault-Justus, S. E.; Hodges, J. C.; Wilson, M. W.
Biotech. Bioeng. (Comb. Chem.) 1998, 61, 17; (b)
Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc. 1996,
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9. Dondoni, A.; Massi, A.; Sabbatini, S. Tetrahedron Lett.
2001, 42, 4495.
10. (a) Biginelli, P. Gazz. Chim. Ital. 1893, 23, 360; (b) For
a recent review see: Kappe, C. O. Acc. Chem. Res.
2000, 33, 879.
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D. M.; Moreland, S.; Hedberg, A.; O’Reilly, B. C. J.
Med. Chem. 1991, 34, 806 and references cited therein;
(b) Atwal, K. S.; Rovnyak, G. C.; Kimball, S. D.;
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1
their structures confirmed by H and 13C analysis.
In conclusion, we have developed an environmentally
friendly procedure for the synthesis of DHPMs. This
involved the use of polymer-bound Yb(III) reagent
under solvent-free conditions in combination with suit-
able polymer-supported scavengers. A collection of
DHPMs has been generated by a parallel synthesis
approach. While we have not used robotic systems in
this study, we believe that this route will be of great
value for the generation of larger DHPMs libraries in
automated parallel synthesis operations. Work is cur-
rently underway to decorate the DHPM scaffold with
polymer supported reagents for the synthesis of more
sophisticated DHPM derivatives.
12. (a) Valverde, M. G.; Dallinger, D.; Kappe, C. O. Syn-
lett 2001, 6, 741; (b) Kappe, C. O. Bioorg. Med. Chem.
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hedron Lett. 1995, 36, 7819.
13. Studer, A.; Jeger, P.; Wipf, P.; Curran, D. P. J. Org.
Chem. 1997, 62, 2917.
14. Bigi, F.; Carloni, S.; Frullanti, B.; Maggi, R.; Sartori,
G. Tetrahedron Lett. 1999, 40, 3465.
15. (a) Ma, Y.; Qian, C.; Wang, L.; Yang, M. J.
Org. Chem. 2000, 65, 3864; (b) Lu, J.; Bai, Y.;
Wang, Z.; Yang, B.; Ma, H. Tetrahedron Lett. 2000,
41, 9075.
Acknowledgements
16. Amberlyst 15 and Ambersep 900 OH were pur-
chased from Aldrich and Fluka, respectively. These
resins were washed with methanol and dried in vacuo
before use.
We gratefully thank the University of Ferrara for finan-
cial support.
17. Yu, L.; Chen, D.; Li, J.; Wang, P. G. J. Org. Chem.
1997, 62, 3575.
References
18. The content of Yb(III) on resin 4 was determined
according to the procedure described in Ref. 17 and
was around 1.5 mmol/g. Urea is partially absorbed
onto 4 and it is released by washing the polymer with a
2 M solution of ammonia in methanol.
19. Under these conditions the contaminants, i.e. excess
urea and by-products, were selectively extracted. On the
other hand a control experiment showed that on treat-
ing pure 5a with A-15 and Ambersep 900 OH (MeOH,
2h) and filtration of the resins, the starting material
was totally recovered.
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idinones 5–12: a screw-capped vial, containing a mag-
netic stirring bar, was charged first with 160 mg of
Yb(III)-resin 4 then with urea 3 (1.5 mmol), aldehyde 2
(0.5 mmol), and b-dicarbonyl compound (0.5 mmol) 3
and heated at 120°C for 5 min. Then 170 mg of
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resin was filtered off and washed thoroughly with
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(400 mg) were added to the combined filtrates. The
suspension was shaken for 2 h then the resins were
filtered off and washed thoroughly with methanol. The
combined filtrates were concentrated to give dihydropy-
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Dondoni, Alessandro
