Helvetica Chimica Acta Vol. 87 (2004)
2611
In summary, a mild, convenient, and inexpensive variant of the three-component
Biginelli reaction has been developed, based on an FeIII/Me3SiCl catalytic system. The
new protocol can be used to react either ureas or carbamates with different electron-
rich or electron-poor aromatic aldehydes and ketones, giving rise to dihydropyrimi-
dines or open-chain b-amino carbonyl compounds, respectively. Our experiments, thus,
extend the versatility of N-containing weak nucleophiles in Mannich reactions. Further
studies concerning the mechanism of and potential asymmetric catalysts for these types
of reactions are now under investigation.
This study was financially supported by the Natural Science Foundation of China (Grant No. 29933050 and
20373082).
Experimental Part
General. All solvents and reagents were purchased and used without further purification. TLC: Silica-gel
(F254) plates; spots visualized under UV light. Flash chromatography (FC): silica gel (100 200 mesh). IR
Spectra: FT-IR apparatus; in cmÀ1. 1H- and 13C-NMR spectra: at 400 and 100 MHz, resp., and were referenced
to internal solvent signals; d in ppm, J in Hz. All compounds were characterized spectroscopically and by GC/
MS (Agilent 6890N GC/5973N MS, HP-5 MS).
General Procedure for the Direct Mannich Reaction of Carbamates. To a soln. of the aldehyde (5.0mmol)
and FeCl3 ¥ 6 H2O (0.5 mmol) in Et2O (10ml) were added, in this order, ethyl carbamate (10mmol) in CH 2Cl2
(10ml), the ketone (5.0mmol), and Me 3SiCl (0.5 equiv.). The mixture was stirred untill the reaction was
complete (TLC). The reaction was quenched with H2O, and the aq. layer was extracted with CHCl3. The
combined org. layers were dried (Na2SO4), filtered, and evaporated. The crude product was purified by FC
(AcOEt/petroleum ether), and all products were fully characterized.
Selected Data for Ethyl N-[1-(2-Chlorophenyl)-3-oxo-3-phenylpropyl]carbamate (Table 2, Entry 7). IR:
1
3313, 3071, 2981, 2908, 1693, 1579, 1551, 1349, 1268, 1239, 1064, 1033. H-NMR: 7.88 (d, J 7.2, 2 H); 7.57 (m,
1 H); 7.41 (m, 2 H); 7.24 (m, 2 H); 6.81 (m, 2 H); 5.63 (br. s, 1 H); 5.22 (dd, J 6.4, 14.0, 1 H); 4.07 (dd, J 6.8,
14.0, 2 H); 3.64 3.74 (m, 2 H); 3.37 3.43 (m, 1 H); 1.20 (t, J 6.4, 15.2, 3 H). 13C-NMR: 198.2; 159.0; 156.1;
136.9; 133.7; 133.6; 128.9; 128.3; 127.8; 114.2; 61.1; 55.5; 51.5; 44.3; 14.8. Anal. calc. for C18H18NO3Cl: C 65.16, H
5.43, N 4.22; found: C 65.12, H 5.41, N 4.25.
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