Fujisawa Hidehiko, Takahashi Eiki, Mukaiyama Teruaki
Center for Basic Research, The Kitasato Institute, 6-15-5 Toshima, Kita-ku, Tokyo 114-0003, Japan.
Chemistry. 2006 Jun 23;12(19):5082-93. doi: 10.1002/chem.200500821.
Lewis base catalyzed Mannich-type reaction between trimethylsilyl enol ethers and N-tosylaldimines is described. Nitrogen anions generated from amides or imides such as lithium benzamide or potassium phthalimide are found to be effective Lewis base catalysts in DMF at room temperature to afford the corresponding beta-amino carbonyl compounds in good to high yields; the oxygen anion generated from carboxylic acids such as lithium acetate was also found to be effective in dry DMF. The above-mentioned lithium acetate-catalyzed Mannich-type reaction between aldimines and various trimethylsilyl (TMS) enol ethers such as silyl ketene acetal proceeded smoothly even in water-containing DMF. Then, Lewis base catalyzed three-component Mannich-type reactions of TMS enol ether, tosylamide, and aromatic aldehyde having electron-withdrawing group such as p-nitrobenzaldehyde were investigated. The reaction proceeded smoothly to afford the corresponding beta-amino ester in good yield. Further, ammonium carboxylates such as tetrabutyl ammonium acetate or tetrabutyl ammonium benzoate were found to be more effective Lewis base catalysts in the above-mentioned Mannich-type reaction. The synthesis proceeded in various solvents at lower temperatures. The reaction between aldimines and TMS enol ethers generated from thioester and various ketones such as propiophenone or cyclohexanone also proceeded smoothly to afford the corresponding beta-amino carbonyl compounds in high yields with good to high anti-selectivities.
描述了路易斯碱催化的三甲基硅烯醇醚与N-甲苯磺酰醛亚胺之间的曼尼希型反应。发现由酰胺或酰亚胺（如苯甲酰胺锂或邻苯二甲酰亚胺钾）产生的氮阴离子在室温下的N,N-二甲基甲酰胺（DMF）中是有效的路易斯碱催化剂，能以良好到高的产率得到相应的β-氨基羰基化合物；由羧酸（如乙酸锂）产生的氧阴离子在无水DMF中也被发现是有效的。上述乙酸锂催化的醛亚胺与各种三甲基硅基（TMS）烯醇醚（如硅基乙烯酮缩醛）之间的曼尼希型反应，即使在含水的DMF中也能顺利进行。然后，研究了路易斯碱催化的三甲基硅烯醇醚、甲苯磺酰胺和具有吸电子基团的芳香醛（如对硝基苯甲醛）的三组分曼尼希型反应。该反应顺利进行，以良好的产率得到相应的β-氨基酯。此外，发现羧酸铵（如乙酸四丁铵或苯甲酸四丁铵）在上述曼尼希型反应中是更有效的路易斯碱催化剂。该合成反应在各种溶剂中于较低温度下进行。醛亚胺与由硫酯和各种酮（如苯丙酮或环己酮）生成的三甲基硅烯醇醚之间的反应也顺利进行，以高收率得到相应的β-氨基羰基化合物，具有良好到高的反式选择性。
