Córdova Armando
Department of Organic Chemistry, The Arrhenius Laboratory, Stockholm University, 106 91 Stockholm, Sweden.
Chemistry. 2004 Apr 19;10(8):1987-97. doi: 10.1002/chem.200305646.
The first proline-catalyzed direct catalytic asymmetric one-pot, three-component cross-Mannich reaction has been developed. The highly chemoselective reactions between two different unmodified aldehydes and one aromatic amine are new routes to 3-amino aldehydes with dr>19:1 and up to >99 % ee. The asymmetric cross-Mannich reactions are highly syn-selective and in several cases the two new carbon centers are formed with absolute stereocontrol. The reaction does not display nonlinear effects and therefore only one proline molecule is involved in the transition state. The reaction was also catalyzed with good selectivity by other proline derivatives. The Mannich products were converted into 3-amino alcohols and 2-aminobutane-1,4-diols with up to >99 % ee. The first one-pot, three-component, direct catalytic asymmetric cross-Mannich reactions between unmodified aldehydes, p-anisidine, and ethyl glyoxylate have been developed. The novel cross-Mannich reaction furnishes either enantiomer of unnatural alpha-amino acid derivatives in high yield and up to >99 % ee. The one-pot, three-component, direct catalytic asymmetric reactions were readily scaled up, operationally simple, and conductible in environmentally benign and wet solvents. The mechanism and stereochemistry of the proline-catalyzed, one-pot, three-component, asymmetric cross-Mannich reaction are also discussed.
首个脯氨酸催化的直接催化不对称一锅三组分交叉曼尼希反应已被开发出来。两种不同的未修饰醛与一种芳香胺之间的高化学选择性反应是合成3-氨基醛的新途径，其非对映体比例（dr）>19:1，对映体过量（ee）高达>99%。不对称交叉曼尼希反应具有高度的顺式选择性，在几种情况下，两个新的碳中心以绝对的立体控制方式形成。该反应不显示非线性效应，因此在过渡态中仅涉及一个脯氨酸分子。其他脯氨酸衍生物也能以良好的选择性催化该反应。曼尼希产物被转化为对映体过量高达>99%的3-氨基醇和2-氨基丁烷-1,4-二醇。首个未修饰醛、对甲氧基苯胺和乙醛酸乙酯之间的一锅三组分直接催化不对称交叉曼尼希反应已被开发出来。这种新型交叉曼尼希反应能以高产率和高达>99%的对映体过量得到非天然α-氨基酸衍生物的任意一种对映体。该一锅三组分直接催化不对称反应易于放大，操作简单，且可在环境友好的湿溶剂中进行。还讨论了脯氨酸催化的一锅三组分不对称交叉曼尼希反应的机理和立体化学。
