Departmento de Química Orgánica I, Universidad del País Vasco, Manuel Lardizabal 3. 20018-San Sebastián, Spain.
Chemistry. 2010 May 10;16(18):5333-42. doi: 10.1002/chem.200903537.
An anti-selective Mannich reaction of aldehydes with N-sulfonyl imines has been developed by using a 4-hydroxypyrrolidine in combination with an external Brønsted acid. The catalyst design is based on three elements: the alpha-substituent of the pyrrolidine, the 4-hydroxy group, and the Brønsted acid, the combination of which is essential for high chemical and stereochemical efficiency. The reaction works with aromatic aldehyde-derived imines, which have rarely been employed in previously reported enamine-based anti-Mannich reactions. Additionally, both N-tosyl and N-nosyl imines can be successfully used and the Mannich adducts can be easily reduced or oxidized, and after N-deprotection the corresponding beta-amino acids and beta-amino alcohols can be obtained with good yields. The results also show that this ternary catalytic system may be practical in other enamine-based reactions.
已开发出一种醛与 N-磺酰亚胺的反选择性曼尼希反应，该反应使用 4-羟基吡咯烷与外部布朗斯台德酸组合。催化剂设计基于三个要素：吡咯烷的α-取代基、4-羟基和布朗斯台德酸，它们的组合对于高化学和立体化学效率是必不可少的。该反应适用于芳醛衍生的亚胺，这些亚胺在以前报道的基于烯胺的反曼尼希反应中很少使用。此外，N-甲苯磺酰基和 N-硝磺酰基亚胺都可以成功使用，曼尼希加成物可以很容易地还原或氧化，并且脱保护后可以以良好的收率得到相应的β-氨基酸和β-氨基醇。结果还表明，该三元催化体系在其他基于烯胺的反应中可能具有实际应用价值。
