Direct asymmetric anti-Mannich-Type reactions catalyzed by a designed amino acid
Direct asymmetric anti-Mannich-Type reactions catalyzed by a designed amino acid
复制标题
DOI：
10.1021/ja056984f
复制
发表时间：
2006-02-01
影响因子：
15
通讯作者：
Barbas, CF
中科院分区：
文献类型：
--
作者：
Mitsumori, S;Zhang, H;Barbas, CF
报道了曼尼希型反应催化剂的开发，该催化剂在温和的条件下和低的催化剂负载量(1−5摩尔%)下提供了良好的非对映选择性和对映选择性的反产物。(3R，5R)-5-甲基-3-吡咯烷甲酸(RR35)是根据(S)-脯氨酸催化的富含对映体合成产物的曼尼希型反应的基本原理设计的。用HF/6-31G*理论水平对上述反应进行的计算研究表明，这种设计将是非常有效的。随后合成了该催化剂，并将其用于未改性醛与n-PMP保护的α-亚胺酯之间的Mannich式有机催化反应。根据设计原则和理论预测，该催化剂催化的反应以良好的产率和良好的非对映选择性和对映体选择性(ANT：SY94：6至98：2，>；97至>；99ee)提供了反产物。
The development of catalysts for Mannich-type reactions that affordanti-products with excellent diastereo- and enantioselectivities under mild conditions and low catalyst loadings (1−5 mol %) is reported. Based on principles gained from the study of (S)-proline-catalyzed Mannich-type reactions that afford enantiomerically enrichedsyn-products, (3R,5R)-5-methyl-3-pyrrolidinecarboxylic acid (RR35) has been designed to catalyze the direct enantioselectiveanti-selective Mannich-type reactions. Computational studies of the above reaction using HF/6-31G* level of theory suggested that this design would be highly effective. The catalyst was subsequently synthesized and studied in organocatalytic Mannich-type reactions between unmodified aldehydes andN-PMP-protected α-imino esters. In accord with the design principles and in quantitative agreement with the theoretical predictions, reactions catalyzed by this catalyst affordedanti-products in good yields with excellent diastereo- and enantioselectivities (anti:syn94:6 to 98:2, >97 to >99% ee).