School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
J Org Chem. 2013 Jul 19;78(14):7131-6. doi: 10.1021/jo4010316. Epub 2013 Jul 10.
Enantiomerically pure 3-methyl-β-proline was synthesized using an asymmetric phase-transfer-catalyzed alkylation of a cyanopropanoate to establish the all-carbon stereogenic center. The catalytic activity of 3-methyl-β-proline in the Mannich-type reaction between a glyoxylate imine and ketones/aldehydes was subsequently investigated. The catalyst was designed and found to be more soluble in nonpolar organic solvents relative to the unsubstituted β-proline catalyst, and as a result allowed for added flexibility during optimization efforts. This work culminated in the development of a highly anti-diastereo- and enantioselective process employing low catalyst loading.
手性纯的 3-甲基-β-脯氨酸通过不对称相转移催化氰基丙酸盐的烷基化反应合成，从而建立全碳立体中心。随后研究了 3-甲基-β-脯氨酸在乙二醛亚胺与酮/醛的Mannich 型反应中的催化活性。设计并发现该催化剂相对于未取代的β-脯氨酸催化剂在非极性有机溶剂中具有更高的溶解度，因此在优化过程中具有更大的灵活性。这项工作最终开发出了一种使用低催化剂负载量的高度反非对映选择性和对映选择性的过程。
