Organocatalytic asymmetric reactions using (S)-homoproline

近年来，脯氨酸或其衍生物催化的不对称碳-碳成键反应如醛醇反应、Michael加成反应和mannich型反应等受到了有机化学家的广泛关注。在各种类型的有机催化不对称反应中均获得了良好的对映选择性，但迈克尔加成法存在一些严重的局限性。例如，有分散的例子超过90%的ee，衬底通用性不是那么高。另一方面，我们利用(5)-同脯氨酸作为手性有机催化剂，开发了一种新的酮与b-硝基苯乙烯及其衍生物的不对称Michael加成反应。该反应以高度非对映选择性和对映选择性的方式进行，ee超过90%。此外，我们已经开发了无溶剂的有机催化不对称共轭加成巯基到a， b不饱和醛。在设计良好的有机催化剂的存在下，反应无需任何有机溶剂即可进行，从而产生相应的手性硫化物，其对构象纯度几乎为99% （ee）。此外，b， b-二取代a， b-不饱和醛也与苯甲硫醇反应。该方法环保、经济、方便。

Recently, proline or its derivatives-catalyzed asymmetric carbon-carbon bond-forming reactions such as aldol reaction, the Michael addition, and Mannich-type reaction were studied intensively by many organic chemists. Excellent enantioselectivity was attained in various types of organocatalytic asymmetric reactions, but the Michael addition has some serious limitations. For example, there are scattered examples over 90% ee, and substrate generality is not so high. On the other hand, we have developed a novel asymmetric Michael addition reaction of ketone to b-nitrostyrene and its derivatives using (5)-homoproline as a chiral organocatalyst. The reaction was performed in a highly diastereoselective and enantioselective manner over 90% ee. Furthermore, we have developed solvent-free organocatalytic asymmetric conjugate addition of thiols to a, b-unsaturated aldehydes. In the presence of well-designed organocatalyst, the reaction proceeds without any organic solvents, giving the corresponding chiral sulfides in almost enantiomerically pure form (up to 99% ee). Moreover, b, b-disubstituted a, b-unsaturated aldehydes also reacted with phenylmethanethiol. This method is environment-friendly, economical, and convenient.