Catalytic Enantioselective Reaction

催化过程中的对映选择性反应是目前公认的有机合成中最重要和最具挑战性的问题之一。已经报道了许多由各种手性配体如氨基醇或亲和体修饰的氨基路易斯酸。然而，这种给电子配体降低了路易斯酸的酸度。为了实现高效的催化过程，我们认为催化剂的加速作用或吸引作用似乎是重要的，除了sterwwcontrol和产物与催化剂上的底物的易于交换。基于这种考虑，我们对用吸电子的手性配体而不是手性醇或亲和体来修饰路易斯酸产生了兴趣。在这种修饰的Lewis酸中，手性配体不仅会提供手性环境，还会增加Lewis酸的酸度。在各种酸性化合物中，我们选择了c_2对称磺胺作为手性配体。我们发展了两种类型的催化对映选择反应。(1)乙醛与二烷基锌、Ti(O-i-Pr)_4和二磺酰胺进行烷基化反应；(2)CH_2I_2、Et_2Zn和二磺酰胺进行烯丙醇环丙化反应。烷基化的显著特点是前所未有的高催化周转率（高达2000次）以及优异的对映体选择性。本发明的环丙烷化是催化和对映选择性环丙烷化的第一个例子。这些结果将有力地证明用手性磺化配体修饰路易斯酸的概念在开发其他类型的催化对映选择反应方面是有希望的。

An enantioselective rraction ffimugh a catalytic process is now recognized as one of the most important and challenging problems in organic synthesis. There have been reported a number of chiml Lewis acids modified by a variety of chiral ligands such as chiml alcohols or amities. However, such an electron-donating ligand decreases the acidity of the Lewis acid. In order to realize efficient catalytic process, we reasoned that the rate accelomting effect or attractive effect of the catalyst seemed to be important in addition to the sterwwntrol and the facile exchange of the product with the substrate on the catalyst. Based on this consideration we became interested in modifying a Lewis acid by electron-withdrawing chiral ligands rather than chiral alcohols or amities. In such a modified Lewis acid, the chiral ligand will not only provide a chiral environment but also increase the acidity of the Lewis acid. Among various acidic compounds we selected C_2-symmetric sulfonamide as a chiral ligand. We have developed two types of catalytic enantioselective reactions. (1) Alkylation of an aldehyde with dialkylzinc, Ti(O-i-Pr)_4 and disulfonamide, and (2) Cyclopropanation of an allylic alcohol using CH_2I_2, Et_2Zn and disulfonamide. Significant features of alkylation are unprecedent high catalytic turnover (up to 2, 000 times) as well as excellent enantioselectivity. The present cyclopropanation is the first example of a catalytic and enantioselective cyclopropanation. And these results will strongly demonstrate that the concept of modifying a Lewis acid with chiral sulfonmft ligand is promising in developing other types of catalytic enantioselective reactions.