Creation of Novel Axially-Chiral Compounds : Developments toward Asymmetric Synthesis

本课题研究了具有1,1′-联萘骨架的轴向手性化合物的不对称合成。重点研究了不对称Wittig反应和不对称质子化反应。由于Wittig反应生成sp^2碳，它在不对称合成中的应用相当有限。我们通过对α -二酮的对映羰基的辨别证明了西格玛对称中位化合物的不对称性。采用具有1,1′-二萘-2,2′-二醇片段的手性膦酸盐作为手性助剂，与刚性环α -二酮实现了高度对映选择性的wittig型反应。分子内不对称witting型反应也可得到中等至高对映选择性的多环酮。由于质子化是化学转化中最简单的操作之一，烯醇酸酯的不对称质子化应该在生产光学活性羰基化合物方面有广泛的应用。我们利用具有1,1'-二萘-8,8'-二醇片段的手性质子源研究了不对称质子化。质子化的对映选择性在很大程度上取决于烯醇化物的反阳离子。四烯酮衍生物的烯醇酸锂只产生9%的ee，而相应的烯醇酸镁则产生94%的ee。

This research project has dealt with asymmetric synthesis using axially chiral compounds which possess 1,1'-binaphthalene skeleton. Especially, asymmetric Wittig reaction and asymmetric protonation were examined. Since Wittig reaction creates sp^2 carbon, its application to asymmetric synthesis had rather been limited. We demonstrated asymmetrization of sigma-symmetrical meso-compounds through discrimination of enantiotopic carbonyls of alpha-diketones. Using chiral phosphonates having 1,1'-binaphthalene-2,2'-diol moiety as a chiral auxiliary, highly enantioselective Wittig-type reactions were achieved with rigid cyclic alpha-diketones. Intramolecular Asymmetric Witting-type reactions were also performed to afford polycyclic ketones in moderate to high enantioselectivity.Since protonation is one of the most simple operations out of chemical transformations, asymmetric protonation of enolates should have wide variety of applications to production of optically active carbonyl compounds. We have investigated asymmetric protonation using chiral proton sources having 1,1'-binaphthalene-8,8'-diol moiety. Enantioselectivity of the protonation depended strongly on the countercation of the enolates. While the lithium enolate of an alpha-tetralone derivative gave the products of only 9% ee, the corresponding magnesium enolare afforded the product of 94% ee.