NEW ASYMMETRIC PROCESSES FOR USE IN ORGANIC SYNTHESIS

这项研究旨在发现和开发新的不对称过程， 用于合成对映体纯的有机物质。 到 这一目标的实现程度，许多精细化学品的合成 产品，特别是药品，将被简化。 大约一年前，在这笔资金的支持下，我们发现了一位将军， 烯烃的不对称二羟基化（ADH）的催化方法。 在 这项建议的核心是发展这种新的不对称的计划， 过程 一项重大的努力将被导向寻找更好的 不对称配体，同时试图实现机械 这将使配体设计工作更加合理。 的ADH 该方法还被扩展到催化氧胺化领域。 将仔细检查工艺的底物范围。 目前 几乎任何烯烃都是可能的候选物，因为不对称诱导 不依赖于底物与催化剂的预先结合。 现在容易获得的纯手性二醇的合成应用将 得到重视。 主要推力依赖于二醇转化为 环氧化物样的二氢负离子，如1，2-环状硫酸盐。 这项工作有一个 “合成方法”的方向，但也包括有计划的合成 各种生物活性物质（例如β-内酰胺，地尔硫卓， 芸苔素、抗生素AT-125、cianidanol等）。 C2对称性的纯手性二醇现在容易制备，并且将在 作为手性助剂/配体用于其他不对称过程。 令人鼓舞的是， 烯烃，该项目的长期目标是不对称的 分离的烯烃的环氧化。

This research seeks to discover and develop new asymmetric processes for use in the synthesis of enantiomerically pure organic substances. To the extent that this aim is realized, the syntheses of many fine chemical products, especially pharmaceuticals, will be simplified. About a year ago, under support by this grant, we discovered a general catalytic method for the asymmetric dihydroxylation (ADH) of olefins. At the heart of this proposal are the plans for developing this new asymmetric process. A major effort will be directed toward finding even better asymmetric ligands while at the same time trying to achieve the mechanistic insight which will make the ligand-design work more rational. The ADH process is also being extended to the area of catalytic oxyamination. The substrate scope of the process will be carefully examined. At present almost any olefin is a possible candidate since the asymmetric induction does not depend on prior binding of the substrate to the catalyst. Synthetic applications for the now readily available homochiral diols will receive emphasis. The main thrust relies on conversion of the diols into epoxide-like synthons, such as 1,2-cyclic sulfates. This work has a "synthetic methods" orientation but also includes planned syntheses of various biologically active substances (e.g. beta-lactams, diltiazem, brassinolide, antibiotic AT-125, cianidanol, etc.). Homochiral diols of C2 symmetry are now easily prepared and will be examined as chiral auxillaries/ligands for other asymmetric processes. Encouraged by the successful asymmetric dihydroxylation of isolated olefins, a continuing long-range goal of this project is asymmetric epoxidation of isolated olefins.