基于芳基乙酮芳基-α-酮酸酯高效一锅法合成及其在不对称氢化中应用探索.pdf

A Dissertation Submitted to Sha nghai Jiao Tong University for Master Degree of Chemistry One-pot synthesis of aryl α-keto esters from aryl α-ketones and its application and exploration in asymmetric hydrogenation Author : Zhuang Jing Specialty: Organic Chemistry Advisor: Asso. Prof. Fang Xie Prof. Wanbin Zhang School of Chemistry and Chemical Engineering Shanghai Jiao T ong University Shanghai, P. R. China Jan. 2010 I 基于芳基乙酮的芳基- α- 酮酸酯的高效一锅法合成及其在不对称氢化中的应用探索摘要芳基- α- 酮酸酯在生物代谢过程中扮演了重要的角色。他们在一些天然产物中作为物质骨架。除此之外,芳基- α- 酮酸酯还被用来作为合成生物活性体的重要中间物,芳基- α- 酮酸酯同时还表现出一定的防晒功效。在过去的几十年,曾出现过很多关于芳基- α- 酮酸酯的合成方法,然而分析所有的这些方法, 发现它们反应条件苛刻、反应步骤复杂、同时伴随着产率较低。这些缺点及不足都限制了芳基- α- 酮酸酯在合成领域的发展应用。在此论文中, 我们报道了一种未经报道的、全新的,由简单易得的原料芳基乙酮出发,采用一锅法制备芳基- α- 酮酸酯的高效合成方法。光学纯芳基- α- 羟基酸及其衍生物在有机合成中是非常有用的原料和活性中间体。例如( R )- α- 羟基-4- 苯基丁酸乙酯就是普利类药物的重要中间体,但到目前为止,其主要来源于拆分,利用不对称氢化获得的成功例子很少。而在所有的制备光学纯的α- 羟基酸及其衍生物方法中, 最为有效的是通过不对称催化氢化相应的α- 酮酸酯来制备。本论文尝试了一系列新概念手性配体来催化芳基- α- 酮酸酯以获得相应的手性芳基- α- 羟基酸酯。关键词: 芳基- α- 酮酸酯,一锅法,芳基- α- 羟基酸酯,不对称氢化 II One-pot synthesis of aryl α-keto esters from aryl α-ketones and its application and exploration in asymmetric hydrogenation ABSTRACT α-Keto esters play an essential role in biological processes. They serve as the backbones in some natural products. In addition, aryl α-keto esters are also used as key intermediates for the synt hesis of pounds. α-Keto esters also show antisunburn effects. In the past several decades, there was much attention fixed on the synthesis of α-keto esters. However all these methods involved either strict conditions, or complicated procedures, or in some cases the low yield and all of these drawbacks extremely limited its application. Herein we report a convenient route to synthesize α-keto esters from aryl-ketones via the one-pot method. Optically pure aryl- α-hydroxyl acid and its deriva tives are very important compounds or active intermediates. ., ( R )- α-hydroxyl-4-phenyl et hyl butyrate is a kind of important int