Practical Application of Ketene Acetal-type Reactive Acylating Reagents

通常，酰化反应通过使用活化的羧酸衍生物如酰基卤来进行。然而，由于反应条件和酸性和/或非挥发性副产物的形成，经常遇到几个问题，包括副反应、分解和/或产物的难以纯化。在本项目中，我们的目标是解决这些问题，并开发新的合成方法，通过使用烯酮缩醛型酰化试剂1，其特征在于温和的反应条件和形成挥发性酯作为单一副产物。根据上述研究建议，主要取得了以下研究成果：1.通过羧酸与乙氧乙炔的加成反应，合成了不同类型的1。建立了以硅烷基烯酮为原料制备新型烯酮缩醛类试剂的前体--硅氧基乙炔类化合物的方法 ...更多信息 使用乙烯基酯进行酰化。然而，该方法具有通过副产物乙醛使酶失活的严重缺点。我们已经阐明，使用的试剂1克服了这个问题，作为一个新的，高活性，和可靠的酰基供体的酶法拆分外消旋醇和前手性二醇的不对称化。3.各种类型的1被应用于高度不对称的脂肪族手性亚砜的Pummerer型重排反应和类似的Pummerer型环化反应。4.利用三氟乙酸酐（TFAA）进行了对亚磺酰基苯酚衍生物的芳香Pummerer型反应，首次实现了芳香环上的含硫官能团向含氧官能团的自位取代，为醌类和二氢醌类化合物的合成提供了一种新的方法。使用1代替TFAA允许我们的醌单O，S-缩醛中间体的第一个分离。少

Usually, the acylation reaction has been carried out by the use of activated carboxylic acid derivatives such as acid halides. However, due to the reaction conditions and formation of acidic and/or non volatile by-products, several problems including side-reactions, decomposition and/or difficult purification of the products have often been encountered. In this project, we have aimed at the resolution of these problems and the development of novel synthetic methods by the use of the ketene acetal-type acylating reagents 1 which feature mild reaction conditions and formation of volatile esters as the single by-product. According to the research proposals, the following results were obtained.1.Various types of 1 are prepared by the ruthenium-catalyzed addition of caboxylic acids to ethoxyacetylene. Preparation of the silyloxyacetylenes, potent precursors for preparation of novel ketene acetal-type reagents, from silylketenes was established.2.The enzymatic resolution of alcohols by trans … More acylation has been carried out by the use of vinyl esters. However, this method has a serious drawback of deactivation of the enzyme by the by-product, acetaldehyde. We have elucidated that the use of the reagents 1 overcomes this problem to act as novel, high reactive, and reliable acyl donors for enzymatic resolution of racemic alcohols and for asymmetrization of prochiral diols.3.Various types of 1 were applied to highly asymmetric Pummerer-type rearrangement reaction of aliphatic chiral sulfoxides and to similar Pummerer-type cyclization reactions. It was elucidated that increasing the electron-donating ability of the acyl group in 1 tended to increase enantioselectivity.4.We have developed the aromatic Pummerer-type reactions of p-sulfinylphenol derivatives by using trifluoroacetic anhydrides (TFAA), which caused the first ipso-substitution of the sulfur functional groups into the oxygen functional groups on the aromatic rings and provided a novel preparation of quinones and dihydroquinones. The use of 1 instead of TFAA allowed us the first isolation of the quinone mono O,S-acetal intermediates. Less