Practical Application of Ketene Acetal-type Reactive Acylating Reagents

通常，酰化反应是通过使用活性的羧酸衍生物如酸卤化物来进行的。然而，由于反应条件和酸性和/或非挥发性副产物的形成，经常会遇到一些问题，包括副反应、分解和/或产物难以提纯。在这个项目中，我们致力于解决这些问题，并开发新的合成方法，使用缩酮缩醛类型的酰化试剂1，其反应条件温和，并作为单一副产物形成挥发性酯。根据研究建议，得到了以下结果：1.通过Ru催化的乙氧基乙炔与羧酸的加成反应制备了不同类型的1，3-二甲基-2-甲基-4-甲基-4-甲基-2-甲基-4-甲基-4-甲基-4-甲基-4，4-甲氧基-1，4-甲氧基-1，4-甲氧基-1，4，4，4，4，4，4，5，5，5，5，5，5，5，5，5，6，5，5，6，5，5，5，6，5，5，5，5，5，6，5，5，5，5，5，5，4，4，4，4，4，5，5，5，5，5，5，5，5，5，5，5，5，5建立了以硅烯酮为原料制备新型烯酮缩醛试剂的有效前体--硅氧基乙炔。2.反式…对醇的酶促拆分更多的酰化反应是通过使用乙烯基酯进行的。然而，这种方法有一个严重的缺点，就是副产物乙醛会使酶失活。我们已经阐明，试剂1的使用克服了这一问题，成为酶促拆分外消旋醇和前手性二醇不对称反应的新型、高活性和可靠的酰基供体。3.各种类型的试剂1被应用于脂肪族手性亚砜的高度不对称Pummerer型重排反应和类似的Pummerer型环化反应。4.我们利用三氟乙酸酐(TFAA)进行了对亚磺基苯酚衍生物的芳香族Pummerer型反应，首次将硫官能团自取代为芳环上的氧官能团，提供了一种新的对苯二酚和二氢对苯二酚的制备方法。用1取代TFAA，首次实现了对苯二酚单O，S缩醛中间体的分离。较少

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