Practical Application of Ketene Acetal-type Reactive Acylating Reagents

乙烯酮缩醛型反应酰化试剂的实际应用

• 批准号: 07557138
• 负责人: KITA Yasuyuki
• 金额: $ 3.01万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557138/
• 关键词: ketene acetal reagent; acylating reagent; asymmetric Pummerer-type reaction; aromatioc Pummerer-type reaction; stereoselective reaction; optical resolution; enzymatic reaction; silyloxyacetylene; 芳香族プメラ-型転位反応; 非対称化反応; シロキシアセチレン; シリル化剤; リパーゼ

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

通常，酰化反应通过使用活化的羧酸衍生物例如酰卤来进行。然而，由于反应条件和酸性和/或非挥发性副产物的形成，常常遇到一些问题，包括副反应、产物分解和/或难以纯化。在这个项目中，我们旨在解决这些问题，并通过使用烯酮缩醛型酰化试剂1开发新的合成方法，该试剂具有温和的反应条件和形成挥发性酯作为单一副产物的特点。根据研究方案，得到如下结果： 1.通过钌催化下羧酸与乙氧基乙炔的加成反应制备了各种类型的1。建立了从甲硅烷基乙烯酮制备甲硅烷氧基乙炔的方法，甲硅烷氧基乙炔是制备新型乙烯酮缩醛型试剂的有效前体。2.使用乙烯基酯进行了反式酰化酶法拆分醇。然而，该方法有一个严重的缺点，即副产物乙醛会使酶失活。我们已经阐明，试剂1的使用克服了这个问题，作为新型、高反应性和可靠的酰基供体，用于酶促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 反应。阐明了增加1中酰基的给电子能力往往会增加对映选择性。4.我们利用三氟乙酸酐(TFAA)开发了对亚磺酰基苯酚衍生物的芳香族Pummerer型反应，导致硫官能团首次自行取代为芳环上的氧官能团，并产生了对亚磺酰基苯酚衍生物。 提供了醌和二氢醌的新制剂。使用 1 代替 TFAA 使我们能够首次分离出醌单 O,S-缩醛中间体。较少的

项目成果

Y.Kita, Y.Takeda, K.Iio, K.Yokogawa, K.Takahashi, and S.Akai: "An Efficient Preparation of peri-Hydroxy Dihydroquinone Derivatives through a Pummerer-type Rearrangement of Sillylene-protected peri-Hydroxy Aromatic Sulfoxides" Tetrahedron Lett.37. 7545-754

Y.Kita、Y.Takeda、K.Iio、K.Yokokawa、K.Takahashi 和 S.Akai：“通过亚硅基保护的近羟基芳香族亚砜的 Pummerer 型重排，有效制备近羟基二氢醌衍生物”

Y.Kita, N.Shibata, N.Yoshida, N.Kawano, C.Fujimori, N.Yoshikawa, and S.Fujita: "Mechanistic Studies of Pummerer-type Reaction in Acyclic and Rigid Cyclic Sulfoxides Induced by O-Silylated Ketene Acetal" J.Chem.Soc., Perkin Trans.1. 2829-2834 (1995)

Y.Kita、N.Shibata、N.Yoshida、N.Kawano、C.Fujimori、N.Yoshikawa 和 S.Fujita：“O-硅烷化乙烯酮缩醛诱导的无环和刚性环状亚砜中 Pummerer 型反应的机理研究”

N.Shibata, S.Fujita, M.Gyoten, K.Matsumoto, and Y.Kita: "A Novel Diastereoselective Synthesis of Chiral, Non-racemic Unsymmetrical Thioacetals Using Silicon-induced Pummerer-type Reaction" Tetrahedron Lett.36. 109-112 (1995)

N.Shibata、S.Fujita、M.Gyoten、K.Matsumoto 和 Y.Kita：“利用硅诱导的普默勒型反应，一种新颖的非对映选择性合成手性非外消旋不对称硫缩醛”四面体 Lett.36。

Kita,Yasuyuki: "Asymmetric Pummerer-Type Reactions Induced by O-Silylated Ketene Acetals (Review)" Synlett. 289-296 (1996)

Kita，Yasuyuki：“O-硅烷化乙烯酮缩醛诱导的不对称 Pummerer 型反应（评论）”Synlett。

Kita, Yasuyuki: "Reaction of Ynolate Anions Derived from Silyketene with Electcophiles : AFacile Preparation of Silyl Ynol Ethers and Functionalized Silylketenes" J. Chem. Soc. Perkin Trans. 1. 1705-1709 (1996)

Kita，Yasuyuki：“源自硅酮的炔醇阴离子与亲电体的反应：硅基炔醇醚和官能化硅酮的轻松制备”J. Chem。