Research Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan.
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamadaoka, Suita, Osaka 565-0871, Japan.
J Org Chem. 2021 Mar 5;86(5):3683-3696. doi: 10.1021/acs.joc.0c02677. Epub 2021 Jan 31.
Ketene acetal derivatives, such as 1-alkoxyvinyl esters and -silyl ketene acetals, belong to the category of -substituted enols of esters, which easily react with various types of nucleophiles, Nu-H, under neutral conditions to give the corresponding acylated and silylated products in excellent yields only by evaporation of the generated volatile esters. Silyl ketene acetals can be easily synthesized by various simple procedures, whereas 1-alkoxyvinyl esters require an equimolar or catalytic amount of a mercury salt to synthesize them. This drawback prevented the advancement of the chemistry of 1-alkoxyvinyl esters. In 1993, we developed a useful synthetic method of 1-alkoxyvinyl esters using a small amount (0.5-1 mol %) of a ruthenium catalyst. Encouraged by this discovery, we subsequently developed various reactions and applied them to the synthesis of natural products. It is noteworthy that the stereoselective total synthesis of fredericamycin A was achieved by the combined use of these reactions. Macrocyclization was variously utilized for the synthesis of natural macrolides by two types of approaches: direct macrolactonization of α,ω-hydroxy acids or intermolecular esterification between an acid and alcohol followed by a ring-closure step. Additionally, several new reactions using 1-alkoxyvinyl esters or their analogs as key intermediates on the basis of our methods were recently reported. In this paper, we introduce our efforts from the synthesis of 1-alkoxyvinyl esters to the application such as natural product syntheses and recent advancements.
烯酮缩醛衍生物，如 1-烷氧基乙烯基酯和 -硅基烯酮缩醛，属于酯的 -取代烯醇，它们在中性条件下很容易与各种类型的亲核试剂 Nu-H 反应，通过蒸发生成的挥发性酯，仅以优异的产率得到相应的酰化和硅烷基化产物。硅基烯酮缩醛可以通过各种简单的程序很容易地合成，而 1-烷氧基乙烯基酯需要等摩尔量或催化量的汞盐来合成。这一缺点阻碍了 1-烷氧基乙烯基酯化学的发展。1993 年，我们开发了一种使用少量（0.5-1mol%）钌催化剂合成 1-烷氧基乙烯基酯的有用方法。受此发现的鼓舞，我们随后开发了各种反应，并将其应用于天然产物的合成。值得注意的是，通过这些反应的结合，实现了弗雷德里克霉素 A 的立体选择性全合成。通过两种方法对天然大环内酯进行大环化：α，ω-羟基酸的直接大环内酯化或酸和醇之间的分子间酯化，然后进行环化步骤。此外，最近根据我们的方法，使用 1-烷氧基乙烯基酯或其类似物作为关键中间体的几种新反应也有报道。在本文中，我们介绍了从 1-烷氧基乙烯基酯的合成到应用于天然产物合成和最新进展的努力。
