Development of Novel Synthetic Methods of Organic Compounds Using Ketene as a Building Block.

烯酮通常是不稳定的和反应性的物种，并且只有少数稳定的单体烯酮可用。烯酮是已知的有用试剂，因为它们由于其特征结构而具有独特的反应性。然而，由于它们缺乏稳定性，迄今为止尚未在有机合成中实现广泛的应用。本研究课题主要致力于发展新型的立体选择性反应，即以乙烯酮为关键中间体的新型反应，众所周知，通过乙烯酮与亚胺的反应可以合成β-内酰胺。由于β-内酰胺结构是一类重要抗生素中发现的基本骨架，我们首先研究了使用手性亚胺的新的不对称方法的发展。结果发现，衍生自1-（2，6-二氯苯基）乙胺的手性亚胺以良好至优异的产率和高立体选择性得到相应的β-内酰胺。接下来，我们设计了具有衍生自邻-2-氨基-1，2-二苯基乙醇的手性恶唑烷酮助剂的烯酮。乙烯酮容易地由相应的羧酸通过与2-氯吡啶鎓盐的脱水反应制备。烯酮与亚胺的反应顺利进行，得到了几乎完全立体选择性的β-内酰胺。还已知烯酮与烯烃以及亚胺反应以提供环丁酮。因此，接下来我们研究了具有双键的手性烯酮的分子内[2+2]环加成反应。结果表明，反应顺利进行，得到了高立体选择性的环丁酮衍生物。

Ketenes are generally unstable and reactive species, and only a few stable monomeric ketenes are available. Ketenes are known as useful reagents since they have unique reactivity due to their characterisric sutucture. However, because of their lack of stability, application over a wide area in organic synthesis has not been achieved so far. This research project is concerned with the development of novel stereoselective reactions, novel type of reactions using a ketene as a key intermediate.It is well known that beta-lactams can be synthesized by the reaction between a ketene and an imine. Since beta-lactams structure is a fundamental skeleton found in an important class of antibiotics, we first examined the development of new asymmetric methodology by using a chiral imine. As a result, it was found that a chiral imine derived from 1-(2,6-dichlorophenyl) ethylamine gave the corresponding beta-lactams in good to excellent yields with high stereoselectivity. Next, we designed a ketene having a chiral oxazolidinone auxiliary derived from erythro-2-amino-1,2-diphenylethanol. The ketene was easily prepared from the corresponding carboxylic acid via dehydration reaction with a 2-chloropyridinium salt. The reaction of the ketene with inines proceeded smoothly to give the desired beta-lactams with almost comlete stereoselectivity. Ketenes are also known to react with alkenes as well as imines to afford cyclobutanones. So, next we investigated intramolecular [2+2] cycloaddition reaction of chiral ketenes having a double bond. As a result, we found that the reaction proceeded smoothly to give the corresponding cyclobutanone derivatives with high stereoselectivity.