Development of Novel Reformatsky Reaction by Using Lewis Acid-Reductant.

我们发现，在温和的条件下，用刘易斯酸和膦的组合可以实现α-溴酰胺的还原。此外，已经报道了当醛与中间体金属烯醇化物反应时可以进行Reformatsky型反应，以良好的产率和高立体选择性得到所需的β-羟基酰胺。本论文首先研究了以α-溴代酮或硫代酯代替α-溴代酰胺的Reformatsky反应。结果，通过使用四氯化钛和三邻甲苯基膦的组合，以良好的产率和高立体选择性获得了所需的Reformatsky型产物。接下来，将该反应应用于其他亲电试剂，如硫酯、缩醛和亚胺。与硫酯的反应顺利地进行，得到还原性的Claisen缩合物，与亚胺的Mannich型反应也被发现以高产率和高立体选择性得到相应的加合物。此外，我们还考察了其它还原反应，发现了α-二酮的半还原、亚砜的脱氧等，特别是后者应用于外消旋膦的动力学拆分，得到了光学活性的膦，发现了几种有用的碳-碳键形成反应、还原官能团的相互转化等。结果表明，该试剂体系在有机合成领域具有广阔的应用前景。

We have found that the reduction of α-bromoamide could be achieved under mild conditions using Lewis acid and phosphine combination. Also, it has been already reported that the Reformatsky-type reaction could proceed when the aldehyde was reacted with the intermediate metal enolate, to give the desired β-hydroxyamide in good yield with high stereoselectivity. In this research, we would like to develop the synthetically useful reactions using this methodology.At first, the Reformatsky reaction using α-bromoketones or thioesters, instead of α-bromoadmides, were investigated. As a result, the desired Reformatsky-type products were obtained in good yield with high stereoselectivity by using the combination of titanium tetrachloride and tri-o-tolylphosphine. Next, this reaction was applied to the other electrophile such as thioesters, acetals, and imines. The reaction with thioester have smoothly proceeded to give the reductive-Claisen condensate, and the Mannich-type reaction with imine was also found to give the corresponding adducts in good yield with high stereoselectivity. Moreover, other reductive reactions were also examined and we found the half-reduction of α-diketones, deoxygenation of sulfoxides and so on. Especially, the later was applied to the kinetic resolution of racemic phosphines to give optically active phosphines.We found the several useful carbon-carbon bond forming reactions, reductive functional group interconversions using this combined reagent system. It was found that the combined reagent system was useful in the field of organic synthesis.