Development of new optical active carbene reagents and its application to the synthesis of unnatural sugars

很早以前人们就知道，以噻唑盐和三唑盐为代表的唑盐用弱碱处理会产生阴离子或共振稳定的碳，碳能作为催化剂促进Stetter反应和安息香缩合。在研究过程中，这些反应向我们展示了新的方面：1)Stetter反应生成季碳和2)选择性交叉苯甲酰胺缩合。以水杨醛衍生物为底物，通过分子内反应合成季碳。在温和的条件下，反应收率高。这个反应也是第一个用Stetter反应构造季碳的例子。在交叉苯甲酸甲酯反应中，我们发现芳香醛和脂肪醛的结合对选择性合成半胱氨酸非常重要，尤其是噻唑盐在交叉苯甲酸甲酯反应中优于其他唑盐。这些成功使我们开发了新的手性唑盐。用一般方法合成了两类手性唑盐。一种是由双酚衍生的噻唑盐，另一种是由去甲麻黄碱衍生的三唑盐。这些盐被用于Stetter反应和安息香酯反应。不幸的是，由联萘酚衍生的手性噻唑盐没有催化活性。另一方面，从去甲麻黄碱衍生的三唑盐作为催化剂，得到了82%的半胱氨酸产物。

It has been known for a long time that the treatment of azolium salts, represented in thiazolium salts and triazolium salts, with weak base generate an anion or a resonance-stabilized carbene which is able to act as catalyst to promote the Stetter reaction and benzoin condensation. During this research these reaction showed us new aspects: 1) formation of quaternary carbon with Stetter reaction and 2) selective cross-benzoin condensation.The construction of quaternary carbon with Stetter reaction was accomplished with the intramolecular reaction using salicylaldehyde derivatives as substrates. This reaction was carried out with good yield under mild conditions. And also this reaction is the first example of the construction of quaternary carbon with Stetter reaction. In the cross-benzoin reaction, we found that the combination of aromatic aldehyde and aliphatic aldehyde is very important for the selective acyloin synthesis, and especially, thiazolium salts is better than other azolium salts in this cross-benzoin reaction.These successes led us the development of new chiral azolium salts. Two types of chiral azolium salts were synthesized with general methods. One was thiazolium salts derived from binaphthol, the other was triazolium salt derived from norephedrine. And these salts were used for the Stetter reaction and benzoin reaction. Unfortunately, the chiral thiazolium salts derived from binaphthol had no catalytic activity. On the other hand, triazolium salts derived from norephedrine acted as catalyst to give 82%ee of an acyloin product.