Superelectrophiles, Formed in Superacids.

Pictet-Spengler反应是2-芳基乙胺的中间体亚胺的酸催化的分子内环化反应，得到1，2，3，4-四氢异喹啉，长期以来一直限于在环化苯环上带有强供电子基团如甲氧基或羟基的活性底物。本文报道了超强酸催化的2-苯乙胺亚胺的Pictet-Spengler反应，包括N-亚甲基-2-苯乙胺的Pictet-Spengler反应，以中到高产率得到母体和1-取代的1，2，3，4-四氢异喹啉。产率取决于介质的酸度。在N-亚甲基-2-苯乙胺及相关亚胺的动力学研究中，发现环化速率与反应介质的酸度之间存在线性关系，强烈支持N-质子化亚胺的额外质子化活化的干预，即双阳离子超亲电体N，N-二质子化亚胺需要强酸性条件来诱导芳基乙烯基酮的Nazarov型环化，尽管与Nazarov反应的化学类比表面上意味着O-质子化一价阳离子的直接电环化反应。本文研究了超强酸催化1-苯基-2-丙烯-1-酮的原型环化反应。这些环化反应的酸度依赖性所揭示的动力学测量强烈建议参与的O，O-二质子化的双阳离子，而不是O-质子化的一价阳离子。也就是说，1-苯基-2-丙烯-1-酮的环化表示氧鎓-碳鎓二价阳离子的电环化。我们还描述了1-苯基-2-丙烯-1-酮的2位取代基的影响。从头计算，基于密度泛函理论，支持的想法，电环化的阳离子比单价阳离子的能量更有利。

The Pictet-Spengler reaction, an acid-catalyzed intramolecular cyclization of intermediate imines of 2-arylethylamine to give 1,2,3,4-tetrahydroisoquinolines, has long been limited to active substrates which bear strongly electron-donating groups such as a methoxy or a hydroxy group on the cyclizing benzene ring. In this paper, we present superacid-catalyzed Pictet-Spengler reactions of imines of 2-phenethylamine, including the prototype Pictet-Spengler reaction of N-methylene-2-phenethylamine, to give the parent and 1-substituted 1,2,3,4-tetrahydroisoquinolines in moderate to high yields. The yields are dependent on the acidity of the media. A linear relationship was found between the rate of the cyclization and the acidity of the reaction media in kinetic studies of N-methylene-2-phenethylamine and related imines, strongly supporting the intervention of an additional protonative activation of the N-protonated imines, that is, the involvement of dicationic superelectrophiles, N,N-diprotonated imines (ammonium-carbenium dications).Strongly acidic conditions are required to induce the Nazarov-type cyclization of arylvinyl ketones, although chemical analogy with the Nazarov reaction would superficially imply a straightforward electrocyclization reaction of the O-protonated monocation. In this paper we describe the superacid-catalyzed prototype cyclization of 1-phenyl-2-propen-1-ones. The acidity-dependence of these cyclization reactions as revealed by kinetic measurements strongly suggests the involvement of the O,O-diprotonated dication rather than the O-protonated monocation. That is, the cyclization of 1-phenyl-2-propen-1-ones represents an electrocyclization of the oxonium-carbenium dication. We also describe the effect of substituents at the 2 position of 1-phenyl-2-propen-1-ones. Ab initio calculations, based on the density functional theory, support the idea that electrocyclzation of the dication is energetically more favorable than that of the monocation.