Justribó Valeria, Pellegrinet Silvina C, Colombo María I
Instituto de Química Orgánica y de Síntesis (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario (2000), Argentina.
J Org Chem. 2007 May 11;72(10):3702-12. doi: 10.1021/jo062669f. Epub 2007 Apr 17.
Studies have been conducted to investigate the reactivity of several bicyclic delta-hydroxynitriles with triflic anhydride in dichloromethane. The reactions of the analogues derived from 1-indanone and 1-tetralone lead to annulated enones. These products arise from an initial elimination reaction that generates an alkene, followed by the addition of the carbon-carbon double bond to the activated cyano group. The intramolecular cyclization of the derivative obtained from 1-benzosuberone unexpectedly followed a different path, giving a cyclic imidate as the major product. In this case, the activated cyano group is directly attacked by the hydroxyl group of the starting delta-hydroxynitrile. Theoretical calculations provide a rationale for the observed reactivity pattern. Both the formation of the triflate via its protonated form, its subsequent ionization to the carbocation, and the cyclization of the resulting alkene to the enone become less favorable when the size of the ring increases due to conformational effects. The opposite trend is observed for the competing Pinner-type cyclization to the imidate. An alternative mechanism for the formation of the lactams from the cyclic imidates under acid-catalyzed conditions has also been proposed.
已经开展了多项研究，以探究几种双环δ-羟基腈在二氯甲烷中与三氟甲磺酸酐的反应活性。源自1-茚满酮和1-四氢萘酮的类似物的反应会生成稠合烯酮。这些产物源于最初的消除反应，该反应生成烯烃，随后碳-碳双键加成到活化的氰基上。从1-苯并环庚酮得到的衍生物的分子内环化意外地遵循了不同的路径，以环状亚氨酸酯作为主要产物。在这种情况下，起始δ-羟基腈的羟基直接进攻活化的氰基。理论计算为观察到的反应活性模式提供了理论依据。由于构象效应，当环的尺寸增大时，通过其质子化形式形成三氟甲磺酸酯、其随后离子化为碳正离子以及所得烯烃环化为烯酮的过程都变得不太有利。对于竞争性的形成亚氨酸酯的Pinner型环化反应，则观察到相反的趋势。还提出了在酸催化条件下由环状亚氨酸酯形成内酰胺的另一种机理。
