Alajarín Mateo, Ortín María-Mar, Sanchez-Andrada Pilar, Vidal Angel
Departamento de Química Organica, Facultad de Química, Campus de Espinardo, Universidad de Murcia, 30100 Murcia, Spain.
J Org Chem. 2006 Oct 13;71(21):8126-39. doi: 10.1021/jo061286e.
N-(2-X-Carbonyl)phenyl ketenimines undergo, under mild thermal conditions, [1,5]-migration of the X group from the carbonyl carbon to the electron-deficient central carbon atom of the ketenimine fragment, followed by a 6pi-electrocyclic ring closure of the resulting ketene to provide 2-X-substituted quinolin-4(3H)-ones in a sequential one-pot manner. The X groups tested are electron-donor groups, such as alkylthio, arylthio, arylseleno, aryloxy, and amino. When involving alkylthio, arylthio, and arylseleno groups, the complete transformation takes place in refluxing toluene, whereas for aryloxy and amino groups the starting ketenimines must be heated at 230 degrees C in a sealed tube in the absence of solvent. The mechanism for the conversion of these ketenimines into quinolin-4(3H)-ones has been studied by ab initio and DFT calculations, using as model compounds N-(2-X-carbonyl)vinyl ketenimines bearing different X groups (X = F, Cl, OH, SH, NH(2), and PH(2)) converting into 4(3H)-pyridones. This computational study afforded two general reaction pathways for the first step of the sequence, the [1,5]-X shift, depending on the nature of X. When X is F, Cl, OH, or SH, the migration occurs in a concerted mode, whereas when X is NH(2) or PH(2), it involves a two-step sequence. The order of migratory aptitudes of the X substituents at the acyl group is predicted to be PH(2) > Cl > SH > NH(2) > F> OH. The second step of the full transformation, the 6pi-electrocyclic ring closure, is calculated to be concerted and with low energy barriers in all the cases. We have included in the calculations an alternative mode of cyclization of the N-(2-X-carbonyl)vinyl ketenimines, the 6pi-electrocyclic ring closure leading to 1,3-oxazines that involves its 1-oxo-5-aza-1,3,5-hexatrienic system. Additionally, the pseudopericyclic topology of the transition states for some of the [1,5]-X migrations (X = F, Cl, OH, SH), for the 6pi-electrocyclization of the ketene intermediates to the 4(3H)-pyridones, and for the 6pi-electrocyclization of the starting ketenimines into 1,3-oxazines could be established on the basis of their geometries, natural bond orbital analyses, and magnetic properties. The calculations predict that the 4(3H)-pyridones are the thermodynamically controlled products and that the 1,3-oxazines should be the kinetically controlled ones.
N-（2-X-羰基）苯基烯酮亚胺在温和的热条件下，X基团从羰基碳发生[1,5]迁移至烯酮亚胺片段中缺电子的中心碳原子上，随后生成的烯酮进行6π-电环化闭环反应，以连续一锅法的方式得到2-X-取代的喹啉-4（3H）-酮。所测试的X基团为供电子基团，如烷硫基、芳硫基、芳硒基、芳氧基和氨基。当涉及烷硫基、芳硫基和芳硒基时，完全转化在回流甲苯中进行，而对于芳氧基和氨基，起始烯酮亚胺必须在无溶剂的密封管中于230℃加热。通过从头算和密度泛函理论计算研究了这些烯酮亚胺转化为喹啉-4（3H）-酮的机理，使用带有不同X基团（X = F、Cl、OH、SH、NH₂和PH₂）的N-（2-X-羰基）乙烯基烯酮亚胺作为模型化合物转化为4（3H）-吡啶酮。该计算研究为序列第一步即[1,5]-X迁移提供了两条一般反应途径，这取决于X的性质。当X为F、Cl、OH或SH时，迁移以协同模式发生，而当X为NH₂或PH₂时，它涉及两步序列。预测酰基上X取代基的迁移能力顺序为PH₂ > Cl > SH > NH₂ > F > OH。完全转化的第二步即6π-电环化闭环反应，经计算在所有情况下都是协同的且能垒较低。我们在计算中纳入了N-（2-X-羰基）乙烯基烯酮亚胺的另一种环化模式，即6π-电环化闭环生成1,3-恶嗪，这涉及到其1-氧代-5-氮杂-1,3,5-己三烯体系。此外，基于一些[1,5]-X迁移（X = F、Cl、OH、SH）、烯酮中间体向4（3H）-吡啶酮的6π-电环化以及起始烯酮亚胺向1,3-恶嗪的6π-电环化的过渡态的几何结构、自然键轨道分析和磁性，可以确定其假周环拓扑结构。计算预测4（3H）-吡啶酮是热力学控制产物，而1,3-恶嗪应该是动力学控制产物。
