Tandem Pseudopericyclic Reactions:  [1,5]-X Sigmatropic Shift/6π-Electrocyclic Ring Closure Converting N-(2-X-Carbonyl)phenyl Ketenimines into 2-X-Quinolin-4(3H)-ones

• Published in: Journal of organic chemistry 2006-10, Vol.71 (21), p.8126-8139
• Main Authors: Alajarín, Mateo, Ortín, María-Mar, Sánchez-Andrada, Pilar, Vidal, Ángel
• Format: Article
• Language: English
• Subjects: Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Kinetics and mechanisms; Organic chemistry; Preparations and properties; Reactivity and mechanisms
• ISSN: 0022-3263; 1520-6904
• 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 6π-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 °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, NH2, and PH2) 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 NH2 or PH2, it involves a two-step sequence. The order of migratory aptitudes of the X substituents at the acyl group is predicted to be PH2 > Cl > SH > NH2 > F> OH. The second step of the full transformation, the 6π-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 6π-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 6π-electrocyclization of the ketene intermediates to the 4(3H)-pyridones, and for the 6π-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.