Silyloxyazadienes: one intermediate and two competitive pericyclic reactions

Abstract

The two competing mechanisms in the reaction of 3-trialkylsilyloxy-2-aza-1,3 dienes to form beta-lactams through a [2+2] electrocyclic ring closure or tetrahydrooxazinan-4-ones via a [4+2] hetero-Diels-Alder reaction were studied using Density Functional computations. Although the [2+2] and [4+2] mechanisms are typical of dienes, their competition, starting from the same diene intermediate, has not yet been observed and analyzed. This competition is governed by a delicate interplay between temperature and substituents at the diene and dienophile, respectively. Clearly, entropy tends to favor the [4+2] hetero-Diels-Alder at low temperatures and the [2+2] electrocyclic ring closure at high temperatures, but simple substituent modifications at the diene and dienophile, can make the [4+2] competitive at high temperatures and sometimes even transform the [4+2] concerted mechanism into a two-step Mukaiyama-type process. Moreover, a study of the global electrophilicity values showed that charge transfer in the hetero-Diels-Alder transition states is driven by chemical hardness rather than by chemical potential.

Stereochemistry and Mechanistic Insight in the [2k+2i+2i] Annulations of Ketenes and Imines

“…The zwitterionic intermediates 6 are synthetically analogous to the neutral and isolable 3-trialkylsilyloxy-2-aza-1,3-dienes . On one hand, both of them can undergo conrotatory ring closure to form four-membered β-lactams.…”

Substituent-Controlled Annuloselectivity and Stereoselectivity in the Sulfa-Staudinger Cycloadditions

“…However, they are to some extent mechanistically different. The former prefers nucleophilic π 4 contatory ring closure and stepwise nucleophilic [4 + 2] annulations to produce β-sultams and 1,2,4-thiadiazinane 1,1-dioxides, respectively, while the latter favors concerted pericyclic reactions, π 4 contatory ring closure and hetero-Diels–Alder cycloaddition, to give rise to β-lactams and 1,3-oxazin-4-ones, respectively …”

Hetero‐Diels–Alder (HDA) Strategy for the Preparation of 6‐Aryl‐ and Heteroaryl‐Substituted Piperidin‐2‐one Scaffolds: Experimental and Theoretical Studies

“…This competition between a [2+2] electrocyclic (EC) reaction and a [4+2] cycloaddition has been already observed by our group with the same diene scaffold and a carbonyl compound as a dienophile. Theoretical studies by density functional computations [36] showed that the competition between the formation of a perhydrooxazinone (arising from a [4+2] HDA reaction) and/or a β-lactam (arising from a [2+2EC] Staudinger reaction) is governed by a delicate interplay between temperature and the very nature of the substituents of the diene and dienophile. Similar computational studies have also been performed in the present case in which there is competition between piperidin-2-one 3f and the β-lactam 4f formation.…”