Deciphering the Mechanistic Dichotomy in the Cyclization of 1-(2-Ethynylphenyl)-3,3-dialkyltriazenes:  Competition between Pericyclic and Pseudocoarctate Pathways

Abstract

The mechanistic aspects of the cyclization of (2-ethynylphenyl)triazenes under both thermal and copper-mediated conditions are reported. For cyclization to an isoindazole, a carbene mechanistic pathway is proposed. The carbene intermediate can react with oxygen, dimerize to give an alkene, or be trapped either intermolecularly (using 2,3-dimethyl-2-butene to generate a cyclopropane) or intramolecularly (using a biphenyl moiety at the terminus of the acetylene to form a fluorene). Density-functional theory (DFT) calculations support a pseudocoarctate pathway for this type of cyclization. Thermal cyclization to give a cinnoline from (2-ethynylphenyl)triazenes is proposed to occur through a pericyclic pathway. DFT calculations predict a zwitterionic dehydrocinnolinium intermediate that is supported by deuterium trapping studies as well as cyclizations performed using a 2,2,6,6-tetramethylpiperidine moiety at the 3-position of the triazene.

A DFT Study of the Concerted Cyclisation of 3‐Azidopropenal to Isoxazole:Is it a Pseudopericyclic Reaction According to Its Magnetic Properties?

“…Some examples have demonstrated the applicability of this method to distinguishing between pericyclic/pseudopericyclic and coarctate/pseudocoarctate reactivity. [3,5,26,27,29] Figure 5 presents the ACID isosurface of the reactant, product and transition state for this reaction at an isosurface value of 0.05 au. Current density vectors are plotted Figure 5.…”

“…[25] Birney [15] found that disconnections can also occur in coarctate reactions, similarly to pseudopericyclic reactions. Kimball et al [26] have termed these reactions pseudocoarctate.…”

Coarctate cyclization reactions: a primer

“…2a shows the ACID isosurface for the 5-membered ring cyclization to the isoindazole. 37 As a reference, the transition state for the all-carbon analogue is shown in Fig. 2b.…”

“…The subsequent mechanism of Et 2 N-loss as the corresponding imine took us a great deal of additional experimental and computational effort to figure out; however, because the focus of this article is on coarctate reactions, we refer the reader to the full paper that lays out the cinnoline mechanistic case in greater detail. 37 …”

“…Heating the Na salt of tosylhydrazone 28, prepared from aldehyde 11g, in ODCB at 200 1C resulted in good conversion to the corresponding cinnoline 12g (Scheme 10). 37 This presumably occurred through regeneration of triazene 9g by coarctate ring-opening of the carbene, analogous to furfurylcarbene in Scheme 8, followed by pericyclic ring-closing to the cinnolinium zwitterion and finally imine loss.…”