Mechanisms for Formation of Diazocinones, Pyridazines, and Pyrazolines from Tetrazines—Oxyanion-Accelerated Pericyclic Cascades?

Abstract

A computational approach is utilized to study the diazocinone- and pyridazine-forming cascade reactions resulting from the reaction of 1,2,4,5-tetrazines with cyclic enolates. Many of the proposed reaction steps can be formulated as oxyanion-accelerated pericyclic processes. In examining these, a unique stepwise version of a formal (4 + 2) cycloaddition/(4 + 2) cycloreversion was discovered. For the key ring-opening step in these cascades, theoretical evidence for two distinct processes is reported. Of these two possibilities, an allowed six-electron electrocyclic ring-opening is predicted to be highly favored both kinetically and thermodynamically. Evidence for an unexpected oxyanion-accelerated 1,2-sigmatropic shift was also found for certain systems, leading to the theoretical prediction that seven- and eight-membered ring-fused pyrazoline systems could be formed experimentally under conditions similar to those for diazocinone and pyridazine formation.

Cyclopenta[b]pyrroles from Triazines: Synthetic and Mechanistic Studies

“…An important synthetic application of substituted 1,2,4-triazines is their reaction as azadienes in inverse electron demand Diels−Alder reactions to generate substituted pyridines. , Analogously, 1,2,4,5-tetrazines are known to react with electron-rich enes to give substituted pyridazines . However, in previous work from our laboratory, we did not obtain the expected pyridazine derivative 5 by the reaction of tetrazine 3 with cyclobutanone enolate 2 . − Rather, instead of intermediate 4 eliminating water to aromatize (→ 5 ), diazocinone 6 was obtained through a ring-expansion reaction (Scheme ). , …”

“…Alternatively, pyrrolidine may simply function as a base and form small quantities of enolate 2 (protonated pyrrolidine is more acidic than cyclobutanone by ∼10 p K a units), which through reaction with 9 would give 11 (X = O − ). Previously 2 , generated using KOH/methanol, was shown to react in a similar manner with a 1,2,4,5-tetrazene. − In fact, employing KOH/methanol, while not effective in preparative reactions, does result in the reaction of cyclobutanone with 9 to give 12 (X = OH) and/or 15 as evidenced by LC/MS of the crude reaction mixture. However, no reaction was observed when DBU was used as base.…”

“…Whether intermediate 11 is formed with X = O − or X = N -pyrrolidinyl, there are at least two possible paths by which it can be converted to 15 . As depicted in Scheme , 11 may undergo a substituent-accelerated six-electron, electrocyclic ring-opening reaction to form the eight-membered system 12 , which could then contract into 14 . Alternatively, a direct 1,2-alkyl shift may occur, as predicted previously for related systems, to produce 13 , a tautomer of 15 .…”

Theory, Experiment and Unusual Features of Potential Energy Surfaces of Pericyclic and Pseudopericyclic Reactions with Sequential Transition Structures

“…Indeed, it is so exothermic that the Bell-Evans-Polanyi principle [32] and the Berson correlation [33] would lead one to ask if it might have no barrier at all. We have measured the rate of the reaction of dimethoxycarbonyltetrazine (22a) with 1-(diethylamino)propyne (23a) using stopped flow kinetics (Scheme 9) [3c].…”

Reaction mechanisms : Part (ii) Pericyclic reactions

“…The complex cascade shown in Scheme 35 was examined by Tantillo and co-workers using B3LYP calculations. 43 The originally proposed mechanism for this process consisted of path A followed by either path C or path D. Computations suggested, however, that path B is more likely than path A, i.e., instead of a [4+2] cycloaddition followed by a [4+2] cycloreversion, a nucleophilic attack followed by an unusual concerted ring-closure/N 2 extrusion reaction is preferred. It was also concluded that both path C and path D can exist, leading to geometric isomers of the product, although path C is generally preferred.…”