3,6-Disubstituted 4,5-dihydropyridazines

Dihydropyridazines result from the addition of Grignard reagents to 3,6-disubstituted pyridazines (Section IV, A) or from... 

According to the mechanism proposed, the 1,4-cycloaddition (Diels-Alder reaction) of the diene part of the tetrazine to the dienophile (olefin) gives an unstable bicyclic intermediate, which spontaneously eliminates a molecule of nitrogen, forming a 4,5-dihydropyridazine, which in the absence of appropriate stabilization by gem disubstitution in positions 4 and 5, easily isomer-izes to the thermodynamically more stable 1,4-dihydropyridazine (38). The structure of the latter intermediates were unambiguously proved using NMR.91,92... 

Warrener reported that when 3,6-disubstituted-s-tetrazine 147 was employed as a heterodiene in Diels-Alder cycloadditions with alkenes such as 146, tandem [4 + 2]/[4 + 2] reaction takes place under high pressure (8-14 kbar, 16h) (Scheme 36) [55]. Due to its high reactivity, initial [4 + 2] cycloaddition of tetrazine 147 and nor-bornene 146 is carried out at atmospheric pressure. Spontaneous elimination of nitrogen from primary formed Diels-Alder adduct liberates the second diene, 1,2-dihydropyridazine. By addition of another equivalent of alkene 148 and application of high pressure, the second [4 + 2] cycloaddition generates the central diazabicy-clo[2.2.2]octene skeleton in high yield. A number of functionalized polynorbornane systems were prepared by this synthetic protocol [56]. 

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