π-Bond Screening in Benzonorbornadienes: The Role of 7-Substituents in Governing the Facial Selectivity for the Diels-Alder Reaction of Benzonorbornadienes with 3,6-Di(2-pyridyl)-s-Tetrazine

Abstract

Benzonorbornadiene 21, 7-spirocyclopropylbenzonorbornadiene 23, 7,7- dimethylbenzonorbornadiene 25, and 7-spirocyclopentylbenzonorbornadiene 27 have been reacted with 3,6-di(2-pyridyl)-s-tetrazine (rate: 21>23>25=27) to form symmetrical 4,5- dihydropyridazines which are stable towards fragmentation but rearrange with varying facility to their 1,4 isomers. The facial selectivity of attack on the π-bond changes from exo-attack for 21 and 23 to endo-attack for 25 and 27. The 7-spirocyclopropyl benzonorbornadiene 23 typically forms a mixture of dihydropyridazines with exo-stereo- chemistry, which undergo further stereochemical isomerisation to an exo-fused product upon acetylation (acetyl chloride in hot pyridine). Oxidation with DDQ of the dihydropyridazines individually or as mixtures gives the corresponding fused 3,6-di(2- pyridyl)pyridazines.

Synthesis of Some Novel Norbornene‐Fused Pyridazines as Potent Inhibitors of Carbonic Anhydrase and Acetylcholinesterase

“…Anal. Calcd for C 17 H 14 N 2 O 4 : C, 65.80; H, 4.55; N, 9.03; found: C, 65.53; H, 4.79; N, 9.23.1,4-Di(pyridin-2-yl)-5,10-dihydro-5,10-methanobenzo[g] phthalazine (9cb)[54].Yield: 94%. Colorless crystals (mp: 198-200°C).…”

Cycloaddition Reactions of Benzonorbornadiene and Homonorbornadiene: New Isoxazoline and Pyridazine Derivatives

“…3). Cycloadditions to the double bond of the compounds such as norbornadiene derivatives were occurred form exo faces because of electron density [5][6][7][8][9][10][11][12][13][14][15][16][17][18]26,27]. The electron density of isolated double bond belongs to benzonorbornadiene (4), and data (NMR and HRMS) of adducts 7a-d are consistent with the proposed structures.…”

“…Norbornadiene derivatives including nitrogen-oxygen atoms and their rearrangement products may be important. Cycloaddition reactions of some strained compounds such as norbornadiene and norbornadiene derivatives with nitrile oxides and tetrazines were reported [12][13][14][15][16][17][18][19][20][21]. To the best of our knowledge, cycloaddition reactions of homonorbornadienes (5) with nitrile oxides and tetrazine have not been investigated.…”

Theoretical Studies on the Mechanism of the Formation of Cyclopentadienes and Dihydropyridazines

“…As a result, there is no straightforward method for the functionalisation of Cps. [15][16][17][18][19][20][21][22][23][24] Although the synthesis of various Cps remains challenging, considerable efforts were devoted towards the functionalised Cps, [1,[25][26][27][28][29][30][31][32][33][34][35][36] particularly by 4π-electrocyclisation. [27,28] Substituted Cps can also be formed directly by nickel catalysed [3 + 2] cycloaddition reaction.…”