A Facile Route to Symmetrical and Unsymmetrical Cycloalkeno[c]fused 2,2′-Bipyridine Ligands via Inverse Electron Demand Diels-Alder Reaction of 5,5′-bi-1,2,4-Triazines

Abstract

A series of 6,6¢-bisfunctionalized symmetrical cycloalkeno[c]fused 2,2¢-bipyridines 4a-h or unsymmetrical cycloalkeno[c]fused 2,2¢-bipyridines 6a-g is described. They were prepared by the Diels-Alder reaction of 3,3¢-disubstituted 5,5¢-bi-1,2,4-triazines 2a,b with cyclic enamines 3a-d. The regioselective reaction of 1-vinylimidazole (3e) with 2a leads to 5-(2-pyridyl)-1,2,4-triazine 9 which undergoes Diels-Alder reaction with cyclic enamines 3a-d to give unsymmetrical 2,2¢-bipyridines 10a-d with one cycloalkene ring attached.Functionalized 2,2¢-bipyridines have a wide range of applications in many areas of chemistry. They are employed as chelating ligands in coordination and supramolecular chemistry, 2 metal containing polymers, 3 molecular electronics and optoelectronic devices 4 and as photoactivated species. 5 Particularly interesting and useful are their annulated derivatives incorporated into the larger macropolycyclic structures, since they form stable luminescent complexes with a variety of lanthanide cations. 6 The latter can be used as luminescent labels for clinical biochemistry and modern medical applications. 7Although there are several methods to synthesize benzo fused annulated bipyridines, 8 only a limited number of reports have appeared regarding their analogues with attached cycloalkene rings. Important synthetic methods for the preparation of cycloalkeno 2,2¢-bipyridines are based on the transition-metal catalyzed heteroaryl cross-coupling reactions of specially prepared pyridines 9 or Kröhnke-type synthesis from pyridinium salts and a,bunsaturated ketones. 10 More recent approaches employ cobalt(I) catalyzed [2+2+2]-cycloadditions between 5-hexenenitryle and 1,3-diynes 11 or the double intramolecular Diels-Alder reaction of a,b-unsaturated hydrazones with 1,3-dialkynes. 12 These approaches have two disadvantages: (i) rather difficult access to suitable substrates, and (ii) both procedures can be effectively applied only to the synthesis of bipyridine derivatives with attached cyclopentene ring. Earlier we have suggested the Diels-Alder reaction of dimeric 1,2,4-triazines with cyclic enamines as a method suitable for obtaining cycloalkeno 2,2¢-bipyridines. 13 The reaction employs readily available reagents and offers high flexibility in the choice of fused pyridine rings. The preparation of annulated pyridine derivatives by the inverse electron demand Diels-Alder Scheme 1Downloaded by: Queen's University. Copyrighted material.

A Convenient Approach to 16‐, 19‐, and 22‐Membered 2,2′‐Bipyridine Thiacrown Ethers and Their Conformation Preferences

“…In contrast, the chemical shifts of bipyridine protons in 5c (δ = 7.85 ppm and their downfield shift ∆δ = 0.42-0.57 ppm) suggest a trans conformation for this pentaethylene chain ligand with the two pyridine nitrogen atoms oriented 180°with respect to each other. This is consistent with the chemical shifts of pyridine protons (δ = 7.85 ppm) in the annulated 6,6Ј-bis-(methylsulfanyl)-2,2Ј-bipyridine [20] 11 (see Figure 2) and the crystal structures of compounds 5a-c (see below). As an extension of these investigations, monosulfoxides 6a-c were obtained after direct asymmetric oxidation in the presence of the chiral oxaziridine developed by Davis et al [22] The highest enantioselectivity was obtained for sulfoxide 6b, which contained a 19-membered ring.…”

A convenient synthesis of 5,5′-bi-1,2,4-triazines via direct S-arylation and its application in the synthesis of 2,2′-bipyridines

“…In the study focused on the synthesis of bis-sulfides of 2,2′-bipyridine, we used our experience in Diels-Alder reaction [10][11][12]. Previously, we have reported the DielsAlder reaction of dimeric 1,2,4-triazines bearing the methylthio or isopropylthio group with a dienophile as a method for obtaining various substituted 2,2′-bipyridine derivatives in good yield.…”

A first approach to 2,2’-bipyridine thiacrown ethers containing bisamide groups

“…The synthetic pathway leading to macrocycles 2a,b and 3a,b starts with 2,2'-bipyridine methyl sulfides 4a and 4b readily prepared using literature procedures, namely Diels-Alder/retro-DielsAlder reaction of easily accessible 3,3'-bis(methylsulfanyl)-5,5'-bi-1,2,4-triazine with norbornadiene 8 or 1-pyrrolidino-1-cyclopentene, 9 respectively. Reactions of 4a and 4b with ethyl bromoacetate under non-basic conditions, without solvent, gave S-transalkylated products 5a and 5b in excellent yield.…”