2,2 :4,4"":6,2"-Quaterpyridine, reaction with

The crude 2,2 -bipyridine obtained from the reaction of pyridine and degassed Raney nickel was found to contain 1.5% of 2 6, 2"-terpyridine, but no 2,2 2, 2" 6 ",2 "-quaterpyridine could be detected. Moreover, experiments with 2,2 -bipyridine and Raney nickel have failed to yield quaterpyridine, and the amount of terpyridine formed in experiments with mixtures of pyridine and 2,2 -bipyridine was found to be no higher than in the reaction with pyridine itself. " ... 

The Boekelheide reaction has been applied to the synthesis of non-natural products with the preparation of quaterpyridines serving as an example. The sequence began with the 2,4-linked bipyridyl-N-oxide 25. Execution under the typical reaction conditions produced the expected bis-pyridone 26. Treatment with POCI3 afforded the corresponding dichloride that was submitted to a palladium-catalyzed coupling with 2-stannyl pyridine to produce the desired quaterpyridine 27. 

The neurotoxic quaterpyridine natural product nemertelline was successfully synthesized by S. Rault et al. using a Suzuki cross-coupiing as the key step. The boronic acid coupling partner, required for the Suzuki reaction, was prepared by first subjecting 3-amino-2-chloropyridine to the conditions of the Sandmeyer reaction followed by a lithium-halogen exchange and trapping the lithiopyridine derivative with triisopropylborate. 

Double Krohnke reactions have been employed in the preparation of quaterpyridines and sexi-pyridines. Thus, the chalcone dimer (77a,b) reacts with the pyridinium salt (78) to provide (79a,b) (Scheme 13).84 An alternative approach involves a bischalcone species based on bpy that can be elaborated to (76c), as well as several 4, 4""-disubstituted derivatives.85 A dimeric analogue of (78), having a central bpy moiety, undergoes condensation with a Krohnke-type salt to provide the parent sexipyridine (76c).86... 

The bis(ethylthio) species (83a,b) may be mono-oxidized with MMPP or m-CPBA to afford the thiones (82a,b). If these species are treated with methylmagnesium bromide, a ring-coupling reaction occurs to provide (83b,c) in yields of 56 and 3%, respectively (Scheme 15). Alternatively (82a,b) may be treated with 6-lithio-2,2 -bipyridine to provide the oligomers (84a,b).88 A similar reaction has been used to prepare a chiral quaterpyridine derivative employing the mono-sulfone of (84a).89... 

Another example involves the reaction of Cu1 with the 2,2 2",6" 6",2" -quaterpyridine ligand (3) (Figure 3).15 A stoichiometric mixture of these molecules at ambient temperature and moderate concentration was found by ES-MS to contain a library of compounds which included the diastereomeric binuclear helicates, (4), and the oligonuclear circular helicates (5), (6), and (7). Concentration of the mixture resulted in an increase in the higher nuclearity species. At concentrations below 10 4 M, however, only the helicates were present. Crystallization transformed the mixture into (6) in the solid state. 

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