Regioselective Cycloaddition of the Dimethyl Ester of Acetylenedicarboxylic Acid to 2,4,6-Triazidopyridines

2,4,6-Triazido-3,5-dichloropyridine was obtained in the reaction of pentachloropyridine with sodium azide. At room temperature, this azide reacts regioslectively with norbornene at the -azide group to give the corresponding 4-(3-azatricyclo3.2.1.0]octanyl)-2,6-diazidopyridine in 88% yield. The cycloaddition of the dimethyl ester of acetylenedicarboxylic acid to this triazide proceeds at the azide groups at C₍₂₎ and C₍₆₎ in the pyridine ring to give 4-azido-2,6-di(4',5'-dimethoxycarbonyl)-1H-1,2,3-triazolopyridine. The analogous reaction of 2,4,6-triazido-3,5-dicyanopyridine with the dimethyl ester of acetylenedicarboxylic acid stops at the formation of 2,4-diazido-6-(4',5'-dimethoxycarbonyl)-1H-1,2,3-triazolopyridine. In contrast to reactions with electron-rich dipolarophiles, the cycloaddition of electron-deficient dipolarophiles to 2,4,6-triazidopyridines proceeds with thermodynamic control primarily a! t the azide groups bearing the highest orbital density in the HOMO.