Facile preparation of a 4-substituted [2,6-14C]pyridine: Synthesis of [14C]SK&F 105809

[ 14 C]Formaldehyde was used in a nucleophile-assisted iminium ion cyclization with N-benzyl-3-butynylamine to provide N-benzyl-4-iodo-1,2,5,6-tetrahydro[2,6- 14 C 2 ]pyridine. Palladium-catalyzed coupling of this vinyl iodide with the organozinc derivative 2 gave the corresponding 4-arylated tetrahydropyridine. Treatment of this compound at elevated temperatures with Pd/Al 2 O 3 in nitrobenzene solution caused hydrogenolysis of the benzyl group and aromatization, generating the 4-substituted [2,6- 14 C 2 ]pyridine 4 in good overall radiochemical yield from [ 14 C]formaldehyde. In high yields, compound 4 was converted via the methylsulfide [ 14 C]SK&F 105561 (1b) to the methylsulfinyl compound [ 14 C]SK&F 105809 (l#). It is proposed that, during the iminium ion cyclization, randomization of label between the 2- and 6-positions of the tetrahydropyridine ring occurs as the result of rapid equilibration between alkynyl and allenyl iminium ions, prior to cyclization.