An efficient coupling of N-tosylhydrazones with 2-halopyridines: synthesis of 2-α-styrylpyridines endowed with antitumor activity.

The synthesis of 2-alpha-styrylpyridines has been carried out by using the coupling of polyoxygenated N-tosylhydrazones with various 2-halopyridines. We demonstrated that the use of a catalytic amount of PdCl2(MeCN)(2) in combination with a bidentate ferrocene DPPF or a monodentate alkyl phosphine (Bu2MeP)-Bu-t-HBF4 constitutes an efficient protocol for this coupling, providing 2-alpha-styrylpyridines 2 in satisfactory to good yields. Among several polyoxygenated derivatives 2 evaluated, compound 2aa was found to exhibit excellent antiproliferative and antimitotic activities comparable to that of the reference compound isoCA-4.