Reaction of magnesiated bases on substituted pyridines: deprotonation or 1,4-addition?

N-(tert-Butyl)pyridine-2-carboxamide (1), N-phenylpyridine-2-carboxamide (7 ) and 2,2-dimethyl-N-(2-pyridyl)propanamide (18) are readily deprotonated a t C3 with a stoichiometric amount of (PrMgCl)-Mg-i or Bu2Mg in THF under re flux. Subsequent trapping with various electrophiles (deuterated water, ald ehydes, iodine and dimethyl disulfide) gives 2,3-disubstituted pyridines ca rrying a useful carboxylic acid- or amino-derived function at C2. When N-(t ert-butyl)pyridine-3-carboxamide (12) and 2,2-dimethyl-N-(3-pyridyl)propana mide (22) are subjected to the same reaction conditions, 1,4-addition to th e pyridine ring occurs, giving 4-alkyl derivatives. Starting from N-(tert-b utyl)pyridine-4-carboxamide (15), 1,2-addition and deprotonation reactions occur simultaneously.