We began by investigating the coupling of 5-methyl Meldrum's acid 2a with pyridine-N-oxide 1a under our previously-developed activation conditions using tosyl chloride and triethylamine. On completion of the substitution reaction, the solvent was swapped for methanol and sodium methoxide added. We were pleased to find that the desired 4-pyridylsubstituted propionate ester 3a was isolated in 63% yield as a single regioisomer, and so examined the scope of the coupling of 2a with various substituted pyridine-N-oxides 2 (Table ). Substitution at the 4-position was also observed with 2-and 3methylpyridine-N-oxides 2b/c to give esters 3b/c, while when 4-substituted pyridine-N-oxide substrates were employed, clean substitution at the 2-position was observed. TABLE 1. Three-Component Coupling: Scope of the Pyridine-N-oxide.