De Novo Synthesis of Polysubstituted 3-Hydroxypyridines Via “Anti-Wacker”-Type Cyclization

We report an efficient method to prepare polysubstituted 3-hydroxypyridines from amino acids, propargyl alcohols, and arylboronic acids. The process involves Pd(0)-catalyzed anti-selective arylative cyclizations of N-propargyl-N-tosyl-aminoaldehydes with acids (“anti-Wacker”-type cyclization), oxidation the resulting 5-substituted-3-hydroxy-1,2,3,6-tetrahydropyridines 3-oxo derivatives, elimination p-toluenesulfinic acid. This provides diverse 3-hydroxypyridines, whose hydroxy group can be further substituted by a cross-coupling reaction via triflate.