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

Abstract

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 arylboronic acids (“anti-Wacker”-type cyclization), oxidation of the resulting 5-substituted-3-hydroxy-1,2,3,6-tetrahydropyridines to 3-oxo derivatives, and elimination of p-toluenesulfinic acid. This method provides diverse polysubstituted 3-hydroxypyridines, whose hydroxy group can be further substituted by a cross-coupling reaction via a triflate.

Keywords

• “anti-Wacker”-type cyclization
• 3-hydroxypyridine
• arylboronic acids
• palladium
• amino acids
• propargyl alcohols