Facile Synthesis of Chiral Cyclic Ureas through Hydrogenation of 2-Hydroxypyrimidine/Pyrimidin-2(1H)-one Tautomers.

Abstract

A facile access to optically active cyclic ureas was developed through palladium-catalyzed asymmetric hydrogenation of pyrimidines containing tautomeric hydroxy group with up to 99 % ee. Mechanistic studies indicated that reaction pathway proceed through hydrogenation of C=N of the oxo tautomer pyrimidin-2(1H)-one, acid-catalyzed isomerization of enamine-imine, and hydrogenation of imine pathway. In addition, the chiral cyclic ureas are readily converted into useful chiral 1,3-diamine and thiourea derivatives without loss of optical purity.