Direct diastereoselective addition of l-menthol to activated 1,2,4-triazin-5(4H)-one

Abstract

For the first time in a triazine series it has been found that addition of a chiral O-nucleophile, l-menthol, to the C6-unsubstituted atom of 3-phenyl-1,2,4-triazin-5(4H)-one 1 activated by aliphatic acid anhydrides proceeds diastereoselectively to form a mixture of 1-acyl-6-[(1′R,3′R,4′S)-menthyl-3′)]-3-phenyl-(6S)-1,6-dihydro-1,2,4-triazin-5(4H)-ones 2 and 1-acyl-6-[(1′R,3′R,4′S)-menthyl-3′)]-3-phenyl-(6R)-1,6-dihydro-1,2,4-triazin-5(4H)-ones 3 in which the diastereomers 2 predominate. The diastereoselectivity of the process improves as the size of the N1-acyl substituent increases.