Direct diastereoselective addition of l -menthol to activated 1,2,4-triazin-5(4 H )-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 C 6 -unsubstituted atom of 3-phenyl-1,2,4-triazin-5(4 H )-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-(6 S )-1,6-dihydro-1,2,4-triazin-5(4 H )-ones 2 and 1-acyl-6-[(1′ R ,3′ R ,4′ S )-menthyl-3′)]-3-phenyl-(6 R )-1,6-dihydro-1,2,4-triazin-5(4 H )-ones 3 in which the diastereomers 2 predominate. The diastereoselectivity of the process improves as the size of the N 1 -acyl substituent increases.