Alternative Methylation for the Synthesis of （＋）-Perophoramidine

An alternative NI-methylation strategy was reported in the late-stage of the total synthesis of （＋）-perophoramidine. Preparation of （＋）-perophoramidine was featured by an acid-catalyzed isomerization of amidine 5 to its C=N double bond tautorner 8, followed by two steps of NJ-methylation with NaHMDS/MeOTf and oxidation with MnO2. In contrast, direct methylation of amidine 5 afforded the NZ3-methylation conformers 9a and 9b, Further oxidation of 9a and 9b led to N23-methylated perophoramidine.