Alternative Methylation for the Synthesis of (+)‐Perophoramidine

An alternative N 1 ‐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 CN double bond tautomer 8 , followed by two steps of N 1 ‐methylation with NaHMDS/MeOTf and oxidation with MnO 2 . In contrast, direct methylation of amidine 5 afforded the N 23 ‐methylation conformers 9a and 9b . Further oxidation of 9a and 9b led to N 23 ‐methylated perophoramidine.