A direct coupling of catharanthine with vindoline to provide vinblastine is detailed along with key mechanistic and labeling studies. Following an Fe (III)-promoted coupling reaction initiated by generation of a presumed catharanthine amine radical cation that undergoes a subsequent oxidative fragmentation and diasteroselective coupling with vindoline, addition of the resulting reaction mixture to an Fe(III)-NaBH4/air solution leads to oxidation of the C15'-C21' double bond reduction of the intermediate iminium ion directly providing vinblastine (43%) and leurosidine (23%), its naturally occuring C21' alcohol isomer. The yield of coupled products, which exclusively possess the natural C16' stereochemistry approaches or exeeds 80%, and the combined yield of the isomeric C21' alcohols is 66%.