Concise syntheses of 13-methylprotoberberine and 13-methyltetrahydroprotoberberine alkaloids

The concise syntheses of eight 13-methylprotoberberine (13-MePB) and eight enantioenriched 13-methyltetrahydroprotoberberine (13-MeTHPB) alkaloids have been achieved in a tactically modular fashion. This synthetic work features a one-pot metal-free Pictet-Spengler/Friedel-Crafts hydroxyalkylation/dehydration/oxidation sequence and a following highly enantioselective Ir-catalyzed hydrogenation. Given such brevity and modularity, our developed synthetic route would be greatly beneficial to the efficient syntheses of existing natural products and new fully synthetic variants of 13-MePB and 13-MeTHPB family.