Electrophilic cyclization of reticuline-type alkaloids in flow via o-quinol intermediates

Herein, we report the first continuous-flow biomimetic cyclization of reticuline derivatives to aporphine alkaloids via ortho-quinol intermediates. The two-step flow process involves an initial oxidative dearomatization of reticuline derivatives to using hypervalent iodine(III) reagents, followed by a TMSOTf-mediated electrophilic cyclization. The high sensitivity of ortho-quinol compounds is mitigated by the mild experimental conditions and fast reaction rates offered by flow reactors. A preliminary structure–reactivity relationship suggests that both steps of the process are favored with strongly electron-rich substrates, similar to what is observed in nature.