Flow Conditions‐Controlled Divergent Oxidative Cyclization of Reticuline‐Type Alkaloids to Aporphine and Morphinandienone Natural Products

Described herein is a divergent continuous‐flow approach for the biomimetic oxidative cyclization of reticuline‐type alkaloids to aporphine and morphinandienone natural products using hypervalent iodine(III) reagents. The method was based on the detailed knowledge of the reaction mechanisms in order to develop robust reaction conditions toward the selective synthesis of either aporphine or morphinandienone natural products. In this frame, we exploited the ability of HFIP to stabilize radical cation intermediates and to activate hypervalent iodine(III) oxidants for the flow synthesis of aporphine natural products such as glaucine, rogersine and nantenine. On the other hand, we established that PhI(OAc)(OTf), prepared by action of TMSOTf on PhI(OAc)2, was a powerful oxidant for the synthesis of morphinandienone natural products such as sebiferine and amurine.