Total Synthesis of Lycoricidine and Narciclasine by Chemical Dearomatization of Bromobenzene

Abstract

The total synthesis of lycoricidine and narciclasine is enabled by an arenophile-mediated dearomative dihydroxylation of bromobenzene.S ubsequent transpositive Suzuki coupling and cycloreversion deliver ak ey biaryl dihydrodiol intermediate,w hichi sr apidly converted into lycoricidine through site-selective syn-1,4-hydroxyamination and deprotection. The total synthesis of narciclasine is accomplished by the late-stage,amide-directed C À Hhydroxylation of alycoricidine intermediate.M oreover,t he general applicability of this strategy to access dihydroxylated biphenyls is demonstrated with several examples.

Visible‐Light‐Induced Dearomatizations

“…For example, conduramine A ( 63 ) was prepared from benzene‐derived diol 61 through arenophile cycloreversion, nitroso‐Diels‐Alder reaction, and subsequent N–O cleavage . Furthermore, the syntheses of Amaryllidaceae alkaloids lycoricidine ( 64 ) and narciclasine ( 65 ) were accomplished from bromobenzene ( 66 ) . In this case, dihydroxylation was conducted using the Narasaka‐Sharpless modification of the Upjohn protocol, providing the dihydroxylated product in a form of boronic ester 68 .…”