Total Synthesis of Lamellarins U and A3 by Interrupting Halogen Dance

A total synthesis of lamellarins U and A3 is described. The synthesis features the interruption of a halogen dance reaction of a metalated alpha,beta-dibromopyrrole. The pyrrolylmagnesium reagent, generated by deprotonative metalation by using (TMP)MgCl center dot LiCl (TMP = 2,2,6,6-tetramethylpiperidide) as the base, was transmetalated to the corresponding organozinc species without causing the halogen dance reaction, which underwent a Negishi coupling to incorporate an aryl group onto the pyrrole ring. The arylated alpha,beta-dibromopyrrole was then converted into lamellarins U and A3 through an alpha-selective halogen-magnesium exchange followed by carboxylation and subsequent palladium-mediated cyclization. The late-stage introduction of another aryl group was performed using a Kosugi-Migita-Stille coupling to provide lamellarins U and A3.

Automated summary

A total synthesis of lamellarins U and A3 is described. The synthesis involves the interruption of a halogen dance reaction and the incorporation of an aryl group onto the pyrrole ring. The final products are obtained through a series of reactions.