Abstract
A total synthesis of lamellarins U and A3 is described. The synthesis features the
interruption of a halogen dance reaction of a metalated α,β-dibromopyrrole. The pyrrolylmagnesium
reagent, generated by deprotonative metalation by using (TMP)MgCl·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 α,β-dibromopyrrole was then converted into
lamellarins U and A3 through an α-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.
Key words
lamellarins - halogen dance - pyrroles - alkaloids - total synthesis - lithiation
- metalation - deprotonation
