Total Synthesis of Lamellarins U and A3 by Interrupting Halogen Dance

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

Publication History

Received: 11 December 2021

Accepted after revision: 11 January 2022

Accepted Manuscript online:
11 January 2022

Article published online:
23 February 2022

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