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DOI: 10.1055/a-1736-7337
Total Synthesis of Lamellarins U and A3 by Interrupting Halogen Dance
This work was financially supported by the Japan Society for the Promotion of Science [JSPS, KAKENHI grants no. JP19H02717 in Scientific Research (B)].
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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 - deprotonationSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1736-7337.
- Supporting Information
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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For the isolation of lamellarin U, see:
For representative reviews on the halogen dance, see:
For representative total syntheses using the halogen dance, see:
Suzuki–Miyaura coupling provided a substantial amount of the debrominated side product, see: