Total Synthesis of Lamellarins U and A3 by Interrupting Halogen Dance

Yuya Okui; Yuto Yasuda; Atsunori Mori; Kentaro Okano

doi:10.1055/a-1736-7337

Synthesis, Table of Contents

Synthesis 2022; 54(11): 2647-2660
DOI: 10.1055/a-1736-7337

paper

Total Synthesis of Lamellarins U and A3 by Interrupting Halogen Dance

Yuya Okui

^aDepartment of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan

,

Yuto Yasuda

^aDepartment of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan

,

Atsunori Mori

^aDepartment of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan

^bResearch Center for Membrane and Film Technology, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan

,

Kentaro Okano ∗

^aDepartment of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan

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Abstract

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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 - deprotonation

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References

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