Palladium-Catalyzed Dearomatization of Benzothiophenes: Isolation and Functionalization of a Discrete Dearomatized Intermediate

Andrew John Intelli; Mohan Pal; Manikandan Selvaraju; Ryan A. Altman

doi:10.1055/a-2092-9012

Synthesis, Table of Contents

Synthesis 2023; 55(21): 3568-3574
DOI: 10.1055/a-2092-9012

special topic

C–H Bond Functionalization of Heterocycles

Palladium-Catalyzed Dearomatization of Benzothiophenes: Isolation and Functionalization of a Discrete Dearomatized Intermediate

Andrew John Intelli ‡

^aDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, USA

,

Mohan Pal‡

^bNuChem Sciences Inc., 2350 Rue Cohen, Suite 201 Saint-Laurent, Quebec, H4R 2N6, Canada

,

Manikandan Selvaraju

^cExemplify Biopharma, 1002 Eastpark Blvd, Cranbury, New Jersey 08512, USA

,

Ryan A. Altman ∗

^aDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, USA

^dDepartment of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA

› Author Affiliations

Abstract

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Abstract

A Pd-catalyzed decarboxylative dearomatization reaction of a heterocyclic substrate enables access to an uncommon reaction intermediate that rearomatizes in the presence of amine bases in a net C–H functionalization sequence. The dearomatized benzo[b]thiophene intermediate bears an exocyclic alkene that can be functionalized through cycloaddition and halogenation reactions to deliver complex heterocyclic products.

Key words

transition metal - C–H functionalization - dearomatization - heterocycles - decarboxylation

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References

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