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

a   Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, USA
,
Mohan Pal
b   NuChem Sciences Inc., 2350 Rue Cohen, Suite 201 Saint-Laurent, Quebec, H4R 2N6, Canada
,
c   Exemplify Biopharma, 1002 Eastpark Blvd, Cranbury, New Jersey 08512, USA
,
a   Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, USA
d   Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
› Author Affiliations
Generous financial support from the National Institute of General Medical Sciences of the National Institutes of Health (R35 GM124661) is gratefully acknowledged. This material is based upon work supported by the National Science Foundation through the Major Research Instrumentation Program under Grant No. CHE 1625543 and CHE-0923449, which was used to purchase the X-ray diffractometers and software used in this manuscript. This work was supported in part by the Research Instrumentation Center in the Department of Chemistry at Purdue University. Funding for the NMR instrumentation at the University of Kansas was provided by NIH Shared Instrumentation Grant # S10OD016360, NSF Major Research Instrumentation Grant # 9977422 and NIH Center Grant # P20GM103418.


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.

Supporting Information



Publication History

Received: 01 February 2023

Accepted after revision: 12 May 2023

Accepted Manuscript online:
12 May 2023

Article published online:
13 June 2023

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