Download PDF
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  ‡
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
,
Manikandan Selvaraju 
c   Exemplify Biopharma, 1002 Eastpark Blvd, Cranbury, New Jersey 08512, USA
,
Ryan A. Altman  ∗
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 AffiliationsGenerous 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.
› Further Information
    Permissions and Reprints All articles of this category


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

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

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Davies HM. L, Morton D. J. Org. Chem. 2016; 81: 343
    CrossrefPubMed
  • 2 Guillemard L, Kaplaneris N, Ackermann L, Johansson MJ. Nat. Rev. Chem. 2021; 5: 522
    CrossrefPubMed
  • 3 Labinger JA, Bercaw JE. Nature 2002; 417: 507
    CrossrefPubMed
  • 4 Hartwig JF. J. Am. Chem. Soc. 2016; 138: 2
    CrossrefPubMed
  • 5 Gensch T, Hopkinson MN, Glorius F, Wencel-Delord J. Chem. Soc. Rev. 2016; 45: 2900
    CrossrefPubMed
  • 6 Yamaguchi J, Yamaguchi AD, Itami K. Angew. Chem. Int. Ed. 2012; 51: 8960
    CrossrefPubMed
  • 7 Tunge JA. Isr. J. Chem. 2020; 60: 351
    Crossref
  • 8 He J, Wasa M, Chan KS. L, Shao Q, Yu JQ. Chem. Rev. 2017; 117: 8754
    CrossrefPubMed
  • 9 Zhang S, Yamamoto Y, Bao M. Adv. Synth. Catal. 2021; 363: 587
    Crossref
  • 10 Li F, Zhang X, Renata H. Curr. Opin. Chem. Biol. 2019; 49: 25
    CrossrefPubMed
  • 11 Yang MH, Hunt JR, Sharifi N, Altman RA. Angew. Chem. Int. Ed. 2016; 55: 9080
    CrossrefPubMed
  • 12 Bao M, Nakamura H, Yamamoto Y. J. Am. Chem. Soc. 2001; 123: 759
    CrossrefPubMed
  • 13 Lu S, Xu Z, Bao M, Yamamoto Y. Angew. Chem. Int. Ed. 2008; 47: 4366
    CrossrefPubMed
  • 14 Li TR, Maliszewski ML, Xiao WJ, Tunge JA. Org. Lett. 2018; 20: 1730
    CrossrefPubMed
  • 15 Kayashima Y, Komatsuda M, Muto K, Yamaguchi J. Chem. Lett. 2020; 49: 836
    Crossref
  • 16 Mendis SN, Tunge JA. Chem. Commun. 2016; 52: 7695
    CrossrefPubMed
  • 17 Recio A, Heinzman JD, Tunge JA. Chem. Commun. 2012; 48: 142
    CrossrefPubMed
  • 18 de Azambuja F, Yang M.-H, Feoktistova T, Selvaraju M, Brueckner AC, Grove MA, Koley S, Cheong PH.-Y, Altman RA. Nat. Chem. 2020; 12: 489
    CrossrefPubMed
  • 19 Tshepelevitsh S, Kütt A, Lõkov M, Kaljurand I, Saame J, Heering A, Plieger PG, Vianello R, Leito I. Eur. J. Org. Chem. 2019; 6735
    Crossref
  • 20 CCDC 2237820 (1a), 2237821 (1b), and 2237648 (8) contain the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
  • 21 Becker MR, Wearing ER, Schindler CS. Nat. Chem. 2020; 12: 898
    CrossrefPubMed
  • 22 Soenen DR, Zimpleman JM, Boger DL. J. Org. Chem. 2003; 68: 3593
    CrossrefPubMed