Synthesis of aryl- and heteroaryl-substituted 3-benzyloxyisothiazoles via Suzuki and Negishi cross-coupling reactions

Birgitte H Kaae; Povl Krogsgaard-Larsen; Tommy N Johansen

doi:10.1021/jo035578g

Synthesis of aryl- and heteroaryl-substituted 3-benzyloxyisothiazoles via Suzuki and Negishi cross-coupling reactions

J Org Chem. 2004 Feb 20;69(4):1401-4. doi: 10.1021/jo035578g.

Authors

Birgitte H Kaae¹, Povl Krogsgaard-Larsen, Tommy N Johansen

Affiliation

¹ Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, 2 Universitetsparken, DK-2100 Copenhagen, Denmark.

PMID: 14961704
DOI: 10.1021/jo035578g

Abstract

Introduction of aryl and heteroaryl substituents into the 5-position of 3-benzyloxyisothiazole (1) using palladium-catalyzed Suzuki and Negishi cross-coupling reactions was investigated. Attempts to generate synthetically viable nucleophilic species from 1 for Suzuki- or Negishi-type cross-couplings were unsuccessful. However, using 3-benzyloxy-5-iodoisothiazole 2 as an intermediate, a range of aromatic and heteroaromatic substituents were successfully introduced under Suzuki or Negishi cross-coupling conditions in good to excellent yields.