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. 2018 Jun 21;74(25):3129-3136.
doi: 10.1016/j.tet.2017.12.040. Epub 2017 Dec 21.

Selective formation of heteroaryl thioethers via a phosphonium ion coupling reaction

Ryan G Anderson  1 , Brianna M Jett  1 , Andrew McNally  1
Affiliations

Selective formation of heteroaryl thioethers via a phosphonium ion coupling reaction

Ryan G Anderson et al. Tetrahedron. .

Abstract

Heteroaryl thioethers, comprised of pyridines and diazines, are an important class of compounds with relevance to medicinal chemistry. Metal-catalyzed cross-couplings and SNAr are traditionally used to form C-S bonds in these systems but are limited by available halogenated precursors. An alternative approach is presented where pyridines and diazines are transformed into heterocyclic phosphonium salts and then C-S bonds are formed by adding thiolate nucleophiles. The process is 4-selective for pyridines, simple to execute and can be used to make derivatives of complex pharmaceuticals.

Keywords: C-S Bonds; Diazines; Heteroaryl thioethers; Late-stage functionalization; Phosphonium salts; Pyridines.

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Figures

Fig. 1.
Fig. 1.
Biologically active heteroaryl ethers and our strategy for C–S bond formation.
Fig. 2.
Fig. 2.
Potential mechanistic pathways for C–S bond formation.
See this image and copyright information in PMC

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