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. 2021 Dec 3;23(23):9089-9093.
doi: 10.1021/acs.orglett.1c03379. Epub 2021 Nov 16.

Synthesis of Bis-heteroaryls Using Grignard Reagents and Pyridylsulfonium Salts

Alexandra M Horan  1 , Vincent K Duong  1 , Eoghan M McGarrigle  1
Affiliations

Synthesis of Bis-heteroaryls Using Grignard Reagents and Pyridylsulfonium Salts

Alexandra M Horan et al. Org Lett. .

Abstract

Herein are reported ligand-coupling reactions of Grignard reagents with pyridylsulfonium salts. The method has wide functional group tolerance and enables the formation of bis-heterocycle linkages, including 2,4'-, 2,3'-, and 2,2'-bipyridines, as well as pyridines linked to pyrimidines, pyrazines, isoxazoles, and benzothiophenes. The methodology was successfully applied to the synthesis of the natural products caerulomycin A and E.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Bis-heteroaryl Syntheses via Ligand-Coupling Reactions to Access 2,2′-, 2,3′-, and 2,4′-Linkages
Scheme 2
Scheme 2. Ligand-Coupling Reactions between Grignard Reagents and Pyridylsulfonium Salt 1a
Reactions performed at 0.3 mmol scale, isolated yields indicated. Ligand-coupling reactions carried out at −78 °C for RLi and rt for RMgX.
Scheme 3
Scheme 3. Testing the Possibility of SNAr
Scheme 4
Scheme 4. (a) Application of Ligand-Coupling Methodology to the Synthesis of Caerulomycins; (b) Gram-Scale Synthesis of Bis-Heterocycle 17
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