N-Heterocyclic Carbene Switchable Radical- or Benzyne-Meditated Arylation of Thiols Using DMF/KOt-Bu

Abstract

A mild, metal, and photoredox-free direct arylation of alkyl and aryl thiols with aryl iodides using a DMF/KOt-Bu system has been developed. In the absence of an N-heterocyclic carbene (NHC) additive, the reaction proceeds via a benzyne intermediate and was suitable for the substitution of thiols with phenyl, while the presence of an NHC or phenanthroline derivative improves regioselectivity for the reaction of substituted aryl iodides via a radical pathway. This protocol features inexpensive materials and good substrate scope and could be useful in the arylation of aryl and alkyl thiols.

Key word

metal-free coupling - thiols - aryl halides - N-heterocyclic carbene - benzyne

Publication History

Received: 10 October 2024

Accepted after revision: 04 November 2024

Accepted Manuscript online:
04 November 2024

Article published online:
28 November 2024

• References and Notes

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• 37 General Procedure for 3a–n To a solution of iodobenzene (1a, 111 μL, 1 mmol, 1.0 equiv) in DMF (3 mL) was added thiol 2 (1.5 mmol, 1.5 equiv) and KOt-Bu (5 mmol, 5.0 equiv), and the mixture was heated to 60 °C for 16 h. The reaction mixture was diluted with Et₂O (15 mL) and H₂O (15 mL), the layers were separated, and the aqueous layer was extracted with Et₂O (15 mL). The combined organic layers were dried over Na₂SO₄, and the volatiles were removed under reduced pressure. The crude was purified via flash column chromatography to yield the desired sulfide 3.
• 38 General Procedure for 3f,g,k,o–t To a solution of aryl iodide 1 (1 mmol, 1.0 equiv) in DMF (3 mL) was added thiophenol (2a, 1.5 mmol, 1.5 equiv), NHC 4 (0.25 mmol, 0.25 equiv), and KOt-Bu (5 mmol, 5.0 equiv), and the mixture was heated to 60 °C for 16 h. The reaction mixture was diluted with Et₂O (15 mL) and H₂O (15 mL), the layers were separated, and the aqueous layer was extracted with Et₂O (15 mL). The combined organic layers were dried over Na₂SO₄, and the volatiles were removed under reduced pressure. The crude was purified via flash column chromatography to yield the desired sulfide 3.