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. 2014 Aug 11;356(11-12):2517-2524.
doi: 10.1002/adsc.201400679.

Palladium-Catalyzed Direct α-Aryation of Benzyl Thioethers with Aryl Bromides

Gustavo Frensch  1 , Nusrah Hussain  2 , Francisco A Marques  3 , Patrick J Walsh  2
Affiliations

Palladium-Catalyzed Direct α-Aryation of Benzyl Thioethers with Aryl Bromides

Gustavo Frensch et al. Adv Synth Catal. .

Abstract

The arylation of sp3-hybridized C-H's bonds is a powerful strategy to build molecular complexity and diversity. A novel and efficient palladium-catalyzed direct sp3 C-H arylation of aryl and alkyl benzyl thioether derivatives with aryl bromides is reported. The reaction involves reversible deprotonation of the benzylic C-H's of the thioether with either LiN(SiMe3)2 or NaN(SiMe3)2 and subsequent cross-coupling to provide the functionalized products in up to 97% yield. A screen of 24 of the most successful ligands in cross-coupling chemistry led to the identification of NiXantPhos as the only viable ligand for this challenging coupling.

Keywords: Arylation; Cross-Coupling; C–H functionalization; Palladium; Sulfides.

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Figures

Figure 1
Figure 1
Structures of van Leeuwen’s NiXantPhos and XantPhos ligands.
Scheme 1
Scheme 1
Direct α-arylation of sulfoxides (A) and sulfones (B) promoted by a palladium catalyst based on Kwong’s indole-based phosphine.
Scheme 2
Scheme 2
Direct α-arylation of sulfides outlined herein.
Scheme 3
Scheme 3
Arylation of benzyl phenyl sulfide with bromobenzene on a 5 mmol scale.
See this image and copyright information in PMC

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