Pd-Catalyzed Arylation of Secondary α-Alkoxytricyclohexylstannanes

We have developed a general process for the formation of alpha-arylethers via the Pd-catalyzed arylation of secondary alpha-alkoxytricyclohexylstannanes. Incorporation of cyclo-hexyl spectator ligands into the alkylstannane and the use of the electron-deficient ligand JackiePhos (1) are critical for achieving selective alkyl transfer in this process. This system circumvents the need for a coordinating/directing oxygen-protecting group to promote selective alkyl transfer and enables alpha-tetrahydropyran, alpha-tetrahydrofuran, and open-chain secondary alpha-alkoxy groups to be employed efficiently in Pd-catalyzed Stille reactions with a broad range of aryl electrophiles. These findings suggest that selective transmetalation of a single marginally activated secondary alkyl unit from Sn to Pd should be broadly achievable provided that unactivated secondary alkyl ligands comprise the other three groups of the tetraalkylstannane.

Automated summary

A general process for the formation of alpha-arylethers via Pd-catalyzed arylation has been developed. This process achieves selective alkyl transfer by incorporating cyclo-hexyl spectator ligands and using the electron-deficient ligand JackiePhos (1), eliminating the need for coordinating/directing oxygen-protecting groups.