Diaryl ether and diaryl thioether syntheses on solid supports via copper (I)-mediated coupling.
An efficient method to synthesize diaryl ethers and thioethers on solid supports is described. Starting from immobilized phenols or arylhalides, coupling with an access of aryliodides/arylbromides or phenolic/thiophenolic substrates in solution was successful in the presence of CuCl and Cs(2)CO(3) as base. Coupling conditions known from solution-phase syntheses of diaryl ethers have been effectively modified and adapted to solid-phase synthesis. Optimized conditions enabled the coupling of sterically hindered and/or electronically deactivated aryl moieties. After coupling, a newly developed diversity-generating linker based on cinnamic acid allowed the diaryl ethers to be cleaved from the resin either via saponification/transesterification or via ozonolysis. Latter offers the possibility of generating several additional compounds by simple variation of the cleavage conditions. The target substances were generally isolated in good to excellent yields and high purities.
Jung
Nicole
N
Institut für Organische Chemie, Universität Karlsruhe (TH), Karlsruhe, Germany.
Bräse
Stefan
S
D020650:Combinatorial Chemistry Techniques; D003300:Copper / Q000737:chemistry*; D004987:Ethers / Q000138:chemical synthesis*; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis*; D012117:Resins, Synthetic / Q000737:chemistry; D013440:Sulfides / Q000138:chemical synthesis*
D004987:Ethers; D006841:Hydrocarbons, Aromatic; D012117:Resins, Synthetic; D013440:Sulfides; D003300:Copper