3.3.4.2 Biaryl Ether Synthesis

Diaryl ethers are important structural units present in many biologically active compounds. The coupling of aryl halides with phenols using copper source, known as Ullman ether synthesis, provides effective protocol for diaryl ether synthesis (Scheme 2). Both symmetrical and unsymmetrical ethers can be synthesized.

Scheme 2

Catalytic version of the reaction has been recently developed with copper(I) salts. The proposed mechanism involves oxidation addition followed by reductive elimination (Scheme 3).

Scheme 3

Examples:

D. Ma, Q. Cai, Org. Lett. 2003, 5, 3799.

M. Wolter, G. Nordmann, G. E. Job, S. L. Buchwald, Org. Lett. 2002, 4, 973.