A new synthesis of 2,2′-disubstituted unsymmetrical biphenyls based on the intramolecular Ullmann coupling reaction utilising salicyl alcohol as a template

Abstract

A synthesis of 2,2′-disubstituted unsymmetrical biphenyls was examined by using the template-directed intramolecular Ullmann coupling reaction as a key step. The Ullmann coupling reaction of the diesters 1–5 showed that the most suitable ring size for the intramolecular Ullmann coupling reaction is an eleven-membered ring. On the basis of these results, salicyl alcohol was selected as a template. Acylations of salicyl alcohol by two different aroyl chlorides proceeded regioselectively in a one-pot procedure to afford the diesters 18 in good yields. The intramolecular Ullmann coupling reaction of 18 by the dropwise-addition method gave the cyclisation products 19 in high yields. Hydrogenolysis of 19 proceeded regioselectively to afford the unsymmetrical biphenyls 21 in quantitative yields, while the regioselective cleavage of the ester bonds of 19 by nucleophilic substitution reactions gave the corresponding 2,2′-disubstituted unsymmetrical biphenyls 22 and 24 in good yields.