A Facile Synthesis of Highly Functionalized Unsymmetrical Heterobiaryls Utilizing the Intramolecular Ullmann Coupling Reaction Directed by Salicyl Alcohol as a Template

Abstract

m -H e t e m b i a r y l s (4) were synthesized in good yields utilizing the inuamolecular Ullmann coupling reaction directed by salicyl alcohol as a template.The regioselective cleavage of the two ester bonds of 4 gave the highly functionalized unsymmetrical hetembiaryls having suhstituents which are incompatible with organometallic reagentsThe highly functionalized unsymmehical heterobiaryls are of considerable interest recently as useful intermediates in the synthesis of biologically active natural products such as tanshinone.]The synthetic methods of heterobiaryls so far reported include those based on the transition metal-catalyzed cross coupling reaction of an aryl metal with an aryl halide and the intermolecuar Ullmann coupling reaction.2.3However, difficulties are frequently encountered in the transition metal-catalyzed cross coupling reactions between two aryls having subsituents which are incompatible with the organometallic reagents.On the other hand, the intermolecular Ullmann coupling reaction gives rise to the undesired symmemcal biiuyls.We recently reported that the templatedirected inuamolecular Ullmann coupling reaction is quite effective in the synthesis of a variety of diphenic acid derivatives4 In connection with our synthetic studies in search of new compounds having intriguing biological activities,5 we now report a facile synthesis of highly functionalized unsymmetrical heterobiaryls utilizing the intramolecular Ullmann coupling reaction directed by salicyl alcohol as a template, followed by regioselective cleavage of the two ester bonds of 4.-