Rhodium(III)-Catalyzed Formal Cycloaddition between Thienopyridine/Thienopyrazine Carboxylic Acids and Alkynes, Triggered by C−H Activation

Abstract

In the last decade, a number of metal-catalyzed technologies for the functionalization of C−H bonds in carbonaceous aromatic substrates have been developed. However, similar reactions with aza-heteroaromatic precursors are more challenging and have been much less developed. Herein, we report for the first time catalytic formal cycloadditions of N,S-heterocycles featuring carboxylic acid substituents, with unsaturated partners (alkynes). The reaction, which works with different symmetrical and unsymmetrical alkynes, produces appealing tricyclic ɑ-pyrones in a straightforward manner. The optimized conditions established for a model reaction employing thieno[2,3-b]pyridine-2-carboxylic acid as substrate, involved the use of Ag2CO3/AgSbF6 as additives, and proved to be general for different alkynes. Moreover, analogous cycloadditions using thieno[3,2-b]pyridine-2-carboxylic acid and thieno[2,3-b]pyrazine-6-carboxylic acid were successfully developed. Overall, this catalytic technology allows to build, in a single step, an interesting variety of pharmaceutically relevant tricyclic ɑ-pyrones exhibiting nitrogen and sulfur heteroatoms