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

Rodrigues, Juliana M.Cendón Mariño, BorjaGulías Costa, MoisésMascareñas Cid, José LuisQueiroz, Maria João2021-07-202022-05-112021J. M. Rodrigues, B. Cendón, M. Gulías, J. L. Mascareñas, M.-J. R. P. Queiroz, Eur. J. Org. Chem. 2021, 2021, 3234.http://hdl.handle.net/10347/26595This is the peer reviewed version of the following article: J. M. Rodrigues, B. Cendón, M. Gulías, J. L. Mascareñas, M.-J. R. P. Queiroz, Eur. J. Org. Chem. 2021, 2021, 3234, which has been published in final form at https://doi.org/10.1002/ejoc.202100439. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsIn 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 heteroatomseng© 2021 Wiley-VCH GmbH. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsAnnulationC−H ActivationN,S-heterocyclesRhodium catalysisTricyclic ɑ-pyronesRhodium(III)-Catalyzed Formal Cycloaddition between Thienopyridine/Thienopyrazine Carboxylic Acids and Alkynes, Triggered by C−H Activationjournal article10.1002/ejoc.2021004391099-0690open access