The gold(I)-catalyzed addition of a broad range of nucleophiles towards alkynes has emerged as a powerful tool in organic synthesis. In the case of arenes as nucleophiles, alkynes undergo Au(I)-catalyzed Friedel-Crafts-type reactions to give hydroarylation products, which are applied in the context of the synthesis of polycyclic and polyheterocyclic derivatives. In this very attractive research field, as part of our ongoing interest in the synthesis of heterocyclic compound of biological relevance by the means of efficient and atom-economical routes, we focused our attention on the cyclization of the propargylic derivatives 1 which could provide the heterocyclic derivatives 2 (scheme 1). Our studies highlighted that the intramolecular hydroarylation reaction (IMHA) proceeds in good to excellent yields under mild condition with a broad range of substrates allowing the preparation of various polycyclic derivatives in good to excellent yields with different functional groups. Furthermore, in the case of unsymmetrically substituted substrates 3 (scheme 2) we investigated the possibility to drive the regiochemical outcome of the annulation towards the formation of compounds 4 or 5 through fine-tuning electronic and steric effects of the gold complexes ligands. Results of our studies highlighted that despite the Au(I)- catalyzed IMHA of derivatives 3 at the ortho- and para-position cyclization could be successfully established by tuning the electronic/steric properties of the catalyst, the procedure seems to be sensitive to some extent to the electronic and steric effects of the arene substituents. The main features of our investigations will be discussed during the communication.

Synthesis of heterocyclic compounds by means of gold-catalyzed intramolecular hydroarylation reaction

ACS Fall 2021

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