Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

A practically convenient and streamlined protocol for the trans-diastereoselective introduction of an aryl substituent at position 4 of the 1,4-dihydroisoquinol-3-one (1,4-DHIQ) scaffold is presented. The protocol involves direct Regitz diazo transfer onto readily available 3(2H)-isoquinolones followed by TfOH-promoted hydroarylation by an arene molecule. Screening of the novel 1,2,4-trisubstituted 1,4-DHIQs against cancer cell lines confirmed high cytotoxicity of selected analogs, which validates this new chemo-type for further investigations as anticancer cytotoxic agents.

Automated summary

This study presents a practically convenient and streamlined protocol for introducing an aryl substituent at position 4 of the 1,4-DHIQ scaffold. The protocol involves Regitz diazo transfer and TfOH-promoted hydroarylation. Screening of the synthesized compounds against cancer cell lines confirmed high cytotoxicity of selected analogs, validating the potential of this new compound as an anticancer agent.