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

Dmitry Dar'in; Grigory Kantin; Alexander Bunev; Mikhail Krasavin

doi:10.3762/bjoc.18.109

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

Beilstein J Org Chem. 2022 Aug 22:18:1070-1078. doi: 10.3762/bjoc.18.109. eCollection 2022.

Authors

Dmitry Dar'in¹, Grigory Kantin¹, Alexander Bunev², Mikhail Krasavin^{1

3}

Affiliations

¹ Saint Petersburg State University, Saint Petersburg 199034, Russian Federation.
² Medicinal Chemistry Center, Togliatti State University, 445020 Togliatti, Russian Federation.
³ Immanuel Kant Baltic Federal University, Kaliningrad 236016, Russian Federation.

Abstract

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 chemotype for further investigations as anticancer cytotoxic agents.

Keywords: 1,4-dihydroisoquinol-3-one; Regitz diazo transfer; heterocyclic diazo compounds; hydroarylation; triflic acid.

Grants and funding

This research was supported by the Russian Science Foundation (project grant 20-13-00024).