Metal-free [2 + 2] and [4 + 2] cycloadditions of N-aryl-substituted ynamides to construct functionalized aminocyclobutenes and 4-aminoquinolines

Abstract

We herein report two efficient intermolecular self-cycloadditions of N-aryl-substituted ynamides via metal-free approaches, leading to attractive and efficient assembly of various valuable aminocyclobutenes and 4-aminoquinoline derivatives with generally good to excellent yields and wide substrate scope. A variety of terminal N-aryl ynamides were initially prepared effectively by our modified method. Then functionalized aminocyclobutenes were afforded via the thermally driven and solvent-free [2 + 2] cycloaddition of terminal N-aryl ynamides, while 4-aminoquinoline derivatives were provided through the TMSOTf/TfOH-catalyzed [4 + 2] cycloaddition of N-aryl ynamides. Moreover, evaluation of their in vitro activity unveiled that some cycloaddition products and their derivatives showed highly potent activities against SARS-CoV-2, DENV-2 and tumor cell lines.