Photoinduced dearomative radical spirocyclization/oximation of nonactivated arenes: access to phosphorylated spirocyclic oximes with pH-responsive fluorescence and antitumor activity

Abstract

Dearomative radical ipso-spirocyclization has emerged as a powerful strategy for the synthesis of valuable three-dimensional spirocyclic compounds from aromatic feedstocks; however, these transformations are predominantly realized with activated arenes. Herein, a photoinduced three-component dearomative radical spirocyclization/1,4-alkenyloximation of nonactivated arenes is described. The reaction tolerates a wide range of N-arylpropiolamides and secondary phosphine oxides, affording phosphorylated spirocyclic oximes in moderate to good yields under photocatalyst-, metal-, and additive-free conditions. Preliminary mechanistic studies were performed to elucidate the reaction mechanism. Furthermore, the spirocyclic products could be used as versatile building blocks for diverse derivatizations, as well as exhibit remarkable aggregation-induced blue-shifted emission and reversible pH-responsive fluorescence properties and promising antitumor activities, demonstrating the great potential applications of this approach.