Programmable Triple Functionalization of Benzenes by Merging Dearomative Functionalization and Skeletal Editing.

Polysubstituted benzenes are ubiquitous in bioactive molecules and functional materials, yet their direct and selective construction from unadorned benzene remains elusive. Herein, we report a programmable triple functionalization of simple arenes by merging dearomative functionalization with double-atom swap. Each of the three newly installed substituents can be altered independently, and the regioselectivity is predictably governed by electronic effects. Diverse arenes, nucleophiles, and dienophiles are tolerated without preinstalled activating or directing groups, efficiently delivering tri- to hexa-substituted benzene derivatives. Its utility is further highlighted by the concise synthesis of a novel lactone-type hexabenzocoronene nanographene that exhibits a large Stokes shift and enhanced fluorescence. Isolation of key intermediates and isotopic labeling experiments support a cascade involving dearomative functionalization, cycloaddition, and cycloreversion. By overcoming the long-standing limitation of prefunctionalized handles, this work provides a step-economic and programmable 1,2,3-trifunctionalization platform for densely functionalized arenes of interest to medicinal chemistry and materials science.