Arene diversification through distal C(sp ² )−H functionalization

Targeting distal C–H bonds in arenes

The Friedel-Crafts reaction is among the oldest in organic chemistry. For well over a century, chemists have relied on electronic effects intrinsic to aryl rings to append substituents at specific sites along the periphery. However, only in the past decade have they devised catalytic techniques that over-ride these preferences so that new groups usually drawn to the neighboring sites of an existing substituent instead wind up two or three carbons away. Dutta et al. review progress in this field, highlighting elaborate directing groups and mediators as well as sophisticated ligand design.

Science , this issue p. eabd5992