Tuning Reactivity and Site Selectivity of Simple Arenes in C-H Activation: Ortho-Arylation of Anisoles via Arene-Metal pi-Complexation

Current approaches to achieve site selectivity in the CH activation of arenes involve the use of directing groups or highly electron-poor arenes. In contrast, simple arenes, such as anisole, are characterized by poor reactivity and selectivity. We report that pi-complexation to a Cr(CO)(3) unit enhances the reactivity of anisoles providing an unprecedented ortho-selective arylation. This mild methodology can be used for the late stage functionalization of bioactive compounds containing the anisole motif, allowing the construction of novel organic scaffolds with few synthetic steps.