Remote C5-Selective Functionalization of Naphthalene Enabled by P-Ru-C Bond-Directed delta-Activation

Site-selective functionalization beyond the ortho-, meta-, and para-positions on naphthalene derivatives is very challenging, especially for the remote C5 position at the para-position of neighboring phenyl rings. Herein, we report the remote C5-selective functionalization of naphthalene via tertiary phosphine-induced ruthenium-catalyzed delta-bond activation. This strategy over-rides traditional site selectivity and efficiently installs different functional groups (alkyl, fluoroalkyl, and aldehyde) in the C5 position with excellent regioselectivity (C5/others >20:1). Moreover, this protocol is also suitable for polycyclic aromatic hydrocarbons and the more remote C8 position. Preliminary mechanistic studies show that the tertiary phosphine group plays two essential roles in the reaction: first, it assists the introduction of Ru-C bond at the C8 position; second, due to the induction effect, it assists the activation of the delta-bond by forming the electron-donating P-Ru-C bond.