Palladium‐Catalyzed Regioselective peri‐ and ortho‐Halogenation of 1‐Naphthaldehydes: Application to the Synthesis of Polycyclic Natural Product Skeletons

Abstract

Herein, a regioselective bromination or chlorination reaction of 1‐naphthaldehydes is described. Without additive, the palladium‐catalyzed C−H halogenation showed a C8‐regioselectivity, whereas the formation of an aromatic imine intermediate allowed a switch to a C2‐reactivity. Mechanistic studies and DFT calculations were performed to explain the regioselectivity and the synthesized halogenated products were used as key building blocks to access polycyclic natural product skeletons.

Palladium‐Catalyzed C8‐Fluoroalkylation and C8‐Fluoroalkenylation of Naphthalenes by C−H Activation

“…Notably, with respect to the C8À H bond involving carbonyl as directing group, substantial improvements have been realized by our research group and others. Presently, employing palladium catalysis, it is feasible to introduce aryls, [21] oxygenated groups, [22] methyl, [23] halogen atoms [24] or alkenes [25] into this position (Scheme 1b). In this context, our interest led us to embark on the development of a novel C8-functionalization method for 1-carbonylnaphthalenes, specifically targeting the introduction of fluorinated groups, with the objective to facilitate the synthesis of polysubstituted naphthalenes featuring fluorinated substituents (Scheme 1c).…”