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Abstract A palladium‐catalyzed dearomativesyn‐1,4‐oxyamination protocol using non‐activated arenes has been developed. This one‐pot procedure utilizes arenophile chemistry, and the correspondingpara‐cycloadducts are treated with oxygen nucleophiles via formal allylic substitution, providing direct access tosyn‐1,4‐oxyaminated products. The reaction conditions permit a range of arenes, as well as different O‐nucleophiles, such as oximes and benzyl alcohols. Moreover, this process was established in an asymmetric fashion, delivering products with high enantioselectivity. The dearomatized products are amenable to a multitude of further derivatizations ranging from olefin chemistry to C−H activation, giving rise to a diverse set of new functionalities. Overall, this dearomative functionalization offers rapid and controlled formation of molecular complexity, enabling straightforward access to functionalized small molecules from simple and readily available arenes. 

Abstract A protocol for palladium‐catalyzed dearomative functionalization of simple, nonactivated arenes with Grignard reagents has been established. This one‐pot method features a visible‐light‐mediated [4+2] cycloaddition between an arene and an arenophile, and subsequent palladium‐catalyzed allylic substitution of the resulting cycloadduct with a Grignard reagent. A variety of arenes and Grignard reagents can participate in this process, forming carboaminated products with exclusivesyn‐1,4‐selectivity. Moreover, the dearomatized products are amenable to further elaborations, providing functionalized alicyclic motifs and pharmacophores. For example, naphthalene was converted into sertraline, one of the most prescribed antidepressants, in only four operations. Finally, this process could also be conducted in an enantioselective fashion, as demonstrated with the desymmetrization of naphthalene. 

Abstract The total synthesis of lycoricidine and narciclasine is enabled by an arenophile‐mediated dearomative dihydroxylation of bromobenzene. Subsequent transpositive Suzuki coupling and cycloreversion deliver a key biaryl dihydrodiol intermediate, which is rapidly converted into lycoricidine through site‐selectivesyn‐1,4‐hydroxyamination and deprotection. The total synthesis of narciclasine is accomplished by the late‐stage, amide‐directed C−H hydroxylation of a lycoricidine intermediate. Moreover, the general applicability of this strategy to access dihydroxylated biphenyls is demonstrated with several examples. 

Aromatic compounds are one of the most abundant classes of organic molecules and find utility as precursors for alicyclic hydrocarbon building blocks. While many established dearomatization reactions are exceptionally powerful, dearomatization with concurrent introduction of functionality, i.e. dearomative functionalization, is still a largely underdeveloped field. This review aims to provide an overview of our recent efforts and progress in the development of dearomative functionalization of simple and nonactivated arenes using arenophile-arene cycloaddition platform. These cycloadducts, formed via a visible-light-mediated [4+2]-photocycloaddition, can be elaborated in situ through olefin chemistry or transition-metal-catalyzed ring-opening with carbon-, nitrogen-, and oxygen-based nucleophiles, providing access to diverse structures with functional and stereochemical complexity. Moreover, the dearomatized products are amenable to further elaborations, which effectively install other functionalities onto the resulting alicyclic carbocycles. The utility of the arenophile-mediated dearomatization methods are also highlighted by the facile syntheses of natural products and bioactive compounds through novel disconnections.