Dearomative dihydroxylation with arenophiles

Abstract

Aromatic hydrocarbons are some of the most elementary feedstock chemicals, produced annually on a million metric ton scale, and are used in the production of polymers, paints, agrochemicals and pharmaceuticals. Dearomatization reactions convert simple, readily available arenes into more complex molecules with broader potential utility, however, despite substantial progress and achievements in this field, there are relatively few methods for the dearomatization of simple arenes that also selectively introduce functionality. Here we describe a new dearomatization process that involves visible-light activation of small heteroatom-containing organic molecules—arenophiles—that results in their para-cycloaddition with a variety of aromatic compounds. The approach uses N–N-arenophiles to enable dearomative dihydroxylation and diaminodihydroxylation of simple arenes. This strategy provides direct and selective access to highly functionalized cyclohexenes and cyclohexadienes and is orthogonal to existing chemical and biological dearomatization processes. Finally, we demonstrate the synthetic utility of this strategy with the concise synthesis of several biologically active compounds and natural products.

Enantioselective Chemo‐ and Biocatalysis: Partners in Retrosynthesis

“…These have been cleverly employed for the production of aw ide range of densely functionalized, optically active cyclohexene building blocks such as 72. [59] Another dearomatizing transformation involves the reduction of 1,3-dihydroxynaphthalenes 73 to b-hydroxy ketones 74 ( Figure 16). [59] Another dearomatizing transformation involves the reduction of 1,3-dihydroxynaphthalenes 73 to b-hydroxy ketones 74 ( Figure 16).…”

Palladium‐Catalyzed Dearomativesyn‐1,4‐Carboamination with Grignard Reagents

“…Fori nstance,t he catalytic dearomatization of arenes has gained much attention in recent years, [6] whereas the application of such transformations has largely been limited to specific classes of activated arenes such as naphthols, [7] naphthylamines, [8] heteroarenes, [9] and arenes bearing benzylic heteroatoms. [11] Recently,w eh ave documented several dearomative functionalization methods based on in situ formation of arene-arenophile cycloadducts (I)b yv isible-light-mediated [4+ +2] cycloadditions, [12] and subsequent elaborations (Figure 1A). [11] Recently,w eh ave documented several dearomative functionalization methods based on in situ formation of arene-arenophile cycloadducts (I)b yv isible-light-mediated [4+ +2] cycloadditions, [12] and subsequent elaborations (Figure 1A).…”

Palladium‐Catalyzed Dearomative syn‐1,4‐Oxyamination

“…[8] An arene undergoes visible-light-induced cycloaddition with an arenophile, N-methyl-1,2,4-triazoline-3,5-dione (MTAD, 1,F igure 1C), to induce dearomatization and provide cycloadduct intermediate I.This cycloadduct can be manipulated in situ to furnish ar ange of different dearomatized products. [8] An arene undergoes visible-light-induced cycloaddition with an arenophile, N-methyl-1,2,4-triazoline-3,5-dione (MTAD, 1,F igure 1C), to induce dearomatization and provide cycloadduct intermediate I.This cycloadduct can be manipulated in situ to furnish ar ange of different dearomatized products.…”