Dearomatization of Nitro(hetero)arenes through Annulation

Abstract

Dearomatization reactions employing simple aromatic compounds have showcased remarkable progress in the recent decade and have emerged as one of the most straightforward and powerful tools for the creation of highly functionalized, three-dimensional molecular frameworks commonly encountered in medicinal chemistry and life sciences. Among the aromatic compounds in use, nitro(hetero)arenes, which feature a less pronounced aromatic character due to the presence of highly electron-withdrawing nitro group, have been extensively used in different types of dearomatization reactions. The dearomative annulation reaction serves as a powerful and versatile method for the construction of complex polycyclic systems. This overview presents a brief summary of recent impressive advances in nitro(hetero)arenes dearomative annulation and provides some inspirations for future research.

Enantioselective Dearomatization of Indoles via SmI2-Mediated Intermolecular Reductive Coupling with Ketones

“…7 Such reactions with intra-or intermolecular electrophiles, 8 nucleophiles, 9 and dipolar species are powerful in preparing diverse polycyclic molecules bearing multiple (quaternary) stereogenic centers. 10 In contrast, the enantioselective dearomatization of indoles with radical species remains relatively underdeveloped. 11 Inspired by the pioneering work from the groups of Schmalz, 12 Reissig, 13 Tanaka, 14 and Procter 15 on the SmI 2mediated reductive coupling between carbonyl groups and various (hetero)arenes, we envisioned that applying suitable chiral ligands in this kind of reaction might boost radicalinitiated asymmetric dearomatization reaction.…”

“…In line with our continuing interest in asymmetric dearomatization, we have developed various dearomatization reactions of indole derivatives enabled by chiral transition-metal or small molecule-based catalysts . Such reactions with intra- or intermolecular electrophiles, nucleophiles, and dipolar species are powerful in preparing diverse polycyclic molecules bearing multiple (quaternary) stereogenic centers . In contrast, the enantioselective dearomatization of indoles with radical species remains relatively underdeveloped …”

Copper-Catalyzed Asymmetric Dearomative [3+2] Cycloaddition of Nitroheteroarenes with Azomethines

“…In sharp contrast, the research with respect to electron-deficient heteroaromatic compounds remains relatively underdeveloped. Because the first palladium-catalyzed asymmetric dearomative [3+2] cycloaddition reaction of simple nitroarenes and trimethylenemethane was reported in 2014 by Trost and coworkers [ 21 ], the research on the catalytic asymmetric dearomatization reaction of electron-deficient nitroheteroarenes, including nitroindoles, nitrobenzofurans, and nitrobenzothiophenes, had attracted great interest from the synthetic organic chemistry community [ 22 , 23 , 24 , 25 , 26 ]. In this research area, the use of electron-deficient nitroheteroarenes as dipolarophiles for the asymmetric dearomative [3+2] cycloaddition reaction with various azomethine ylides has been sporadically reported.…”

Palladium-Catalyzed Asymmetric Decarboxylation of 5-Vinyloxazolidine-2,4-Diones Triggering the Dearomatization of Electron-Deficient Indoles for the Synthesis of Chiral Highly Functionalized Pyrroloindolines

“…Notably, all the three reports focus only on the synthesis of racemic pyrroloindolines, , whereas the construction of the corresponding optically pure scaffolds has not been reported. In this context, compared with the well-explored electron-rich heteroarenes serving as donors, the CADA reaction of electron-deficient heteroaromatic compounds acting as acceptors for the synthesis of pyrroloindolines would be an alternative approach and remains underdeveloped. , Therefore, the development of an efficient method by taking advantage of the CADA reaction of nitroindoles to access chiral pyrroloindolines is a highly desirable but challenging task.…”