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This article explores the use of chromium-promoted dearomative hydrocyanoalkylation in organic synthesis. The authors emphasize the versatility of the cyano group and the potential for using simple alkylnitriles as cost-effective sources. They acknowledge the challenges of dearomatization reactions and the limited range of current methods. The authors present their own research on the efficient dearomative hydrocyanoalkylation of chromium-bound (hetero)arenes using simple alkylnitriles, with a focus on optimizing reaction conditions. This research has the potential to expand the scope of dearomative hydrocyanoalkylation reactions and provide new synthetic building blocks. Additionally, the article discusses a new method for synthesizing complex cyclohexadiene compounds using a chromium-mediated reaction. The authors demonstrate the broad applicability of the reaction by successfully synthesizing various arenes and heteroarenes with different substituents and functional groups. They also extend the methodology to include the synthesis of deuterated cyclohexadienes and the transformation of the products into more structurally complex compounds. The authors highlight the potential applications of this method in the synthesis of bioactive natural products and alkaloids. [Extracted from the article]

Although dearomative functionalizations enable the direct conversion of flat aromatics into precious three‐dimensional architectures, the case for simple arenes remains largely underdeveloped owing to the high aromatic stabilization energy. We herein report a dearomative sequential addition of two nucleophiles to arene π‐bonds through umpolung of chromium–arene complexes. This mode enables divergent dearomative carbonylation reactions of benzene derivatives by tolerating various nucleophiles in combination with alcohols or amines under CO‐gas‐free conditions, thus providing modular access to functionalized esters or amides. The tunable synthesis of 1,3‐ or 1,4‐cyclohexadienes as well as the construction of carbon quaternary centers further highlight the versatility of this dearomatization. Diverse late‐stage modifications and derivatizations towards synthetically challenging and bioactive molecules reveal the synthetic utility. A possible mechanism was proposed based on control experiments and intermediate tracking. [ABSTRACT FROM AUTHOR]

Amides are ubiquitous in physical and life sciences. Given the significant abundance of arenes, dearomative aminocarbonylation of arenes would lead to a large and underexplored chemical space for amide discovery. However, such reactions are challenging due to the high degree of resonance stabilization and selectivity issues. Herein, we disclose an unprecedented dearomative trifluoromethylative aminocarbonylation of arenes via bifunctional coordination to chromium, providing a modular platform for the construction of amides possessing trifluoromethyl (CF3) groups and three‐dimensional rings. Its versatility further enabled a switchable difluoromethylation or trifluoromethylation aminocarbonylation of arene C−H bonds. A possible mechanism was proposed based on control experiments. Finally, the synthetic utility was well demonstrated by diverse applications in the total synthesis of CF3‐functionalized amide‐type drugs, including praziquantel, nateglinide, maraviroc and alloyohimbane. [ABSTRACT FROM AUTHOR]

Amides are ubiquitous in physical and life sciences. Given the significant abundance of arenes, dearomative aminocarbonylation of arenes would lead to a large and underexplored chemical space for amide discovery. However, such reactions are challenging due to the high degree of resonance stabilization and selectivity issues. Herein, we disclose an unprecedented dearomative trifluoromethylative aminocarbonylation of arenes via bifunctional coordination to chromium, providing a modular platform for the construction of amides possessing trifluoromethyl (CF3) groups and three‐dimensional rings. Its versatility further enabled a switchable difluoromethylation or trifluoromethylation aminocarbonylation of arene C−H bonds. A possible mechanism was proposed based on control experiments. Finally, the synthetic utility was well demonstrated by diverse applications in the total synthesis of CF3‐functionalized amide‐type drugs, including praziquantel, nateglinide, maraviroc and alloyohimbane. [ABSTRACT FROM AUTHOR]

The incorporation of the privileged amino functionality is of paramount importance in organic synthesis. In contrast to the well‐developed amination methods for alkenes, the dearomative amination of arenes is largely underexplored due to the inherently inert reactivity of arene π‐bonds and selectivity challenges. Herein, we report an intermolecular dearomative aminofunctionalization via direct nucleophilic addition of simple amines to chromium‐bound arenes. This multicomponent 1,2‐amination/carbonylation reaction enables rapid access to complicated alicyclic compounds containing amino and amide functionalities from benzene derivatives under CO‐gas‐free conditions, which also represents the first application of nitrogen‐based nucleophiles in η6‐coordination‐induced arene dearomatizations. [ABSTRACT FROM AUTHOR]