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Dearomative trifluoromethylation of arenes provides an ideal method for constructing CF3‐containing three‐dimensional architectures which are of increasing interest in drug discovery. However, such transformation is rare and challenging because of the inherently low reactivity of arene π‐systems and selectivity issues. Herein, we disclose a general dearomative 1,2‐hydrotrifluoromethylation of (hetero)arenes utilizing activation by temporary π‐complexation to chromium, thus affording convenient access to 1,3‐cyclohexadienes bearing the privileged CF3 group. The versatility of this strategy further enables a dearomative 1,2‐deuterotrifluoromethylation with high deuterated ratios. The related dearomative 1,2‐(deutero)hydroperfluoroethylation reactions were conducted well for a range of chromium‐bound (hetero)arenes. Finally, a reasonable mechanism was proposed based on the intermediate capture and control experiments. [ABSTRACT FROM AUTHOR]

Herein, a general strategy for chemo‐ and regioselective 1,2‐reduction of chromium‐bound arenes was developed, thus providing rapid access to 1,3‐cyclohexadienes. Selective arene activation via π‐complexation along with the use of mild hydride Ph3SiH can overcome the inherently low reactivity of arene π‐bonds while tolerating various reduction‐sensitive functional groups. Its versatility further enables a regiodivergent deuteration. Using different sequences of (non)deuterated hydride and acid reagents, the deuterated positions as well as the degrees of deuterium incorporation can be controlled precisely, which leads to a large and previously inaccessible chemical space for 1,3‐cyclohexadiene isotopologues. A reasonable mechanism was proposed based on intermediate capture and control experiments. The synthetic value of this selective 1,2‐reduction was demonstrated in the formal total synthesis of (±)‐galanthamine and (±)‐lycoramine. [ABSTRACT FROM AUTHOR]

The front cover of the journal "Advanced Synthesis & Catalysis" showcases the transformation of benzene derivatives into valuable trifluoromethyl-containing cyclohexadienes using a chromium-mediated strategy. This process involves activating inert arene π-bonds to achieve dearomative 1,2-hydrotrifluoromethylation and dearomative 1,2-deuterotrifluoromethylation. The research, conducted by Wei Li and colleagues, is detailed in the Communication published in the journal. [Extracted from the article]

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]

Inside Cover: Chemoselective 1,2-Reduction and Regiodivergent Deuteration of Chromium-Bound Arenes (Angew. Keywords: 1,3-Cyclohexadiene; Arene Reduction; Chromium; Deuterium; Reductive Deuteration EN 1,3-Cyclohexadiene Arene Reduction Chromium Deuterium Reductive Deuteration 1 1 1 04/19/23 20230424 NES 230424 B Arene 1,2-reduction b and regiodivergent deuteration via SP 6 sp -coordination have been developed by Wei Li and co-workers in their Research Article (e202218961). 1,3-Cyclohexadiene, Arene Reduction, Chromium, Deuterium, Reductive Deuteration. [Extracted from the article]