Umpolung‐Enabled Divergent Dearomative Carbonylations

• Published in: Angewandte Chemie International Edition Vol. 63; no. 33; pp. e202403917 - n/a
• Main Authors: Wang, Ming‐Yang, Zeng, Wei‐Long, Chen, Lin, Yuan, Yu‐Fei, Li, Wei
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 12.08.2024
• Edition: International ed. in English
• Subjects: Alcohols; Amides; Amines; Arenes; Aromatic compounds; Benzene; Carbon cycle; Carbonylation; Carbonyls; Chemical synthesis; Chromium; Dearomatization; Dimensional tolerances; Direct conversion; Esters; Nucleophiles; Tracking control; Umpolung; Chromium; Dearomatization; Umpolung; Arenes; Carbonylation
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202403917

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. A novel dearomative carbonylation mode involving sequential nucleophile/nucleophile addition across benzene π‐bonds enables the divergent synthesis of esters and amides by tolerating a broad spectrum of benzene derivatives, nucleophilic partners, alcohols, and amines. The versatility of the process further allows for the tunable synthesis of 1,3‐ or 1,4‐cyclohexadienes and the construction of quaternary carbon centers.