Rapid Construction of a Benzo-Fused Indoxamycin Core Enabled by Site-Selective C−H Functionalizations

• Published in: Angewandte Chemie Vol. 128; no. 29; pp. 8410 - 8414
• Main Authors: Bedell, T. Aaron, Hone, Graham A. B., Valette, Damien, Yu, Jin-Quan, Davies, Huw M. L., Sorensen, Erik J.
• Format: Journal Article
• Language: English; German
• Published: Weinheim Blackwell Publishing Ltd 11.07.2016; Wiley Subscription Services, Inc
• Subjects: Architecture; C-H-Aktivierung; Carbenes; Carbon; Chemical bonds; Chemical synthesis; Chemistry; Collaboration; Construction; Cooperation; Design; Hydrogen; Hydrogen bonding; Hydrogen bonds; Insertion; Laboratories; Metabolites; Naturstoffe; Palladierungen; Rhodium-Carbene; Secondary metabolites; Synthesemethoden; Synthesis; Synthesis (chemistry)
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201602024

Methods for functionalizing carbon–hydrogen bonds are featured in a new synthesis of the tricyclic core architecture that characterizes the indoxamycin family of secondary metabolites. A unique collaboration between three laboratories has engendered a design for synthesis featuring two sequential C−H functionalization reactions, namely a diastereoselective dirhodium carbene insertion followed by an ester‐directed oxidative Heck cyclization, to rapidly assemble the congested tricyclic core of the indoxamycins. This project exemplifies how multi‐laboratory collaborations can foster conceptually novel approaches to challenging problems in chemical synthesis. Methoden zur Funktionalisierung von C‐H‐Bindungen wurden in der Synthese des tricyclischen Gerüsts der Sekundärmetabolite der Indoxamycin‐Familie angewendet. Schlüsselschritte der Synthese sind eine diastereoselektive Rhodium‐Carben‐Insertion und eine Ester‐dirigierte oxidative Heck‐Cyclisierung.