Rhodium Catalysts Based on Phenyl Substituted Cp Ligands for Indole Synthesis via Oxidative Coupling of Acetanilides and Alkynes

• Published in: Advanced synthesis & catalysis Vol. 366; no. 22; pp. 4729 - 4736
• Main Authors: Kharitonov, Vladimir B., Muratov, Dmitry V., Rodionov, Alexey N., Nelyubina, Yulia V., Navasardyan, Mher A., Nechaev, Mikhail S., Loginov, Dmitry A.
• Format: Journal Article
• Language: English
• Published: Heidelberg Wiley Subscription Services, Inc 19-11-2024
• Subjects: Acetanilide; Alkynes; Annulation; Catalysts; Catalytic activity; Chemical synthesis; Coupling; C−H activation; Functional groups; Homogeneous catalysis; Indoles; Isocoumarins; Ligands; Rhodium
• DOI: 10.1002/adsc.202400716
• EISSN: 1615-4169
• ISSN: 1615-4150

Rhodium‐catalyzed oxidative coupling of acetanilides and alkynes via C−H activation is the most powerful synthetic tool for producing the indole motif from commercially available precursors. However, this reaction usually requires large catalyst loadings (5 mol% of rhodium). In this study, a 1,2‐diphenylcyclopentadienyl ligand‐based catalyst was developed that works well at 1 mol% loading of rhodium. DFT calculations of the C−H activation step provided insight into its high catalytic activity. The catalyst efficiency was also demonstrated in the synthesis of naturally occurring isocoumarins, such as polygonolide, tubakialactone B and penicimarine F. The developed catalytic protocols tolerate a wide range of functional groups, for example, halide, nitro, hydroxy, and alkoxy.