Electrophilic Iron Catalyst Paired with a Lithium Cation Enables Selective Functionalization of Non‐Activated Aliphatic C−H Bonds via Metallocarbene Intermediates

• Published in: Angewandte Chemie International Edition 2019-09, Vol.58 (39), p.13904-13911
• Main Authors: Hernán‐Gómez, Alberto, Rodríguez, Mònica, Parella, Teodor, Costas, Miquel
• Format: Article
• Language: English
• Subjects: Aliphatic compounds; Bonding strength; carbenes; Catalysis; Catalysts; Cations; Chemical reactions; C−H activation; Hydrogen bonds; Intermediates; Iron; Lithium; reaction mechanisms; Reagents; Rhodium; Selectivity
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201905986

Combining an electrophilic iron complex [Fe(Fpda)(THF)]2 (3) [Fpda=N,N′‐bis(pentafluorophenyl)‐o‐phenylenediamide] with the pre‐activation of α‐alkyl‐substituted α‐diazoesters reagents by LiAl(ORF)4 [ORF=(OC(CF3)3] provides unprecedented access to selective iron‐catalyzed intramolecular functionalization of strong alkyl C(sp3)−H bonds. Reactions occur at 25 °C via α‐alkyl‐metallocarbene intermediates, and with activity/selectivity levels similar to those of rhodium carboxylate catalysts. Mechanistic investigations reveal a crucial role of the lithium cation in the rate‐determining formation of the electrophilic iron‐carbene intermediate, which then proceeds by concerted insertion into the C−H bond. Li and Fe pairing: Pairing a strong Lewis‐acidic iron catalyst with the lithium salt LiAl(ORF)4 [ORF=(OC(CF3)3], for pre‐activation of diazo reagents, leads to electrophilic iron‐carbene species capable of insertion into non‐activated aliphatic C−H bonds. Reactions occur at 25 °C via α‐alkyl‐metallocarbene intermediates and the lithium cation plays a crucial role in the rate‐determining formation of the electrophilic iron‐carbene intermediate.