Iron-Catalyzed Tandem Cyclization and Cross-Coupling Reactions of Iodoalkanes and Aryl Grignard Reagents

• Published in: European journal of organic chemistry 2015-03, Vol.2015 (8), p.1781-1789
• Main Authors: Kim, Jae Gon, Son, Young Hoon, Seo, Jin Won, Kang, Eun Joo
• Format: Article
• Language: English
• Subjects: Cross-cou­pling; Domino reactions; Grignard reaction; Iron; Radical reactions
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201403511

A range of arylmethyl‐substituted pyrrolidines and tetrahydrofurans were produced by FeCl2‐catalyzed tandem cyclization and cross‐coupling reactions of alkyl iodides and aryl Grignard reagents. The substituents on alkenes had a profound effect on the progress of the tandem reactions, with di‐ and tri‐substituted alkenes affording cyclized pyrrolidines. Several experimental results, such as cyclopropyl ring opening, the stereochemical outcome of the reaction with a secondary iodide substrate, and intermediate identification with 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO), support the conclusion that a radical process is involved in this catalytic system. Moreover, deuterium labeling experiments indicated that radical disproportionation could occur in the termination reactions of the cyclized alkyl radical species. A range of arylmethyl‐substituted pyrrolidines, tetrahydrofurans, and indoline were produced by FeCl2‐catalyzed tandem cyclization and cross‐coupling reactions of alkyl iodides and aryl Grignard reagents. Several experimental results indicate that a single electron transfer process occurs in this catalytic system, which accounts for the outstanding reactivity of Fe catalysis towards alkyl halides.