Iron-catalyzed cross-coupling reactions have been intensely investigated in recent years, while palladium- and nickel-catalyzed cross-coupling reactions of aryl and vinyl halides have evolved over decades into mature tools for advanced organic synthesis. The most valuable characteristic of iron catalysis in cross-coupling reactions may be the unprecedented reactivity toward alkyl halides. Alkyl halides are considered challenging substrates because they resist oxidative addition, and the resulting metal reagents have proclivity for β-hydride elimination. Despite a number of reports on iron-catalyzed cross-coupling reactions of alkyl halides, the tandem reaction protocol was not investigated in detail.
We have demonstrated that tandem cyclization and alkyl-aryl cross-coupling of primary and secondary alkyl iodides with aryl Grignard reagents can be realized by using an FeCl2 catalyst to afford arylmethyl-substituted heterocycles; a range of arylmethyl substituted pyrrolidines and tetrahydrofurans. Several experimental results, such as stereochemical outcome of secondary iodide substrate and intermediate identification with TEMPO, support the radical process of this catalytic system. In future studies, we aim to discover efficient tandem reactions expanded by this versatile iron catalysis to fully explore its preparative scope.