The Validity of Iron as Catalyst for Cross-Coupling Reactions

Cross-coupling reactions are important reactions that create carbon-carbon and bonds, which are significant as precursors for synthesis of natural products and pharmaceuticals. The catalysts which drive these reactions are diverse, with different advantages and drawbacks. Cross-coupling reactions catalyzed by iron are interesting to chemists because they are relatively inexpensive materials and are significantly less toxic than other heavy metals that have been used as catalysts. Iron catalyzed cross-coupling reactions can proceed without the need of ligands and proceed at relatively fast rates when compared to palladium-catalyzed reactions. Iron salts are able to catalyze reactions with organomanganate, trialkylzincates, heterocyclic grignards in THF, and n-alkyl and sec-alkylmagnesium as nucleophiles, but were not successful in catalyzing reactions with organolithium or organoaluminum. Iron-catalyzed cross-coupling reactions resulted in better yields with aryl chlorides, triflates, and tosylates than palladium-catalyzed reactions. These reactions resulted in biologically relevant products such as antimicrobial active 1-ethyl derivative and the cytotoxin montipyridine, which are normally isolated from organisms. These biologically relevant reactions do not require a ligand, have short reaction times, and can catalyze normally unreactive substrates. The understanding of iron catalysts in cross-coupling can be furthered by comparing the synthesis of amphidinolide, with a focus on the difference between iron salt and palladium as the catalyst.