The use of iron catalysts in carbon–carbon bond forming reactions is of interest as an alternative to precious metal catalysts, offering reduced cost, lower toxicity, and different reactivity. While well-defined ligands such as N-heterocyclic carbenes (NHCs) and phosphines can be highly effective in these reactions, additional additives such as N-methylpyrrolidone (NMP), N,N,N′,N′-tetramethylethylenediamine (TMEDA), and iron salts that alter speciation can also be employed to achieve high product yields. However, in contrast to well-defined iron ligands, the roles of these additives are often ambiguous, and molecular-level insights into how they achieve effective catalysis are not well-defined. Using a unique physical–inorganic in situ spectroscopic approach, detailed insights into the effect of additives on iron speciation, mechanism, and catalysis can inform further reaction development. In this Perspective, recent advances will be discussed as well as ongoing challenges and potential opportunities in iron-catalyzed reactions.

Herein, we expand the current molecular-level understanding of one of the most important and effective additives in iron-catalyzed cross-coupling reactions, N,N,N',N'-tetramethylethylenediamine (TME-DA). Focusing on relevant phenyl and ethyl Grignard reagents and slow nucleophile addition protocols commonly used in effective catalytic systems, TMEDAiron(II)-aryl intermediates are identified via in situ spectroscopy, X-ray crystallography, and detailed reaction studies to be a part of an iron(II)/(III)/(I) reaction cycle where radical recombination with FePhBr-(TMEDA) (2 Ph ) results in selective product formation in high yield. These results differ from prior studies with mesityl Grignard reagent, where poor product selectivity and low catalytic performance can be attributed to homoleptic iron-ate species. Overall, this study represents a critical advance in how amine additives such as TMEDA can modulate selectivity and reactivity of organoiron species in cross-coupling.

In this work, we aim to formally design iron(0) complexes combined with a phenanthroline-type ligand (phen) and investigate their utility in cycloaddition catalysis. Owing to the strong noninnocence of the phen scaffold, its ligation to reduced iron oxidation states classically affords particularly unstable species. The reported examples of such well-defined coordination complexes are thus particularly scarce. We demonstrate herein that a strategic steric protection of the C4 and C7 positions of the phen ring leads to neutral (N,N)2Fe species, which exhibits an unprecedented thermal and kinetic stability, amenable to its easy use as an in situ generated precursor in catalytic processes. The electronic structure of this noninnocent complex has been fully rationalized, and its promising catalytic activity in alkyne [2 + 2 + 2] cyclizations is discussed. Given its intrinsic thermal stability due to the noninnocent behavior of the (N,N) ligand, (N,N)2Fe appears to be an efficient dormant state of the catalytic process, precluding deactivation of iron as nonreactive aggregates.

The molecular-level role of alkoxide salts, used as alternative additive to N-methylpyrrolidone in iron-catalyzed alkyl-alkenyl/aryl cross-coupling reactions, is investigated. Detailed spectroscopic studies reveal that alkoxides promote the formation of homoleptic...

Herein, we expand the current molecular‐level understanding of one of the most important and effective additives in iron‐catalyzed cross‐coupling reactions, N,N,N′,N′‐tetramethylethylenediamine (TMEDA). Focusing on relevant phenyl and ethyl Grignard reagents and slow nucleophile addition protocols commonly used in effective catalytic systems, TMEDA‐iron(II)‐aryl intermediates are identified via in situ spectroscopy, X‐ray crystallography, and detailed reaction studies to be a part of an iron(II)/(III)/(I) reaction cycle where radical recombination with FePhBr(TMEDA) (2Ph) results in selective product formation in high yield. These results differ from prior studies with mesityl Grignard reagent, where poor product selectivity and low catalytic performance can be attributed to homoleptic iron–ate species. Overall, this study represents a critical advance in how amine additives such as TMEDA can modulate selectivity and reactivity of organoiron species in cross‐coupling.