The use of N-methylpyrrolidone (NMP) as a co-solvent in ferric salt catalyzed cross-coupling reactions is crucial for achieving the highly selective, preparative scale formation of cross-coupled product in reactions utilizing alkyl Grignard reagents. Despite the critical importance of NMP, the molecular level effect of NMP on in situ formed and reactive iron species that enables effective catalysis remains undefined. Herein, we report the isolation and characterization of a novel trimethyliron(II) ferrate species, [Mg(NMP) ][FeMe ] (1), which forms as the major iron species in situ in reactions of Fe(acac) and MeMgBr under catalytically relevant conditions where NMP is employed as a co-solvent. Importantly, combined GC analysis and Fe Mössbauer spectroscopic studies identified 1 as a highly reactive iron species for the selective formation generating cross-coupled product. These studies demonstrate that NMP does not directly interact with iron as a ligand in catalysis but, alternatively, interacts with the magnesium cations to preferentially stabilize the formation of 1 over [Fe Me ] cluster generation, which occurs in the absence of NMP.

Since the pioneering work of Kochi in the 1970s, iron has attracted great interest for crosscoupling catalysis due to its low cost and toxicity as well as its potential for novel reactivity compared to analogous reactions with precious metals like palladium. Today there are numerous iron-based cross-coupling methodologies available, including challenging alkyl-alkyl and enantioselective methods. Furthermore, cross-couplings with simple ferric salts and additives like NMP and TMEDA (N-methylpyrrolidone and tetramethylethylenediamine) continue to attract interest in pharmaceutical applications. Despite the tremendous advances in iron cross-coupling methodologies, in situ formed and reactive iron species and the underlying mechanisms of catalysis remain poorly understood in many cases, inhibiting mechanism-driven methodology development in this field. This lack of mechanism-driven development has been due, in part, to the challenges of applying traditional characterization methods such as nuclear magnetic resonance (NMR) spectroscopy to iron chemistry due to the multitude of paramagnetic species that can form in situ. The application of a broad array of inorganic spectroscopic methods (e.g., electron paramagnetic resonance, 57 Fe Mössbauer, and magnetic circular dichroism) removes this barrier and has revolutionized our ability to evaluate iron speciation. In conjunction with inorganic syntheses of unstable organoiron intermediates and combined inorganic spectroscopy/gas chromatography studies to evaluate in situ iron reactivity, this approach has dramatically evolved our understanding of in situ iron speciation, reactivity, and mechanisms in iron-catalyzed cross-coupling over the past 5 years. This Account focuses on the key advances made in obtaining mechanistic insight in iron-catalyzed carboncarbon cross-couplings using simple ferric salts, iron-bisphosphines, and iron-N-heterocyclic carbenes (NHCs). Our studies of ferric salt catalysis have resulted in the isolation of an unprecedented iron-methyl cluster, allowing us to identify a novel reaction pathway and solve a decades-old mystery in iron chemistry. NMP has also been identified as a key to accessing more stable intermediates in reactions containing nucleophiles with and without β-hydrogens. In ironbisphosphine chemistry, we have identified several series of transmetalated iron(II)-bisphosphine complexes containing mesityl, phenyl, and alkynyl nucleophile-derived ligands, where mesityl systems were found to be unreliable analogues to phenyls. Finally, in iron-NHC cross-coupling, unique chelation effects were observed in cases where nucleophile-derived ligands contained *

Boron monofluoride (BF) is a diatomic molecule with 10 valence electrons, isoelectronic to carbon monoxide (CO). Unlike CO, which is a stable molecule at room temperature and readily serves as both a bridging and terminal ligand to transition metals, BF is unstable below 1800°C in the gas phase, and its coordination chemistry is substantially limited. Here, we report the isolation of the iron complex Fe(BF)(CO)2(CNArTripp2)2 [ArTripp2, 2,6-(2,4,6-(i-Pr)3C6H2]2C6H3; i-Pr, iso-propyl], featuring a terminal BF ligand. Single-crystal x-ray diffraction as well as nuclear magnetic resonance, infrared, and Mössbauer spectroscopic studies on Fe(BF)(CO)2(CNArTripp2)2 and the isoelectronic dinitrogen (N2) and CO complexes Fe(N2)(CO)2(CNArTripp2)2 and Fe(CO)3(CNArTripp2)2 demonstrate that the terminal BF ligand possesses particularly strong σ-donor and π-acceptor properties. Density functional theory and electron-density topology calculations support this conclusion.

Iron-catalyzed cross-coupling reactions have attracted significant research interest, as they offer numerous favorable features compared with cross-coupling reactions with precious metal catalysis. While this research has contributed to an empirical understanding of iron-catalyzed cross-coupling, the underlying fundamental mechanisms of reaction and structures of catalytically active species have remained poorly defined. The lack of such detail can be attributed to the difficulties associated with studying such iron-catalyzed reactions, where unstable paramagnetic intermediates abound. Recently, the combined application of physical-inorganic spectroscopic methods, concomitant organic product analysis, and air- and temperature-sensitive inorganic synthesis has yielded the most detailed insight currently available on reactivity and mechanism in iron-catalyzed cross-coupling. This Perspective highlights this approach and the limitations of the contributing techniques as well as some of the key features of the catalytic reactions studied and lessons learned.

The effects of b-hydrogen-containing alkyl Grignard reagents in simple ferric salt cross-couplings have been elucidated. The reaction of FeCl 3 with EtMgBr in THF leads to the formation of the cluster species [Fe 8 Et 12 ] 2À ,arare example of as tructurally characterized metal complex with bridging ethyl ligands.Analogous reactions in the presence of NMP,akey additive for effective cross-coupling with simple ferric salts and b-hydrogen-containing alkyln ucleophiles, result in the formation of [FeEt 3 ] À .R eactivity studies demonstrate the effectiveness of [FeEt 3 ] À in rapidly and selectively forming the cross-coupled product upon reaction with electrophiles.T he identification of iron-ate species with EtMgBr analogous to those previously observed with MeMgBr is acritical insight, indicating that analogous iron species can be operative in catalysis for these two classes of alkyl nucleophiles.