Search

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. [ABSTRACT FROM AUTHOR]

The use of N-methylpyrrolidone (NMP) as a cosolvent 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)6][FeMe3]2 (1), which forms as the major iron species in situ in reactions of Fe(acac)3 and MeMgBr under catalytically relevant conditions where NMP is employed as a co-solvent. Importantly, combined GC analysis and 57Fe 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 [Fe8Me12]- cluster generation, which occurs in the absence of NMP. [ABSTRACT FROM AUTHOR]

Detailed studies of iron speciation and mechanism in iron-catalyzed cross-coupling reactions are critical for providing the necessary fundamental insight to drive new reaction development. However, such insight is challenging to obtain due to the prevalence of mixtures of unstable, paramagnetic organoiron species that can form in this chemistry. A physical-inorganic research approach combining freeze-trapped inorganic spectroscopic studies, organometallic synthesis and GC/kinetic studies provides a powerful method for studying such systems. Mössbauer, EPR and MCD spectroscopy enable the direct investigation of in situ formed iron species and, combined with GC analysis, the direct correlation of reactions of specific iron species to the generation of organic products. This review focuses on a description of the key methods involved in this physical-inorganic approach, as well as examples of its application to investigations of iron-SciOPP catalyzed cross-coupling catalysis. [ABSTRACT FROM AUTHOR]

Iron-catalyzed cross-coupling reactions using alkynyl nucleophiles represent an attractive approach for the incorporation of alkynyl moieties into organic molecules. In the present study, a multitechnique approach combining inorganic spectroscopic methods, inorganic synthesis, and reaction studies is applied to iron-SciOPP catalyzed alkynyl-alkyl cross-couplings, providing the first detailed insight into the effects of variation from sp²- to sp-hybridized nucleophiles on iron speciation and reactivity. Reaction studies demonstrate that reaction of FeBr2(SciOPP) with 1 equiv (triisopropylsilyl)ethynylmagnesium bromide (TIPS-CC-MgBr) leads to a distribution of mono-, bis-, and tris-alkynylated iron(II)-SciOPP species due to rapid alkynyl ligand redistribution. While solvents such as THF promote these complex redistribution pathways, nonpolar solvents such as toluene enable increased stabilization of these iron species and further enabled assessment of their reactivity with electrophile. While the tris-alkynylated iron(II)-SciOPP species was found to be unreactive with the cycloheptyl bromide electrophile over the average turnover time of catalysis, the in situ formed neutral mono- and bis-alkynylated iron(II)-SciOPP complexes are consumed upon reaction with the electrophile with concomitant generation of cross-coupled product at catalytically relevant rates, indicating the ability of one or both of these species to react selectively with the electrophile. The nature of the reaction solvent and Grignard reagent addition rate were found to have broader implications in overall reaction selectivity, reaction rate, and accessibility of off-cycle iron(I)-SciOPP species. Additionally, the effects of steric substitution of the alkynyl Grignard reagent on catalytic performance were investigated. Fundamental insight into iron speciation and reactivity with alkynyl nucleophiles reported herein provides an essential foundation for the continued development of this important class of reactions. [ABSTRACT FROM AUTHOR]

Transition metal–catalyzed cross-coupling reactions are some of the most widely used methods in chemical synthesis. However, despite notable advantages of iron (Fe) as a potentially cheaper, more abundant, and less toxic transition metal catalyst, its practical application in multicomponent cross-couplings remains largely unsuccessful. We demonstrate 1,2-bis(dicyclohexylphosphino)ethane Fe–catalyzed coupling of a-boryl radicals (generated from selective radical addition to vinyl boronates) with Grignard reagents. Then, we extended the scope of these radical cascades by developing a general and broadly applicable Fe-catalyzed multicomponent annulation–cross-coupling protocol that engages a wide range of p-systems and permits the practical synthesis of cyclic fluorous compounds. Mechanistic studies are consistent with a bisarylated Fe(II) species being responsible for alkyl radical generation to initiate catalysis, while carbon-carbon bond formation proceeds between a monoarylated Fe(II) center and a transient alkyl radical. [ABSTRACT FROM AUTHOR]

While previous studies have identified Fe- Mes2(SciOPP) as the active catalyst species in iron--SciOPP catalyzed Kumada cross-coupling of mesitylmagnesium bromide and primary alkyl halides, the active catalyst species in cross-couplings with phenyl nucleophiles, where low valent iron species might be prevalent due to accessible reductive elimination pathways, remains undefined. In the present study, in situ Mossbauer and magnetic circular dichroism spectroscopic studies combined with inorganic syntheses and reaction studies are employed to evaluate the in situ formed iron species and identify the active catalytic species in iron-SciOPP catalyzed Suzuki-Miyaura and Kumada cross-couplings of phenyl nucleophiles and secondary alkyl halides. While reductive elimination to form Fe(η6-biphenyl) (SciOPP) occurs upon reaction of FeCl2(SciOPP) with phenyl nucleophiles, this iron(O) species is not found to be kinetically competent for catalysis. Importantly, mono- and bis-phenylated iron(II)-- SciOPP species that form prior to reductive elimination are identified, where both species are found to be reactive toward electrophile at catalytically relevant rates. The higher selectivity toward the formation of cross-coupled product observed for the monophenylated species combined with the undertransmetalated nature of the in situ iron species in both Kumada and Suzuki- Miyaura reactions indicates that Fe(Ph)X(SciOPP) (X = Br, CI) is the predominant reactive species in cross-coupling. Overall, these studies demonstrate that low-valent iron is not required for the generation of highly reactive species for effective aryl-alkyl cross-couplings. [ABSTRACT FROM AUTHOR]

While iron-catalyzed Kumada cross-coupling reactions with simple iron salts have been known since the early 1970s, the nature of the in situ-formed iron species remains elusive. Herein, we report the synthesis of the homoleptic tetralkyliron(lll) ferrate complex [MgCl-(THF)5][FeMe4] from the reaction of FeCl3 with MeMgBr in THF. Upon warming, this distorted squareplanar S = 3/2 species converts to the S = ½ species originally observed by Kochi and co-workers with concomitant formation of ethane, consistent with its intermediacy in the reduction pathway of FeCl3 to generate the reduced iron species involved in catalysis. [ABSTRACT FROM AUTHOR]

Ironphosphine complexes prove to be good precatalysts for thecross-coupling of alkyl, benzyl, and allyl halides with not only aryltriorganoborate salts but also related aluminum-, gallium-, indium-,and thallium-based nucleophiles. Mechanistic studies revealed thatwhile Fe(I) can be accessed on catalytically relevant time scales,lower average oxidation states are not formed fast enough to be relevantto catalysis. EPR spectroscopic studies reveal the presence of bis(diphosphine)iron(I)complexes in representative catalytic reactions and related processeswith a range of group 13 nucleophiles. Isolated examples were studiedby Mössbauer spectroscopy and single-crystal X-ray structuralanalysis, while the electronic structure was probed by dispersion-correctedB3LYP DFT calculations. An EPR study on an iron system with a bulkydiphosphine ligand revealed the presence of an S= 1/2species consistent with the formation of a mono(diphosphine)iron(I)species with inequivalent phosphine donor environments. DFT analysisof model complexes allowed us to rule out a T-shaped Fe(I) structure,as this is predicted to be high spin. [ABSTRACT FROM AUTHOR]

While iron-bisphosphines have emerged as effective catalysts for C—C cross-coupling, the nature of the in situ formed iron species, elucidation of the active catalysts and the mechanisms of catalysis have remained elusive. A combination of 57Fe Mössbauer and magnetic circular dichroism (MCD) spectroscopies of well-defined and in situ formed mesityl-iron(II)-SciOPP species combined with density functional theory (DFT) investigations provides the first direct insight into electronic structure, bonding and in situ speciation of mesityl-iron(Il)-bisphosphines in the Kumada cross-coupling of MesMgBr and primary alkyl halides using FeCl2(SciOPP). Combined with freeze-trapped solution Mossbauer studies of reactions with primary alkyl halides, these studies demonstrate that distorted square-planar FeMes2(SciOPP) is the active catalyst for cross-coupling and provide insight into the molecular-level mechanism of catalysis. These studies also define the effects of key reaction protocol details, including the role of the slow Grignard addition method and the addition of excess SciOPP ligand, in leading to high product yields and selectivities. [ABSTRACT FROM AUTHOR]

A correction to the article "A Combined Mossbauer, Magnetic Circular Dichroism, and Density Functional Theory Approach for Iron Cross-Coupling Catalysis: Electronic Structure, In Situ Formation, and Reactivity of Iron-Mesityl-Bisphosphines" by Stephanie L. Daifuku, Malik H. Al-Afyouni, Benjamin E. R. Snyder, Jared L. Kneebone, and Michael L. Neidig that appeared in a 2014 issue is presented.