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The assembly of chiral molecules with multiple stereogenic elements is challenging, and, despite of indisputable advances, largely limited to toxic, cost-intensive and precious metal catalysts. In sharp contrast, we herein disclose a versatile C–H alkylation using a non-toxic, low-cost iron catalyst for the synthesis of substituted indoles with two chiral elements. The key for achieving excellent diastereo- and enantioselectivity was substitution on a chiralN-heterocyclic carbene ligand providing steric hindrance and extra represented by noncovalent interaction for the concomitant generation of C–N axial chirality andC-stereogenic center. Experimental and computational mechanistic studies have unraveled the origin of the catalytic efficacy and stereoselectivity.

 

Hemoproteins have recently emerged as promising biocatalysts for new-to-nature carbene transfer reactions. However, mechanistic understanding of the interplay between productive and unproductive pathways in these processes is limited. Using spectroscopic, structural, and computational methods, we investigate the mechanism of a myoglobin-catalyzed cyclopropanation reaction with diazoketones. These studies shed light on the nature and kinetics of key catalytic steps in this reaction, including the formation of an early heme-bound diazo complex intermediate, the rate-determining nature of carbene formation, and the cyclopropanation mechanism. Our analyses further reveal the existence of a complex mechanistic manifold for this reaction that includes a competing pathway resulting in the formation of an N-bound carbene adduct of the heme cofactor, which was isolated and characterized by X-ray crystallography, UV-Vis, and Mössbauer spectroscopy. This species can regenerate the active biocatalyst, constituting a non-productive, yet non-destructive detour from the main catalytic cycle. These findings offer a valuable framework for both mechanistic analysis and design of hemoprotein-catalyzed carbene transfer reactions.

 

A mechanistic study is performed on the reaction method for iron-catalyzed C–H methylation with AlMe 3 reagent, previously proposed to involve cyclometalated iron( iii ) intermediates and an iron( iii )/( i ) reaction cycle. Detailed spectroscopic studies ( 57 Fe Mössbauer, EPR) during catalysis and in stoichiometric reactions identify iron( ii ) complexes, including cyclometalated iron( ii ) intermediates, as the major iron species formed in situ under catalytic reaction conditions. Reaction studies identify a cyclometalated iron( ii )-methyl species as the key intermediate leading to C–H methylated product upon reaction with oxidant, consistent with a previously proposed iron( ii )/iron( iii )/iron( i ) reaction manifold for C–H arylation. 

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 α-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 π-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. 

Magnetic circular dichroism (MCD) spectroscopy is a powerful experiment used to probe the electronic structure and bonding in paramagnetic metal-based complexes. While C -term MCD spectroscopy has been utilized in many areas of chemistry, it has been underutilized in studying paramagnetic organometallic transition metal and f-element complexes. From the analysis of isolated organometallic complexes to the study of in situ generated species, MCD can provide information regarding ligand interactions, oxidation and spin state, and geometry and coordination environment of paramagnetic species. The pratical aspects of this technique, such as air-free sample preparation and cryogenic experimental temperatures, allow for the study of highly unstable species, something that is often difficult with other spectroscopic techniques. This perspective highlights MCD studies of both transition metal and f-element organometallic complexes, including in situ generated reactive intermediates, to demonstrate the utility of this technique in probing electronic structure, bonding and mechanism in paramagnetic organometallic chemistry. 

Fe‐based catalysts are an active, selective, and low‐cost option for tuning Fischer‐Tropsch synthesis (FTS) selectivity toward desirable light olefins. By encapsulating Fe within ZSM‐5, the resultant core‐shell catalysts have the potential to control the product distribution via secondary reactions that occur over the acid sites of the zeolite shell. In this paper, Fe is encapsulated within ZSM‐5 via the seed‐directed growth technique and characterized with a suite of analytical techniques including Mössbauer spectroscopy and X‐ray absorption fine structure (XAFS). Characterization of the core‐shell catalysts indicates that some of the Fe‐based active phase is destabilized during seed‐directed growth, demonstrating the challenges associated with encapsulating an Fe‐based active phase within zeolites. However, comparing FTS performance of the core‐shell catalyst with the Fe‐based control synthesized via incipient wetness impregnation demonstrates improved selectivity toward the desired C₂‐C₄olefins and C₅₊hydrocarbons.

 

Synthetic methods that utilise iron to facilitate C–H bond activation to yield new C–C and C–heteroatom bonds continue to attract significant interest. However, the development of these systems is still hampered by a limited molecular-level understanding of the key iron intermediates and reaction pathways that enable selective product formation. While recent studies have established the mechanism for iron-catalysed C–H arylation from aryl-nucleophiles, the underlying mechanistic pathway of iron-catalysed C–H activation/functionalisation systems which utilise electrophiles to establish C–C and C–heteroatom bonds has not been determined. The present study focuses on an iron-catalysed C–H allylation system, which utilises allyl chlorides as electrophiles to establish a C–allyl bond. Freeze-trapped inorganic spectroscopic methods ( 57 Fe Mössbauer, EPR, and MCD) are combined with correlated reaction studies and kinetic analyses to reveal a unique and rapid reaction pathway by which the allyl electrophile reacts with a C–H activated iron intermediate. Supporting computational analysis defines this novel reaction coordinate as an inner-sphere radical process which features a partial iron–bisphosphine dissociation. Highlighting the role of the bisphosphine in this reaction pathway, a complementary study performed on the reaction of allyl electrophile with an analogous C–H activated intermediate bearing a more rigid bisphosphine ligand exhibits stifled yield and selectivity towards allylated product. An additional spectroscopic analysis of an iron-catalysed C–H amination system, which incorporates N -chloromorpholine as the C–N bond-forming electrophile, reveals a rapid reaction of electrophile with an analogous C–H activated iron intermediate consistent with the inner-sphere radical process defined for the C–H allylation system, demonstrating the prevalence of this novel reaction coordinate in this sub-class of iron-catalysed C–H functionalisation systems. Overall, these results provide a critical mechanistic foundation for the rational design and development of improved systems that are efficient, selective, and useful across a broad range of C–H functionalisations. 

We report the syntheses of a family of tetrahedral iron complexes bearing a bulky redox active o -phenylenediamide ligand. The electronic structures of these complexes have been investigated by Mössbauer spectroscopy, magnetic susceptibility measurements, and X-ray crystallography.