Recent advances using [Cp*Co(CO)I2] catalysts as a powerful tool for C-H functionalisation

Expansion of the synthetic chemists' toolbox is currently a topic of great interest, with successes providing access to novel compounds and more efficient routes towards new and known pharmaceuticals and agrochemicals. In this context, the development and application of first-row transition metal-catalysed C-H functionalisation protocols is seen as a key opportunity. This perspective provides a brief background of the discovery and application of high-valent cobalt-catalysis in C-H functionalisation, before detailing examples of recent advances in this field using the powerful [Cp*Co(CO)I2] catalysts for both terminal couplings and heterocycle formation. Finally, a discussion on the detection and isolation of elusive reactive intermediates in high-valent cobalt-catalysed C-H functionalisation, shedding light on how these catalyst systems operate, will be provided

Applied Organometallics: Cp*Co(III)-Catalysed C-H Functionalisation as a Maturing Tool for the Synthesis of Heterocyclic Compounds

Heterocycle compounds are prevalent throughout the natural world and therefore it is unsurprising that they have become a key component in many pharmaceutically relevant molecules. Unfortunately, synthetic methods for their preparation are often complicated and exhibit poor sustainability. In order to develop more efficient and sustainable routes to the synthesis of these useful and valuable heterocyclic compounds chemists have started to develop new innovative approaches. One approach which has provided a number of successes in recent times are synthetic procedures operating through a key direct C?H bond functionalisation step. This chapter highlights the state-of-the-art for preparing a diverse range of heterocyclic compounds using a cobalt-catalysed C?H bond functionalisation approach, specifically applying Cp*Co(iii)-type catalysts

Chemoselective cycloadditions to epoxide derivatives of erucic acid with CO2 and CS2: controlled access to value-added bio-derived compounds

The potential for application of bio-derived molecules in our everyday lives is attracting vast interest as attention moves towards development of a truly circular and sustainable economy. Whilst a large number of molecules are naturally available and contain a variety of functional groups, few of these compounds are able to be immediately transferred to applications where they can directly replace established oil-derived species. This issue presents both a challenge and an opportunity for the synthetic chemistry community. This study demonstrates how erucic acid, a molecule containing an olefin and a carboxylic acid, which is readily available from commonly cultivated rapeseed oils, can be used as a platform to be chemoselectively converted into a range of value-added compounds using established and high yielding synthetic procedures. In particular, the work showcases approaches towards the chemoselective (and in cases regioselective) oxidation with m-CPBA and incorporation of cyclic carbonate and cyclic dithiocarbonate functionalities which have potential to be employed in a range of applications. Expedient routes to unusual derivatives containing both cyclic carbonate and cyclic dithiocarbonates are also presented taking advantage of the distinct reactivities of the two different epoxides in the intermediate compounds. This work also provides a rare example of the synthesis of internal cyclic dithiocarbonates. These new products have potential to be applied as monomers in the growing field of bio-based non-isocyanate polyurethane synthesis.Comunidad de MadridMinisterio de Ciencia, Innovación y UniversidadesUniversidad de Alcal

A challenging redox neutral Cp*Co(III)-catalysed alkylation of acetanilides with 3-buten-2-one: synthesis and key insights into the mechanism through DFT calculations

Traditional, established palladium cross-coupling procedures are widely applied in complex molecule synthesis; however, there is a significant disadvantage in the requirement for pre-functionalised substrates (commonly halides/triflates). Direct C–H activation protocols provide the opportunity for a novel approach to synthesis, although this field is still in its relative infancy and often transferability between substrate classes remains unresolved and limitations not fully understood. This study focuses on the translation of an established Cp*Co(III)-catalysed alkylation of benzamides to related acetanilides using 3-buten-2-one as coupling partner. The developed procedure provides a wide substrate scope in terms of substituted acetanilides, although the optimised conditions were found to be more forcing than those for the corresponding benzamide substrates. Interestingly, density functional theory (DFT) studies reveal that the major impediment in the mechanism is not the C–H activation step, but instead and unexpectedly, effective competition with more stable compounds (resting states) not involved in the catalytic cycle

Oxidant-Free Au(I)-Catalyzed Halide Exchange and Csp2–O Bond Forming Reactions

Au has been demonstrated to mediate a number of organic transformations through the utilization of its π Lewis acid character, Au(I)/Au(III) redox properties or a combination of both. As a result of the high oxidation potential of the Au(I)/Au(III) couple, redox catalysis involving Au typically requires the use of a strong external oxidant. This study demonstrates unusual external oxidant-free Au(I)-catalyzed halide exchange (including fluorination) and Csp2–O bond formation reactions utilizing a model aryl halide macrocyclic substrate. Additionally, the halide exchange and Csp2–O coupling reactivity could also be extrapolated to substrates bearing a single chelating group, providing further insight into the reaction mechanism. This work provides the first examples of external oxidant-free Au(I)-catalyzed carbon–heteroatom cross-coupling reactions

Isolation of Key Organometallic Aryl-Co(III) Intermediates in Cobalt-Catalyzed C(sp2)–H Functionalizations and New Insights into Alkyne Annulation Reaction Mechanisms

The selective annulation reaction of alkynes with substrates containing inert C–H bonds using cobalt as catalyst is currently a topic attracting significant interest. Unfortunately, the mechanism of this transformation is still relatively poorly understood, with little experimental evidence for intermediates, although an organometallic Co(III) species is generally implicated. Herein, we describe a rare example of the preparation and characterization of benchtop-stable organometallic aryl-Co(III) compounds (NMR, HRMS, XAS, and XRD) prepared through a C(sp2)–H activation, using a model macrocyclic arene substrate. Furthermore, we provide crystallographic evidence of an organometallic aryl-Co(III) intermediate proposed in 8-aminoquinoline-directed Co-catalyzed C–H activation processes. Subsequent insights obtained from the application of our new organometallic aryl-Co(III) compounds in alkyne annulation reactions are also disclosed. Evidence obtained from the resulting regioselectivity of the annulation reactions and DFT studies indicates that a mechanism involving an organometallic aryl-Co(III)-alkynyl intermediate species is preferred for terminal alkynes, in contrast to the generally accepted migratory insertion pathway

Ga‐catalyzed temperature‐dependent oxazolidinone/piperazine synthesis from phenyl aziridines involving a divergent ligand‐assisted mechanism

Application of a binary Ga‐based catalyst system for the coupling of CO2 and aziridines to form oxazolidinones is presented. It has been possible to optimize the catalyst system for the selective formation of a single regioisomer, in excellent yield, under relatively mild reaction conditions. The optimized catalyst system has been successfully applied to a range of substituted aziridines derived from styrene oxide. It has been observed that aziridines bearing two aromatic substituents result in piperazine formation through an unexpected dimerization reaction. These piperazine products can be selectively formed in the absence of CO2 or are favored at lower reaction temperatures. A detailed DFT study into the reaction mechanism for the formation of both products has been carried out and an unusual ligand assistance in the case of oxazolidinone synthesis has been identified. More specifically, this ligand interaction promotes the initial ring‐opening of the aziridine and this work presents the first fully elucidated mechanism involving this intermediate

Catalytic Formation of Cyclic Carbonates using Gallium Aminotrisphenolate Compounds and Comparison to their Aluminium Congeners: A Combined Experimental and Computational Study

Abstract: This work reports on the use of gallium aminotrisphenolate compounds as catalysts for the synthesis of cyclic carbonates from epoxides and CO2. The results show that they are highly active, and more so than the corresponding aluminium congeners. The catalyst system is applicable at low and elevated temperatures across a wide substrate scope including terminal, internal, multiple and fully deuterated epoxides. Applying low catalyst loadings has allowed for a TON of 344,000 to be obtained, highlighting their stability. A DFT investigation has confirmed that the gallium catalysts have lower energetic profiles compared to the aluminium congeners. Measurement of the Lewis acidity of both the gallium and aluminium aminotrisphenolate compounds using the Gutmann‐Beckett method provides the experimental proof that the gallium compounds are more Lewis acidic than their aluminium congeners. Finally, Ab‐Initio Molecular Dynamic (AIMD) simulations have investigated and quantified the dynamic behaviour of the catalytic systems, highlighting an important increase in fluxionality in some cases which helps to explain the increase in catalytic activity

Acid-Triggered O−O Bond Heterolysis of a Nonheme FeIII (OOH) Species for the Stereospecific Hydroxylation of Strong C−H Bonds

A novel hydroperoxoiron(III) species [FeIII(OOH)(MeCN)(PyNMe3)]2+ (3) has been generated by reaction of its ferrous precursor [FeII(CF3SO3)2(PyNMe3)] (1) with hydrogen peroxide at low temperatures. This species has been characterized by several spectroscopic techniques and cryospray mass spectrometry. Similar to most of the previously described low‐spin hydroperoxoiron(III) compounds, 3 behaves as a sluggish oxidant and it is not kinetically competent for breaking weak C−H bonds. However, triflic acid addition to 3 causes its transformation into a much more reactive compound towards organic substrates that is capable of oxidizing unactivated C−H bonds with high stereospecificity. Stopped‐flow kinetic analyses and theoretical studies provide a rationale for the observed chemistry, a triflic‐acid‐assisted heterolytic cleavage of the O−O bond to form a putative strongly oxidizing oxoiron(V) species. This mechanism is reminiscent to that observed in heme systems, where protonation of the hydroperoxo intermediate leads to the formation of the high‐valent [(Porph.)FeIV(O)] (Compound I)

Exploitation of Mechanistic Product Selectivity for the Two‐step Synthesis of Optically Active Bio‐derived Cyclic Carbonates Incorporating Amino Acids

The synthesis of bio‐derived cyclic carbonates is attracting a lot of attention as the incorporation of bio‐derived functionality into these compounds provides the opportunity to prepare previously unknown structures, whilst also improving their sustainability profiles. This study presents a facile preparation of diastereomerically pure bio‐derived cyclic carbonates displaying a range of optical rotation values. These compounds are obtained from glycidol, amino acids and CO2 in a facile two‐step approach. Initially, the diastereomerically pure amino acid functionalised epoxides are prepared through a robust Steglich esterification of enantiopure glycidol (R or S) and an amino acid (D or L). Thereafter, in a second step, cycloaddition of the epoxide with CO2 results in the retention of the initial stereochemistry of the epoxide, furnishing novel diastereomerically pure and optically active cyclic carbonate products. A DFT study has explained the basis of this observed retention of configuration for these compounds. Further, results from this DFT study also provide new mechanistic information concerning a co‐catalyst‐free cycloaddition reaction starting from glycidol when using the gallium‐catalyst, which is found to operate through metal‐ligand cooperativity