Mark R. Crimmin’s research while affiliated with Imperial College London and other places

Herein we present the discovery of a ligand-catalyzed bond breaking and making processes that occurs in the coordination sphere of a novel Ni–Al heterometallic complex. While combinations of Ni pre-catalysts and Al additives are known for site-selective C–H functionalisation, detailed studies of such systems are rare. Combining [Ni(COD)2] and a molecular aluminum dihydride [(BDI)AlH2] (1; BDI = 2,6-diisopropylphenyl-beta-methyldiketiminate), results in facile formation of a Ni–Al heterometallic complex [(COD)Ni{H)2Al(BDI)}] (2; COD = 1,5-cyclooctadiene). Once generated, this species can effect the C(sp2)–H activation of 4-dimethylaminopyridine (DMAP) or pyridine with concomitant H2 evolution; a process that is accelerated through addition of an exogenous phosphine ligand, PCy3. Intimate steps of the mechanism of C(sp2)–H bond activation and H2 elimination were studied through kinetics, kinetic isotope effects (KIEs), isotope labelling studies, and computational modeling. The reaction is 1st order in PCy3 and proceeds with a low KIE of 0.9-1.1. Support is provided for a mechanism involving stepwise oxidative addition and reductive elimination processes that require the synergistic action of both metals, promoted by reversible coordination of the phosphine. These data strongly suggest that both C–H activation and H2 reductive elimination steps in this system are low energy and readily accessible and are not rate limiting. This finding has implications for future catalyst design using the synergistic behavior of Ni and Al metals and suggests that choice of ligand and control of ligand exchange steps, may well be the most important consideration in determining the rate of reaction.

In this review, we describe synthetic methods that harvest fluoride (F–) from fluorocarbons and deliver it to other molecules through either transfer fluorination or fluoride shuttling. We also summarise related approaches, transfer hydrofluorination and HF shuttling in which hydrogen fluoride (HF) is generated in situ from one fluorocarbon and used to prepare another, along with recent breakthroughs in fluoroalkene cross-metathesis. Our focus is on reactions that can be applied to industrially relevant fluorochemicals, namely refrigerants (HFCs and HFOs) and fluoropolymers (PTFE, PVDF, PVF). We provide insight into the mechanisms that break and remake carbon–fluorine bonds as part of linear reaction sequences or catalytic manifolds. Limitations of the current methodologies are highlighted and opportunities for future developments discussed.

Oxidative addition most commonly involves the addition of a substrate to a metal centre. This reaction is fundamental across synthetic chemistry and underpins numerous catalytic methods. In the textbook description of oxidative addition reactions, a net increase in the formal oxidation state of the metal occurs with simultaneous bond breaking at the substrate. The majority of known oxidative addition reactions, however, involve substrates bearing relatively electronegative elements (for example, hydrogen, carbon, nitrogen, oxygen and halogens) and there has been little discussion of how addition processes may fundamentally change if substrates were constructed from more electropositive elements. Here we show that the zinc–zinc bonded complex, Cp*ZnZnCp* (Cp* = pentamethylcyclopentadienyl), which is isoelectronic with dihydrogen, undergoes facile addition to the metal (or semi-metal) centres of a series of main group carbene analogues based on silicon, aluminium, gallium or indium. Reactions proceed with complete breaking of the zinc–zinc bond and an increase in the coordination number of the central metal from two to four. Our analysis suggests that these addition processes are not oxidative, but rather there is likely a continuum of redox outcomes spanning oxidative, redox neutral and reductive. The addition of Cp*ZnZnCp* to silicon(II) provides the most compelling case for a prototypical reductive addition process.

The production of fluorochemicals is currently achieved through a linear manufacturing process starting from fluorspar (CaF2). While fluorochemicals improve our quality of life, there is increasing concern over their negative impact on health and the environment. Here we report an approach to preparing fluorine-containing molecules through recycling. Treatment of hydrofluorocarbons (HFCs) with a potassium base (KHMDS, KOtBu, KBn) results in rapid defluorination to produce anhydrous potassium fluoride. The scope of fluorochemicals that can be recycled includes industrially relevant HFCs, hydrofluoroolefins (HFOs), fluoroethers – including anaesthetics and battery additives, perfluorooctanoic acid (PFOA), and poly(vinylidene difluoride) (PVDF). The in situ generated potassium fluoride harvested from these materials can then be used to prepare a wide range of fluorinated organic and inorganic molecules.

A series of boron, aluminum, and gallium difluoride complexes [{(ArNCMe)2CH}MF2] (M = B, Al, Ga) are reported as catalysts for the defluorofunctionalization of electron-deficient arenes. Thiodefluorination reactions between TMS–SPh and poly(fluorinated aromatics) proceed under forcing conditions. Evidence is presented for the fluoride entering the catalytic cycle through a metathesis reaction with TMS–SPh to form metal thiolate intermediates, e.g., [{(ArNCMe)2CH}MF(SPh)], which are then nucleophiles for addition to the aromatic substrate, likely through a concerted SNAr mechanism. Attempts to expand the scope of reactivity to include the hydrodefluorination of electron-deficient arenes met with limited success. Activity could, however, be recovered through the addition of NaBArF4 as a catalytic additive (ArF = 3,5-C6H3(CF3)2). NMR titrations suggest that NaBArF4 is capable of coordinating with aluminum and gallium fluoride complexes, most likely through weak M–F---Na interactions (M = Al, Ga), and can play a role in lowering the barrier of metathesis between [{(ArNCMe)2CH}MF2] and Et3SiH to form the group 13 hydrido fluoride [{(ArNCMe)2CH}M(H)F], facilitating catalytic turnover. DFT calculations indicate that this weak interaction leads to a polarization of the M–F bond. The discovery of this additive effect has potentially broad implications in developing new reactivity and applications of thermodynamically stable metal fluorides.

We report the synthesis and solid-state characterization of two unusual Pd2Zn2 clusters formed from the partial reduction of [PdL2Cl2] precursors (L2 = dcpe or dppe) with metallic zinc. The new clusters have been characterized by single crystal X-ray diffraction and contain a Pd2Zn2Cl3 core capped by two chelating phosphine ligands with Zn in the formal +1.5 oxidation state. While they possess a near tetrahedral arrangement of metal ions, calculations and bonding analysis (NBO, AIM) suggest that there is limited Zn- - -Zn bonding in these species. Characterization in the solution state is suggestive of dynamic behavior on dissolution, with both diamagnetic and paramagnetic species observed by NMR and EPR spectroscopy. One of these Pd2Zn2 clusters was shown to be an effective precursor for the homocoupling of an aryl bromide.

Aryl aldehydes are key synthetic intermediates in the manufacturing of active pharmaceutical ingredients. They are generated on scale (>1000 kg) through the palladium-catalyzed formylation of aryl bromides using syngas (CO/H2). The best-in-class catalyst system for this reaction employs di-1-adamantyl-n-butylphosphine (cataCXium A), palladium(II) acetate, and tetramethylethylenediamine. Despite nearly 20 years since its initial report, a mechanistic understanding of this system remains incomplete. Here, we use automation, kinetic analysis, and DFT calculations to develop a mechanistic model for this best-in-class catalyst. We suggest that a combination of the migratory insertion step and dihydrogen activation step is likely involved in the turnover-limiting sequence. The reaction kinetics are responsive to the nature of the substrate, with electron-rich aryl bromides reacting faster and more selectively than their electron-poor counterparts due to the influence of electronics in the migratory insertion step. Our findings add additional insight into the proposed mechanism of palladium-catalyzed formylation of aryl bromides.

Trifluoromethane (HCF3) is a byproduct of fluoropolymer production that has limited applications. It is often stored or destroyed at the point of production, but if released into the environment is a potent greenhouse gas with global warming potential of 14,600 times that of CO2. State-of-the-art chemical technologies for upgrading HCF3 typically occur with conservation of the CF3 group. These approaches will come under increased scrutiny as concern over the environmental impact of perfluoroalkyl substances (PFAS) continues to grow. A more sustainable approach involves synthetic transformations that repurpose the atomic content of HCF3 while also destroying the CF3 group. In this paper, we report a rare example of the transformation of HCF3 into a fluoroalkene functional group through defluoroalkylation. We rationalise product formation through DFT calculations, scale-up the synthesis through continuous flow methods, and show that a fluoroalkene reagent derived from HCF3 is a competent nucleophile for the fluoroethenylation of a range of aldehydes

A series of molecular boron, aluminium, and gallium difluoride complexes [{(ArNCMe)2CH}MF2] (M = B, Al, Ga) are reported as catalysts for the defluorofunctionalisation of electron-deficient arenes. Thiodefluorination reactions between TMS–SPh and poly(fluorinated aromatics) proceed with group 13 catalysis under forcing conditions. Evidence is presented for the fluoride entering the catalytic cyclic through a metathesis reaction with TMS–SPh to form metal thiolate intermediates, e.g. [{(ArNCMe)2CH}MF(SPh)], that are then competent nucleophiles for addition to the aromatic substrate, likely through a cSNAr mechanism. Attempts to expand the scope of reactivity to include the hydrodefluorination of electron-deficient arenes with the same group 13 difluoride catalysts met with limited success. Activity could, however, be recovered through addition of NaBArF4 as a catalytic additive (ArF = 3,5-C6H3(CF3)2). NMR titrations suggest that NaBArF4 is capable of coordinating to aluminium and gallium fluoride complexes, most likely through weak M–F---Na interactions (M = Al, Ga) and can play a role in lowering the barrier of metathesis between [{(ArNCMe)2CH}MF2] and Et3SiH to form the group 13 hydrido fluoride [{(ArNCMe)2CH}M(H)F], facilitating catalytic turnover. DFT calculations indicate this weak interaction, leads to a polarization of the M–F bond. The discovery of this additive effect has potentially broad implications in developing new reactivity and applications of thermodynamically stable metal–fluorides.

Reaction of a molecular zinc–hydride [{(ArNCMe)2CH}ZnH] (Ar=2,6‐di‐isopropylphenyl) with 0.5 equiv. of [Ni(CO)Cp]2 led to the isolation of a nickel–zinc hydride complex containing a bridging 3‐centre,2‐electron Ni−H−Zn interaction. This species has been characterized in the solid‐state by single crystal X‐ray diffraction. DFT calculations are consistent with its formulation as a σ‐complex derived from coordination of the zinc–hydride to a paramagnetic nickel(I) fragment. Continuous‐wave and pulse EPR experiments suggest that this species is labile in solution. Further experiments show that in the presence of catalytic quantities of nickel(I) precursors, zinc–hydride bonds can undergo either H/D‐exchange with D2 or dehydrocoupling to form Zn−Zn bonds. In combination, the data support the activation and functionalisation of zinc–hydride bonds at nickel(I) centres.