ERC FUNDED PROJECTS

This ERC-CoG 2020 proposal, ALLOWE outlines a strategy for the development of low-valent aluminium systems through their synthesis, isolation, and reactivity investigation of neutral, ambiphilic, low-valent aluminium compounds, denoted “alumylenes”. Their dimeric form “dialumenes” featuring an aluminium-aluminium double bond will also be within the scope of the project. These low-valent aluminium species are expected to provide, along with greater understanding of the fundamental behaviour of low-valent aluminium, a varied and deep reactivity profile. These highly reactive compounds will offer a cheap, sustainable and non-toxic alternative to the current transition metal-based industrial chemical processes. The proposed scheme of work begins with the synthesis of neutral alumylenes and dialumenes, respectively. This will be achieved through the use of donor ligands (i.e. N-heterocyclic carbenes) and substituents with differing electronic and steric properties. With these compounds in hand, the reactivity towards small molecules will be investigated along with development of low-valent aluminium based catalysts. Furthermore, incorporation of transition metals into these aluminium systems will be targeted as these may possess unique and interesting properties. Established methodologies such as reductive dehalogenation or reductive dehydrohalogenation will provide access to novel low-valent aluminium compounds bearing bulky substituents and donor ligands. The synthetic portion of the work will also be supported by theoretical calculations. The outcome of ALLOWE will provide (i) in-depth insight and understanding into low-valent aluminium’s bonding nature, particularly emphasis laid on ambiphilic aluminium center (ii) plethora of striking reactivity towards transition metal free stoichiometric and catalytic activation of small molecules, and (iii) various potential applications in aluminium-based material chemistry.

1 997 750 €

Start date: 2021-06-01, End date: 2026-05-31

Alkylation, in particular carbon-carbon (C-C) bond formation, is one of the most important and challenging synthetic transformations in chemistry. Current chemical approaches for C-alkylation require the use of expensive and toxic transition metals with complex ligands that have limited selectivity. Developing sustainable methods for the controlled formation of C-C bonds with regio- and stereospecificity in high yields has the potential to change organic chemistry and provide access to new molecules. Enzymes, Nature’s catalysts that enhance reaction rates, can selectively catalyze such reactions, with current limitations due to high energy co-substrates and the requirement for specific starting materials, sometimes leading to undesired side products, therefore unsustainable to upscale. I aim at developing the synthetic potential of key oxidoreductase enzymes towards the sustainable selective production of highly valuable compounds through C-C bond formation. Oxidoreductases traditionally catalyze reduction and oxidation reactions and are increasingly used at industrial scale for their mild reaction conditions and exquisite chemo-, regio- and stereoselectivity. I will use the inherent mechanism of two particular oxidoreductases, ene reductases and alcohol dehydrogenases, and develop them towards selective C-C bond formation. BioAlk aims at being disruptive in catalysis and organic synthesis by enabling new approaches for bench mark sustainable methods towards highly selective biocatalytic C-alkylation with industrially relevant oxidoreductases. I will design and develop non-natural enzymatic processes with ene reductase-catalyzed selective inter- and intramolecular α-alkylation of carbonyl and related compounds, and alcohol dehydrogenase-catalyzed nucleophilic reductive alkylation, while exploring the enzyme reaction mechanisms.

1 625 000 €

Start date: 2021-01-01, End date: 2025-12-31

The classical distinction between transition metal and main group compounds has recently been challenged. This is due to the extraordinary properties and reactivity of low-valent and radical main group species, which chemists have begun to unveil. The development of reliable synthetic approaches to new types of low-valent main group compounds and the thorough understanding of their bonding situation, (electronic) structure, and reactivity is one of the major challenges of modern main group chemistry. Bismuth (Bi), a non-precious, non-toxic, heavy p-block element, offers unique properties for the use in synthesis and catalysis. Its large and diffuse atomic orbitals (AOs) result in an inefficient overlap with AOs of other atoms, leading to low homolytic bond dissociation energies. Also, relativistic effects contribute to the stabilisation of Bi radical species. In combination, these effects allow for reversible homolytic bond dissociations of molecular Bi species. Due to the lack of effective strategies for the exploitation of these remarkable properties, Bi compounds remain underexplored. This ERC proposal is designed to tackle this challenge by creating innovative methods to explore novel Bi compounds in radical reactions and unlocking their tremendous potential in synthetic chemistry. It comprises three projects: P1) Bi complexes tailored to undergo (reversible) homolytic bond dissociations, P2) novel strategies for the generation of Bi(I) species with unique (singlet vs. triplet) electronic structures, and P3) geometrically constrained complexes with Bi−Bi bonds susceptible to tuneable homolysis. The compounds targeted in P1-P3 will be exploited in novel radical reactions aimed at element–element bond formation, CH activation, small-molecule activation, and catalysis for organic synthesis. The ERC project will benefit from the extensive experience gained by the applicant’s group in Bi chemistry. Preliminary results have been obtained for all three sub-projects.

1 470 753 €

Start date: 2021-05-01, End date: 2026-04-30

All primary chemical bonds, covalent and supramolecular, weaken under tension. This imposes fundamental limits on the mechanical stability of molecules and their materials. Nature has evolved to secondary bonds that break through these limits and strengthen under tension. These so-called catch bonds, which know no synthetic equivalent to date, are used in Nature as a rule, rather than exception, in scenarios where supramolecular bonds are exposed to large stresses. This change in the fundamental mechanical nature of bonds has a profound effect on the mechanics of the materials in which they are integrated. Yet, to date, there have been no systematic studies that establish how the mechanics of individual catch bonds is programmed by their chemical design or how their collective action results in enhanced mechanics of their materials. As a result, our understanding of the ubiquitous use of catch bonds in Nature is incomplete nor do we have clear guides how their potential can be harnessed in creating bio-mimetic soft materials with programmable mechanics. Project CATCH tackles these challenges by bringing catch bonds to the synthetic domain for the first time. Their de-novo creation gives unprecedented control to establish the design rules for the mechano-activity of single bonds. Moreover, CATCH will systematically explore how the concerted action of many catch bonds within a material lead to material properties that cannot be accessed by any other means, such as the adaptive reduction of strain localisation and the filtering of mechanical signals, which is of crucial importance for mechanical communication between cells in tissue engineering. Through a multidisciplinary approach that builds on my expertise in synthetic and materials chemistry, single-molecule experiments, and multiscale mechanical experiments and modelling, this project will decipher and harness one of Nature’s most ubiquitous, but poorly understood, mechanical design strategies.

1 995 060 €

Start date: 2021-07-01, End date: 2026-06-30