Project acronym XBCBCAT
Project From Supramolecular Chemistry to Organocatalysis: Fundamental Studies on the Use of Little-Explored Non-Covalent Interactions in Organic Synthesis
Researcher (PI) Stefan Matthias Huber
Host Institution (HI) RUHR-UNIVERSITAET BOCHUM
Call Details Starting Grant (StG), PE5, ERC-2014-STG
Summary Hydrogen-bonds have found widespread use in various fields of chemistry, including supramolecular chemistry, organic chemistry, and more lately organocatalysis. Although a multitude of structurally different hydrogen-bond donors has been developed, their mode of action is in all cases necessarily based on the same interacting atom, hydrogen.
In this proposal, we aim to develop first applications for two, previously very little explored non-covalent interactions that are based on electrophilic halogen or chalcogen substituents (“halogen-bonds” and “chalcogen bonds”).
The first objective is to open the way for the use of chiral multidentate halogen-bond donors (i.e., halogen-based Lewis acids) for enantiodiscrimination. After the synthesis of suitable candidate compounds, we will apply them in the following research areas: a) the resolution of racemic mixtures by co-crystallization with chiral halogen-bond donors, and b) the use of these Lewis acids in enantioselective organocatalysis.
Within the second objective, we will strive to establish first-of-its-kind applications of chalcogen-based Lewis acids in organic synthesis and organocatalysis. In contrast to halogen-bonds, chalcogen-bonds feature two substituents on the interacting atom as well as two electrophilic axes. In the first phase of this aim, we will synthesize neutral and cationic, mono- and bidentate candidate compounds and determine their association constants with a variety of Lewis bases. Based on this date, we subsequently seek to use these novel Lewis acids as activators or catalysts in organic transformations.
We anticipate that the realization of these applications, all of which are unprecedented, will be a crucial first step towards establishing further non-covalent interactions as useful tools in chiral recognition and chemical synthesis. In the long-term, we foresee these little-explored interactions becoming powerful complements to the ubiquitous hydrogen-bonds.
Summary
Hydrogen-bonds have found widespread use in various fields of chemistry, including supramolecular chemistry, organic chemistry, and more lately organocatalysis. Although a multitude of structurally different hydrogen-bond donors has been developed, their mode of action is in all cases necessarily based on the same interacting atom, hydrogen.
In this proposal, we aim to develop first applications for two, previously very little explored non-covalent interactions that are based on electrophilic halogen or chalcogen substituents (“halogen-bonds” and “chalcogen bonds”).
The first objective is to open the way for the use of chiral multidentate halogen-bond donors (i.e., halogen-based Lewis acids) for enantiodiscrimination. After the synthesis of suitable candidate compounds, we will apply them in the following research areas: a) the resolution of racemic mixtures by co-crystallization with chiral halogen-bond donors, and b) the use of these Lewis acids in enantioselective organocatalysis.
Within the second objective, we will strive to establish first-of-its-kind applications of chalcogen-based Lewis acids in organic synthesis and organocatalysis. In contrast to halogen-bonds, chalcogen-bonds feature two substituents on the interacting atom as well as two electrophilic axes. In the first phase of this aim, we will synthesize neutral and cationic, mono- and bidentate candidate compounds and determine their association constants with a variety of Lewis bases. Based on this date, we subsequently seek to use these novel Lewis acids as activators or catalysts in organic transformations.
We anticipate that the realization of these applications, all of which are unprecedented, will be a crucial first step towards establishing further non-covalent interactions as useful tools in chiral recognition and chemical synthesis. In the long-term, we foresee these little-explored interactions becoming powerful complements to the ubiquitous hydrogen-bonds.
Max ERC Funding
1 497 916 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym XNA
Project Development of an artificial information system
Researcher (PI) Piet Herdewyn
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Advanced Grant (AdG), PE5, ERC-2012-ADG_20120216
Summary "Artificial genetic sequences have become an important tool for the development of new therapeutics but may also define a trait of technological innovation. The possibility to synthesize genes, plasmids and chromosomes combined with the possibilities of directed mutagenesis and genetically reprogramming organisms and directing their evolution will become a crucial issue in synthetic biology. The uniformity of genetic alphabets, the universality of the genetic code, the ubiquity of genetic interchanges and the risks of genetic pollution cannot be overlooked. On the other hand, synthetic nucleic acids will become more and more important as potential new drugs.
It is proposed to develop an additional type of nucleic acids for the use as information system for the propagation of specific information of non-natural origin. It is the aim of the project to contribute to the development of an artificial genetic system orthogonal to the natural system that can be used as well in synthetic biology as in medicine.
Therefore we have to select & develop the appropriate chemical and enzymatic tools. This means (chemically) the selection of unnatural nucleic acids, their precursors and their modification for uptake in bacteria. Specialized polymerases as well as ligases will need to be developed for this purpose. The goal of the project is to design and synthesize a first orthogonal plasmid and new series of aptamers. A first application is the production of new therapeutics. This is a multidisciplinary project involving mainly chemistry and biotechnology. The general project architecture is to explore experimental progress in vivo and in vitro to reach the final assembly of an XNA episome."
Summary
"Artificial genetic sequences have become an important tool for the development of new therapeutics but may also define a trait of technological innovation. The possibility to synthesize genes, plasmids and chromosomes combined with the possibilities of directed mutagenesis and genetically reprogramming organisms and directing their evolution will become a crucial issue in synthetic biology. The uniformity of genetic alphabets, the universality of the genetic code, the ubiquity of genetic interchanges and the risks of genetic pollution cannot be overlooked. On the other hand, synthetic nucleic acids will become more and more important as potential new drugs.
It is proposed to develop an additional type of nucleic acids for the use as information system for the propagation of specific information of non-natural origin. It is the aim of the project to contribute to the development of an artificial genetic system orthogonal to the natural system that can be used as well in synthetic biology as in medicine.
Therefore we have to select & develop the appropriate chemical and enzymatic tools. This means (chemically) the selection of unnatural nucleic acids, their precursors and their modification for uptake in bacteria. Specialized polymerases as well as ligases will need to be developed for this purpose. The goal of the project is to design and synthesize a first orthogonal plasmid and new series of aptamers. A first application is the production of new therapeutics. This is a multidisciplinary project involving mainly chemistry and biotechnology. The general project architecture is to explore experimental progress in vivo and in vitro to reach the final assembly of an XNA episome."
Max ERC Funding
2 500 000 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
Project acronym YlideLigands
Project Tailoring Ylidic Compounds as Ligands for Organometallic Chemistry
Researcher (PI) Viktoria Daeschlein-Gessner
Host Institution (HI) RUHR-UNIVERSITAET BOCHUM
Call Details Starting Grant (StG), PE5, ERC-2015-STG
Summary Lewis bases are a fundamental class of compounds that are of utmost importance in almost any chemical transformation. According to the HSAB concept, they determine important properties such as the stability or solubility of compounds or the selectivity of reactions. Yet, Lewis bases are used far beyond simple acid-base pairs. In coordination chemistry they act as efficient σ-donor ligands, which crucially affect the electronics of the metal and thus its reactivity. Additionally, bulky Lewis bases as part of Frustrated Lewis Pairs are applicable in bond activation reactions and also in catalysis. Typical Lewis bases are neutral compounds with a free pair of electrons, such as amines or phosphines. In contrast, carbon-centred Lewis bases such as carbenes have long been underestimated due to their usually high reactivity and sensitivity. Yet, the last decades have revealed a revolution in this context. Carbenes in particular have proven to be powerful reagents not only as ligands, but also in organocatalysis and bond activation chemistry. Bisylides and their dianionic congeners (methandiides) with formally two electron pairs at carbon are further classes of carbon bases that have started to find applications, but which are still profoundly underdeveloped.
This project takes aim at the development and application of novel ylidic, carbon-centred Lewis bases. By means of a smart molecular design, systems with unusual electronic properties and donor capacities will be prepared and their reactivity towards main group element compounds and transition metal complexes will be explored. Employing experimental and computational methods a fundamental understanding of the electronic structure and its influencing factors will be provided. This will allow a manipulation and tailoring of the properties and reactivities and thus open applications such as in bond activation reactions or their use as electronically flexible ligands in catalytically active metal complexes.
Summary
Lewis bases are a fundamental class of compounds that are of utmost importance in almost any chemical transformation. According to the HSAB concept, they determine important properties such as the stability or solubility of compounds or the selectivity of reactions. Yet, Lewis bases are used far beyond simple acid-base pairs. In coordination chemistry they act as efficient σ-donor ligands, which crucially affect the electronics of the metal and thus its reactivity. Additionally, bulky Lewis bases as part of Frustrated Lewis Pairs are applicable in bond activation reactions and also in catalysis. Typical Lewis bases are neutral compounds with a free pair of electrons, such as amines or phosphines. In contrast, carbon-centred Lewis bases such as carbenes have long been underestimated due to their usually high reactivity and sensitivity. Yet, the last decades have revealed a revolution in this context. Carbenes in particular have proven to be powerful reagents not only as ligands, but also in organocatalysis and bond activation chemistry. Bisylides and their dianionic congeners (methandiides) with formally two electron pairs at carbon are further classes of carbon bases that have started to find applications, but which are still profoundly underdeveloped.
This project takes aim at the development and application of novel ylidic, carbon-centred Lewis bases. By means of a smart molecular design, systems with unusual electronic properties and donor capacities will be prepared and their reactivity towards main group element compounds and transition metal complexes will be explored. Employing experimental and computational methods a fundamental understanding of the electronic structure and its influencing factors will be provided. This will allow a manipulation and tailoring of the properties and reactivities and thus open applications such as in bond activation reactions or their use as electronically flexible ligands in catalytically active metal complexes.
Max ERC Funding
1 500 000 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
