Periodic Reporting for period 1 - PHOTOCARBOX (Increasing the scope of CO2-utilising photoreactions: asymmetric photosynthesis of amino acids)
Periodo di rendicontazione: 2020-06-01 al 2022-05-31
Carbon dioxide is a major waste product that is considered the main cause of global warming. It is released to the atmosphere on a large scale due to the burning of fossil fuels, yet its recycling is very limited. The main difficulties of utilising CO2 as a chemical feedstock are its thermodynamic and kinetic stability. Overcoming these problems requires an energy-input (for example highly reactive chemicals, electricity or light), and catalysis, respectively. On the one hand, catalytic reactions employing highly activated starting materials can produce value-added products such as cyclic carbonates or carboxylic acids when reacting with CO2, but require specific reactive groups (e.g. epoxides or organometalates, respectively). On the other hand, photocatalytic processes like reduction to ‘C1-fuels’ such as CO, formic acid, methanol or methane have been the main focus to reintroduce CO2 into the energy-cycle, but are as of yet not economically viable. For a more sustainable circular economy carbon-based materials need to be produced from waste streams instead of fossil fuels. It is therefore important to drastically widen the scope of (photo)chemical reactions employing CO2. New methods utilising CO2 can lead to the development of reactions for large-scale application, balancing the carbon cycle more efficiently. In this project, we aimed to develop a novel conversion pathway involving CO2 that can provide the fundamental basis for such novel methodologies.
Photochemical carboxylation of sp3 C‒H bonds is a very recent innovation that is growing quickly as a field. It will provide a very useful synthetic tool next to the standard catalytic carboxylation of carbon halides or other catalytic chemical transformations on the one hand, and photocatalytic reduction on the other. Utilisation of CO2 as a C1 feedstock contributes to the concept of a circular economy, ensuring a sustainable future. For the field to mature beyond its current state, that is, radical coupling of free CO2•–, new catalytic methods are required. The proposed reactive intermediate [Re-CO2] is prepared using visible light, in contrast to previous methods requiring high-energy UV light that complicates reaction setups and leads to highly unstable intermediates. Such mild conditions will increase the scope of substrates, and combined with organocatalysis allow the conversion of primary amines to biologically active primary amino acids, which so far are elusive products in CO2 conversion. Lastly, by using chiral catalysts to perform asymmetric photocatalysis, we provide a new unique methodology of converting CO2 towards chiral products. The projected approach allows for synthesis of industrially relevant building blocks offering new potential arousing commercial interest as an alternative to Strecker synthesis or fermentation pathways.
The main aim of PHOTOCARBOX was to utilise [Re-CO2] as a reactive intermediate to perform catalytic radical coupling of amines and CO2 and provide enantioselective control over the amino-acid products. We studied the photocatalytic synthesis of α-amino-acids using lower-energy blue light. PHOTOCARBOX was divided into three specific objectives:
1: employing [Re-CO2] as a reactive intermediate to carboxylate tertiary amines
2: synthesis of racemic α-amino acids from primary amines
3: enantioselective synthesis of chiral α-amino acids
Photochemical carboxylation of sp3 C‒H bonds is a very recent innovation that is growing quickly as a field. It will provide a very useful synthetic tool next to the standard catalytic carboxylation of carbon halides or other catalytic chemical transformations on the one hand, and photocatalytic reduction on the other. Utilisation of CO2 as a C1 feedstock contributes to the concept of a circular economy, ensuring a sustainable future. For the field to mature beyond its current state, that is, radical coupling of free CO2•–, new catalytic methods are required. The proposed reactive intermediate [Re-CO2] is prepared using visible light, in contrast to previous methods requiring high-energy UV light that complicates reaction setups and leads to highly unstable intermediates. Such mild conditions will increase the scope of substrates, and combined with organocatalysis allow the conversion of primary amines to biologically active primary amino acids, which so far are elusive products in CO2 conversion. Lastly, by using chiral catalysts to perform asymmetric photocatalysis, we provide a new unique methodology of converting CO2 towards chiral products. The projected approach allows for synthesis of industrially relevant building blocks offering new potential arousing commercial interest as an alternative to Strecker synthesis or fermentation pathways.
The main aim of PHOTOCARBOX was to utilise [Re-CO2] as a reactive intermediate to perform catalytic radical coupling of amines and CO2 and provide enantioselective control over the amino-acid products. We studied the photocatalytic synthesis of α-amino-acids using lower-energy blue light. PHOTOCARBOX was divided into three specific objectives:
1: employing [Re-CO2] as a reactive intermediate to carboxylate tertiary amines
2: synthesis of racemic α-amino acids from primary amines
3: enantioselective synthesis of chiral α-amino acids
At the start of the project, a photoreactor was designed in order to be able to use high pressures of CO2 and LED light irradiation, and built by ICIQ’s mechanical workshop. Then, three rhenium CO2-reduction catalysts were synthesized for the purpose of binding CO2 upon reduction in objective 1. A large number of tertiary amines were screened with various combinations of rhenium-complexes, photocatalysts and additives (such as HAT-catalysts or LiCl). Various products were identified during the course of the project, but conditions to produce more than traces of carboxylated products were not found. A second objective was to employ an activating group to allow primary amines to act as substrates under photocatalytic conditions. While in principle the strategy works (the 4-piperidone activating group could be cleaved from certain products), there were several important drawbacks: using N-substituted-4-piperidone led to regioselectivity issues that led to dehydrogenation of the piperidone ring, and the cleavage of the piperidone group was too specific for the substrates and did not work for the carboxylated products. The third objective of PHOTOCARBOX was to perform the reaction in an enantioselective manner. However, since the reaction was unsuccessful, this objective could not be achieved. Instead, focus was shifted to a different dual catalytic reaction: the photo/transition-metal catalysed stereoselective allylation of aldehydes. The study of this reaction allowed for largely the same bidirectional knowledge transfer as well as scientific training of the researcher.
The project has pushed the state-of-the-art by providing the researcher with invaluable knowledge regarding the interplay between tertiary amines, several photocatalysts and several rhenium catalysts. The results leading from the project provide the researcher with a starting point for future research, as the fundamental knowledge that underlies synthetic photoredox catalysis is still underdeveloped. As such, the researcher has focused on a another dual photo/transition-metal catalyzed reaction that synthetically was successful, but required mechanistic understanding. This has impacted the career of the researcher greatly, as the work led to a publication in J. Am. Chem. Soc. as corresponding author. In addition, the project development led to a large international visibility for the researcher, who presented the work at 5 international conferences and seminars, of which for two he was an invited speaker. The training the researcher received in terms of courses on leadership or hands-on training for grant writing make the researcher ready to take on a principal investigator position in the near future.