Periodic Reporting for period 1 - AsymFeCH (Development and mechanistic investigations of efficient Fe-catalysed asymmetric C–H activation)
Okres sprawozdawczy: 2020-10-01 do 2022-09-30
In an age where the world is experiencing extraordinary population growth, the demand for goods and services necessary to maintain a high quality of life is higher than ever. To address this need, the concept of sustainability was introduced which encompasses economic development, social development, and environmental protection. Consequently, there is a high demand for developing sustainable technologies which will allow the production of goods not only at a low cost (economic development) but also in a fashion that protects human health (social development) and does not harm the environment (environmental protection). At the same time, the development of metal-mediated catalysis has revolutionized the chemicals manufacturing industry enabling access to a plethora of products that increase life quality and expectancy (pharmaceuticals, pesticides, detergents, synthetic materials, etc.). However, current technologies rely on the use of precious and toxic metals with the concurrent generation of large amounts of waste and therefore are not sustainable.
The asymmetric iron-catalyzed C–H activation project (AsymFeCH) was developed to cover the need for highly sustainable catalytic systems by combining the versatility and ability of C–H activation to access useful organic products in fewer steps (byproduct reduction), using inexpensive, non-toxic, and abundant iron-based catalysts. In addition, understanding how the developed systems operate through detailed mechanistic investigations opens the path for the development of asymmetric reactions where only one of the two enantiomeric products is obtained further increasing the sustainability of the overall process. Therefore, the AsymFeCH project contributes to the development of sustainable technologies that aim towards making products accessible to everyone in society and reducing the impact that their production has on the environment and human health.
Consequently, the objective of this Marie Skłodowska Curie Action (MSCA) is to first understand the way iron-catalyzed C–H activation reactions operate through detailed mechanistic investigations. Subsequently, the obtained knowledge can be used for the development of environmentally benign, sustainable reactions and ultimately for developing challenging enantioselective systems. At the same time, the skill of the researcher is further developed enabling him in that way to further contribute to the current socioeconomic needs through his research in the field. These objectives were achieved by understanding the mechanism by which low valent iron-catalyzed systems operate which in turn led to the development of novel highly sustainable iron-photocatalyzed C–H activations.
The asymmetric iron-catalyzed C–H activation project (AsymFeCH) was developed to cover the need for highly sustainable catalytic systems by combining the versatility and ability of C–H activation to access useful organic products in fewer steps (byproduct reduction), using inexpensive, non-toxic, and abundant iron-based catalysts. In addition, understanding how the developed systems operate through detailed mechanistic investigations opens the path for the development of asymmetric reactions where only one of the two enantiomeric products is obtained further increasing the sustainability of the overall process. Therefore, the AsymFeCH project contributes to the development of sustainable technologies that aim towards making products accessible to everyone in society and reducing the impact that their production has on the environment and human health.
Consequently, the objective of this Marie Skłodowska Curie Action (MSCA) is to first understand the way iron-catalyzed C–H activation reactions operate through detailed mechanistic investigations. Subsequently, the obtained knowledge can be used for the development of environmentally benign, sustainable reactions and ultimately for developing challenging enantioselective systems. At the same time, the skill of the researcher is further developed enabling him in that way to further contribute to the current socioeconomic needs through his research in the field. These objectives were achieved by understanding the mechanism by which low valent iron-catalyzed systems operate which in turn led to the development of novel highly sustainable iron-photocatalyzed C–H activations.
The work conducted was organized into five overlapping work packages (WP). The first work package, on preparation and management, included activities such as monitoring the literature on iron-catalyzed C–H activation and learning new techniques described therein (e.g. construction of optical fibers for LED NMR spectroscopic investigations). It also included other support activities such as planning experiments, ordering chemicals and equipment, ensuring safety measures in handling chemicals were followed, keeping a detailed lab journal, filling in the timesheet for the action, and preparing the career development and data management plans. WP2 involved the synthesis and characterization (a combination of spectroscopic, spectrometric, and crystallographic methods was used) of a variety of previously reported and novel iron complexes that were used either as precatalysts or as precursors for stoichiometric and catalytic reactions aiming to obtain better mechanistic understanding of the developed catalytic systems. Part of the work conducted in WP2 also involved the challenging isolation and crystallographic characterization of catalytically relevant intermediates which facilitated the construction of solid mechanistic proposals. During WP3, novel iron-catalyzed transformations were developed by screening several substrates and precatalysts. Subsequently, the reaction conditions were varied to improve the performance of the reaction in terms of yield and selectivity and to increase its sustainability by decreasing the reaction temperature (reaction optimization). With the optimized conditions in hand, the robustness of the reaction in terms of functional group tolerance was probed by performing substrate scope. The obtained products were isolated using flash column chromatography and fully characterized with nuclear magnetic resonance (NMR) and infra-red (IR) spectroscopies as well as with mass spectrometry (MS). In the fourth and most complex working package, mechanistic investigations were performed that aimed to understand the way the developed reactions operate. For this purpose, a combination of spectroscopic (NMR, IR, UV-Vis, Mossbauer, EPR) and spectrometric (LIFDI, HESI) techniques were used to profile the reactions and perform kinetic studies. The appropriate training on LIFDI mass spectrometry, HESI mass spectrometry, electron paramagnetic resonance (EPR) spectroscopy as well as Mossbauer spectroscopy was also provided to the researcher in addition to training in the advanced use of NMR instruments. Lastly, density functional calculations (DFT) were performed in collaboration with members of the group to explore alternative mechanistic pathways that are difficult to probe experimentally.
Part of the work described above (WP5) is now published in ACS catalysis (Cyclometallated Iron(II) Alkoxides in Iron-Catalyzed C–H Activations by Weak O-Carbonyl Chelation) while the rest has been submitted to Nature Catalysis, both high impact journals. In addition, the work has been presented at three conferences (two in Athens and one in Göttingen) and the ACS catalysis publication has already been cited twice. The researcher was also invited to the Moraitis school in Athens to discuss the project and research in the field of chemistry with students. In addition, results were also disseminated within the group through presentations and informal discussions with colleagues.
Part of the work described above (WP5) is now published in ACS catalysis (Cyclometallated Iron(II) Alkoxides in Iron-Catalyzed C–H Activations by Weak O-Carbonyl Chelation) while the rest has been submitted to Nature Catalysis, both high impact journals. In addition, the work has been presented at three conferences (two in Athens and one in Göttingen) and the ACS catalysis publication has already been cited twice. The researcher was also invited to the Moraitis school in Athens to discuss the project and research in the field of chemistry with students. In addition, results were also disseminated within the group through presentations and informal discussions with colleagues.
To date, the development of iron-catalyzed C–H activation systems is lagging far behind its precious metal counterparts. This is not only because iron catalysis is a relatively new technology, but also due to limited mechanistic understanding. In addition, the air-sensitive nature of the various iron precatalysts and intermediate complexes further discourages organic chemists from exploring this very promising field. This MSCA has demonstrated how simple iron-catalyzed C–H activation systems can be developed and has provided methodologies for their detailed mechanistic investigation. It has established the concept of developing highly sustainable catalytic systems based on environmentally benign iron with a full atom economy and no organic byproducts produced. The currently published results have already been cited in a review and a publication where similar systems were developed. Therefore, an additional step towards the replacement of precious and toxic metals with inexpensive, abundant, and non-toxic iron has been made. This will lead to the development of more sustainable catalytic systems to produce chemicals that contribute to a high quality of life in modern society such as pharmaceuticals, pesticides, and functional materials among others.