Periodic Reporting for period 5 - CATA-LUX (Light-Driven Asymmetric Organocatalysis)
Okres sprawozdawczy: 2021-03-01 do 2021-10-31
Visible light photocatalysis and metal-free organocatalytic processes are powerful strategies of modern chemical research with extraordinary potential for the sustainable preparation of organic molecules. However, these environmentally respectful approaches have to date remained largely unrelated. In the CATA-LUX project, we have merged these fields of molecule activation to redefine their synthetic potential.
Light-driven processes considerably enrich the modern synthetic repertoire, offering a potent way to build complex organic frameworks. In contrast, it is difficult to develop asymmetric catalytic photoreactions that can create chiral molecules with a well-defined three-dimensional arrangement. By developing innovative methodologies to effectively address this issue, CATA-LUX successfully provided a novel reactivity framework for conceiving light-driven enantioselective organocatalytic processes.
Our major aim was to translate the effective tools governing the success of ground-state asymmetric organocatalysis into the realm of photochemical reactivity, exploiting the potential of key organocatalytic intermediates to directly participate in the photoexcitation of substrates. At the same time, the chiral organocatalyst ensured effective stereochemical control. This single catalyst system, where stereoinduction and photoactivation merge in a sole organocatalyst, served for developing novel enantioselective photoreactions, with no counterpart in the ground-state regime.
CATA-LUX was a very successful project. We could successfully identify visible-light-mediated strategies for asymmetric catalysis, which traditional methodologies have not been able to address, thus expanding the way chemists think about making chiral molecules sustainably
Light-driven processes considerably enrich the modern synthetic repertoire, offering a potent way to build complex organic frameworks. In contrast, it is difficult to develop asymmetric catalytic photoreactions that can create chiral molecules with a well-defined three-dimensional arrangement. By developing innovative methodologies to effectively address this issue, CATA-LUX successfully provided a novel reactivity framework for conceiving light-driven enantioselective organocatalytic processes.
Our major aim was to translate the effective tools governing the success of ground-state asymmetric organocatalysis into the realm of photochemical reactivity, exploiting the potential of key organocatalytic intermediates to directly participate in the photoexcitation of substrates. At the same time, the chiral organocatalyst ensured effective stereochemical control. This single catalyst system, where stereoinduction and photoactivation merge in a sole organocatalyst, served for developing novel enantioselective photoreactions, with no counterpart in the ground-state regime.
CATA-LUX was a very successful project. We could successfully identify visible-light-mediated strategies for asymmetric catalysis, which traditional methodologies have not been able to address, thus expanding the way chemists think about making chiral molecules sustainably
CATA-LUX was a very successful project. We have addressed all the milestones and the objectives originally planned, including the more challenging ones. Despite the second part of the project developed during the COVID pandemic, the CATA-LUX team could continue the research activities in a successful way.
CATA-LUX aimed to deliver conceptually novel strategies for efficiently making chiral molecules using light. The main target was to establish the potential of key organocatalytic intermediates to participate in the photoexcitation of substrates. In this context, we have successfully developed an enamine-based EDA complex activation for the enantioselective formal α-methylation and α-benzylation of aldehydes (reported in Angew. Chem. Intl. Ed. 2017, 56, 4447), a chemical transformation for which there is no counterpart in the traditional ground-state regime. We have also identified that chiral iminium ions can directly reach an electronically excited state upon light absorption to become strong chiral oxidants that can activate reagents via single-electron transfer manifolds. The resulting visible-light-mediated strategy was used for the asymmetric C−H functionalization of toluene derivatives. This study showed that feedstock chemicals generally used as solvents, such as toluene, can be used as substrates for making chiral molecules with high enantioselectivity. The results were published in J. Am. Chem. Soc. 2018, 140, 8439. This novel strategy has brought about the development of many unconventional methodologies, published in Nature Chem. 2017, 9, 868; Angew. Chem. Int. Ed. 2018, 57, 1068; Angew. Chem. Int. Ed. 2019, 58, 1213; Angew. Chem. Int. Ed. 2021, 60, 5357, among others.
The scientific results of CATA-LUX allowed me to further consolidate my role within the field of organic synthesis, photochemistry, and enantioselective catalysis. As a recognition of these achievements, I was recently invited to write a review to outline the historical context and the scientific motivations for combining photocatalysis and organocatalysis. The manuscript has been published in a topical interdisciplinary journal: "Expanding the potential of enantioselective organocatalysis with light”, Nature 2018, 554, 41-49.
Many of the developed strategies are based on the photoactivation of molecules based on the formation of electron donor-acceptor (EDA) complexes, which was the underlying photochemical principle of CATA-LUX. Recently, I wrote a review to detail the synthetic potential of the EDA complex strategy, which was pioneered by my research group thanks to the present ERC project and has now evolved into an active research field, spawning over 300 publications. ‘Synthetic methods driven by the photoactivity of electron-donor acceptor complexes’, G. E. M. Crisenza, D. Mazzarella, P. Melchiorre, J. Am. Chem. Soc. 2020, 142, 5461–5476 (manuscript already cited about 200 times).
We expect that the knowledge and the new methodologies developed during CATA-LUX could provide fresh opportunities to design new stereocontrolled processes for making chiral molecules using visible light
CATA-LUX aimed to deliver conceptually novel strategies for efficiently making chiral molecules using light. The main target was to establish the potential of key organocatalytic intermediates to participate in the photoexcitation of substrates. In this context, we have successfully developed an enamine-based EDA complex activation for the enantioselective formal α-methylation and α-benzylation of aldehydes (reported in Angew. Chem. Intl. Ed. 2017, 56, 4447), a chemical transformation for which there is no counterpart in the traditional ground-state regime. We have also identified that chiral iminium ions can directly reach an electronically excited state upon light absorption to become strong chiral oxidants that can activate reagents via single-electron transfer manifolds. The resulting visible-light-mediated strategy was used for the asymmetric C−H functionalization of toluene derivatives. This study showed that feedstock chemicals generally used as solvents, such as toluene, can be used as substrates for making chiral molecules with high enantioselectivity. The results were published in J. Am. Chem. Soc. 2018, 140, 8439. This novel strategy has brought about the development of many unconventional methodologies, published in Nature Chem. 2017, 9, 868; Angew. Chem. Int. Ed. 2018, 57, 1068; Angew. Chem. Int. Ed. 2019, 58, 1213; Angew. Chem. Int. Ed. 2021, 60, 5357, among others.
The scientific results of CATA-LUX allowed me to further consolidate my role within the field of organic synthesis, photochemistry, and enantioselective catalysis. As a recognition of these achievements, I was recently invited to write a review to outline the historical context and the scientific motivations for combining photocatalysis and organocatalysis. The manuscript has been published in a topical interdisciplinary journal: "Expanding the potential of enantioselective organocatalysis with light”, Nature 2018, 554, 41-49.
Many of the developed strategies are based on the photoactivation of molecules based on the formation of electron donor-acceptor (EDA) complexes, which was the underlying photochemical principle of CATA-LUX. Recently, I wrote a review to detail the synthetic potential of the EDA complex strategy, which was pioneered by my research group thanks to the present ERC project and has now evolved into an active research field, spawning over 300 publications. ‘Synthetic methods driven by the photoactivity of electron-donor acceptor complexes’, G. E. M. Crisenza, D. Mazzarella, P. Melchiorre, J. Am. Chem. Soc. 2020, 142, 5461–5476 (manuscript already cited about 200 times).
We expect that the knowledge and the new methodologies developed during CATA-LUX could provide fresh opportunities to design new stereocontrolled processes for making chiral molecules using visible light
Some of the results obtained during the CATA-LUX project have surpassed in novelty our expectations. One of the targets of the project was to exploit the potential of chiral organocatalytic intermediates, such as enamines and iminium ions, to directly reach an excited state upon visible-light absorption. The light excitation of organocatalytic intermediates can turn on novel catalytic functions unavailable to conventional ground-state organocatalysis. We have applied this approach to excite chiral enamines and iminium ions, and trigger asymmetric photochemical processes unattainable under thermal conditions.
But we found that this photoexcitation strategy is not limited to organocatalytic intermediates, since it can be applied to other organic molecules. For example, we established that 4-substituted-1,4-dihydropyridines (DHPs) can directly reach an electronically excited state upon light absorption, and trigger the generation of radicals without the need for an external photocatalyst. In addition, selective excitation of DHPs with a violet LED turns them into strong reducing agents that can modulate the oxidation state of a metal via single-electron transfer manifolds. We have applied this strategy to develop photochemical cross-coupling reactions mediated by nickel, and the results were published in: Angew. Chem. Int. Ed. 2017, 56, 15039; Angew. Chem. Int. Ed. 2019, 58, 16878; and Angew. Chem. Int. Ed. 2020, 59, 5248, among others.
In the las part of CATA-LUX, my team also discovered that the concept of ‘switching on new reactivity using light’ could be expanded to the field of asymmetric metal-catalysis. Specifically, we demonstrated how, simply by using visible light, we can divert the established ionic reactivity of an organometallic complex to switch on completely new catalytic functions. This study found publication in a general chemistry journal: ‘Catalytic asymmetric C–C cross-couplings enabled by photoexcitation’, G. E. M. Crisenza, A. Faraone, E. Gandolfo, D. Mazzarella, P. Melchiorre, Nature Chem. 2021, 13, 575–580.
We could not anticipate the reactivity behavior of DHPs and the chiral organocatalytic intermediate when planning the research of CATA-LUX. Overall, these studies highlight that the concept of direct excitation of molecules transcend the field of organocatalysis and it can influence other established fields of research. This new concept can offer new vistas on the way synthetic chemists plan to prepare their target molecules.
But we found that this photoexcitation strategy is not limited to organocatalytic intermediates, since it can be applied to other organic molecules. For example, we established that 4-substituted-1,4-dihydropyridines (DHPs) can directly reach an electronically excited state upon light absorption, and trigger the generation of radicals without the need for an external photocatalyst. In addition, selective excitation of DHPs with a violet LED turns them into strong reducing agents that can modulate the oxidation state of a metal via single-electron transfer manifolds. We have applied this strategy to develop photochemical cross-coupling reactions mediated by nickel, and the results were published in: Angew. Chem. Int. Ed. 2017, 56, 15039; Angew. Chem. Int. Ed. 2019, 58, 16878; and Angew. Chem. Int. Ed. 2020, 59, 5248, among others.
In the las part of CATA-LUX, my team also discovered that the concept of ‘switching on new reactivity using light’ could be expanded to the field of asymmetric metal-catalysis. Specifically, we demonstrated how, simply by using visible light, we can divert the established ionic reactivity of an organometallic complex to switch on completely new catalytic functions. This study found publication in a general chemistry journal: ‘Catalytic asymmetric C–C cross-couplings enabled by photoexcitation’, G. E. M. Crisenza, A. Faraone, E. Gandolfo, D. Mazzarella, P. Melchiorre, Nature Chem. 2021, 13, 575–580.
We could not anticipate the reactivity behavior of DHPs and the chiral organocatalytic intermediate when planning the research of CATA-LUX. Overall, these studies highlight that the concept of direct excitation of molecules transcend the field of organocatalysis and it can influence other established fields of research. This new concept can offer new vistas on the way synthetic chemists plan to prepare their target molecules.