Periodic Reporting for period 3 - ELICOS (Enantioselective Light-induced Catalysis for Organic Synthesis)
Reporting period: 2019-01-01 to 2020-06-30
Given the continuing success, which enantioselective catalysis has encountered over the last decades, it is striking that it has – until very recently – not played a role in the photochemical synthesis of chiral molecules (for more information, see: Angew. Chem. Int. Ed. 2015, 54, 3872). The fact, that photochemistry lags behind the development in enantioselective catalysis, is critical since there is a large number of biologically relevant molecular scaffolds that are only accessible by photochemical but not by thermal reactions. Major reasons for this lack in progress towards enantioselective light-induced catalysis are intrinsic difficulties encountered when designing potential catalysts for such a process. By definition, photochemical reactions occur upon absorption of light, which in turn involves a significant change in the electronic structure of the photoexcited molecule. The molecule is promoted to a higher energy level, from which successive reactions compete with decay pathways to the ground state (fluorescence, internal conversion). Efficient photochemical reactions consequently have relatively low activation barriers and product formation is rapid while many thermal reactions have significant activation barriers and proceed with very low reaction rates even at elevated temperature. A catalyst of a thermal reaction lowers the activation barrier by interacting with the substrate and can be favorably used to eventually create a new stereogenic center. In a photochemical reaction, the situation is different because catalysis is not necessarily required to drive the reaction forward. The critical issue is to find chiral catalysts that interact with a photochemical substrate while it is excited from the ground state to the excited state. Reaction pathways have to be devised which avoid uncatalyzed racemic background reactions.
The goal of the ELICOS project is to develop catalytic methods that allow for the enantioselective synthesis of a broad variety of compound classes by light-induced reactions. The mode of action of potential catalysts is based on energy transfer or on wavelength-selective excitation. If successful, a widespread application of enantioselective photochemical reactions in organic synthesis will be secured and a multitude of structurally diverse products will become available in enantiomerically form for high-tech applications.
For more information, see also: http://portal.mytum.de/pressestelle/faszination-forschung/2016nr18/05_Millions_at_my_Beck.pdf
Two new concepts for the activation of photochemical substrates in a catalytic fashion have been discovered. The first concept relies on the temporary formation of cations which show a long-wavelength (bathochromic) shift relative to their precursors. They can thus be excited by visible light and react in a reaction that is unprecedented for this substrate class. The second concept is based on the reversible formation of iminium ions from carbonyl compounds. It was shown that the triplet energy of the ions is lower than the triplet energy of the carbonyl compounds. When employing a suitable sensitizer with a triplet energy that is sufficient to excite the iminium ion but not the carbonyl compound a selective photoreaction becomes possible. The two concepts were disclosed in publications which appeared in the journal Angewandte Chemie (DOI: 10.1002/anie.201700837; DOI: 10.1002/anie.201710441).
In the same journal, the conceptual approaches towards enantioselective photochemical reactions based on chromophore activation have been recently summarized (DOI: 10.1002/anie.201804006).
Science-based Impact: It has been shown in several examples that previously known racemic photochemical reactions can be modified to prepare enantiopure compounds. In addition, new catalytic photochemical reactions have been discovered which now wait to be exploited in an enantioselective fashion. It is noted that the area of photochemistry receives increasing interest form the scientific community which in part is due to the activities of the project (see also the Editorial which was written on the occasion of the year of light: DOI:10.1002/anie.201507439).
Socio-economic Impact: The power of photochemical reactions rests on the fact that they do not require any external energy but the energy of photons. They are in this regard optimal transformations which allow to harvest the energy of solar photons and to convert it into unique structures. The impact of the project on society rests on the efficient use of energy and on the construction of molecular structures which promise applications in medicine and technology.