Enantioselective Light Induced Catalysis for Organic Synthesis (ELICOS)

Chirality is one of the most fascinating and important properties of matter. The interaction of small molecules with biological systems is determined by the orientation of their atoms in three-dimensional space. As a consequence, enantiomeric molecules may have completely different pharmacological properties and this fact has stimulated extensive research efforts towards the synthesis of enantiomerically pure compounds. With regard to organic compounds, the key issue is to install the first stereogenic carbon atom with high enantioselectivity as the creation of consecutive stereogenic centers will lead to diastereoisomers. Although chiral compounds available from Nature still play an important role as starting materials in organic synthesis, the most important and effective way to create enantiomerically pure compounds de novo is based on enantioselective (asymmetric) catalysis. The Nobel Prize in Chemistry 2001 recognized the pioneering efforts of W. S. Knowles, R. Noyori and K. B. Sharpless towards the development of enantioselective catalytic oxidation and hydrogenation reactions. Modern pharmaceutical drug production, a market of more than 1012 €, relies heavily on enantioselective catalytic methods.

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.

Publications

  • Graßl, Raphaela; Jandl, Christian; Bach, Thorsten: Visible Light-Mediated Photochemical Reactions of 2-(2′-Alkenyloxy)cycloalk-2-enones. J. Org. Chem. 85 (17), 2020, 11426-11439 mehr…
  • Hörmann, Fabian M.; Kerzig, Christoph; Chung, Tim S.; Bauer, Andreas; Wenger, Oliver S.; Bach, Thorsten: Triplet Energy Transfer from Ruthenium Complexes to Chiral Eniminium Ions: Enantioselective Synthesis of Cyclobutane­carbaldehydes by [2+2] Photocycloaddition. Angew. Chem. Int. Ed. 59 (24), 2020, 9659-9668 mehr…
  • Pecho, Franziska; Zou, You-Quan; Gramüller, Johannes; Mori, Tadashi; Huber, Stefan M.; Bauer, Andreas; Gschwind, Ruth M.; Bach, Thorsten: A Thioxanthone Sensitizer with a Chiral Phosphoric Acid Binding Site: Properties and Applications in Visible Light‐Mediated Cycloadditions. Chem. Eur. J. 26, 2020, 5190-5194 mehr…
  • Leverenz, Malte; Merten, Christian; Dreuw, Andreas; Bach, Thorsten: Lewis Acid Catalyzed Enantioselective Photochemical Rearrangements on the Singlet Potential Energy Surface. J. Am. Chem. Soc. 141, 2019, 20053-20057 mehr…
  • Stegbauer, Simone; Jeremias, Noah; Jandl, Christian; Bach, Thorsten: Reversal of reaction type selectivity by Lewis acid coordination: the ortho photocycloaddition of 1- and 2-naphthaldehyde. Chem. Sci. 10, 2019, 8566-8570 mehr…
  • Mohr, Lisa-Marie; Bauer, Andreas; Jandl, Christian; Bach, Thorsten: Visible light-mediated intermolecular [2 + 2] photocycloaddition of 1-aryl-2-nitroethenes and olefins. Org. Biomol. Chem. 17, 2019, 7192-7203 mehr…
  • Poplata, Saner; Bauer, Andreas; Storch, Golo; Bach, Thorsten: Intramolecular [2+2] Photocycloaddition of Cyclic Enones: Selectivity Control by Lewis Acids and Mechanistic Implications. Chem. Eur. J. 25, 2019, 8135–8148 mehr…
  • Modha, Sachin G.; Pöthig, Alexander; Dreuw, Andreas; Bach, Thorsten: [6π] Photocyclization to cis-Hexahydrocarbazol-4-ones: Substrate Modification, Mechanism, and Scope. J. Org. Chem. 84, 2019, 1139-1153 mehr…
  • Stegbauer, Simone; Jandl, Christian; Bach, Thorsten: Enantioselective Lewis Acid Catalyzed ortho Photocycloaddition of Olefins to Phenanthrene-9-carboxaldehydes. Angew. Chem. Int. Ed. 57, 2018, 14593-14596 mehr…
  • Brenninger, Christoph; Jolliffe, John D.; Bach, Thorsten: Chromophore Activation of α,β-Unsaturated Carbonyl Compounds and Its Application to Enantioselective Photochemical Reactions. Angew. Chem. Int. Ed. 57, 2018, 14338-14349 mehr…
  • Brenninger, Christoph; Bach, Thorsten: α-Thio Carbocations (Thionium Ions) as Intermediates in Brønsted Acid-Catalyzed Reactions of Enone-Derived 1,3-Dithianes and 1,3-Dithiolanes. Top. Catal. 91, 2018, 623-629 mehr…
  • Poplata, Saner; Bach, Thorsten: Enantioselective Intermolecular [2+2] Photocycloaddition Reaction of Cyclic Enones and Its Application in a Synthesis of (−)-Grandisol. J. Am. Chem. Soc. 140, 2018, 3228-3231 mehr…
  • Hörmann, Fabian M.; Chung, Tim S.; Rodriguez, Elsa; Jakob, Matthias; Bach, Thorsten: Evidence for Triplet Sensitization in the Visible-Light-Induced [2+2] Photocycloaddition of Eniminium Ions. Angew. Chem. Int. Ed. 57, 2018, 827-831 mehr…
  • Zou, You-Quan; Hörmann, Fabian M.; Bach, Thorsten: Iminium and Enamine Catalysis in Enantioselective Photochemical Reactions. Chem. Soc. Rev. 47, 2018, 278-290 mehr…
  • Mayr, Florian; Mohr, Lisa-Marie; Rodriguez, Elsa; Bach, Thorsten: Synthesis of Chiral Thiourea-Thioxanthone Hybrids. Synthesis 49, 2017, 5238-5250 mehr…
  • Mohr, Lisa-Marie; Bach, Thorsten: Intermolecular [2+2] Photocycloaddition of β-Nitrostyrenes to Olefins upon Irradiation with Visible Light. Synlett 28, 2017, 2946-2950 mehr…
  • Edtmüller, Verena; Pöthig, Alexander; Bach, Thorsten: Enantioselective Photocyclisation Reactions of 2-Aryloxycyclohex-2-enones mediated by a chiral Copper-Bisoxazoline Complex. Tetrahedron 73, 2017, 5038-5047 mehr…
  • Brenninger, Christoph; Pöthig, Alexander; Bach, Thorsten: Brønsted Acid Catalysis in Visible-Light-Induced [2+2] Photocycloaddition Reactions of Enone Dithianes. Angew. Chem. Int. Ed. 56, 2017, 4337-4341 mehr…
  • Mayr, Florian; Brimioulle, Richard; Bach, Thorsten: A Chiral Thiourea as a Template for Enantioselective Intramolecular [2 + 2] Photocycloaddition Reactions. J. Org. Chem. 81 (16), 2016, 6965–6971 mehr…
  • Poplata, Saner; Tröster, Andreas; Zou, You-Quan; Bach, Thorsten: Recent Advances in the Synthesis of Cyclobutanes by Olefin [2+2] Photocycloaddition Reactions. Chem. Rev. 116 (17), 2016, 9748-9815 mehr…