Photoisomerization an Access to Transition State Combinations in Thiourea-, Iminium- and Dienaminecatalysis
Final Report Abstract
Aim of the project was to elucidate reaction pathways, intermediate structures and stereoinduction modes on examples in organocatalytic enamine, dienamine, and iminium catalysis via a combination of experimental NMR spectroscopic techniques, theoretical calculations, and photo isomerization. In enamine catalysis the formation pathways of the cental enamine intermediate could be revealed in detail for the first time via a kinetic analysis of the transformation pathways between the intermediates. In addition, CEST (chemical exchange saturation transfer) was for the first time successfully applied in studies of chemical reaction mechanisms. On the elusive iminium intermediates in enamine catalysis we could show that CEST allows in an indirect way to qualitatively and quantitatively detect intermediates below the NMR detection limit. The broad applicability of CEST opens up a new dimension in the NMR based research of chemical reactions. Starting from enamines and nitronates the first organocatalytic enine formation is reported. The E/Z-dilemma in dienamines could be addressed, since for the first time a faster reaction of the Z-intermediates was detected. This showed the broad significance of E/Z-isomers, their formation and abreaction pathways for the stereoinduction in catalysis. Furthermore, together with the photoisomerization of E- and Z-isomers it allows to change the ratios between E and Z in a designed way enabling new methods in reaction mechanism analysis and even changes in stereoinduction. Therefore, photoisomerisation was one main topic of the project’s second period. Organocatalytic cyclization reactions were accelerated by a photoisomerization of E-isomers. In iminium catalysis so far elusive reaction intermediates could be boosted, identified and assigned by photoisomerisation. The main challenge for the successful application of photoisomerisations in catalysis and reaction analysis are fast thermal back isomerisation and inefficient or unselective forward isomerisation. This is even more critical in case of reaction intermediates. Therefore, kinetic NMR approaches, the benefits of 19 F spectra and the influence of variable temperatures on isomerizations were developed and investigated on stabile azophotoswitches. During the extensive investigations of effects of photo isomerizations in iminium catalysis we observed special ionic aggregate effects on the thermal back isomerization. This enabled also to understand ionic aggregate effects in C(sp3)–H fluorination reactions. Via reaction mechanism analysis the efficiency could be increased to such an extend that an international patent has been applied for. Overall, in this project we gained unique insights into the intermediate structures and reaction pathways in enamine, dienamine and iminium catalysis. In addition, new NMR techniques were developed to detect reaction intermediates below the NMR detection limit and to experimentally measure their kinetics and thermodynamics.
Publications
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The Proline Enamine Formation Pathway Revisited in Dimethyl Sulfoxide: Rate Constants Determined via NMR. Journal of the American Chemical Society, 137(40), 12835-12842.
Haindl, Michael H.; Hioe, Johnny & Gschwind, Ruth M.
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Remote-Stereocontrol in Dienamine Catalysis: Z-Dienamine Preferences and Electrophile–Catalyst Interaction Revealed by NMR and Computational Studies. Journal of the American Chemical Society, 138(31), 9864-9873.
Seegerer, Andreas; Hioe, Johnny; Hammer, Michael M.; Morana, Fabio; Fuchs, Patrick J. W. & Gschwind, Ruth M.
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Enamine/Dienamine and Brønsted Acid Catalysis: Elusive Intermediates, Reaction Mechanisms, and Stereoinduction Modes Based on in Situ NMR Spectroscopy and Computational Studies. Accounts of Chemical Research, 50(12), 2936-2948.
Renzi, Polyssena; Hioe, Johnny & Gschwind, Ruth M.
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Chemical Exchange Saturation Transfer in Chemical Reactions: A Mechanistic Tool for NMR Detection and Characterization of Transient Intermediates. Journal of the American Chemical Society, 140(5), 1855-1862.
Lokesh, N.; Seegerer, Andreas; Hioe, Johnny & Gschwind, Ruth M.
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Unprecedented Mechanism of an Organocatalytic Route to Conjugated Enynes with a Junction to Cyclic Nitronates. European Journal of Organic Chemistry, 2019(2-3), 328-337.
Streitferdt, Verena; Haindl, Michael H.; Hioe, Johnny; Morana, Fabio; Renzi, Polyssena; von Rekowski, Felicitas; Zimmermann, Alexander; Nardi, Martina; Zeitler, Kirsten & Gschwind, Ruth M.
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Combination of illumination and high resolution NMR spectroscopy: Key features and practical aspects, photochemical applications, and new concepts. Progress in Nuclear Magnetic Resonance Spectroscopy, 114-115, 86-134.
Nitschke, Philipp; Lokesh, Nanjundappa & Gschwind, Ruth M.
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Benzoates as photosensitization catalysts and auxiliaries in efficient, practical, light-powered direct C(sp3)–H fluorinations. Chemical Science, 13(47), 14041-14051.
Yakubov, Shahboz; Stockerl, Willibald J.; Tian, Xianhai; Shahin, Ahmed; Mandigma, Mark John P.; Gschwind, Ruth M. & Barham, Joshua P.
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Substrate Photoswitching for Rate Enhancement of a Organocatalytic Cyclization Reaction. European Journal of Organic Chemistry, 2022(26).
Žabka, Matej & Gschwind, Ruth M.
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Azotriptycenes: Photoswitchable Molecular Brakes. Chemistry – A European Journal, 30(6).
Stockerl, Willibald J.; Reißenweber, Lilli; Gerwien, Aaron; Bach, Nicolai N.; Thumser, Stefan; Mayer, Peter; Gschwind, Ruth M. & Dube, Henry
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Photo enhancement reveals (E,Z) and (Z,Z) configurations as additional intermediates in iminium ion catalysis. Chemical Communications, 59(10), 1325-1328.
Stockerl, Willibald J. & Gschwind, Ruth M.
