Browsing by Author "Herrmann, Justin"

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    Cooperative Lewis acid‐1,2,3‐triazolium‐aryloxide catalysis : pyrazolone addition to nitroolefins as entry to diaminoamides
    (2023) Wanner, Daniel M.; Becker, Patrick M.; Suhr, Simon; Wannenmacher, Nick; Ziegler, Slava; Herrmann, Justin; Willig, Felix; Gabler, Julia; Jangid, Khushbu; Schmid, Juliane; Hans, Andreas C.; Frey, Wolfgang; Sarkar, Biprajit; Kästner, Johannes; Peters, René
    Pyrazolones represent an important structural motif in active pharmaceutical ingredients. Their asymmetric synthesis is thus widely studied. Still, a generally highly enantio- and diastereoselective 1,4-addition to nitroolefins providing products with adjacent stereocenters is elusive. In this article, a new polyfunctional CuII-1,2,3-triazolium-aryloxide catalyst is presented which enables this reaction type with high stereocontrol. DFT studies revealed that the triazolium stabilizes the transition state by hydrogen bonding between C(5)-H and the nitroolefin and verify a cooperative mode of activation. Moreover, they show that the catalyst adopts a rigid chiral cage/pore structure by intramolecular hydrogen bonding, by which stereocontrol is achieved. Control catalyst systems confirm the crucial role of the triazolium, aryloxide and CuII, requiring a sophisticated structural orchestration for high efficiency. The addition products were used to form pyrazolidinones by chemoselective C=N reduction. These heterocycles are shown to be valuable precursors toward β,γ’-diaminoamides by chemoselective nitro and N-N bond reductions. Morphological profiling using the Cell painting assay identified biological activities for the pyrazolidinones and suggest modulation of DNA synthesis as a potential mode of action. One product showed biological similarity to Camptothecin, a lead structure for cancer therapy.
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    Tunable endo/exo selectivity in direct catalytic asymmetric 1,3‐dipolar cycloadditions with polyfunctional Lewis acid / azolium-aryloxide catalysts
    (2025) Bürstner, Adrian; Becker, Patrick M.; Allgaier, Alexander; Pfitzer, Lucca; Wanner, Daniel M.; Dollinger, Johanna; Willig, Felix; Herrmann, Justin; Miskov‐Pajic, Vukoslava; Hans, Andreas C.; Frey, Wolfgang; van Slageren, Joris; Kästner, Johannes; Peters, René
    Catalytic asymmetric 1,3‐dipolar cycloadditions (1,3‐DCA) using iminoesters as ylide precursors offer a powerful approach to accessing stereochemically complex, biologically relevant pyrrolidines. Although previous studies have already achieved impressive stereoselectivities, catalytic productivity remains a challenge, with turnover numbers (TON) typically below 20. In this article, we introduce a novel concept for catalytic 1,3‐DCA that enables remarkable productivity for both endo (TON up to 4000) and the more challenging exo products (TON up to 1500). This approach, making use of modular polyfunctional Lewis acid/azolium‐aryloxide catalysts, allows for precise control over endo ‐ and exo ‐diastereoselectivity. The switch from endo ‐ to exo ‐selectivity is accomplished by modifying the metal center, the azolium moiety, and steric factors. As detailed DFT studies reveal, both the endo ‐ and exo ‐selective catalyst systems exhibit an almost perfect spatial alignment of their key functional sites, allowing for a unique interplay of Brønsted acids and bases, Lewis acids, and hydrogen bonding. The computational studies further demonstrate that these polyfunctional catalysts dramatically lower the energetic barriers of the concerted or stepwise cycloaddition key steps. However, they also precisely orchestrate and accelerate all accompanying transformations-reminiscent of enzymatic machineries.