Browsing by Author "Wanner, Daniel M."

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Open Access
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.
Open Access
Diastereospecific enantiodivergent allylation of pyrazolones as an entry to β‐aminoamides
(2022) Wannenmacher, Nick; Heberle, Martin; Yu, Xin; Demircan, Aysegül; Wanner, Daniel M.; Pfeffer, Camilla; Peters, René
A diastereospecific enantiodivergent allylation of pyrazolones is reported which is catalyzed by a planar chiral pentaphenylferrocene based palladacycle. With the same catalyst batch both product enantiomers were selectively available. The method is applicable to structurally diverse substrates and gave products with enantiomeric excesses between 85 and 94%. In addition, we could show that pyrazolones are transformable into β‐aminoamides.
Open Access
Enantiodivergent [4+2] cycloaddition of dienolates by polyfunctional Lewis acid/zwitterion catalysis
(2020) Miskov‐Pajic, Vukoslava; Willig, Felix; Wanner, Daniel M.; Frey, Wolfgang; Peters, René
Diels-Alder reactions have become established as one of the most effective ways to prepare stereochemically complex six‐membered rings. Different catalysis concepts have been reported, including dienophile activation by Lewis acids or H‐bond donors and diene activation by bases. Herein we report a new concept, in which an acidic prodiene is acidified by a Lewis acid to facilitate deprotonation by an imidazolium-aryloxide entity within a polyfunctional catalyst. A metal dienolate is thus formed, while an imidazolium-ArOH moiety probably forms hydrogen bonds with the dienophile. The catalyst type, readily prepared in few steps in high overall yield, was applied to 3‐hydroxy‐2‐pyrone and 3‐hydroxy‐2‐pyridone as well as cyclopentenone prodienes. Maleimide, maleic anhydride, and nitroolefin dienophiles were employed. Kinetic, spectroscopic, and control experiments support a cooperative mode of action. High enantioselectivity was observed even with unprecedented TONs of up to 3680.
Open Access
A practical and robust zwitterionic cooperative Lewis acid/acetate/benzimidazolium catalyst for direct 1,4‐additions
(2023) Hans, Andreas C.; Becker, Patrick M.; Haußmann, Johanna; Suhr, Simon; Wanner, Daniel M.; Lederer, Vera; Willig, Felix; Frey, Wolfgang; Sarkar, Biprajit; Kästner, Johannes; Peters, René
A catalyst type is disclosed allowing for exceptional efficiency in direct 1,4‐additions. The catalyst is a zwitterionic entity, in which acetate binds to CuII, which is formally negatively charged and serving as counterion for benzimidazolium. All 3 functionalities are involved in the catalytic activation. For maleimides productivity was increased by a factor >300 compared to literature (TONs up to 6700). High stereoselectivity and productivity was attained for a broad range of other Michael acceptors as well. The polyfunctional catalyst is accessible in only 4 steps from N‐Ph‐benzimidazole with an overall yield of 96 % and robust during catalysis. This allowed to reuse the same catalyst multiple times with nearly constant efficiency. Mechanistic studies, in particular by DFT, give a detailed picture how the catalyst operates. The benzimidazolium unit stabilizes the coordinated enolate nucleophile and prevents that acetate/acetic acid dissociate from the catalyst.