A5083596542- Synthesis and Catalytic Reactions
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Catalytic C–H Functionalization Methods
- Asymmetric Synthesis and Catalysis
- Synthetic Organic Chemistry Methods
- Sulfur-Based Synthesis Techniques
- Carbohydrate Chemistry and Synthesis
- Chemical Synthesis and Analysis
- Advanced Synthetic Organic Chemistry
- Asymmetric Hydrogenation and Catalysis
- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- Crystallography and molecular interactions
- Fluorine in Organic Chemistry
- HIV/AIDS drug development and treatment
- Chemical Synthesis and Reactions
- Organophosphorus compounds synthesis
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Cyclopropane Reaction Mechanisms
- Chemical Reactions and Mechanisms
- German Literature and Culture Studies
- Cyclization and Aryne Chemistry
- Innovative Microfluidic and Catalytic Techniques Innovation
- Enzyme Structure and Function
RWTH Aachen University
2014-2023
An efficient kinetic resolution of sulfoximines with enals was realized using chiral N-heterocyclic carbene (NHC) catalysts. The stereoselective amidation proceeds without additional acyl transfer agent. Both enantiomers the can be obtained excellent ee values (up to 99% and −97% ee, respectively). Performing catalysis on a gram scale allowed recovered sulfoximine (+)-1j in an asymmetric synthesis FXa inhibitor F.
Iron works: Enantioselective nitrene transfer to sulfide was accomplished by a chiral iron(III)/PyBOX catalyst (see scheme). Various sulfimides were thus obtained in high enantioselectivities and yields. Applications of this protocol the syntheses enantioenriched sulfoximines an epoxide also demonstrated. As service our authors readers, journal provides supporting information supplied authors. Such materials are peer reviewed may be re-organized for online delivery, but not copy-edited or...
Kinetic resolution of racemic sulfoxides requires either custom substrates or shows moderate enantioselectivity, leading to achiral coproducts (such as sulfones) an intrinsic part the process. A new strategy is demonstrated that allows through catalytic asymmetric nitrene-transfer reactions. This approach gives rise both optically active and highly enantioenriched sulfoximines. By using a chiral iron catalyst readily available iodinane reagent, high selectivity factors have been achieved...
Abstract Mechanosynthesis is a valuable technique, offering attractive alternatives for the preparation of organic, inorganic, and organometallic products. Surprisingly, mechanochemical enzymatic transformations have only scarcely been studied until now. Here, we demonstrate use lipase B from Candida antarctica (CALB) in acylative kinetic resolutions secondary alcohols mixer planetary mills. Despite mechanical stress caused by high‐speed ball milling, biocatalyst proved highly effective,...
For the first time, chiral sulfoximine derivatives have been applied as asymmetric organocatalysts. In combination with a thiourea-type backbone sulfonimidoyl moiety leads to organocatalysts showing good reactivity in catalytic desymmetrization of cyclic meso -anhydride and moderate enantioselectivity Biginelli reaction. Straightforward synthetic routes provide newly designed thiourea-sulfoximine catalysts high overall yields without affecting stereohomogeneity sulfur-containing core fragment.
N-Alkynylated sulfoximines have been obtained by copper-catalyzed cross-coupling reactions starting from NH-sulfoximines and bromoacetylenes in moderate to good yields. The reaction conditions are mild, the substrate scope is wide.
Abstract Vinylogous Mukaiyama‐type aldol reactions have been catalyzed by a combination of Cu(OTf) 2 and readily available C 1 ‐symmetric aminosulfoximines. After fine‐tuning the reaction conditions an optimization modularly assembled ligand structure, high stereoselectivities excellent yields achieved in involving various electrophile/nucleophile combinations. The relative absolute configurations two products were assigned X‐ray single crystal structure analysis comparison calculated...
A method for halocyclizations of S-alkenylsulfoximines is reported. When unsaturated NH-sulfoximines are treated with a combination iodobenzene diacetate and potassium iodide, transformation to the corresponding five- six-membered cyclic products occurs providing S-oxides dihydro isothiazoles tetrahydro-1,2-thiazines, respectively, in moderate high yields good diastereoselectivities excellent regioselectivities.
Abstract A procedure that enables high yielding access to phosphonic γ‐(hydroxyalkyl)butenolides with excellent regio‐, diastereo‐ and enantiocontrol is reported. The simultaneous construction of up two adjacent quaternary stereogenic centers by a catalytic asymmetric vinylogous Mukaiyama aldol reaction unites biologically medicinally relevant entities, namely α‐hydroxy phosphonates γ‐(hydroxyalkyl)butenolides. This achieved utilizing readily available chiral copper‐sulfoximine catalyst...
In control: A new catalytic vinylogous Mukaiyama aldol reaction provides products with high diastereo- and enantioselectivities (up to 99 % de ee; see scheme). The relative absolute stereochemistry of a representative product was rigorously assigned by NMR CD spectroscopies (measured calculated), X-ray diffraction, quantum-chemical calculations.
Abstract A C 1 ‐symmetric amino sulfoximine has been used as a chiral ligand in copper‐catalyzed asymmetric halogenation reactions of β‐oxo esters. Both the catalyst itself and reaction conditions were optimized, 26 fluorinated, chlorinated, brominated products obtained with enantioselectivities up to 91 % ee yields 99 %. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Structural analogues of PFI-1 varying at the sulfur core were prepared, and their activities as BET inhibitors in myeloid cell lines primary cells from patients with acute leukemia studied. Docking calculations followed by molecular dynamics simulations revealed binding mode newly prepared inhibitors, suggesting explanations for observed high enantiospecificity inhibitory activity.
Amides with quaternary stereogenic centers have been synthesised by catalytic asymmetric vinylogous Mukaiyama aldol reactions. The chiral copper–sulfoximine catalyst gives rise to products moderate good yields and up 92% ee.
An enantio- and regioselective allylic alkylation of sulfoximines with Morita–Baylis–Hillman carbonates was developed. The asymmetric reaction is directed by a quinidine-derived organocatalyst providing range optically active α-methylene β-sulfoximidoyl esters in high yields (up to 93%) good excellent enantiomeric excesses 95%) under mild conditions.
Abstract A highly stereoselective vinylogous Mukaiyama Michael reaction (VMMR) leading to α‐keto phosphonate‐containing γ‐butenolides with two stereogenic centers is described. The presented transformation catalyzed by a combination of commercially available C 2 ‐symmetric bisoxazoline (BOX) ligand and copper salt tolerates variety nucleophiles electrophiles. stereoselectivities the reactions are good excellent products obtained in moderate high yields.
N-Alkyl sulfoximines react with arynes generated in situ under mild conditions providing o-sulfinylanilines good yields. The transformation is characterized by a broad substrate scope and functional group tolerance. structure of reaction product was confirmed single-crystal X-ray diffraction.
Many homodimeric enzymes tune their functions by exploiting either negative or positive cooperativity between subunits. In the SARS-CoV-2 Main protease (Mpro) homodimer, latter has been suggested symmetry in most of 500 reported protease/ligand complex structures solved macromolecular crystallography (MX). Here we apply to both covalent and noncovalent ligands with Mpro. Strikingly, our experiments show that occupation active sites dimer originates from an excess ligands. Indeed, cocrystals...
An N-heterocyclic carbene (NHC)-catalyzed highly diastereo- and enantioselective formal [3+2] reaction of o-hydroxy aromatic aldimines cinnamaldehydes for the preparation enantioenriched trans-γ-lactams was developed. internal hydrogen bond between imine function crucial reactivity chemical selectivity. Trans-γ-lactam 3 d easily oxidized to multifunctional 1,4-benzoquinone 8, which could further be transformed biaryl 9 in presence a phosphoric acid. Finally, preliminary results kinetic...
Abstract Sulfoximines are popular scaffolds in drug discovery due to their hydrogen bonding properties and chemical stability. In recent years, the role of reactive intermediates such as nitrenes has been studied synthesis degradation sulfoximines. this work, photochemistry N ‐phenyl dibenzothiophene sulfoximine [5‐(phenylimino)‐5 H ‐5λ 4 ‐dibenzo[ b,d ]thiophene S ‐oxide] was analyzed. The structure resembles a combination iminodibenzothiophene ‐oxide, which generate nitrene O( 3 P) upon...
An unexpected substitution reaction providing sulfoximidoyl-containing carbamates was observed when Morita-Baylis-Hillman carbonates and NH-sulfoximines were mixed in acetonitrile at elevated temperature. Key ingredients triethylamine ortho-hydroxybenzoic acid, which both had to be present catalytic quantities.
Many homodimeric enzymes tune their function by exploiting either negative or positive cooperativity between subunits. In the SARS-CoV-2 Main protease (Mpro) homodimer, latter has been suggested symmetry in most of 500 reported protease/ligand complex structures solved macromolecular crystallography. Here we apply to both covalent and non-covalent ligands with Mpro. Strikingly, our experiments show that occupation active sites dimer originates from an excess ligands. Indeed, co-crystals...