0000000001299336
AUTHOR
Imre Pápai
showing 43 related works from this author
Dual Hydrogen Bond - Enamine Catalysis Enables a Direct Enantioselective Three-Component Domino Reaction
2011
A dual system, composed of an enantioselective enamine catalyst and a multiple-hydrogen-bond catalyst achieves the three-component enantioselective aldehyde—nitroalkene—aldehyde domino reaction using either two similar or two different aldehydes.
ChemInform Abstract: A Catalyst Designed for the Enantioselective Construction of Methyl- and Alkyl-Substituted Tertiary Stereocenters.
2016
Tertiary methyl-substituted stereocenters are present in numerous biologically active natural products. Reported herein is a catalytic enantioselective method for accessing these chiral building blocks using the Mukaiyama-Michael reaction between silyl ketene thioacetals and acrolein. To enable remote enantioface control on the nucleophile, a new iminium catalyst, optimized by three-parameter tuning and by identifying substituent effects on enantioselectivity, was designed. The catalytic process allows rapid access to chiral thioesters, amides, aldehydes, and ketones bearing an α-methyl stereocenter with excellent enantioselectivities, and allowed rapid access to the C4-C13 segment of (-)-b…
ChemInform Abstract: Dual Hydrogen-Bond/Enamine Catalysis Enables a Direct Enantioselective Three-Component Domino Reaction.
2011
A dual system, composed of an enantioselective enamine catalyst and a multiple-hydrogen-bond catalyst achieves the three-component enantioselective aldehyde—nitroalkene—aldehyde domino reaction using either two similar or two different aldehydes.
Stereocontrol in Diphenylprolinol Silyl Ether Catalyzed Michael Additions : Steric Shielding or Curtin-Hammett Scenario?
2017
The enantioselectivity of amine-catalyzed reactions of aldehydes with electrophiles is often explained by simple steric arguments emphasizing the role of the bulky group of the catalyst that prevents the approach of the electrophile from the more hindered side. This standard steric shielding model has recently been challenged by the discovery of stable downstream intermediates, which appear to be involved in the rate-determining step of the catalytic cycle. The alternative model, referred to as Curtin-Hammett scenario of stereocontrol, assumes that the enantioselectivity is related to the stability and reactivity of downstream intermediates. In our present computational study, we examine th…
Stereoelectronic Requirements for Optimal Hydrogen-Bond-Catalyzed Enolization
2011
Protein crystallographic analysis of the active sites of enolizing enzymes and structural analysis of hydrogen-bonded carbonyl compounds in small molecule crystal structures, complemented by quantum chemical calculations on related model enolization reactions, suggest a new stereoelectronic model that accounts for the observed out-of-plane orientation of hydrogen-bond donors (HBDs) in the oxyanion holes of enolizing enzymes. The computational results reveal that the lone-pair directionality of HBDs characteristic for hydrogen-bonded carbonyls is reduced upon enolization, and the enolate displays almost no directional preference for hydrogen bonding. Positioning the HBDs perpendicular to the…
Mukaiyama–Michael Reactions with trans-2,5-Diarylpyrrolidine Catalysts: Enantioselectivity Arises from Attractive Noncovalent Interactions, Not from …
2013
The scope of the enantioselective Mukaiyama-Michael reactions catalyzed by trans-2,5-diphenylpyrrolidine has been expanded to include both α- and β-substituted enals. However, the rationalization of the observed enantioselectivity is far from obvious since the catalyst is not very sterically hindered. DFT calculations were carried out to rationalize the observed stereoselectivities. Transition states of the C-C bond formation between iminium intermediates and silyloxyfurans were located and their relative energies were used to estimate the stereoselectivity data. We find excellent agreement between the predicted and observed stereoselectivities. The analysis of intermolecular forces reveals…
Cross-Dehydrogenative Couplings between Indoles and beta-Keto Esters: Ligand-Assisted Ligand Tautomerization and Dehydrogenation via a Proton-Assiste…
2014
Cross-dehydrogenative coupling reactions between β-ketoesters and electron-rich arenes, such as indoles, proceed with high regiochemical fidelity with a range of β-ketoesters and indoles. The mechanism of the reaction between a prototypical β-ketoester, ethyl 2-oxocyclopentanonecarboxylate, and N-methylindole has been studied experimentally by monitoring the temporal course of the reaction by (1)H NMR, kinetic isotope effect studies, and control experiments. DFT calculations have been carried out using a dispersion-corrected range-separated hybrid functional (ωB97X-D) to explore the basic elementary steps of the catalytic cycle. The experimental results indicate that the reaction proceeds v…
ChemInform Abstract: Cross-Dehydrogenative Couplings Between Indoles and β-Keto Esters: Ligand-Assisted Ligand Tautomerization and Dehydrogenation vi…
2014
Cross-dehydrogenative coupling reactions between β-ketoesters and electron-rich arenes, such as indoles, proceed with high regiochemical fidelity with a range of β-ketoesters and indoles. The mechanism of the reaction between a prototypical β-ketoester, ethyl 2-oxocyclopentanonecarboxylate, and N-methylindole has been studied experimentally by monitoring the temporal course of the reaction by (1)H NMR, kinetic isotope effect studies, and control experiments. DFT calculations have been carried out using a dispersion-corrected range-separated hybrid functional (ωB97X-D) to explore the basic elementary steps of the catalytic cycle. The experimental results indicate that the reaction proceeds v…
ChemInform Abstract: Mukaiyama-Michael Reactions with trans-2,5-Diarylpyrrolidine Catalysts: Enantioselectivity Arises from Attractive Noncovalent In…
2014
The 2,5-diphenylpyrrolidine-catalyzed enantioselective Mukaiyama—Michael reaction between substituted furans and enals is studied.
Dihydrooxazine Oxides as Key Intermediates in Organocatalytic Michael Additions of Aldehydes to Nitroalkenes
2012
Pause and play: dihydrooxazine oxides are stable intermediates that are protonated directly, without the intermediacy of the zwitterions, in organocatalytic Michael additions of aldehydes and nitroalkenes (see scheme, R=alkyl). Protonation of these species explains both the role of the acid co-catalyst in these reactions, and the observed stereochemistry when the reaction is conducted with α-alkylnitroalkenes.
A Catalyst Designed for the Enantioselective Construction of Methyl- and Alkyl-Substituted Tertiary Stereocenters
2015
Tertiary methyl-substituted stereocenters are present in numerous biologically active natural products. Reported herein is a catalytic enantioselective method for accessing these chiral building blocks using the Mukaiyama-Michael reaction between silyl ketene thioacetals and acrolein. To enable remote enantioface control on the nucleophile, a new iminium catalyst, optimized by three-parameter tuning and by identifying substituent effects on enantioselectivity, was designed. The catalytic process allows rapid access to chiral thioesters, amides, aldehydes, and ketones bearing an α-methyl stereocenter with excellent enantioselectivities, and allowed rapid access to the C4-C13 segment of (-)-b…
Organocatalysts Fold to Generate an Active Site Pocket for the Mannich Reaction
2017
Catalysts containing urea, thiourea and tertiary amine groups fold into a three-dimensional organized structure in solution both in the absence as well as in the presence of substrates or substrate analogues, as indicated by solution NMR and computational studies. These foldamer catalysts promote Mannich reactions with both aliphatic and aromatic imines and malonate esters. Hammett plot and secondary kinetic isotope effects provide evidence for the C-C bond forming event as the turnoverlimiting step of the Mannich reaction. Computational studies suggest two viable pathways for the C-C bond formation step, differing in the activation modes of the malonate and imine substrates. The results sh…
Dimerization of (+)-Lysergic Acid Esters
2007
Dimer isomer mixtures, characterized by a bridgehead C8-C8' bond, (6a-7a; 6b-7b) were obtained from (+)-lysergic acid methyl or ethyl ester (1b; 1c) in a solution of methanol or ethanol. The isomers were separated, and their structures were determined by detailed NMR measurements and X-ray analysis. Density functional theory was applied to provide insight into the reaction mechanism. Based on an extended examination and the theoretical calculations, a plausible reaction sequence leading to dimers is also presented. The proposed mechanism has been verified by detecting the formation of the superoxide radical anion (O 2 * -).
Folding Patterns in a Family of Oligoamide Foldamers
2015
A series of small, unsymmetrical pyridine-2,6-dicarboxylamide oligoamide foldamers with varying lengths and substituents at the end groups were synthetized to study their conformational properties and folding patterns. The @-type folding pattern resembled the oxyanion-hole motifs of enzymes, but several alternative folding patterns could also be characterized. Computational studies revealed several alternative conformers of nearly equal stability. These folding patterns differed from each other in their intramolecular hydrogen-bonding patterns and aryl-aryl interactions. In the solid state, the foldamers adopted either the globular @-type fold or the more extended S-type conformers, which w…
ChemInform Abstract: Dihydrooxazine Oxides as Key Intermediates in Organocatalytic Michael Additions of Aldehydes to Nitroalkenes.
2013
Pause and play: dihydrooxazine oxides are stable intermediates that are protonated directly, without the intermediacy of the zwitterions, in organocatalytic Michael additions of aldehydes and nitroalkenes (see scheme, R=alkyl). Protonation of these species explains both the role of the acid co-catalyst in these reactions, and the observed stereochemistry when the reaction is conducted with α-alkylnitroalkenes.
Total Synthesis of Stemoamide, 9a-epi-Stemoamide, and 9a,10-epi-Stemoamide: Divergent Stereochemistry of the Final Methylation Steps
2020
Total syntheses of stemoamide, 9a-epi-stemoamide, and 9a,10-epi-stemoamide by a convergent A + B ring-forming strategy is reported. The synthesis required a diastereoselective late-stage methylation of the ABC stemoamide core that successfully enabled access to three of the four possible diastereomeric structures. For the natural stemoamide series, the diastereoselectivity can be rationalized both by kinetic and thermodynamic arguments, whereas for the natural 9a-epi-stemoamide series, the kinetic selectivity is explained by the prepyramidalization of the relevant enolate.
Conformationally Locked Pyramidality Explains the Diastereoselectivity in the Methylation of trans-Fused Butyrolactones
2020
A stereoselectivity model inspired by the total synthesis of stemona alkaloids is developed to explain why enolate-derived 3,4-fused butyrolactones are methylated with a preference for syn alkylation. The model shows how conformational locking present in nonplanar enolate structures favors syn over anti methylation, due to less significant structural distortions in the syn pathway. The developed model was also successfully used to rationalize selectivities of previously documented methylation reactions. peerReviewed
Cooperative Assistance in Bifunctional Organocatalysis: Enantioselective Mannich Reactions with Aliphatic and Aromatic Imines
2012
both of which contain a thiourea moiety (Scheme 1).The catalysts are capable of deprotonating suitable nucleo-philes, such as activated carbonyl compounds. This proton-transfer reaction generates an ion pair, which is composed ofthe protonated catalyst and the anionic nucleophile interact-ing through hydrogen bonds. At least one of the NH moietiesin the protonated catalyst is involved in activating theelectrophilic reaction partner.
ChemInform Abstract: Cooperative Assistance in Bifunctional Organocatalysis: Enantioselective Mannich Reactions with Aliphatic and Aromatic Imines.
2013
both of which contain a thiourea moiety (Scheme 1).The catalysts are capable of deprotonating suitable nucleo-philes, such as activated carbonyl compounds. This proton-transfer reaction generates an ion pair, which is composed ofthe protonated catalyst and the anionic nucleophile interact-ing through hydrogen bonds. At least one of the NH moietiesin the protonated catalyst is involved in activating theelectrophilic reaction partner.
Dynamic Refolding of Ion-Pair Catalysts in Response to Different Anions.
2019
Four distinct folding patterns were identified in two foldamer-type urea-thiourea catalysts bearing a basic dimethylamino unit by a combination of X-ray crystallography, solution NMR studies, and computational studies (DFT). These patterns are characterized by different intramolecular hydrogen bonding schemes that arise largely from different thiourea conformers. The free base forms of the catalysts are characterized by folds where the intramolecular hydrogen bonds between the urea and the thiourea units remain intact. In contrast, the catalytically relevant salt forms of the catalyst, where the catalyst forms an ion pair with the substrate or substrate analogues, appear in two entirely dif…
Carboxylate catalyzed isomerization of β,γ‐unsaturated N-acetylcysteamine thioesters
2022
We demonstrate herein the capacity of simple carboxylate salts – tetrametylammonium and tetramethylguanidinium pivalate – to act as catalysts in the isomerization of β,γ-unsaturated thioesters to α,β-unsaturated thioesters. The carboxylate catalysts gave reaction rates comparable to those obtained with DBU, but with fewer side reactions. The reaction exhibits a normal secondary kinetic isotope effect ( k 1H / k 1D = 1.065±0.026) with a β,γ−deuterated substrate. Computational analysis of the mechanism provides a similar value ( k 1H / k 1D = 1.05) with a mechanism where γ-reprotonation of the enolate intermediate is rate determining. peerReviewed
CCDC 1901894: Experimental Crystal Structure Determination
2023
Related Article: Antti J. Neuvonen, Dimitris Noutsias, Filip Topić, Kari Rissanen, Tamás Földes, Imre Pápai, Petri M. Pihko|2019|J.Org.Chem.|84|15009|doi:10.1021/acs.joc.9b01980
CCDC 1973338: Experimental Crystal Structure Determination
2020
Related Article: Imre Pápai, Petri M. Pihko, Juha H. Siitonen, Dániel Csókás|2020|Synlett|31|1581|doi:10.1055/s-0040-1707201
CCDC 1038219: Experimental Crystal Structure Determination
2015
Related Article: Minna Kortelainen, Aku Suhonen, Andrea Hamza, Imre Pápai, Elisa Nauha, Sanna Yliniemelä-Sipari, Maija Nissinen, Petri M. Pihko|2015|Chem.-Eur.J.|21|9493|doi:10.1002/chem.201406521
CCDC 1038222: Experimental Crystal Structure Determination
2015
Related Article: Minna Kortelainen, Aku Suhonen, Andrea Hamza, Imre Pápai, Elisa Nauha, Sanna Yliniemelä-Sipari, Maija Nissinen, Petri M. Pihko|2015|Chem.-Eur.J.|21|9493|doi:10.1002/chem.201406521
CCDC 1038221: Experimental Crystal Structure Determination
2015
Related Article: Minna Kortelainen, Aku Suhonen, Andrea Hamza, Imre Pápai, Elisa Nauha, Sanna Yliniemelä-Sipari, Maija Nissinen, Petri M. Pihko|2015|Chem.-Eur.J.|21|9493|doi:10.1002/chem.201406521
CCDC 1901892: Experimental Crystal Structure Determination
2023
Related Article: Antti J. Neuvonen, Dimitris Noutsias, Filip Topić, Kari Rissanen, Tamás Földes, Imre Pápai, Petri M. Pihko|2019|J.Org.Chem.|84|15009|doi:10.1021/acs.joc.9b01980
CCDC 1556565: Experimental Crystal Structure Determination
2017
Related Article: Antti J. Neuvonen, Tamás Földes, Ádám Madarász, Imre Pápai, and Petri M. Pihko|2017|ACS Catalysis|7|3284|doi:10.1021/acscatal.7b00336
CCDC 1038220: Experimental Crystal Structure Determination
2015
Related Article: Minna Kortelainen, Aku Suhonen, Andrea Hamza, Imre Pápai, Elisa Nauha, Sanna Yliniemelä-Sipari, Maija Nissinen, Petri M. Pihko|2015|Chem.-Eur.J.|21|9493|doi:10.1002/chem.201406521
CCDC 1003178: Experimental Crystal Structure Determination
2014
Related Article: Mikko V. Leskinen , Ádám Madarász , Kai-Tai Yip , Aini Vuorinen , Imre Pápai , Antti J. Neuvonen , and Petri M. Pihko|2014|J.Am.Chem.Soc.|136|6453|doi:10.1021/ja501681y
CCDC 1038217: Experimental Crystal Structure Determination
2015
Related Article: Minna Kortelainen, Aku Suhonen, Andrea Hamza, Imre Pápai, Elisa Nauha, Sanna Yliniemelä-Sipari, Maija Nissinen, Petri M. Pihko|2015|Chem.-Eur.J.|21|9493|doi:10.1002/chem.201406521
CCDC 1901895: Experimental Crystal Structure Determination
2023
Related Article: Antti J. Neuvonen, Dimitris Noutsias, Filip Topić, Kari Rissanen, Tamás Földes, Imre Pápai, Petri M. Pihko|2019|J.Org.Chem.|84|15009|doi:10.1021/acs.joc.9b01980
CCDC 1003179: Experimental Crystal Structure Determination
2014
Related Article: Mikko V. Leskinen , Ádám Madarász , Kai-Tai Yip , Aini Vuorinen , Imre Pápai , Antti J. Neuvonen , and Petri M. Pihko|2014|J.Am.Chem.Soc.|136|6453|doi:10.1021/ja501681y
CCDC 1901899: Experimental Crystal Structure Determination
2023
Related Article: Antti J. Neuvonen, Dimitris Noutsias, Filip Topić, Kari Rissanen, Tamás Földes, Imre Pápai, Petri M. Pihko|2019|J.Org.Chem.|84|15009|doi:10.1021/acs.joc.9b01980
CCDC 1901897: Experimental Crystal Structure Determination
2023
Related Article: Antti J. Neuvonen, Dimitris Noutsias, Filip Topić, Kari Rissanen, Tamás Földes, Imre Pápai, Petri M. Pihko|2019|J.Org.Chem.|84|15009|doi:10.1021/acs.joc.9b01980
CCDC 1901898: Experimental Crystal Structure Determination
2023
Related Article: Antti J. Neuvonen, Dimitris Noutsias, Filip Topić, Kari Rissanen, Tamás Földes, Imre Pápai, Petri M. Pihko|2019|J.Org.Chem.|84|15009|doi:10.1021/acs.joc.9b01980
CCDC 1973339: Experimental Crystal Structure Determination
2020
Related Article: Imre Pápai, Petri M. Pihko, Juha H. Siitonen, Dániel Csókás|2020|Synlett|31|1581|doi:10.1055/s-0040-1707201
CCDC 1038216: Experimental Crystal Structure Determination
2015
Related Article: Minna Kortelainen, Aku Suhonen, Andrea Hamza, Imre Pápai, Elisa Nauha, Sanna Yliniemelä-Sipari, Maija Nissinen, Petri M. Pihko|2015|Chem.-Eur.J.|21|9493|doi:10.1002/chem.201406521
CCDC 1038223: Experimental Crystal Structure Determination
2015
Related Article: Minna Kortelainen, Aku Suhonen, Andrea Hamza, Imre Pápai, Elisa Nauha, Sanna Yliniemelä-Sipari, Maija Nissinen, Petri M. Pihko|2015|Chem.-Eur.J.|21|9493|doi:10.1002/chem.201406521
CCDC 1038215: Experimental Crystal Structure Determination
2015
Related Article: Minna Kortelainen, Aku Suhonen, Andrea Hamza, Imre Pápai, Elisa Nauha, Sanna Yliniemelä-Sipari, Maija Nissinen, Petri M. Pihko|2015|Chem.-Eur.J.|21|9493|doi:10.1002/chem.201406521
CCDC 1038218: Experimental Crystal Structure Determination
2015
Related Article: Minna Kortelainen, Aku Suhonen, Andrea Hamza, Imre Pápai, Elisa Nauha, Sanna Yliniemelä-Sipari, Maija Nissinen, Petri M. Pihko|2015|Chem.-Eur.J.|21|9493|doi:10.1002/chem.201406521
CCDC 1901893: Experimental Crystal Structure Determination
2023
Related Article: Antti J. Neuvonen, Dimitris Noutsias, Filip Topić, Kari Rissanen, Tamás Földes, Imre Pápai, Petri M. Pihko|2019|J.Org.Chem.|84|15009|doi:10.1021/acs.joc.9b01980
CCDC 1901896: Experimental Crystal Structure Determination
2023
Related Article: Antti J. Neuvonen, Dimitris Noutsias, Filip Topić, Kari Rissanen, Tamás Földes, Imre Pápai, Petri M. Pihko|2019|J.Org.Chem.|84|15009|doi:10.1021/acs.joc.9b01980