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Norbert De Kimpe - One of the best experts on this subject based on the ideXlab platform.
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Reactivity of Aziridinium Salts in Different Solvents Unraveled by a Combined Theoretical and Experimental Approach
Topics in Heterocyclic Chemistry, 2014Co-Authors: Hannelore Goossens, Norbert De Kimpe, Saron Catak, Frank De Proft, Paul Geerlings, Michel Waroquier, Dietmar Hertsen, Karen Mollet, Matthias D'hooghe, Veronique Van SpeybroeckAbstract:This chapter focuses on the importance of aziridinium ions as intermediates in organic chemistry. The principal aim is to gain insight into the factors to take into account for the selective synthesis of a variety of functionalized amines via aziridinium salts, such as the nature of the aziridinium ion (ring strain and N- and C-substituents of the aziridine ring), the nucleophile, and the solvent environment. Molecular modeling is used to investigate kinetics, electrostatics, and frontier molecular orbitals of reactions involving intermediate aziridinium ions, such as the nucleophilic ring opening of Aziridines, the ring expansion of nitrogen heterocycles, and the ene reactions with triazolinedione. Open image in new window
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synthesis of γ δ aziridino α amino acid derivatives and their stereoselective ring transformation to 2 aminomethyl 1 aminocyclopropanecarboxylic acid derivatives
European Journal of Organic Chemistry, 2014Co-Authors: Stijn De Brabandere, Sven Mangelinckx, Santosh T Kadam, Yahya Nural, Koen Augustyns, Pieter Van Der Veken, Karl W Tornroos, Norbert De KimpeAbstract:1-Benzyl-2-(bromomethyl)aziridine was successfully substituted with protected glycine esters to afford alkyl 3-(N-benzylaziridin-2-yl)-2-aminopropanoates, as constrained heterocyclic diamino acid derivatives, in good isolated yields. These new Aziridines proved to be excellent building blocks for ring transformation to the corresponding stereochemically defined 2-(aminomethyl)-1-aminocyclopropanecarboxylic acid derivatives, including methyl esters, piperidyl amides, and free carboxylic acids.
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nucleophile directed selective transformation of cis 1 tosyl 2 tosyloxymethyl 3 trifluoromethyl aziridine into Aziridines azetidines and benzo fused dithianes oxathianes dioxanes and thio morpholines
Chemistry: A European Journal, 2013Co-Authors: Sara Kenis, Karl W Tornroos, Guido Verniest, Maaike Reybroeck, Tuyet Anh Dang Thi, Tham Thi Pham, Matthias Dhooghe, Nguyen Van Tuyen, Norbert De KimpeAbstract:A five-step procedure for the synthesis of cis-1-tosyl-2-tosyloxymethyl-3-(trifluoromethyl)aziridine was developed, starting from 1-ethoxy-2,2,2-trifluoroethanol, involving imination, aziridination, ester reduction, hydrogenation, and N-,O-ditosylation steps. Further synthetic elaborations revealed a remarkable difference in the reactivity of cis-1-tosyl-2-tosyloxymethyl-3-(trifluoromethyl)aziridine with respect to aromatic sulfur and oxygen nucleophiles, thus enabling the selective deployment of this versatile substrate as a building block for the synthesis of functionalized Aziridines, azetidines, and benzo-fused dithianes, oxathianes, dioxanes, and (thio)morpholines.
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radical mediated nitrile translocation as the key step in the stereoselective transformation of 2 4 chloro 2 cyanobutyl Aziridines to methyl cis 1 arylmethyl 4 phenylpiperidin 2 yl acetates
Organic and Biomolecular Chemistry, 2012Co-Authors: Karel Vervisch, Karl W Tornroos, Matthias Dhooghe, Norbert De KimpeAbstract:Non-activated 2-(4-chloro-2-cyano-2-phenylbutyl)Aziridines were used as building blocks for the stereoselective synthesis of novel cis-2-cyanomethyl-4-phenylpiperidines via a microwave-assisted aziridine to piperidine ring expansion followed by a radical-induced nitrile translocation through initial formation and subsequent cleavage of intermediate bicyclic iminyl radicals. Furthermore, these 2-(cyanomethyl)piperidines were shown to be eligible substrates for the preparation of methyl cis-(1-arylmethyl-4-piperidin-2-yl)acetates through a Pinner reaction using gaseous HCl in methanol.
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reactivity of activated versus nonactivated 2 bromomethyl Aziridines with respect to sodium methoxide a combined computational and experimental study
Journal of Organic Chemistry, 2011Co-Authors: Hannelore Goossens, Norbert De Kimpe, Matthias Dhooghe, Karel Vervisch, Saron Catak, Sonja Stankovic, Frank De Proft, Paul Geerlings, Michel Waroquier, Veronique Van SpeybroeckAbstract:The difference in reactivity between the activated 2-bromomethyl-1-tosylaziridine and the nonactivated 1-benzyl-2-(bromomethyl)aziridine with respect to sodium methoxide was analyzed by means of DFT calculations within the supermolecule approach, taking into account explicit solvent molecules. In addition, the reactivity of epibromohydrin with regard to sodium methoxide was assessed as well. The barriers for direct displacement of bromide by methoxide in methanol are comparable for all three heterocyclic species under study. However, ring opening was found to be only feasible for the epoxide and the activated aziridine, and not for the nonactivated aziridine. According to these computational analyses, the synthesis of chiral 2-substituted 1-tosylAziridines can take place with inversion (through ring opening/ring closure) or retention (through direct bromide displacement) of configuration upon treatment of the corresponding 2-(bromomethyl)Aziridines with 1 equiv of a nucleophile, whereas chiral 2-substituted 1-benzylAziridines are selectively obtained with retention of configuration (via direct bromide displacement). Furthermore, the computational results showed that explicit accounting for solvent molecules is required to describe the free energy profile correctly. To verify the computational findings experimentally, chiral 1-benzyl-2-(bromomethyl)Aziridines and 2-bromomethyl-1-tosylAziridines were treated with sodium methoxide in methanol. The presented work concerning the reactivity of 2-bromomethyl-1-tosylaziridine stands in contrast to the behavior of the corresponding 1-tosyl-2-(tosyloxymethyl)aziridine with respect to nucleophiles, which undergoes a clean ring-opening/ring-closure process with inversion of configuration at the asymmetric aziridine carbon atom.
Matthias Dhooghe - One of the best experts on this subject based on the ideXlab platform.
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nucleophile directed selective transformation of cis 1 tosyl 2 tosyloxymethyl 3 trifluoromethyl aziridine into Aziridines azetidines and benzo fused dithianes oxathianes dioxanes and thio morpholines
Chemistry: A European Journal, 2013Co-Authors: Sara Kenis, Karl W Tornroos, Guido Verniest, Maaike Reybroeck, Tuyet Anh Dang Thi, Tham Thi Pham, Matthias Dhooghe, Nguyen Van Tuyen, Norbert De KimpeAbstract:A five-step procedure for the synthesis of cis-1-tosyl-2-tosyloxymethyl-3-(trifluoromethyl)aziridine was developed, starting from 1-ethoxy-2,2,2-trifluoroethanol, involving imination, aziridination, ester reduction, hydrogenation, and N-,O-ditosylation steps. Further synthetic elaborations revealed a remarkable difference in the reactivity of cis-1-tosyl-2-tosyloxymethyl-3-(trifluoromethyl)aziridine with respect to aromatic sulfur and oxygen nucleophiles, thus enabling the selective deployment of this versatile substrate as a building block for the synthesis of functionalized Aziridines, azetidines, and benzo-fused dithianes, oxathianes, dioxanes, and (thio)morpholines.
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radical mediated nitrile translocation as the key step in the stereoselective transformation of 2 4 chloro 2 cyanobutyl Aziridines to methyl cis 1 arylmethyl 4 phenylpiperidin 2 yl acetates
Organic and Biomolecular Chemistry, 2012Co-Authors: Karel Vervisch, Karl W Tornroos, Matthias Dhooghe, Norbert De KimpeAbstract:Non-activated 2-(4-chloro-2-cyano-2-phenylbutyl)Aziridines were used as building blocks for the stereoselective synthesis of novel cis-2-cyanomethyl-4-phenylpiperidines via a microwave-assisted aziridine to piperidine ring expansion followed by a radical-induced nitrile translocation through initial formation and subsequent cleavage of intermediate bicyclic iminyl radicals. Furthermore, these 2-(cyanomethyl)piperidines were shown to be eligible substrates for the preparation of methyl cis-(1-arylmethyl-4-piperidin-2-yl)acetates through a Pinner reaction using gaseous HCl in methanol.
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reactivity of activated versus nonactivated 2 bromomethyl Aziridines with respect to sodium methoxide a combined computational and experimental study
Journal of Organic Chemistry, 2011Co-Authors: Hannelore Goossens, Norbert De Kimpe, Matthias Dhooghe, Karel Vervisch, Saron Catak, Sonja Stankovic, Frank De Proft, Paul Geerlings, Michel Waroquier, Veronique Van SpeybroeckAbstract:The difference in reactivity between the activated 2-bromomethyl-1-tosylaziridine and the nonactivated 1-benzyl-2-(bromomethyl)aziridine with respect to sodium methoxide was analyzed by means of DFT calculations within the supermolecule approach, taking into account explicit solvent molecules. In addition, the reactivity of epibromohydrin with regard to sodium methoxide was assessed as well. The barriers for direct displacement of bromide by methoxide in methanol are comparable for all three heterocyclic species under study. However, ring opening was found to be only feasible for the epoxide and the activated aziridine, and not for the nonactivated aziridine. According to these computational analyses, the synthesis of chiral 2-substituted 1-tosylAziridines can take place with inversion (through ring opening/ring closure) or retention (through direct bromide displacement) of configuration upon treatment of the corresponding 2-(bromomethyl)Aziridines with 1 equiv of a nucleophile, whereas chiral 2-substituted 1-benzylAziridines are selectively obtained with retention of configuration (via direct bromide displacement). Furthermore, the computational results showed that explicit accounting for solvent molecules is required to describe the free energy profile correctly. To verify the computational findings experimentally, chiral 1-benzyl-2-(bromomethyl)Aziridines and 2-bromomethyl-1-tosylAziridines were treated with sodium methoxide in methanol. The presented work concerning the reactivity of 2-bromomethyl-1-tosylaziridine stands in contrast to the behavior of the corresponding 1-tosyl-2-(tosyloxymethyl)aziridine with respect to nucleophiles, which undergoes a clean ring-opening/ring-closure process with inversion of configuration at the asymmetric aziridine carbon atom.
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synthesis of 3 methoxyazetidines via an aziridine to azetidine rearrangement and theoretical rationalization of the reaction mechanism
Journal of Organic Chemistry, 2011Co-Authors: Sonja Stankovic, Matthias Dhooghe, Hannelore Goossens, Saron Catak, Michel Waroquier, Veronique Van Speybroeck, Kourosch Abbaspour Tehrani, Pieter Bogaert, Norbert De KimpeAbstract:The synthetic utility of N-alkylidene-(2,3-dibromo-2-methylpropyl)amines and N-(2,3-dibromo-2-methylpropylidene)benzylamines was demonstrated by the unexpected synthesis of 3-methoxy-3-methylazetidines upon treatment with sodium borohydride in methanol under reflux through a rare aziridine to azetidine rearrangement. These findings stand in contrast to the known reactivity of the closely related N-alkylidene-(2,3-dibromopropyl)amines, which are easily converted into 2-(bromomethyl)Aziridines under the same reaction conditions. A thorough insight into the reaction mechanism was provided by both experimental study and theoretical rationalization.
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opposite regiospecific ring opening of 2 cyanomethyl Aziridines by hydrogen bromide and benzyl bromide experimental study and theoretical rationalization
Journal of Organic Chemistry, 2010Co-Authors: Saron Catak, Norbert De Kimpe, Matthias Dhooghe, Michel Waroquier, Toon Verstraelen, Karen Hemelsoet, Andries Van Nieuwenhove, Hyunjoon Ha, Veronique Van SpeybroeckAbstract:Ring opening of 1-arylmethyl-2-(cyanomethyl)Aziridines with HBr afforded 3-(arylmethyl)amino-4-bromobutyronitriles via regiospecific ring opening at the unsubstituted aziridine carbon. Previous experimental and theoretical reports show treatment of the same compounds with benzyl bromide to furnish 4-amino-3-bromobutanenitriles through ring opening at the substituted aziridine carbon. To gain insights into the regioselective preference with HBr, reaction paths have been analyzed with computational methods. The effect of solvation was taken into account by the use of explicit solvent molecules. Geometries were determined at the B3LYP/6-31++G(d,p) level of theory, and a Grimme-type correction term was included for long-range dispersion interactions; relative energies were refined with the meta-hybrid MPW1B95 functional. Activation barriers confirm preference for ring opening at the unsubstituted ring carbon for HBr. HBr versus benzyl bromide ring opening was analyzed through comparison of the electronic structure of corresponding aziridinium intermediates. Although the electrostatic picture fails to explain the opposite regiospecific nature of the reaction, frontier molecular orbital analysis of LUMOs and nucleophilic Fukui functions show a clear preference of attack for the substituted aziridine carbon in the benzyl bromide case and for the unsubstituted aziridine carbon in the HBr case, successfully rationalizing the experimentally observed regioselectivity.
Junliang Zhang - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of Unsaturated N-Heterocycles by Cycloadditions of Aziridines and Alkynes
ACS Catalysis, 2016Co-Authors: Jian-jun Feng, Junliang ZhangAbstract:The unique structure and reactivity of the aziridine ring has attracted the interest of organic chemists for many years. Of these, the cycloaddition of alkynes with Aziridines via C–C bond and C–N bond cleavage is an atom-efficient and convergent approach to the preparation of valuable unsaturated N-heterocycles. In this Perspective, progress in this field is outlined on the basis of the key intermediate involved in the reaction. In addition to the cycloadditions of azomethine ylides generated by carbon–carbon bond cleavage and aziridinium ions and zwitterionic 1,3-dipoles generated by carbon–nitrogen bond cleavage, the new type of cycloadditions of Aziridines and alkynes involving metalla-azetidine intermediates has been highlighted in this short review. The use of methyleneaziridine in the cycloaddition reactions with alkynes is also discussed. Contrary to noncatalytic cycloadditions of Aziridines with alkynes via azomethine ylides or aziridinium ions, the catalytic cycloadditions for synthesis of unsat...
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modular access to the stereoisomers of fused bicyclic azepines rhodium catalyzed intramolecular stereospecific hetero 5 2 cycloaddition of vinyl Aziridines and alkenes
Angewandte Chemie, 2015Co-Authors: Jian-jun Feng, Taoyan Lin, Junliang ZhangAbstract:The first rhodium-catalyzed intramolecular hetero-[5+2] cycloaddition reaction of vinyl Aziridines and alkenes was realized, wherein both internal and terminal alkenes were applicable. With this method, a variety of unique substituted chiral fused bicyclic azepines, bearing multiple contiguous stereogenic centers, were facilely accessed in a straightforward, high-yielding, and highly stereoselective manner under mild reaction conditions. Notably, the E/Z geometry of the CC bonds in the vinyl aziridine-alkene substrates impact the cis/trans stereochemistry of the cycloadducts and up to six stereoisomers could be delivered.
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transfer of chirality in the rhodium catalyzed intramolecular formal hetero 5 2 cycloaddition of vinyl Aziridines and alkynes stereoselective synthesis of fused azepine derivatives
Journal of the American Chemical Society, 2015Co-Authors: Jian-jun Feng, Taoyan Lin, Junliang ZhangAbstract:By taking advantage of vinyl Aziridines as a heteroatom-containing five-atom component in rhodium-catalyzed intramolecular formal hetero-[5 + 2] cycloaddition reactions with alkynes, a highly efficient method for the synthesis of fused azepine derivatives at 30 °C was developed. The reaction has broad substrate scope and tolerates a wide range of functional groups. The chirality of vinyl aziridine-alkyne substrates can be completely transferred to the cycloadducts, representing an atom-economic and enantiospecific protocol for the construction of fused 2,5-dihydroazepines for the first time.
Seijiro Matsubara - One of the best experts on this subject based on the ideXlab platform.
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diastereoselective synthesis of 1 3 oxazolidines via cationic iron porphyrin catalyzed cycloaddition of Aziridines with aldehydes
Organic Letters, 2019Co-Authors: Satoru Teranishi, Kazuki Maeda, Takuya Kurahashi, Seijiro MatsubaraAbstract:An efficient iron porphyrin Lewis acid-catalyzed cycloaddition of Aziridines with aldehydes has been developed to provide oxazolidines with high regio- and diastereoselectivity. The cycloaddition proceeds in toluene with 1 mol % of the iron catalyst at 25 °C. A theoretical study and synchrotron-based X-ray absorption fine structure measurements provided fundamental insights into the aziridine–iron porphyrin complex, which is the key intermediate for the generation of the 1,3-dipole synthon.
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Diastereoselective Synthesis of 1,3-Oxazolidines via Cationic Iron Porphyrin-catalyzed Cycloaddition of Aziridines with Aldehydes
2019Co-Authors: Satoru Teranishi, Kazuki Maeda, Takuya Kurahashi, Seijiro MatsubaraAbstract:An efficient iron porphyrin Lewis acid-catalyzed cycloaddition of Aziridines with aldehydes has been developed to provide oxazolidines with high regio- and diastereoselectivity. The cycloaddition proceeds in toluene with 1 mol % of the iron catalyst at 25 °C. A theoretical study and synchrotron-based X-ray absorption fine structure measurements provided fundamental insights into the aziridine–iron porphyrin complex, which is the key intermediate for the generation of the 1,3-dipole synthon
Nikos Hadjichristidis - One of the best experts on this subject based on the ideXlab platform.
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Organocatalytic Synthesis of Polysulfonamides with Well-Defined Linear and Brush Architectures from a Designed/Synthesized Bis(N‑sulfonyl aziridine)
'American Chemical Society (ACS)', 2021Co-Authors: Linlin Zhu, Ying Wang, Zhen Zhang, Huishan Huang, Nikos HadjichristidisAbstract:We report a new synthetic methodology for polysulfonamides with well-defined linear and brush architectures by organocatalytic polymerizations. A new monomer, bis(2,3-disubstituted N-sulfonyl aziridine), has been rationally designed/synthesized and used in step-growth polymerization with various bisnucleophiles (dicarboxylic acids, diphenols, and dithiols). The branches or cross-linkages derived from the ring-opening polymerization of N-sulfonyl Aziridines are suppressed using this specific bis(aziridine) monomer, resulting in a well-controlled linear polysulfonamide architecture. The synthesized polysulfonamides emit blue fluorescence in solution and exhibit excellent thermal properties with decomposition temperature at 5% weight loss (Td,5%) up to 360.0 °C and glass-transition temperature (Tg) ranging from 62.5 to 199.2 °C. Furthermore, a fast one-pot cascade approach has been developed toward polysulfonamide brush copolymers with a well-controlled grafted chain length
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2 azaallyl anion initiated ring opening polymerization of n sulfonyl Aziridines one pot synthesis of primary amine ended telechelic polyAziridines
Macromolecules, 2019Co-Authors: Ying Wang, Ruhan Yang, Zhunxuan Li, Zhen Zhang, Chuande Wu, Nikos HadjichristidisAbstract:Using the easily accessible 2-azaallyl anions as initiators, the one-pot synthesis of well-defined primary amine-ended telechelic polyAziridines (α-NH2 PAzs) has been achieved through the ring-opening polymerization (ROP) of N-sulfonyl Aziridines followed by hydrolysis of the diphenylketimine moiety (—N═C—Ph2). The 2-azaallyl anions were synthesized from the reaction of diphenylketimine or N-[aryl-methylene]-α-phenylbenzenemethanamine with potassium bis(trimethylsilyl) amide (KHMDS) in situ and used to initiate the ROP of Aziridines leading to well-defined α-(Ph2C═N)-α′-aryl-ω-NH PAzs. Along with the diphenylketimine group (—N═C—Ph2), aryl functionalities, such as pyridine and triphenylphosphine moieties, can also be incorporated to the chain end. Chain extension has been applied for the synthesis of poly(N-sulfonyl aziridine)-block-poly(e-caprolactone) (PAz-b-PCL) block copolymers by utilization of the primary amine end group as initiating sites for the ROP of e-caprolactone catalyzed by tin 2-ethyl hexa...
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2‑Azaallyl Anion Initiated Ring-Opening Polymerization of N‑Sulfonyl Aziridines: One-Pot Synthesis of Primary Amine-Ended Telechelic PolyAziridines
2019Co-Authors: Ying Wang, Ruhan Yang, Zhen Zhang, Wenyi Luo, Nikos HadjichristidisAbstract:Using the easily accessible 2-azaallyl anions as initiators, the one-pot synthesis of well-defined primary amine-ended telechelic polyAziridines (α-NH2 PAzs) has been achieved through the ring-opening polymerization (ROP) of N-sulfonyl Aziridines followed by hydrolysis of the diphenylketimine moiety (NCPh2). The 2-azaallyl anions were synthesized from the reaction of diphenylketimine or N-[aryl-methylene]-α-phenylbenzenemethanamine with potassium bis(trimethylsilyl) amide (KHMDS) in situ and used to initiate the ROP of Aziridines leading to well-defined α-(Ph2CN)-α′-aryl-ω-NH PAzs. Along with the diphenylketimine group (NCPh2), aryl functionalities, such as pyridine and triphenylphosphine moieties, can also be incorporated to the chain end. Chain extension has been applied for the synthesis of poly(N-sulfonyl aziridine)-block-poly(ε-caprolactone) (PAz-b-PCL) block copolymers by utilization of the primary amine end group as initiating sites for the ROP of ε-caprolactone catalyzed by tin 2-ethyl hexanoate (SnOct2). Taking advantage of this synthetic approach, core cross-linked multiarm star (CCS) polymers with an outermost shell having amino and triphenylphosphine functionalities have been synthesized via “arm-first” strategy
