Article
Chemistry, Physical
Viktoria Kozma, Gyorgy Szollosi
Summary: In this study, asymmetric Michael additions of 1,3-dicarbonyl compounds to N-substituted maleimides were carried out using primary amine-(thio)phosphoramide bifunctional chiral organocatalysts derived from optically pure C-2-symmetric 1,2-diamines. The results show that the addition of ethyl 2-fluoroacetoacetate using the thiophosphoramide catalyst derived from 1,2-diphenylethane-1,2-diamine afforded succinimides substituted with fluorine bearing quaternary carbon in high yields, good diastereomeric ratios and excellent enantiomeric excesses. The bulkiness of the N-substituent of the maleimide ring influenced mostly the conversions. Additionally, the thiophosphoramide catalyst was found efficient in the addition of ethyl 2-fluoroacetoacetate to beta-nitrostyrenes.
MOLECULAR CATALYSIS
(2022)
Article
Chemistry, Organic
Viera Polackova, Dominika Kristofikova, Boglarka Nemethova, Renata Gorova, Maria Meciarova, Radovan Sebesta
Summary: Bifunctional N-sulfinylureas and thioureas with an appended pyrrolidine unit were synthesized and evaluated as organocatalysts in Michael additions. The N-sulfinyl-urea catalyst was more efficient than the corresponding thiourea, achieving up to 98% ee enantioselectivities for some substrates. The mode of action was elucidated through DFT calculations, confirming a dual activation mode involving enamine activation of aldehydes and hydrogen-bond activation of nitroalkenes.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Zubeda Begum, Haruka Sannabe, Chigusa Seki, Yuko Okuyama, Eunsang Kwon, Koji Uwai, Michio Tokiwa, Suguru Tokiwa, Mitsuhiro Takeshita, Hiroto Nakano
Summary: Simple primary beta-amino alcohols act as efficient organocatalysts in the asymmetric Michael addition of beta-keto esters with nitroalkenes, producing highly pure chiral Michael adducts. The choice of catalyst and reaction temperature determines the enantiomeric outcome of the adducts.
Article
Chemistry, Physical
Fangfang Guo, Jiean Chen, Yong Huang
Summary: Recently, chiral N-heterocyclic carbenes (NHCs) have been established as powerful catalysts for enantioselective bond-forming processes via noncovalent interactions. A bifunctional NHC with an embedded hydrogen-bonding motif has been reported in this study, showing remarkable tolerance of various Michael acceptors in an asymmetric aza-conjugate addition reaction, with catalytic efficiency far exceeding that of the benchmark tertiary amine-thiourea scaffold.
Article
Chemistry, Multidisciplinary
Guanglong Su, Connor J. Thomson, Ken Yamazaki, Daniel Rozsar, Kirsten E. Christensen, Trevor A. Hamlin, Darren J. Dixon
Summary: This study presents an efficient synthesis of enantioenriched hydroquinazoline cores using a novel catalyst, with high yields and enantioselectivities, demonstrating potential industrial applicability. The origin of the enantioselectivity and reactivity enhancement provided by the catalyst has been computationally uncovered.
Article
Chemistry, Multidisciplinary
Maria Sanchez-Rosello, Marcos Escolano, Daniel Gavina, Carlos del Pozo
Summary: The asymmetric intramolecular aza-Michael reaction (IMAMR) is a convenient strategy for generating heterocycles with nitrogen-substituted stereocenters, finding widespread applications in the total synthesis of alkaloids and biologically relevant compounds. Recent developments in asymmetric versions of IMAMR mainly involve the use of organocatalysts, such as chiral imidazolidinones and diaryl prolinol derivatives. The use of N-sulfinyl imines with dual roles has also emerged as a versatile mode for performing the asymmetric IMAMR.
Review
Chemistry, Applied
Yong-Xing Song, Da-Ming Du
Summary: The aza-Michael addition cascade reaction is an important synthetic method for constructing functionalized C-N bonds, widely used in the synthesis of chiral drugs, intermediates, and natural products. This review highlights recent developments in asymmetric synthesis, including various types of aza-Michael addition triggered cascade reactions, reaction mechanisms, and derivatization experiments.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Bing-Syuan Wu, Yu-Wei Chao, Hong-Sing Chen, Cheng-Che Tsai
Summary: This paper presents the desymmetrization of cyclohexadienones through a stereoselective intramolecular aza-Michael addition using a tethered chiral sulfinamide nucleophile. The reaction was facilitated by phase-transfer catalysis and resulted in the formation of various nitrogen-containing bicyclic compounds with high yields up to 93% and diastereomeric ratios exceeding 20:1.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Viktoria Kozma, Zsolt Szakonyi, Gyorgy Szollosi
Summary: This study reveals the structural effects of beta-amino acids on the asymmetric Michael additions, including the impact of substituent bulkiness on selectivity, the beneficial arrangement of functional groups in cis isomers, and the influence of nitrogen substituents on reaction rate and enantioselectivity.
Article
Biochemistry & Molecular Biology
Zoran Glasovac, Luka Baresic, Davor Margetic
Summary: The reaction mechanism of guanidinium chlorides with dimethyl acetylenedicarboxylate in a aza-Michael addition reaction/intramolecular cyclization was investigated using DFT M06-2X and B3LYP computational approaches. The energies of the products were compared with experimental data or product ratios obtained from other methods. The diversity of the products was explained by the formation of different tautomers upon deprotonation. The initial nucleophilic addition was found to be the most energetically demanding step, and the overall reaction was exergonic due to methanol elimination during cyclization.
Article
Chemistry, Organic
Daeil Bae, Jin Won Lee, Do Hyun Ryu
Summary: New bifunctional secondary amine organocatalysts derived from L-proline were synthesized and applied in enantioselective Michael reactions in water, yielding high product yields and stereoselectivity. Investigations on the effect of phenyl group at (R)-C6 in the catalyst were conducted, and the successful formal synthesis of a novel histamine H3 receptor agonist, Sch 50971, demonstrated the synthetic utility of this reaction.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Priti Singh, Santosh Kumar Sahoo, Nerella Sridhar Goud, Baijayantimala Swain, Venkata Madhavi Yaddanapudi, Mohammed Arifuddin
Summary: A protocol has been developed for the synthesis of 2-aryl/heteroaryl-4-quinolones using readily available and affordable starting materials. The reaction, conducted under microwave conditions with a copper catalyst, proceeded with moderate to high yields. The method is characterized by short reaction time, good functional group tolerance, high atom economy, non-toxic byproduct, and no need for special ligands, highlighting its applicability in organic synthesis.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Xiao-Yan Dong, Da-Ming Du
Summary: This paper investigated the organocatalytic asymmetric 1,4-Michael addition reaction of azadienes and alpha-thiocyanoindanones, successfully synthesizing a series of chiral thiocyano compounds. By describing a possible reaction mechanism, it broadens the scope of application of azadiene substrates.
Article
Biochemistry & Molecular Biology
Alper Yildirim, Ufuk Atmaca, Ertan Sahin, Parham Taslimi, Tugba Taskin-Tok, Murat Celik, Ilhami Gulcin
Summary: This article examines the use of oxazolidinones in various applications such as antibiotics and protein synthesis inhibition. The synthesized compounds were found to have potent inhibitory effects on enzymes such as acetylcholinesterase and carbonic anhydrase. Molecular docking and ADMET analysis were conducted to correlate the experimental data.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Applied
Laura A. Bryant, Kenneth Shankland, Hannah E. Straker, Callum D. Johnston, Nicholas R. Lees, Alexander J. A. Cobb
Summary: The article describes a rare organocatalytic intramolecular cyclization of resorcinols with a high enantioselectivity using a specific organocatalyst. The obtained bicyclic resorcinols show excellent utility in the synthesis of cannabinoid-like compounds, and exhibit anticonvulsant activity.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
