Article
Chemistry, Organic
Howard Diaz-Salazar, Eddy I. Jimenez, Wilmer E. Vallejo Narvaez, Tomas Rocha-Rinza, Marcos Hernandez-Rodriguez
Summary: The study analyzed the reactivity of bifunctional squaramides with benzyl-like fragments in a Michael addition reaction, finding that non-cyclic benzyl substituents exhibited better selectivity than chiral phenylethyl analogs. The cyclic substituents showed varying results, with non-chiral tricyclic groups having lower selectivity due to unfavorable orientation of the phenyl group, while chiral 1-tetrahydronaphthyl groups seemed to offer optimal aryl ring disposition. A multivariate linear regression model was used to correlate these trends with the strength of pi contacts and energy required for active conformation adoption. The model suggested that the most selective catalyst incorporating 1-aminotetraline amine could be explained by the phenyl group being in its lowest energy conformation and having a double inductive effect from vicinal alkyl groups, leading to high selectivities across different nucleophiles and electrophiles. Additionally, quantum chemical topology analysis revealed that the transition state to the major enantiomer formed additional hydrogen bonds with the nucleophile and had a stronger association with the electrophile.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Polymer Science
Mithun Kumar Debnath, Wako Oyama, Yuya Ono, Takuya Sugimoto, Rina Watanabe, Naoki Haraguchi
Summary: Polymer microsphere-supported chiral pyrrolidine catalysts were successfully synthesized and applied to asymmetric Michael addition reactions. Detailed investigation revealed that these catalysts exhibited high reactivity and enantioselectivity, and could be reused multiple times without significant loss of activity.
JOURNAL OF POLYMER SCIENCE
(2021)
Article
Chemistry, Organic
Naoki Sakai, Kyohei Kawashima, Masashi Kajitani, Seiji Mori, Takeshi Oriyama
Summary: This study reported the first asymmetric Michael addition of alpha-aminomaleimides as Michael donors to beta-nitrostyrenes using an organocatalyst derived from a Cinchona alkaloid. Density functional theory investigations were crucial for improving the enantioselectivity of the adduct.
Article
Chemistry, Organic
Steeva Sunny, Mohit Maingle, Kapileswar Seth
Summary: The application of bifunctional organocatalysts, specifically squaramides, in organic chemistry has significantly advanced due to their stability, low toxicity, ease of handling, and recoverability. This review article provides a comprehensive report on the fine-tunable bifunctional chiral squaramide-catalyzed sulfa-Michael addition, emphasizing the construction of complex molecular entities with multiple stereocenters. The article also summarizes the progress made in chiral squaramide-catalyzed asymmetric sulfa-Michael addition and subsequent cascade reactions between 2011 and 2022.
Article
Biochemistry & Molecular Biology
Jae Ho Shim, Seok Hyun Cheun, Hyeon Soo Kim, Deok-Chan Ha
Summary: The study utilized thiourea as an organocatalyst to promote enantioselective Michael addition reaction between isobutyraldehydes and maleimides in water, achieving high yield and enantioselectivity. The solvent effect was explained by theoretical calculations suggesting the participation of a hydrogen bond activated CF3 substituent of the catalyst by surrounding water molecules, enabling low catalyst loading in organic reactions of chiral substances for pharmaceutical applications.
Article
Chemistry, Organic
Ming-Hui Xu, Yong-Hai Yuan, Dong-Dong Liang, Xiao-Ming Zhang, Fu-Min Zhang, Yong-Qiang Tu, Ai-Jun Ma, Kun Zhang, Jin-Bao Peng
Summary: A novel spiro-pyrrolidine-derived bifunctional thiourea catalyst has been developed for stereoselective conjugate addition of furfurals to beta,gamma-unsaturated alpha-ketoesters. The rigid spirocyclic framework of the catalyst is essential for highly enantioselective transformation in the asymmetric trienamine catalysis of benzylic C-H functionalization of 5-benzylfurfurals.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Organic
Daiki Ishii, Shin-ichi Hirashima, Kosuke Nakashima, Hiroshi Akutsu, Takaaki Sakai, Yasuyuki Matsushima, Masahiro Kawada, Tsuyoshi Miura
Summary: A new organocatalyst efficiently promotes the asymmetric direct vinylogous conjugate additions of alpha-angelica lactones to benzoyl acrylonitrile derivatives, resulting in products with excellent enantioselectivities. The chiral gamma,gamma-disubstituted gamma-butenolides obtained can be readily transformed to valuable synthetic intermediates.
Article
Chemistry, Organic
Koichi Kodama, Kazuhisa Maruyama, Takuji Hirose
Summary: Chiral 1,3-aminosquaramides derived from cis-2-benzamidocyclohexanecarboxylic acid were synthesized and used as bifunctional organocatalysts for asymmetric Michael addition reaction. The optimized organocatalyst achieved an enantioselectivity of up to 96% in the reaction of 1,3-diketones and 1,3-ketoesters with β-nitrostyrenes. Plausible transition state was proposed based on previous reports and DFT calculations.
Article
Chemistry, Physical
Jae Ho Shim, Seok Hyun Cheun, Hyeon Soo Kim, Deok-Chan Ha
Summary: Michael addition is a significant reaction for synthesizing natural products or complex compounds with biological activities. In this study, a selective Michael addition reaction was achieved by using thiourea as an organic catalyst and double activation mechanism. The reaction exhibited high degree of enantioselectivity and diastereoselectivity, leading to the formation of Michael products with excellent yields.
Article
Chemistry, Physical
Jae Ho Shim, Byung Kook Ahn, Ji Yeon Lee, Hyeon Soo Kim, Deok-Chan Ha
Summary: The study focused on the asymmetric Michael addition of nitroalkenes and cycloketones using (R, R)-1,2-diphenylethylenediamine (DPEN)-based thiourea organocatalyst. The reactions led to the formation of chiral products with high levels of enantioselectivity (76-99% syn ee) and diastereoselectivity (syn/anti = 9/1) with yields ranging from 88-99% depending on the ketone used. The primary amine in DPEN reacted with the ketone to form an enamine, which then underwent 1,4-addition to an alkene for the formation of a new carbon-carbon bond with double activation through hydrogen bonding of the nitro group and thiourea.
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, 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
Hongkun Xu, Xuan Qin, Yaping Zhang, Chuan Wan, Rui Wang, Zhanfeng Hou, Xiaofeng Ding, Hailing Chen, Ziyuan Zhou, Yang Li, Chenshan Lian, Feng Yin, Zigang Li
Summary: The modification and functionalization of peptides play a crucial role in biotechnology and drug development. A highly reactive Michael-type warhead is reported here for the covalent modification of cysteine on peptides and proteins. By incorporating a vinyl group onto a methionine residue, the resulting vinyl sulfonium can be efficiently nucleophilically added by a suitable cysteine residue, leading to the formation of cyclized peptides. This peptide cyclization strategy demonstrates improved cell penetration and stability. Furthermore, a peptide ligand containing vinyl sulfonium can covalently bind to cysteine in the target protein, indicating the potential of vinyl sulfonium as a novel warhead for developing covalent peptide inhibitors.
CHINESE CHEMICAL LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Mahmoud A. Abdelkawy, Christopher Davin, El-Saied A. Aly, Mahmoud A. El-Badawi, Shinichi Itsuno
Summary: Repetitive Mizoroki-Heck (MH) coupling polymerization was employed to synthesize novel chiral polyureas containing cinchona alkaloids in the main chain. Some chiral polyureas were successfully polymerized through self polycondensation to serve as catalysts for the asymmetric Michael addition reaction. Phenolic-based chiral polymers demonstrated high catalytic activity and excellent enantioselectivities as heterogeneous catalysts for the enantioselective Michael reaction, with the ability to be recycled and reused.
Article
Chemistry, Organic
Jakob D. E. Lane, Stuart N. Berry, William Lewis, Junming Ho, Katrina A. Jolliffe
Summary: The study reports the synthesis of diaminomethylenemalononitriles (DMMs) and diaminomethyleneindanediones (DMIs) as dual H-bond donors and their anion binding ability, showing that DMMs have affinity for monovalent anions, while DMIs do not bind monovalent anions under similar conditions.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Fuying Zhu, Yamei Lin
Summary: In this study, a low-metal iron-supported catalyst (Fe20/NC-Mg) was reported for the efficient synthesis of quinoxaline compounds, using water as a solvent and without additional bases. The synergistic effect of FeNx site and Mg (OH)2 nanorods in the catalyst played a key role in achieving high yields (82-91%) in 16 examples. The gram-level synthesis and reusability of the catalysts after four cycles demonstrated its industrial application potential.
Article
Chemistry, Organic
Mikhail Kozlov, Alexey Tyurin, Andrey Dmitrenok, Vyacheslav Rusak, Aleksander Fedorov, Igor Zavarzin, Yulia Volkova
Summary: This study presents a novel and practical synthesis method for phosphorus-substituted 1,3,4-thiadiazolines using phosphorylthioformic acid hydrazides and ketones. The protocol demonstrates operational simplicity, availability of reagents, and tolerance towards different functional groups.
Article
Chemistry, Organic
Jisna Jose, Thomas Mathew
Summary: 2-Cyclopentenone and its derivatives are highly esteemed synthetic intermediates with exceptional utility in organic synthesis. They are favored structural motifs in numerous pharmaceutical drugs and natural products, highlighting their significance. The review discusses the various methods used to synthesize cyclopentenones from 2016 to 2023.
