Review
Chemistry, Physical
Mercedes Zurro, Aitor Maestro
Summary: This paper reviews the recent literature on the catalytic methodologies for the derivatization of aza-QM, including organocatalytic and organometallic approaches. The review analyzes various catalytic systems, involving chiral NHC carbenes, phosphoric acids, phosphoramidites, phosphine, copper, and palladium catalysis, showcasing their applicability for the synthesis of a diverse array of N-containing compounds, many of which exhibit biological activity.
Article
Chemistry, Organic
Lu Lei, Yu-Feng Liang, Cui Liang, Jiang-Ke Qin, Cheng-Xue Pan, Gui-Fa Su, Dong-Liang Mo
Summary: A variety of tetrahydroquinoline-fused bicycles with multiple stereocenters are synthesized in good yields with high diastereoselectivity through Cu2O-catalyzed [4 + 2] cycloaddition. Mechanistic studies show that the Cu(i) catalyst facilitates the formation of ao-QMs through a radical process and accelerates the [4 + 2] cycloaddition. The reaction can be easily scaled up and the products obtained can be converted into diverse tetrahydroquinoline scaffolds.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Organic
Xiao-Yu He, Yu-Hong Ma, Qing-Qing Yang, Wen-Jing Xiao
Summary: Aza-ortho-quinone methides are important reactive intermediates with broad applications in synthetic chemistry. The 1,4-elimination of ortho-chloromethyl aniline derivatives has emerged as a novel and powerful method for their generation. This review highlights the recent applications of aza-ortho-quinone methide precursors in annulation reactions to access various biologically important nitrogen-containing heterocycles.
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Organic
Martha C. Mayorquin-Torres, Armando Navarro-Huerta, Mauricio Maldonado-Dominguez, Marcos Flores-Alamo, Braulio Rodriguez-Molina, Martin A. Iglesias-Arteaga
Summary: A series of hybrid dimers with orthogonal steroidal cores bridged by a chroman ketal moiety were obtained through Pd-catalyzed three-component reactions, showing one L-shaped scaffold with large channels. Monte Carlo simulations indicate these voids preferentially allocate n-hexane, suggesting potential applications as selective hosts for small molecules.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Hong Liu, Kai Li, Shengli Huang, Hailong Yan
Summary: This study reports the first isolation and comprehensive characterization of vinylidene orlho-quinone methides (VQMs), demonstrating their significant role in asymmetric catalysis and potential as starting materials.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Xiaochen Tian, Xiaoli Zhang, Xiaohan Hou, Weiwu Ren, Xiaoyang Li, Fei Zhao, Houchao Tao, Yang Wang
Summary: A base-promoted formal [4+1] cycloaddition of ortho- and para-quinone methides with 3-chlorooxindoles has been reported to provide various functionalized 3,2'-tetrahydrofuryl spirooxindoles in high yields under mild conditions. Unexpected reversal in diastereoselectivity was observed in these reactions. Computational studies have revealed the origin of the diastereoselectivity, showing that different configurations of 1,4-addition and 1,6-addition at the oxindole carbanionic center result in different diastereomers. The anti-tumor activity of these structurally unique spirooxindole derivatives has been reported.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Jiaying Sun, Wenxuan Zhang, Ran Song, Daoshan Yang, Jian Lv
Summary: Catalytic direct [4 + 2] cycloaddition reactions and Friedel-Crafts reactions of ortho-alkynylnaphthols with benzofurans have been developed. They afford high yields of functionalized hydrobenzofuro[3,2-b]chromans and hydroarylation products, respectively, with high chemoselectivity.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Adam Mark Palvoelgyi, Florian Ehrschwendtner, Michael Schnuerch, Katharina Bica-Schroeder
Summary: We have successfully developed a photocatalyst- and additive-free radical hydroacylation reaction under mild reaction conditions. By utilizing 4-acyl-Hantzsch ester radical reservoirs, various substrates including Michael acceptors, enones, and para-quinone methides can be reacted. This protocol allows for further derivatizations and can also be extended to unactivated alkenes. Furthermore, the nature of the radical process has been investigated.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Bao-Cheng Wang, Li Rao, Kai-Xin Fang, Bao-Le Qu, Fen-Ya Xiong, Ying Feng, Ying Tan, Liang-Qiu Lu, Wen-Jing Xiao
Summary: Metal-polarized aza-ortho-quinone methides (aza-o-QMs) have been effectively utilized in azaheterocycle synthesis, and a new reaction mode involving transient dearomatized spiroaziridine intermediates has been discovered. This has led to the efficient and flexible divergent synthesis of bis-nitrogen heterocycles through sequential dearomatization-rearomatization reactions. Experimental, theoretical, and cellular evaluations have been conducted to explain the mechanisms, selectivity, and potential medicinal applications of the synthesized compounds.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Applied
Navpreet Kaur, Priyanka Singh, Prabal Banerjee
Summary: An efficient protocol for the synthesis of spiro-imidazolidinone-cyclohexadienones from p-quinone methides and dialkyloxy ureas is reported, showing good functional group tolerance and providing a straightforward method for accessing the desired compounds. Additionally, the debenzylation of spiroimidazolidinones to give N-hydroxycyclic ureas has been demonstrated in follow-up chemistry.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Hai-Qing Wang, Wenjing Ma, Ao Sun, Xin-Yue Sun, Chao Jiang, Yu-Chen Zhang, Feng Shi
Summary: A base-promoted cyclization method has been developed for generating aza-o-quinone methides from N-(o-chloromethyl)aryl amides, which react with azlactones to produce dihydroquinolinone derivatives in good yields (up to 98%). This approach not only advances reactions involving aza-o-quinone methides, but also provides a useful strategy for constructing biologically important dihydroquinolinone frameworks.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Review
Chemistry, Organic
Yu-Hong Ma, Xiao-Yu He, Qing-Qing Yang, Amina Boucherif, Jun Xuan
Summary: This review summarizes recent advancements in organocatalytic asymmetric cycloaddition reactions involving ortho-quinone methides (o-QMs). Organocatalysts have become a privileged class of catalytic systems in asymmetric synthesis, leading to significant achievements worldwide. The review focuses on works published from January 2016 to December 2020, excluding discussions on catalytic systems combining metal catalysts and organocatalysts.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Huaxin Lin, Senling Tang, Yang Pan, Peng Liang, Xiaofeng Ma, Wei Jiao, Huawu Shao
Summary: A new method for the synthesis of 2-aminobenzofurans using Sc(OTf)(3) has been described, utilizing o-QMs as intermediates and providing a straightforward and efficient approach for the construction of the scaffold.
Article
Chemistry, Physical
Guosong Shen, Faqian He, Wansen Xie, Huanchao Gu, Xiaoyu Yang
Summary: Asymmetric diastereodivergent catalysis is an important strategy for accessing different stereoisomers of a molecule. In this study, a new method for the asymmetric diastereodivergent synthesis of chromanes with C2,C3-contiguous tetrasubstituted stereocenters was reported using chiral phosphoric acid catalysts.
Article
Chemistry, Organic
Rupashri Dash, Sudhir Kumar Hota, Sandip Murarka
Summary: We describe an efficient higher order conjugate addition reaction of azauracils to substituted para-quinone methides (p-QMs) mediated by triethylamine, forming previously unknown diarylmethane scaffolds through C-N bond formation. This protocol offers mild conditions, high atom economy, broad scope, and allows convenient access to biologically relevant new chemical entities (NCEs) consisting of p-QM and azauracil hybrids in good to excellent yields.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Applied
Pengzhi Wang, Keegan P. Fitzpatrick, Karl A. Scheidt
Summary: The research presents a method for synthesizing gamma-aryloxyketones via combined NHC/photoredox catalysis, where an α-aryloxymethyl radical is coupled with styrene derivatives and then with an azolium radical to produce the desired products.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Tapas R. Pradhan, Mukti Paudel, Taisiia Feoktistova, Paul Ha-Yeon Cheong, Jin Kyoon Park
Summary: This article describes a highly stereo- and regiocontrolled multicomponent approach for the synthesis of skipped 1,4-dienes decorated with one boryl and two silyl functionalities. The advantages of this method include atom-economy, efficient coupling, and excellent selectivity, and it has been demonstrated to be applicable for various valuable chemical transformations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Samuel M. Smith, Mark D. Greenhalgh, Taisiia Feoktistova, Daniel M. Walden, James E. Taylor, David B. Cordes, Alexandra M. Z. Slawin, Paul Ha-Yeon Cheong, Andrew D. Smith
Summary: This study reports the full scope and limitations of catalytic acylative kinetic resolution of a range of tertiary heterocyclic alcohols using a commercially available Lewis basic isothiourea catalyst. The protocol is highly effective for the synthesis of enantioenriched compounds and a detailed kinetic analysis of the reaction mechanism has been provided.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Hea Jung Park, Claire Louise Boelke, Paul Ha-Yeon Cheong, Do-Hoon Hwang
Summary: Red and near-infrared (NIR) phosphorescent double-decker dinuclear Pt(II) complexes were synthesized and characterized for their structural and spectroscopic properties. The complexes were found to exist as racemic mixtures with different intramolecular Pt-Pt distances controlled by the electronic characteristics of the C^N ligands. The Pt-Pt distances significantly influenced the band gap energies and corresponding emission wavelengths of the complexes, suggesting a method to finely tune the phosphorescence of these Pt(II) complexes.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Sagar Arepally, Ponnusamy Nandhakumar, Gisela A. Gonzalez-Montiel, Alina Dzhaparova, Gyeongho Kim, Ahyeon Ma, Ki Min Nam, Haesik Yang, Paul Ha-Yeon Cheong, Jin Kyoon Park
Summary: Electrochemical access to organometallic redox reagents allows for selective synthesis of various benzene derivatives with different regioisomers. A unified electrochemical strategy is presented for the selective cyclotrimerization of terminal alkynes to access both 1,3,5- and 1,2,4-regioisomeric trisubstituted benzene derivatives. The regiocontrol can be switched by the addition of a carboxylic acid.
Article
Chemistry, Multidisciplinary
Seunghwan Byun, Abdikani Omar Farah, Henry R. Wise, Andrew Katchmar, Paul H. -Y. Cheong, Karl A. Scheidt
Summary: This study reveals an approach for the copper-catalyzed synthesis of enantioenriched amides bearing an alpha-stereogenic center. The addition of an allyl copper species to an isocyanate allows access to alpha-substituted chiral amides in high yields and high-to-excellent enantioselectivities. The utility of alpha-vinyl beta-boryl amides in synthesis is highlighted by the diversification of products to afford highly useful scaffolds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Joshua L. Zhu, Cullen R. Schull, Anthony T. Tam, Angel Renteria-Gomez, Achyut Ranjan Gogoi, Osvaldo Gutierrez, Karl A. . Scheidt
Summary: Stable acyl azolium salts can undergo intermolecular HAT reaction upon LED irradiation to afford ketones.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Kyungsup Lee, Jordan L. Harper, Tae Hyeon Kim, Hee Chan Noh, Dongwook Kim, Paul Ha-Yeon Cheong, Phil Ho Lee
Summary: Regiodivergent transition metal-catalyzed B(4)- and C(1)-selenylation reactions of o-carboranes have been demonstrated, with Ru(ii)-catalysis selectively generating B(4)-selenylated o-carboranes and Pd(ii) catalysis exclusively providing C(1)-selenylated o-carboranes. DFT studies revealed the contrasting mechanisms of these reactions.
Article
Chemistry, Medicinal
Dalton R. Kim, Meghan J. Orr, Ada J. Kwong, Kristine K. Deibler, Hasan H. Munshi, Cory Seth Bridges, Taylor Jie Chen, Xiaoyu Zhang, H. Daniel Lacorazza, Karl A. Scheidt
Summary: The mitogen-activated protein kinase (MAPK) signaling cascade is essential for regulating various cellular activities across eukaryotes. In this study, a novel class of irreversible MAP2K7 inhibitors was designed and synthesized, with promising in vitro potency and selectivity, as well as favorable cellular activity. These compounds show potential as powerful tools for studying pediatric T cell acute lymphoblastic leukemia (T-ALL).
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Qiupeng Peng, Achyut Ranjan Gogoi, Osvaldo Gutierrez, Angel Renteria-Gomez, Karl A. Scheidt
Summary: This article reports a divergent process for the synthesis of α-hydroxy/amino ketones or β-keto-phosphonates through a light-induced coupling of activated carboxylic acids and alcohols/amines via single-electron chemistry. This process enables new carbon-carbon bond formation using a phosphorous linchpin strategy.
Article
Chemistry, Multidisciplinary
Seunghwan Byun, Meemie U. Hwang, Henry R. Wise, Anna V. Bay, Paul H. -Y. Cheong, Karl A. Scheidt
Summary: This study explores the enantioselective carbene-catalyzed radical-radical coupling reaction of acyl imidazoles and racemic Hantzsch esters, leading to the synthesis of chiral alpha-aryl aliphatic ketones. The method shows potential application in pharmaceutical synthesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Michael J. Rourke, Matthew J. McGill, Daniel Yang, Emelia J. Farnam, Joshua L. Zhu, Karl A. Scheidt
Summary: Potassium trifluoroborates have been widely used as coupling partners in organic synthesis, and also as radical precursors to generate carbon-centered radicals under oxidative conditions. These versatile reagents have found new applications in photoredox catalysis, including radical substitution, conjugate-addition reactions, and transition-metal dual catalysis. In addition, this photomediated redox-neutral process enables radical-radical coupling with persistent radicals in the absence of metals, which remains to be fully explored.
Article
Chemistry, Multidisciplinary
Jing Cao, Joshua L. Zhu, Karl A. Scheidt
Summary: In this study, a cerium-catalyzed acylation reaction was reported, which can acylate unactivated C(sp3)-H bonds under mild and operationally-friendly conditions. The reaction shows excellent generality, accommodating a wide range of feedstock chemicals, and facilitating the late-stage functionalization of pharmaceuticals.
Article
Chemistry, Organic
Suvajit Koley, Kaylee T. Cayton, Gisela A. Gonzalez-Montiel, M. Ramu Yadav, Douglas L. Orsi, Andrew J. Intelli, Paul Ha-Yeon Cheong, Ryan A. Altman
Summary: A Cu-based catalyst system is used to couple gem-difluoroalkenes with phenols under aerobic conditions, resulting in the formation of alpha,alpha-difluorinated-alpha-phenoxyketones, a previously unstudied hybrid fluorinated functional group. Computational predictions and experimental evidence suggest that the phenoxy-substituted fluorinated ketone favors the sp(3)-hybridized hydrate form over the nonether variant, and that modulation of the ketone's electronic character promotes hydrate formation. This study is significant as it provides insights into the covalent inhibition of proteases and other enzymes, and also offers possibilities for accessing other useful fluorinated functional groups.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Anna Bay, Karl A. Scheidt
Summary: Chemists have used the polarity reversal reactivity of N-heterocyclic carbenes (NHCs) to build key chemical bonds, and their redox properties enable the synthesis of stable radical species. This has greatly contributed to the field of synthetic chemistry and the revival of radical chemistry.
TRENDS IN CHEMISTRY
(2022)