Article
Chemistry, Organic
Dmitri Trubitson, Jevgenija Martonova, Marina Kudrjasova, Kristin Erkman, Ivar Jarving, Tonis Kanger
Summary: An efficient enantioselective organocatalytic method has been developed for the synthesis of N-alkylated indoles with alpha-branched alkyl substituents from unsaturated indolyl ketones via a Michael addition. The resulting products exhibit high enantioselectivities and good yields, with tolerance towards various nucleophiles and substitution patterns of the indole ring. Both electron-withdrawing and electron-donating substituents can be accommodated at any position of the heteroaromatic ring.
Article
Chemistry, Organic
Noboru Hayama, Yusuke Kobayashi, Yoshiji Takemoto
Summary: This review summarizes the first catalytic asymmetric Michael addition of heteroatomic nucleophiles to alpha,beta-unsaturated carboxylic acids. Hybrid catalysts are designed to activate the unsaturated carboxylic acids, leading to synthetic applications to biologically active compounds. The mechanistic consideration of multicomponent borate complexes is also discussed in this work.
Article
Chemistry, Organic
Rayhan G. Biswas, Sumit K. Ray, Rajshekhar A. Unhale, Vinod K. Singh
Summary: A bifunctional urea catalyzed cascade reaction of 5-alkenyl thiazolones and monofluorinated beta-diketones, derived from quinine, has been developed, yielding fluorine containing 4-acyloxy thiazoles with high yields and good diastereo- and excellent enantioselectivities. Synthetic transformations, including the synthesis of 4-hydroxy thiazoles, have been successfully demonstrated.
Article
Chemistry, Multidisciplinary
Shou-Shan Yang, Ying-Zheng Ren, Yu-Yu Guo, Guang-Fen Du, Zhi-Hua Cai, Lin He
Summary: An organic superbase-catalyzed aminocarbonylation reaction of alpha,beta-unsaturated ketones was reported, leading to the synthesis of alpha-siloxyamides or alpha-hydroxyamides in good yields.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Chemistry, Organic
Patricia B. Momo, Eduardo F. Mizobuchi, Radell Echemendia, Isabel Baddeley, Matthew N. Grayson, Antonio C. B. Burtoloso
Summary: Enantioselective sulfa-Michael additions to alpha,beta-unsaturated diazocarbonyl compounds have been developed using quinine-derived squaramide as the catalyst. This method allows the formation of C-S bonds with high stereoselectivity for alkyl and aryl thiols. The synthesis of 22 examples showed enantiomeric ratios up to 97:3 and reaction yields up to 94%. Density functional theory (DFT) calculations were used to determine the mechanism and origins of enantioselectivity.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Alpa Y. Dave, Akanksha Mishra, Mrinal Talukdar, Eeshwaraiah Begari
Summary: By using reusable and low toxic eucalyptol as a green solvent, and Fe(OTs)(3)center dot 6H(2)O as green catalyst for the Michael addition reaction of indoles to alpha,beta-unsaturated ketones and nitrostyrene, the methodology offers broad substrate scope and excellent yields (up to 90%) in short reaction times.
Article
Chemistry, Organic
Hiroki Murakami, Ayano Yamada, Kenichi Michigami, Yoshiji Takemoto
Summary: A novel method has been developed in this study for controlling carbonyl alpha-chirality and functionalizing beta-position through the conjugate addition-asymmetric protonation (CAAP) of alpha,beta-unsaturated carboxylic acids using chiral thiourea-amino boronic acid hybrid catalysts. This method is also applied in the asymmetric synthesis of biologically active compounds.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Tianyi Zhang, Yuji Nishiura, Alexander Q. Cusumano, Brian M. Stoltz
Summary: A general method for the asymmetric conjugate addition of arylboronic acids to beta-alkyl/aryl alpha,beta-unsaturated lactams has been reported, which enables the high-yielding and enantioselective synthesis of chiral beta,beta-disubstituted lactams.
Article
Chemistry, Multidisciplinary
Jiaming Liu, Shang Gao, Evangelos Miliordos, Ming Chen
Summary: Cu-catalyzed highly stereoselective and enantiodivergent syntheses of (Z)- or (E)-beta,?-unsaturated ketones from 1,3-butadienyl silanes are developed. The nature of the silyl group of the dienes has a significant impact on the stereo- and enantioselectivity of the reactions. The reactions result in the formation of (Z)-beta,?-unsaturated ketones with excellent enantioselectivities and high Z-selectivities or (E)-beta,?-unsaturated ketones with high optical purities and excellent E-selectivities, depending on the silyl group used.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Zhuang Ni, Ran Sun, Jihong Wu, Chao Xu, Jinwen Huang, Fanhong Wu
Summary: The novel indium-mediated difluoroalkylation of iododifluoromethyl ketones with alpha, beta-unsaturated ketones provides a significant route to access 1,2-addition product with excellent regioselectivity. This method has a wide substrate scope, high efficiency, and mild reaction conditions. Furthermore, it can be applied to the synthesis of difluoro derivatives of biologically active molecules containing unsaturated ketone structures, serving as potentially valuable fluorinated intermediates in drug discovery.
Article
Chemistry, Multidisciplinary
Jiaming Liu, Shang Gao, Evangelos Miliordos, Ming Chen
Summary: Highly stereoselective and enantiodivergent syntheses of (Z)- or (E)-beta,gamma-unsaturated ketones from 1,3-butadienyl silanes using Cu catalysts have been developed. The nature of the silyl group of the dienes significantly affects the stereo- and enantioselectivity of the reactions, resulting in the formation of different chiral and stereoselective products.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Saideh Rajai-Daryasarei, Mir Sadra Hosseini, Saeed Balalaie
Summary: A novel and practical method for accessing saturated ketones from unsaturated ketone derivatives using a CS2/t-BuOK system in dimethyl sulfoxide (DMSO) is presented. The in situ generation of xanthate salt through the reaction of carbon disulfide and potassium tert-butoxide is crucial for this transformation. Deuterium-labeling experiments showed that DMSO can act as a hydrogen donor.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Muneer-Ul-Shafi Bhat, Majid Ahmad Ganie, Bhahwal Ali Shah
Summary: A metal-free approach for tunable 1,2-difunctionalization of terminal alkynes, involving tandem installation of C-C and C-S bonds, has been developed. The key factor enabling this approach is the use of acetic acid as an acyl source to synthesize beta-substituted alpha,beta-unsaturated ketones. The reaction at different temperatures results in regioselective acylation at the terminal carbon and the more substituted carbon of the alkynes respectively.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Miguel Espinosa, Antonio Iborra-Torres, Amparo Sanz-Marco, Gonzalo Blay, Luz Cardona, Isabel Fernandez, Jose R. Pedro
Summary: Magnesium (II)-BOX complexes catalyze the enantioselective Michael addition of malonates to beta-trifluoromethyl enones and their N-sulfonyl imines to give ketones or (E)-enamines bearing a trifluoromethylated stereogenic center, respectively, with good yields and high enantiomeric excesses. The magnesium complexes exhibit higher activity and stereoselectivity than zinc and copper analogues in these reactions.
Article
Biochemistry & Molecular Biology
Max Sauerland, Ralf Mertes, Chiara Morozzi, Aimee L. Eggler, Luke F. Gamon, Michael J. Davies
Summary: Humans are exposed to ABuCs from smoke and exhaust fumes, with varying reactivity towards different Cys residues. Acrolein shows the highest reactivity, while dimethylfumarate reacts readily with protein Cys residues, particularly Cys151 on Keap-1. Steric/electronic interactions play a more important role than Cys ionization in the reactions of crotonaldehyde, dimethylfumarate, and cyclohex-1-en-2-one with Cys residues.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Callum Prentice, James Morrison, Andrew D. Smith, Eli Zysman-Colman
Summary: The donor-acceptor thermally activated delayed fluorescent compounds DiKTa and Mes(3)DiKTa were found to have comparable or better product yields than 4CzIPN in a range of photocatalytic reactions. Among them, DiKTa stands out due to its lower cost, making it a valuable addition to any chemist's collection of photocatalysts.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Grant J. Sherborne, Paul Kemmitt, Callum Prentice, Eli Zysman-Colman, Andrew D. Smith, Charlene Fallan
Summary: This study developed a light-mediated cyclisation method for the selective synthesis of tetrahydroquinolines or quinoline derivatives. The method is efficient, atom economical, and tolerant to functional groups, including azaarene-bearing substrates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Angeliki Giannoulis, Katrin Ackermann, Alexey Bogdanov, David B. B. Cordes, Catherine Higgins, Joshua Ward, Alexandra M. Z. Slawin, James E. E. Taylor, Bela E. E. Bode
Summary: Nitroxides, a unique class of persistent radicals, have a wide range of applications, from spin probes to polarizing agents. This study focuses on the synthesis of pyrroline-based nitroxide radicals and compares two possible synthetic routes for forming two key intermediates. The synthesized compounds were characterized using X-ray crystallography and their electronic communication was quantified using Continuous Wave Electron Paramagnetic Resonance (CW-EPR). This research expands the repertoire of mono- and bis-nitroxides and paves the way for studying quantum coherence effects and using them as polarizing agents.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Organic
Yihong Wang, Claire M. M. Young, David B. B. Cordes, Alexandra M. Z. Slawin, Andrew D. D. Smith
Summary: The isothiourea-catalyzed formal [2+ 2] cycloaddition of C(1)-alkyl and C(1)-unsubstituted ammonium enolates with beta- and alpha,beta-substituted trifluoromethylenones has been developed. The reaction exhibited preferential [2 + 2]-cycloaddition over the alternative [4 + 2]-cycloaddition, resulting in beta-lactones with excellent diastereo- and enantioselectivity. The regioselectivity of the reaction was determined by the substituents on both reactants.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
James Harnedy, Hussain A. Maashi, Albara A. M. A. El Gehani, Matthew Burns, Louis C. Morrill
Summary: Here, an electrochemical approach is presented for the deconstructive functionalization of cycloalkanols, utilizing alcohols, carboxylic acids, and N-heterocycles as nucleophiles. The method is demonstrated to work on various cycloalkanol substrates, with different ring sizes and substituents, resulting in useful remotely functionalized ketone products (36 examples). Additionally, the method is scaled up to gram scale using single-pass continuous flow, showing increased productivity compared to batch processing.
Article
Chemistry, Multidisciplinary
Alastair J. Nimmo, Jacqueline Bitai, Claire M. Young, Calum McLaughlin, Alexandra M. Z. Slawin, David B. Cordes, Andrew D. Smith
Summary: This study demonstrates an unusual reversible Michael addition reaction, using an isothiourea as a Lewis base catalyst, which produces stereoselective products. The basicity of the reaction conditions and the reactivity of the catalyst affect the selectivity of the products. By combining the reversible Michael addition with a crystallisation-induced diastereomer transformation, high yields and stereocontrol of the products can be achieved.
Article
Chemistry, Multidisciplinary
Albara A. M. A. El Gehani, Hussain A. Maashi, James Harnedy, Louis C. Morrill
Summary: This review summarises recent advances (2012-present) in electrochemical approaches for generating and utilizing alkoxy radicals. It discusses the application of these radicals in various transformations, including reaction mechanisms and limitations, and highlights future challenges in sustainable synthesis.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Callum Prentice, Alice E. E. Martin, James Morrison, Andrew D. D. Smith, Eli Zysman-Colman
Summary: The key intramolecular [2 + 2] photochemical cycloaddition step in the synthesis of dimethyl cubane-1,4-dicarboxylate is achieved using substoichiometric amounts of benzophenone as a photosensitizer. The reaction proceeds through a Dexter energy transfer process between the triplet excited state of benzophenone and a known cubane precursor diene. The use of the inexpensive and readily available benzophenone as a photosensitizer allows for the use of lower energy light compared to traditional photochemical processes.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Organic
Grant J. Sherborne, Coura Diene, Paul Kemmitt, Andrew D. Smith
Summary: The preparation of bridged benzo-[1,5]-oxazocines and benzo-[1,4]-diazepines from simple starting materials was demonstrated. The reaction involves a one-pot condensation/6 pi electrocyclization followed by an intramolecular trapping step to obtain bridged seven- and eight-membered products. The use of specific aldehydes results in stable zwitterionic structures that undergo diastereoselective reduction under hydrogenative conditions. A similar cyclization/hydrogenation pathway with excellent diastereoselectivity was also observed.
Article
Chemistry, Multidisciplinary
Ding Yuan, Alister S. Goodfellow, Kevin Kasten, Zhuan Duan, Tengfei Kang, David B. Cordes, Aidan P. Mckay, Michael Buhl, Gregory R. Boyce, Andrew D. Smith
Summary: This study demonstrates the enantioselective conjugate addition of carbo- and heterocyclic alpha-substituted beta-ketoesters to alpha,beta-unsaturated aryl esters using HyperBTM as a catalyst. Divergent diastereoselectivity is observed depending on the substituents of the beta-ketoesters, but both cyclopentanone-derived and indanone-derived beta-ketoesters generate desired products with high selectivity.
Article
Chemistry, Organic
Miguel A. Valle-Amores, Claudia Feberero, Ana Martin-Somer, Sergio Diaz-Tendero, Andrew D. Smith, Alberto Fraile, Jose Aleman
Summary: In this study, a highly enantioselective organocatalyzed [3 + 2] cycloaddition reaction between furanone derivatives and azomethine ylides was presented. The success of this reaction is attributed to intramolecular hydrogen bond activation and the formation of highly multifunctional bicyclic adducts with five stereogenic centers. The reaction also achieved a highly efficient kinetic resolution of butenolides, leading to the formation of furan-2(5H)-ones and furo[3,4-c]pyrrolidinones with high enantioselectivities. Quantum chemistry calculations revealed the crucial role of hydrogen bonding in promoting facial discrimination and achieving a highly selective kinetic resolution.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Callum Prentice, James Morrison, Eli Zysman-Colman, Andrew D. Smith
Summary: The recently reported organic multi-resonant thermally activated delayed fluorescence (MR-TADF) photocatalyst DiKTa enables the modular synthesis of 1,4-diketones under mild and metal-free conditions. The reaction proceeds via a three-component relay process in the presence of an N-heterocyclic carbene (NHC) organocatalyst.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Alex C. Seastram, Mishra Deepak Hareram, Thomas M. B. Knight, Louis C. Morrill
Summary: An electrochemical method for the azidocyanation of alkenes via 1,4-nitrile migration has been developed. The method is applicable to various alkene containing cyanohydrins and provides access to a broad range of synthetically useful 1,2-azidonitriles. The methodology has also been extended to alkene sulfonylcyanation and the synthesis of a trifunctionalized hexanenitrile.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Jerson E. Lapetaje, Claire M. Young, Chang Shu, Andrew D. Smith
Summary: The isothiourea-catalyzed formal enantioselective conjugate addition of 2-hydroxybenzophenone imine derivatives to alpha,beta-unsaturated para-nitrophenyl esters has been developed, producing a range of beta-imino ester and amide derivatives in moderate to good isolated yields with excellent enantioselectivity. Electron-withdrawing substituents within the alpha,beta-unsaturated ester component are required for good product yield.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Roberto del Rio-Rodriguez, Matthew T. Westwood, Marina Sicignano, Martin Juhl, Jose A. Fernandez-Salas, Jose Aleman, Andrew D. Smith
Summary: This study combines the photocatalytic generation of alpha-amino radicals with chiral isothiourea derived alpha,beta-unsaturated acyl ammonium intermediates. The reaction proceeds via a [3+2] radical-polar crossover mechanism to generate gamma-lactams with good yields and enantioselectivities. The enantioselective radical conjugate addition was carried out under batch and flow conditions.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Faiza Diaba, Gisela Trenchs
Summary: The first violet light-mediated synthesis of gamma- and delta-lactams from N-alkenyl trichloroacetamides is reported in this paper. The reactions are conducted in tetrahydrofuran or 2-methyltetrahydrofuran as the sole solvent without catalysts or additives, under non-anhydrous conditions in an air atmosphere where the solvent serves as the radical initiator.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Feroze Hussain, Sajjad Ahmed, Ashiq Hussain Padder, Qazi Naveed Ahmed
Summary: This study reports a novel and efficient one-pot synthesis method for mixed phosphorotrithioates, which does not require supplementary additives and shows broad applicability.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Hyunjin Oh, Ikyon Kim
Summary: A new 1,2,4-triazole-pyrrolo[1,2-a]pyrazine hybrid system, 6-acylpyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, was synthesized using a catalyst-free method. This method involved sequential exposure of pyrrole-2-carbonitrile-derived substrates to DMF-DMA and acyl hydrazide, resulting in the formation of acylated pyrazine and 1,2,4-triazole rings, enabling the installation of various substituents at specific positions on the core skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Ming Yan, Si-fan Wang, Yong-po Zhang, Jin-zhong Zhao, Zhuo Tang, Guang-xun Li
Summary: Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. The reaction allows for the gram-scale preparation of sulfinamides and the one-pot synthesis of various sulfonyl amides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Farzaneh Bandehali-Naeini, Zahra Tanbakouchian, Noushin Farajinia-Lehi, Nicolas Mayer, Morteza Shiri, Martin Breugst
Summary: Two tandem catalytic systems were developed for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts. Different maleimide structures can be synthesized using either Pd or Cu catalysis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Tanya Raghava, Anjan Chattopadhyay, Subhadeep Banerjee, Nivedita Sarkar
Summary: Amine substitution of two ortho fluorine atoms of tetrafluoroterephthalonitrile through SNAr chemistry is easily achievable. But further fluorine substitution is only possible under forcing conditions, yielding valuable fluorophores for bioimaging.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Review
Chemistry, Organic
Anju Chadha, Santosh Kumar Padhi, Selvaraj Stella, Sowmyalakshmi Venkataraman, Thangavelu Saravanan
Summary: Alcohol dehydrogenases are enzymes that use cofactors for oxidation or reduction reactions of alcohols or carbonyl compounds. They are utilized in green chemistry and have applications in the production of pharmaceuticals. Recombinant enzymes have solved the challenge of producing purified enzymes in large quantities. Engineered alcohol dehydrogenases have been used in asymmetric synthesis in industry. Various methods have been established for regenerating expensive cofactors to make the enzymatic process more efficient and economically viable.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)