Article
Chemistry, Organic
Hualing He, Xiaoxue Tang, Yang Cao, Jon C. Antilla
Summary: A catalytic enantioselective reduction of alpha-trifluoromethylated imines has been developed using a BINOL-derived boro-phosphate as catalyst and catecholborane as hydride source. This method provides an efficient route to prepare synthetically useful chiral alpha-trifluoromethylated amines in high yields and excellent enantioselectivities under mild conditions (up to 98% yield and 96% ee).
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jin Huang, Guang-xun Li, Gao-feng Yang, Ding-qiang Fu, Xiao-kang Nie, Xin Cui, Jin-zhong Zhao, Zhuo Tang
Summary: N-Substituted tetrahydroquinoxalines were efficiently synthesized in good yield and enantioselectivity using readily available substrates. The reaction involves a regioselective Heyns rearrangement/enantioselective transfer hydrogenation in one pot, and both the substrate scope and reaction mechanism were systematically investigated.
Article
Chemistry, Multidisciplinary
Vasco Corti, Riccardo Riccioli, Ada Martinelli, Sofia Sandri, Mariafrancesca Fochi, Luca Bernardi
Summary: This study presents a one-pot approach to enantioenriched beta-branched beta-trifluoromethyl alpha-amino acid derivatives, grounded on the reduction - ring opening of Erlenmeyer-Plochl azlactones. The configurations of the two chirality centers of the products are established during each of the two catalytic steps, enabling a stereodivergent process.
Article
Thermodynamics
Irina V. Andreeva, Sergey P. Verevkin
Summary: This study systematically investigated the thermodynamic properties of substituted acetophenones using experimental measurements and structure-property correlations. Additionally, a quantum chemical method for estimating the enthalpies of formation of substituted acetophenones was validated.
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
(2022)
Article
Chemistry, Organic
Ye Zheng, Martin Wills
Summary: In this study, the reduction of Bpin-containing ketones by asymmetric transfer hydrogenation (ATH) was investigated. It was found that the reaction products exhibited high ee when the Bpin group was in the para- or meta-position.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
Kaixia Jian, Bingnan Li, Shuxian Zhu, Qingqing Xuan, Qiuling Song
Summary: In this study, a catalyst-free and efficient method using H3N•BH3 for the chemoselective reduction of α,β-unsaturated cycloketones and acyclic α,β-unsaturated ketones is described. The method is expedient, green, and applicable.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Fangyuan Wang, Tilong Yang, Ting Wu, Long-Sheng Zheng, Congcong Yin, Yongjie Shi, Xiang-Yu Ye, Gen-Qiang Chen, Xumu Zhang
Summary: A catalytic protocol for the enantio- and diastereoselective reduction of alpha-substituted-beta-keto carbonitriles is described, providing high yields of beta-hydroxy carbonitrile compounds with excellent selectivity. The methodology is suitable for rapid access to pharmaceutical intermediates Ipenoxazone and Tapentadol.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Xiaolei Ji, Chaoren Shen, Xinxin Tian, Kaiwu Dong
Summary: A palladium-catalyzed asymmetric hydroesterification reaction was developed for preparing chiral alpha-substituted succinates with moderate yields and high ee values. The kinetic profile of the reaction progress indicated that the alkene substrate underwent hydroesterification followed by esterification with alcohol. The enantioselectivity was elucidated by density functional theory computation.
Article
Chemistry, Multidisciplinary
Wenyan Li, Xinying Lin, Jing Long, Bo Zheng, Zhaorui Pan, Leiming Lang, Guangxiang Liu
Summary: The mesoporous core-shell structure Ag@SiO2 nanospheres are constructed to prevent aggregation of Ag nanoparticles during hydrogenation, leading to superior catalytic performance in terms of 100% conversion and selectivity in the hydrogenation of nitro compounds, with good recycling performance for multiple uses.
Article
Chemistry, Multidisciplinary
Yue Ji, Xue Zhang, Weiwei Han, Sichang Wang, Ya Wu, Keliang Zhang, Penghui Yang, Pei Xiao, Yitao Wei
Summary: The concise synthesis of alpha-cyano tetrahydroisoquinolines with a quaternary center via the Strecker reaction was achieved using TMSCN as cyano source and KF as fluoride source, yielding products with up to 99% yield. Additionally, an isomerization reaction of alpha-cyano tetrahydroisoquinoline was observed under alkaline conditions, resulting in the formation of the isomer through [1,3]-H shift.
Article
Chemistry, Multidisciplinary
Zefei Xu, Jinhui Feng, Peiyuan Yao, Qiaqing Wu, Dunming Zhu
Summary: A general chemo-enzymatic approach for the efficient asymmetric synthesis of chiral 3-substituted tetrahydroquinolines has been developed, combining biocatalysis and the Buchwald-Hartwig cross-coupling reaction. The method involves a one-pot ene reductase (ERED)/imine reductase (IRED) cascade and successfully addresses the issue of racemization of the intermediate. This method offers a practical strategy for the construction of chiral 3-substituted tetrahydroquinolines.
Article
Chemistry, Organic
Jingjing Chen, Wei Meng, Xiangqing Feng, Haifeng Du
Summary: A metal-free asymmetric hydrogenation of racemic 3-alkylidene flavanones has been achieved using achiral FLPs and chiral phosphoric acids as relay catalysts. This provides a successful alternative for the challenging hydrogenation of 3-substituted flavones, yielding a wide range of trans- and cis-flavanones with high yields and <= 97% ee.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Xiu-Qin Dong, Xuanliang Yang, Gang Liu, Xun Xiang, Dezheng Xie, Jinyu Han, Zhengyu Han
Summary: Efficient Ni/(S,S)-Ph-BPE-catalyzed asymmetric hydrogenation of alpha-substituted alpha,beta-unsaturated phosphine oxides/phosphonates/phosphoric acids has been successfully developed, and a wide range of chiral alpha-substituted phosphine hydrogenation products were obtained in generally high yields with excellent enantioselective control (92%-99% yields, 84%->99% ee). This method features a cheap transition metal nickel catalytic system, high functional group tolerance, wide substrate scope generality, and excellent enantioselectivity. A plausible catalytic cycle was proposed for this asymmetric hydrogenation according to the results of deuterium-labeling experiments.
Article
Chemistry, Inorganic & Nuclear
Zeyu Wu, Longfei Li, Wan Li, Xuena Lu, Yaoming Xie, Henry F. Schaefer
Summary: In this study, a novel carbonylic-carbon-centered mechanism for the multicarbonyl manganese pincer complex-catalyzed alpha-methylation reaction is discovered, where the catalytic center is located on the carbonyl ligand instead of the metal atom. The chemoselectivity of enone hydrogenation is explained by the donor-acceptor electron transfer from the C=C bond to the C=O antibond in the presence of a manganese pincer catalyst. In contrast, the Noyori-type RuH2(diphosphine)(diamine) catalysts prefer C=O hydrogenation through donor-acceptor interaction associated with the O center dot center dot center dot H-N hydrogen bond.
Article
Chemistry, Organic
Yuan-Zheng Wang, Le'an Hu, Shao-Tao Bai, Xumu Zhang
Summary: A user-friendly and simple catalytic method for the synthesis of high value primary &α;-(trifluoromethyl)aryl-methylamines via ruthenium-catalyzed asymmetric reductive amination of aryl-trifluoromethylketones using cheap NH4OAc as the nitrogen source and H-2 as the reductant is reported. This method tolerates various aromatic functions with electron-withdrawing or -donating substituents, as well as challenging heteroaromatic functions, leading to the formation of primary &α;-(trifluoromethyl)aryl-methylamines with excellent chemoselectivities, enantioselectivities, and useful yields (80-97% ee, 51-92% isolated yields).
Article
Chemistry, Multidisciplinary
Nicole Hauser, Michael A. Imhof, Sarah S. Eichenberger, Tomas Kundig, Erick M. Carreira
Summary: The first total syntheses of the indole diterpenoids (+)-shearinine G and D were achieved through late-stage coupling, diastereoselective intramolecular cyclopropanation, Sharpless dihydroxylation/Achmatowicz reaction, and Prins cyclization. Tuning of the substituents on the parent arylcarboxaldehyde led to divergent products, further transformed into shearinines G and D, with unexpected stereochemical outcomes in the Riley-type oxidation of a bicyclic enone.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Editorial Material
Chemistry, Multidisciplinary
Erick M. Carreira
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Medicinal
Juan M. Decara, Henar Vazquez-Villa, Jose Brea, Monica Alonso, Raj Kamal Srivastava, Laura Orio, Francisco Alen, Juan Suarez, Elena Baixeras, Javier Garcia-Carceles, Andrea Escobar-Pena, Beat Lutz, Ramon Rodriguez, Eva Codesido, F. Javier Garcia-Ladona, Teresa A. Bennett, Juan A. Ballesteros, Jacobo Cruces, Maria Loza, Bellinda Benhamu, Fernando Rodriguez de Fonseca, Maria L. Lopez-Rodriguez
Summary: Peptidic agonists of the GLP-1 receptor have been successful in treating type-2 diabetes and obesity by reducing food intake. Small molecules acting as positive allosteric modulators of GLP-1R, such as compound 9, show promise in improving drug efficacy with oral administration and reduced side effects. The identified GLP-1R PAM, particularly compound 9, exhibits significant in vivo activity in reducing food intake and improving glucose handling in rodents, suggesting a potential therapeutic approach for obesity-associated diabetes.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Nils Trapp, Michael Worle, Bernd Kuhn, Paul Gerber, Raffael Vorberg, Erick M. M. Carreira, Klaus Mueller
Summary: The molecular and crystal structures of 19 N-alkyl-substituted pipecolamide derivatives, including partial fluorination patterns, were presented. The different fluorination patterns in the N-alkyl group resulted in diastereomeric compounds with distinct crystal and molecular structures. The study also revealed an extraordinary conformational diversity in the various N-alkylpiperidine units, and provided insight into consistent conformational patterns and their modulation factors.
HELVETICA CHIMICA ACTA
(2023)
Article
Chemistry, Multidisciplinary
Supratim Ghosh, Avtar Changotra, David A. Petrone, Mayuko Isomura, Erick M. Carreira, Raghavan B. Sunoj
Summary: In this study, the mechanism of a chiral Ir-phosphoramidite-catalyzed asymmetric reductive deoxygenation reaction was investigated using density functional theory. It was found that Bi(OTf)3 promotes ionic and noncovalent interactions, which play a crucial role in nucleophile selectivity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
David M. Fischer, Henry Lindner, Willi M. Amberg, Erick M. Carreira
Summary: Intermolecular cyclopropanation of mono-, di-, and trisubstituted olefins with alpha-bromo-beta-ketoesters and alpha-bromomalonates under organophotocatalysis is reported. The transformation exhibits broad functional group tolerance, producing highly substituted cyclopropanes. Mechanistic investigations, including Stern-Volmer quenching, quantum yield determination, and deuteration experiments, provide insights into the catalytic cycle.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Marlene Fadel, Erick M. Carreira
Summary: The first total synthesis of (+)-pedrolide, a tigliane-derived diterpenoid featuring an unprecedented 5-5-6-6-3 carbon skeleton, was achieved. A key step in the synthesis involved the construction of the bicyclo[2.2.1]heptane core via an intramolecular cyclopentadiene-Diels-Alder cycloaddition. A norbornadiene was used as a surrogate for cyclopentadiene, and the unmasking of the cyclopentadiene was achieved through a complex Diels-Alder reaction cascade. This synthesis also provided a novel approach to a densely functionalized carane in an efficient and enantioselective manner.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Editorial Material
Chemistry, Multidisciplinary
Erick M. Carreira
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Sven M. Papidocha, Hendrik H. Bulthaupt, Erick M. Carreira
Summary: The first total synthesis of heavily oxidized cassane-type diterpenoids, neocaesalpin A, AA, and nominal neocaesalpin K, was achieved using a redox-flexible platform as a key intermediate. The synthesis involved an intermolecular Diels-Alder reaction and a novel late-stage oxidation method for furfuryl acetate.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Henry Lindner, Willi M. Amberg, Erick M. Carreira
Summary: In this study, unactivated olefins are converted into alkyl azides using bench-stable NaN3 in the presence of FeCl3·6H2O under blue-light irradiation. The reaction exhibits anti-Markovnikov selectivity and can be conducted under mild ambient conditions in the presence of air and moisture.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Hendrik H. Bulthaupt, Fabian Glatz, Sven M. Papidocha, Chunyan Wu, Shawn Teh, Susanne Wolfrum, Lucia Balazova, Christian Wolfrum, Erick M. Carreira
Summary: This study reports the synthesis and enantioselectivity of a series of compounds, and reveals the stimulating effect of one of the compounds on the respiration of brown adipocytes, which has potential applications in obesity treatment.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
David M. Fischer, Manuel Freis, Willi M. Amberg, Henry Lindner, Erick M. Carreira
Summary: We have developed a method for difunctionalization of unactivated, terminal olefins using intermolecular addition of alpha-bromoketones, -esters, and -nitriles followed by formation of 4- to 6-membered heterocycles with pendant nucleophiles. The reaction can be conducted with alcohols, acids, and sulfonamides as nucleophiles, yielding products with 1,4 functional group relationships that can be further manipulated. The reaction employs a benzothiazinoquinoxaline organophotoredox catalyst at a low catalyst loading and is tolerant to air and moisture.
Article
Chemistry, Multidisciplinary
Monica Guberman, Miroslav Kosar, Anahid Omran, Erick M. Carreira, Marc Nazare, Uwe Grether
Summary: Labeled chemical probes are crucial for the development and commercialization of drugs. They play a significant role in various research phases and provide valuable tools for specific application needs. The reverse-design approach enables the generation of high-quality probes based on previously optimized small molecules, fostering collaborations between academia and industry.
Article
Chemistry, Medicinal
Javier Garcia-Carceles, Henar Vazquez-Villa, Jose Brea, David Ladron de Guevara-Miranda, Giovanni Cincilla, Melchor Sanchez-Martinez, Anabel Sanchez-Merino, Sergio Algar, Maria Teresa de los Frailes, Richard S. Roberts, Juan A. Ballesteros, Fernando Rodriguez de Fonseca, Bellinda Benhamu, Maria Loza, Maria L. Lopez-Rodriguez
Summary: The development of tolerance caused by dopamine replacement and therapeutic drawbacks of dopaminergic receptors activation highlight the urgent need for a safe and effective treatment for Parkinson's disease. Compound 26, a new synthetic compound designed as a selective modulator of D-1 receptor, demonstrates dose-dependent increase in dopamine's maximal effect in human and mouse D-1 receptors, while being inactive in the absence of dopamine. It shows subtype selectivity and low binding competition with orthosteric ligands. Compound 26 enhances cocaine-induced locomotion and L-DOPA recovery of locomotor activity in reserpinized mice, suggesting its potential as a positive allosteric modulator for Parkinson's disease.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
David M. Fischer, Moritz Balkenhohl, Erick M. Carreira
Summary: The cycloisomerization of beta-, gamma-, and delta-unsaturated N-acyl sulfonamides to N-sulfonyl lactams and imidates using a CoIII(salen) catalyst with t-BuOOH or air as the oxidant is reported in this study. The method exhibits good functional group tolerance and provides a new class of cyclic building blocks. The strong solvent dependence of the transformation and the synthetic versatility of the N-sulfonyl imidate product class are highlighted.
