Review
Chemistry, Applied
Jaume Rostoll-Berenguer, Gonzalo Blay, Jose R. Pedro, Carlos Vila
Summary: This review summarizes recent publications on asymmetric oxidative Mannich reactions using amines as electrophiles, including the different oxidants used and the scope and limitations of the different catalytic systems.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Multidisciplinary
Zhaokun Li, Feng Zhao, Wei Ou, Pei-Qiang Huang, Xiaoming Wang
Summary: Inert tertiary amides have been effectively transformed into chiral propargylamines with high yields and good to excellent enantioselectivities through a relayed sequence of partial reduction and asymmetric alkynylation. The practical utilities and robust nature of this protocol have been demonstrated through the transformations of representative products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Applied
Yong Tang, Kaihong Liu, Ye Wu, Siyu Zhou, Tanyu Cheng, Guohua Liu
Summary: The development of cooperative catalysis is important for multi-step sequential enantioselective organic transformations. This study presents the design of an integrated Cu/bisoxazoline and Ru/diamine co-catalyst system for the direct preparation of 1,3-distereocentered beta-sulfonamido alcohols. The cascade reaction enables efficient and selective synthesis of chiral products.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Zhiheng Li, Danran Li, Huaming Xiang, Jian Huang, Yinuo Zheng, Cuiju Zhu, Xiuling Cui, Chao Pi, Hao Xu
Summary: In this study, a highly enantioselective propargylic substitution reaction of anthrones with propargylic esters using copper salts with chiral N, N, P-ligand was disclosed. This strategy shows broad substrate compatibility, mild reaction conditions, excellent yields with remarkable enantioselectivity, and enables the synthesis of diverse products.
CHINESE CHEMICAL LETTERS
(2022)
Review
Chemistry, Multidisciplinary
Huiting Lv, Yongli Du, Haibin Zhang, Yong Zheng, Zhijia Yan, Ning Dong
Summary: Mannich-type reactions utilize active alpha-H compounds, amines, and aldehydes to synthesize valuable beta-aminocarbonyl compounds. The yield, selectivity, and regioselectivity of the reaction are influenced by catalysts and the structural characteristics of the substrates. This article summarizes the developments in symmetric and asymmetric Mannich-type reactions according to the type of substrates and analyzes the factors affecting reaction outcomes.
Article
Chemistry, Physical
William R. R. Cassels, Evan T. T. Crawford, Jeffrey S. S. Johnson
Summary: We report a simple catalytic crystallization-driven enantio- and diastereoselective Mannich reaction for the synthesis of stereodefined alpha-monosubstituted-ss-ketoesters, dissymmetric ss-diesters, dissymmetric ss-diketones, and ss-keto amides. This method efficiently leverages product epimerization in solution. Mechanistic studies suggest that the initial enantioselective, diastereodivergent skeletal assembly is catalyzed by a chiral tertiary amine organocatalyst, followed by crystallization-induced diastereoconvergence to provide the challenging alpha-stereocenter in excellent stereoselectivity.
Article
Chemistry, Multidisciplinary
Yuan-Yuan Gao, Chun-Lin Zhang, Ming-Lei Jin, Zhong-Hua Gao, Song Ye
Summary: N-heterocyclic carbene (NHC)-catalyzed enantioselective Mannich-type reactions of biomass-derived compound CMF with imines were developed, giving high-value-added chiral amines with good yields and excellent stereocontrol. The use of bifunctional NHC derived from L-pyroglutamic acid directed the remote addition of the trienolate intermediate to the imine in a highly stereocontrolled manner. This is the first enantioselective reaction proceeding via an NHC-bound trienolate intermediate.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Marta Gil-Ordonez, Camille Aubry, Cristopher Nino, Alicia Maestro, Jose M. Andres
Summary: A series of N-Boc ketimines derived from pyrazolin-5-ones have been successfully used as electrophiles in enantioselective Mannich reactions with different 1,3-dicarbonyl compounds. The reaction enables the synthesis of 4-amino-5-pyrazolone derivatives with diverse structures, including the beta-diketone and pyrazolinone substructures. The use of a quinine-derived bifunctional squaramide as an organocatalyst with a very low loading proves to be highly effective in terms of yield and enantioselectivity. The obtained products can be further transformed into enantioenriched diheterocyclic systems, which show potential as drug candidates.
Article
Multidisciplinary Sciences
Qi Liu, Jian Zheng, Xue Zhang, Shengming Ma
Summary: In this study, visible light was successfully integrated into a transition metal-catalyzed coupling reaction to selectively form substituted allenenitriles. Mechanistic studies have shown that the reaction proceeds through a visible light-induced redox-neutral reductive quenching radical mechanism.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Patricia Cmelova, Peter Sramel, Barbora Zahradnikova, Viktoria Modrocka, Henrich Szabados, Maria Meciarova, Radovan Sebesta
Summary: This paper presents the synthesis and evaluation of a bifunctional organic catalyst that can efficiently catalyze the selective synthesis of polyfunctional molecules. The hybrid organocatalysts consist of Pro-Pro dipeptide and thiourea moiety connected via a 1,2-diaminocyclohexane unit.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Zhaofeng Gao, Jingwen Liu, Haizhou Huang, Huiling Geng, Mingxin Chang
Summary: The research reports on efforts to merge two asymmetric reductive amination reactions into a single-step transformation, utilizing specific catalyst and acid additives to successfully synthesize enantiopure secondary amine products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Ajijur Rahaman, Rupali Dasharath Shinde, Sukalyan Bhadra
Summary: A copper-based system enables the methylene insertion reaction between an amine and a milder nucleophile, such as a terminal alkyne, through the cleavage of the C-N bond in N,N-dimethylacetamide. This method provides a convenient access to propargylic amines with good to excellent yields. The wide substrate scope and the ability to functionalize complex molecules at late stages make this protocol practically valuable.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Jeffrey S. Johnson, William R. Cassels, Evan T. Crawford
Summary: A simple catalytic crystallization-driven enantio- and diastereoselective Mannich reaction was disclosed for the synthesis of stereodefined alpha-monosubstituted-keto esters, dissymmetric diesters, dissymmetric diketones, and keto amides that productively leveraged product epimerization in solution. Mechanistic studies suggested that the initial enantioselective, diastereodivergent skeletal assembly was catalyzed by a chiral tertiary amine organocatalyst, which then facilitated second stage crystallization-induced diastereoconvergence to provide the challenging alpha-stereocenter in excellent stereoselectivity.
Article
Chemistry, Organic
Chao-Jiu Long, Hong-Ping Pu, Ya-Nan Zhao, Yan-Hong He, Zhi Guan
Summary: Researchers developed a new enantioselective oxidative cross-dehydrogenative coupling method by combining photocatalysis and l-/d-proline catalysis. Acyclic benzylic secondary amines were successfully transformed into beta-amino carbonyl compounds with good yields up to 86% and high enantio- and diastereoselectivities (up to 99% ee and > 99 : 1 dr) under mild and oxidant-free conditions. This method has wide substrate scope, excellent functional group tolerance, and simple operation.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Physical
Chunming Gui, Yuanyuan Peng, Yang Zhou, Yixuan Zheng, Haifeng Wang, Qiongjiao Yan, Hui Zhou, Wei Wang, Fen-Er Chen
Summary: This paper reports the copper-catalyzed asymmetric propargylic substitution reaction, which efficiently synthesizes multifunctionalized products bearing a terminal alkyne unit with good stereoselectivity. The products can also be easily derivatized into other potentially valuable organic compounds, showing great potential for pharmaceutical development.
Article
Chemistry, Multidisciplinary
Teresa E. Campano, Igor Iriarte, Olatz Olaizola, Julen Etxabe, Antonia Mielgo, Inaki Ganboa, Jose M. Odriozola, Jesus M. Garcia, Mikel Oiarbide, Claudio Palomo
CHEMISTRY-A EUROPEAN JOURNAL
(2019)
Article
Chemistry, Multidisciplinary
Inaki Urruzuno, Odei Mugica, Giovanna Zanella, Silvia Vera, Enrique Gomez-Bengoa, Mikel Oiarbide, Claudio Palomo
CHEMISTRY-A EUROPEAN JOURNAL
(2019)
Article
Chemistry, Multidisciplinary
June Izquierdo, Noemie Demurget, Aitor Landa, Tore Brinck, Jose M. Mercero, Peter Diner, Mikel Oiarbide, Claudio Palomo
CHEMISTRY-A EUROPEAN JOURNAL
(2019)
Article
Chemistry, Multidisciplinary
Rosa Lopez, Claudio Palomo
Summary: N,N-Diacylaminals are flexible molecular scaffolds commonly used as amide surrogates in peptidomimetics. Recently, their singularity as an N-acyl imine equivalent and hydrogen-bond donor has led to new synthetic opportunities, particularly in the field of asymmetric catalysis. This concept article highlights the diverse synthetic potential of N,N-Diacylaminals and provides the necessary elements for further developments.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Review
Chemistry, Multidisciplinary
Mikel Oiarbide, Claudio Palomo
Summary: The catalyst-controlled functionalization of unmodified carbonyl compounds is an important operation in organic synthesis, especially when high levels of site- and stereo-selectivity can be achieved. Recent contributions in this field have shown that some subsets of enolizable substrates can now be functionalized through various types of activation mechanisms.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Organic
Silvia Vera, Ana Vazquez, Ricardo Rodriguez, Sandra Del Pozo, Inaki Urruzuno, Abel de Cozar, Antonia Mielgo, Claudio Palomo
Summary: This study reports a highly enantio- and syn-selective synthesis of beta-hydroxy alpha-amino acids from glycine imine derivatives under Bronsted base catalysis. The key lies in the use of benzophenone-derived imine of glycine o-nitroanilide as a pronucleophile, where the o-nitroanilide framework provides an efficient hydrogen-bonding platform that accounts for nucleophile reactivity and diastereoselectivity.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Rosa Lopez, Claudio Palomo
Summary: This Minireview highlights the limited but significant catalytic methods for the generation of planar chirality in strained molecules, and serves as an inspiration for the development of new unconventional procedures in the future.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Organic
Silvia Vera, Ane Garcia-Urricelqui, Antonia Mielgo, Mikel Oiarbide
Summary: Thiourea- and squaramide-based bifunctional base catalysts have become a powerful tool for enantioselective transformations in asymmetric catalysis. Recent developments have focused on incorporating additional H-bond donor sites into the catalyst structure, resulting in more active and selective catalysts. This review presents the pioneering ideas and recent contributions to the field, organized according to the nature of the additional H-bond donor functionality, and discusses the advantages, limitations, and prospects of these new multifunctional catalysts.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Leire Villaescusa, Iker Hernandez, Laura Azcune, Ainhoa Rudi, Jose M. Mercero, Aitor Landa, Mikel Oiarbide, Claudio Palomo
Summary: The catalytic addition of hydantoin surrogates to rigidified vinylidene bis(sulfone) reagents was achieved, overcoming the unreactivity of commonly used beta-substituted vinylic sulfones. The resulting adducts were transformed into enantioenriched 5,5-disubstituted hydantoins through hydrolysis and reductive desulfonylation processes, offering new structures for potential bioassays. Density functional theory studies provided insights into the observed reactivity and stereoselectivity trends.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Eider Dunabeitia, Aitor Landa, Rosa Lopez, Claudio Palomo
Summary: The study demonstrates the capability of bicyclic acylpyrrol lactims to act as pronucleophiles and form carbon-carbon bonds under organocatalytic conditions, leading to the synthesis of chiral pyrrolodiketopiperazines. The use of ureidoaminal-derived Bronsted bases in the Michael addition to nitroolefins allows for the generation of heterocyclic scaffolds with a high degree of skeletal diversity.
Article
Chemistry, Multidisciplinary
Mikel Oiarbide, Claudio Palomo
Summary: Chiral Bronsted base (BB) catalyzed asymmetric transformations are important for synthesis. These transformations involve transiently generated enolate intermediates that react with a variety of electrophiles. Our group focused on developing BB-catalyzed asymmetric reactions of enolizable carbonyl substrates, with an additional challenge of controlling site-selectivity. This account illustrates the opportunities and challenges of these methods, with a focus on generating quaternary carbon stereocenters. New bifunctional BB catalysts and achiral templates were developed during this process.
Article
Biochemistry & Molecular Biology
Laura Sanchez-Sanchez, Javier Garcia, Roberto Fernandez, Ekaterina Noskova, June Egiguren-Ortiz, Marina Gulak, Eneko Ochoa, Antonio Laso, Mikel Oiarbide, Jose Ignacio Santos, Maria Fe Andres, Azucena Gonzalez-Coloma, Albert Adell, Egoitz Astigarraga, Gabriel Barreda-Gomez
Summary: Cannabis has been used as a palliative therapy for cancer treatment due to its beneficial effects on pain and nausea. The main compounds in Cannabis, THC and CBD, exert their actions through receptor-mediated and non-receptor-mediated mechanisms, affecting the formation of reactive oxygen species. Evidence suggests a potential antitumor effect of cannabinoids in different types of cancer, although controversial results limit their implementation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
