Article
Chemistry, Physical
Xing-Yu Wang, Xiao-Bing Wang, Yin Tian, Cheng Peng, Ming-Sheng Xie, Hai-Ming Guo
Summary: A highly enantioselective dearomative [3 + 2] annulation reaction was achieved using quinolines, isoquinolines, and pyridines with donor-acceptor aminocyclopropanes. By utilizing a C-1-symmetric imidazoline-pyrroloimidazolone pyridine as the tridentate ligand and Co(OTf)2 as the Lewis acid, chiral indolizidine and benzo-fused indolizidine derivatives were obtained with good yields (up to 98%), excellent diastereoselectivities (>20:1 dr), and excellent enantioselectivities (up to 98% ee). Mechanistic experiments and DFT calculations revealed that the tridentate nitrogen ligand acted as a bifunctional chiral ligand, coordinating with the Co(II) salt and forming a H-bond to facilitate the nucleophilic attack of N-heteroaromatics and achieve high enantioselectivity.
Article
Chemistry, Organic
Wei Wu, Na Liao, Qi Wei, Jiaying Huang, Qi Huang, Yungui Peng
Summary: An efficient asymmetric tandem reaction catalyzed by chiral silver imidodiphosphate has been developed for the synthesis of chiral 1,2-dihydroisoquinoline analogues with a tertiary stereocenter at the C1 position. The products can be further elaborated into beta-aminophosphonates or PARP1-inhibitor analogues with high yields and ee values.
Article
Chemistry, Physical
Saeesh R. Mangaonkar, Hiroki Hayashi, Hideaki Takano, Wataru Kanna, Satoshi Maeda, Tsuyoshi Mita
Summary: The radical anion of CO2 is a highly nucleophilic radical species with many potential applications in organic chemistry. In this study, a robust method for introducing CO2 center dot- into stable heteroaromatics was developed. The resulting reactions produced synthetically useful alpha-oxy, alpha-thio, and alpha-amino acid derivatives, as well as carboxylated tetrahydronaphthalene derivatives. These dearomative carboxylation reactions are unprecedented and provide a synthetic option for introducing a C1 source into stable (hetero)aromatics.
Article
Chemistry, Physical
Xiao-Qing Han, Lei Wang, Ping Yang, Jing-Yuan Liu, Wei-Yan Xu, Chao Zheng, Ren-Xiao Liang, Shu-Li You, Junliang Zhang, Yi-Xia Jia
Summary: A palladium-catalyzed intramolecular enantioselective Mizoroki-Heck reaction of naphthalenes has been developed, leading to the formation of a series of unique heterocyclic compounds with enantiomeric excess values retained. The reaction relies on the use of a chiral sulfonamide phosphine ligand to inhibit competitive and undesired reactions.
Article
Multidisciplinary Sciences
Hui Cao, Qiang Cheng, Armido Studer
Summary: This article introduces a highly selective method for functionalization of pyridines at the meta position, achieving trifluoromethylation, perfluoroalkylation, chlorination, bromination, iodination, nitration, sulfanylation, and selenylation through a dearomatization-rearomatization process. The method can be applied for late-stage functionalization of drugs.
Article
Chemistry, Multidisciplinary
Melania Gomez-Martinez, Maria del Carmen Perez-Aguilar, Dariusz G. Piekarski, Constantin G. Daniliuc, Olga Garcia Mancheno
Summary: An enantioselective anion-binding organocatalytic approach using versatile N,N-dialkylhydrazones as polarity-reversed nucleophiles is presented. A highly ordered hydrogen-bond network was envisioned between a CF3-substituted triazole-based multidentate HB-donor catalyst, the ionic substrate, and the hydrazone in a supramolecular chiral ion-pair complex. Experimental and computational studies supported the formation of this network, showing the crucial role of the anion as a template unit. The asymmetric reaction provided highly enantiomerically enriched hydrazones that could be further derivatized to value-added compounds with up to three stereocenters.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Peter Bellotti, Torben Rogge, Fritz Paulus, Ranjini Laskar, Nils Rendel, Jiajia Ma, K. N. Houk, Frank Glorius
Summary: This study presents a unique method for the one-step synthesis of aza-acenaphthenes through peri-(3 + 2) cycloaddition of simple quinolines with alkynes. A commercial iridium complex is used as a dual-function photosensitizer and photoredox catalyst, enabling a cyclization/rearomatization cascade. The method demonstrates excellent regio- and diastereoselectivity when applied to 8-substituted quinolines and phenanthrolines.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Na Luo, Yu-Fei Ao, De-Xian Wang, Qi-Qiang Wang
Summary: The article briefly reviews the emergence and development of anion-pi interactions, emphasizing the concept of anion-pi catalysis and key progress in this area. The content is organized based on the role of anion-pi interactions in catalysis, from ground-state and transition-state stabilization to cooperative pi-face activation. A concluding remark and outlook on future development are also provided.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Suman Yadav, Ruchir Kant, Malleswara Rao Kuram
Summary: In this study, a metal-free domino reaction was achieved to generate quinoline and isoquinoline-derived cyclic amidines via the cycloaddition of azides with in situ generated enamines through dearomatization.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Alafate Adili, John-Paul Webster, Chenfei Zhao, Sharath Chandra Mallojjala, Moises A. Romero-Reyes, Ion Ghiviriga, Khalil A. Abboud, Mathew J. Vetticatt, Daniel Seidel
Summary: The enantioselective oxa-Pictet-Spengler reactions of tryptophol with aldehydes were successfully conducted under weakly acidic conditions using a combination of indoline HCl salt and bisthiourea compound as catalysts. Mechanistic investigations determined the roles of both catalysts and confirmed the involvement of oxocarbenium ion intermediates, ruling out alternative scenarios. A stereochemical model derived from density functional theory calculations provided the basis for the development of a highly enantioselective stereodivergent variant with racemic tryptophol derivatives.
Article
Chemistry, Multidisciplinary
Zhiguo Zhang, Xiyang Cao, Xiaoqing Song, Gang Wang, Bingbing Shi, Xiang Li, Nana Ma, Lantao Liu, Guisheng Zhang
Summary: Atom- and step-economy in IBX-assisted diversity-oriented synthesis is achieved with a versatile AQ auxiliary alpha-amino acid analogs, offering rapid access to polycyclic spiro-quinolines featuring a quaternary stereocenter in 20%-91% yields under mild conditions via 7,8-dearomatization of quinolines. The highlight of this intramolecular oxidation spiroannulation tandem reaction is the absence of a preinstalled activation group. These traditionally difficult-to-access N-heterospirocycles may provide a potentially interesting scaffold for synthetic and medicinal chemistry.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Chao Hu, Cuong Vo, Rohan R. Merchant, Si-Jie Chen, Jonathan M. E. Hughes, Byron K. Peters, Tian Qin
Summary: Heterocycles play a crucial role in modern medical chemistry and drug development. In this study, a simple and efficient method was developed to selectively synthesize hydrosilylated and reduced N-heterocycles from abundant aromatic building blocks. This approach has the potential to facilitate the synthesis of novel medicinally relevant scaffolds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Applied
Ben-Jie Jiang, Song-Lin Zhang
Summary: A general method is developed for the synthesis of quinolines and C2-functionalized quinolines from ortho-alkenyl anilines using a difluorocarbene precursor. The method involves the in-situ generation of isocyanides from primary aniline and difluorocarbene, which then undergo alpha-addition by neighboring alkenyl groups to form the quinoline ring. In the presence of Se, selenoisocyanate intermediates are generated, leading to the synthesis of 2-SeH quinolines. The method allows for the modular synthesis of various C2-functionalized quinolines in one step, using readily available starting compounds.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Hong-Ying Duan, Shi-Tao Han, Tian-Guang Zhan, Li-Juan Liu, Kang-Da Zhang
Summary: In this study, a visible-light-switchable telluro-triazole/triazolium-based chalcogen bonding system was demonstrated for the first time. The binding strength between the receptors and halide anions could be reversibly regulated by different wavelengths of visible light. The cis-bidentate receptor exhibited enhanced binding ability compared to the trans-monodentate receptor. The telluro-triazolium-based receptor showed both high and significantly photoswitchable binding affinities for halide anions, making it an efficient photocontrolled organocatalyst.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Zidan Ye, Wei Liu, Huanchao Gu, Xiaoyu Yang
Summary: Highly efficient and stereoselective dearomatization of substituted phenols was achieved through chiral phosphoric acid-catalyzed electrophilic para-amination. This method readily provides chiral 2,5-cyclohexadienones bearing 4-aza-quaternary stereocenters with excellent yields and enantioselectivities (≤99% yield and >99% ee). The reaction can be easily scaled up to gram scale and the chiral products can be easily derivatized into α-tertiary amines and α-tertiary heterocycles derivatives, demonstrating the potential of this method.
Article
Chemistry, Multidisciplinary
Melania Gomez-Martinez, Maria del Carmen Perez-Aguilar, Dariusz G. Piekarski, Constantin G. Daniliuc, Olga Garcia Mancheno
Summary: An enantioselective anion-binding organocatalytic approach using versatile N,N-dialkylhydrazones as polarity-reversed nucleophiles is presented. A highly ordered hydrogen-bond network was envisioned between a CF3-substituted triazole-based multidentate HB-donor catalyst, the ionic substrate, and the hydrazone in a supramolecular chiral ion-pair complex. Experimental and computational studies supported the formation of this network, showing the crucial role of the anion as a template unit. The asymmetric reaction provided highly enantiomerically enriched hydrazones that could be further derivatized to value-added compounds with up to three stereocenters.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Florian Ostler, Dariusz G. Piekarski, Tobias Danelzik, Mark S. Taylor, Olga Garcia Mancheno
Summary: The study introduced a novel chiral tetrakis-iodo-triazole structure as a neutral halogen bond donor for chiral anion-recognition and enantioinduction in ion-pair organocatalysis. It demonstrated selective recognition of chiral dicarboxylates and asymmetric induction in a benchmark organocatalytic reaction using the halogen bond donor, with inversions in chiral recognition, enantioselectivity, and chiroptical properties relative to the related hydrogen donor.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Organic
Jan H. Kuhlmann, Mustafa Uygur, Olga Garcia Mancheno
Summary: The first visible-light-mediated photocatalytic, metal- and base-free protodesilylation of arylsilanes is achieved using a commercially available acridinium salt. Two simple approaches using either aerobic or hydrogen atom transfer cocatalytic conditions enable efficient and selective desilylation of a wide range of simple and complex arylsilanes under mild conditions.
Review
Chemistry, Organic
Lukas-M Entgelmeier, Olga Garcia Mancheno
Summary: Over the past two decades, enantioselective anion-binding catalysis has emerged as a powerful strategy for inducing chirality in organic transformations. This review provides an overview of the different activation modes in asymmetric anion-binding catalysis by looking at representative examples and recent advances in this field.
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Organic
Sumi Joseph, Qui-Nhi Duong, Lukas Schifferer, Olga Garcia Manchen
Summary: An enantioselective anion-binding catalyzed allylation method has been developed for the rapid synthesis of chiral α-allyl dihydroquinolines. Using a tetrakis-triazole-based hydrogen-bond donor catalyst, these chiral N-heterocycles were obtained in good yields (up to 90%) and with high enantioselectivity (up to 89:11 e. r.). Moreover, the versatility of the allyl moiety in the products was demonstrated through selective post-epoxidation and aziridination reactions, resulting in highly decorated chiral molecules with up to four stereocenters and high enantioselectivity (up to 94:6 e. r.).
Article
Chemistry, Organic
Tobias Danelzik, Sumi Joseph, Christian Mueck-Lichtenfeld, Constantin G. Daniliuc, Olga Garcia Mancheno
Summary: This work demonstrates the efficient use of benzotriazolium salts as bench-stable Lewis acid catalysts in allylic and Nazarov cyclization reactions. These catalysts exhibit promising reactivity and can be used at low catalytic loadings.
Article
Chemistry, Multidisciplinary
Jorge C. Herrera-Luna, Maria Carmen Perez-Aguilar, Leon Gerken, Olga Garcia Mancheno, M. Consuelo Jimenez, Raul Perez-Ruiz
Summary: A novel method for the formation of carbon-aryl sulfide bonds through electron donor-acceptor (EDA) complexes of alkylamines with 5- and 6-membered (hetero)arene halides under visible light is presented. This method represents the first EDA-based thiolation method that does not rely on pi-pi or a thiolate-anion-pi interactions, providing an easy access to heteroarene radicals, which can be trapped by disulfide derivatives to form versatile arylsulfides. Mechanistic investigations using spectroscopic measurements confirm the formation of the hypothesized EDA complexes, and the strength of this method is demonstrated through gram-scale synthesis of thiolated products and late-stage derivatization of an anticoagulant drug.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Review
Chemistry, Organic
Olga Garcia Mancheno, Mario Waser
Summary: Since the early reports by von Liebig, Knoevenagel and Bredig, asymmetric organocatalysis has come a long way, culminating in the 2021 Nobel Prize in Chemistry. This Perspective provides a brief introduction by discussing the historical development, classical methods, and selected advanced recent examples that have opened new directions in this growing field.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Jan H. Kuhlmann, Jan H. Dickoff, Olga Garcia Mancheno
Summary: A straightforward method for desilylation of arylsilanes using visible-light-triggered thiyl radicals was developed. This reaction provides a mild cleavage at a late-stage, allowing for new possibilities and disconnection routes. Commercially available and cheap disulfides were employed for the first time in this type of cleavage reactions, offering a fast and simple approach for a broad variety of arylsilanes. The methodology also shows its robustness and synthetic application potential for natural products and therapeutic derivatives.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Alica C. Keuper, Kevin Fengler, Florian Ostler, Tobias Danelzik, Dariusz G. Piekarski, Olga Garcia Mancheno
Summary: A new approach to achieve highly enantioselective halogen-bonding catalysis has been developed by designing fine-tuned halogen-halogen interactions. This strategy utilizes both the electron cloud and sigma-hole site of the substrate's halogen substituent to form a tight chiral complex, enabling controlled induction of high levels of chirality transfer. Remarkable enantioselectivities of up to 95:5 e.r. (90% ee) have been achieved in a model dearomatization reaction using tetrakis-iodotriazole multidentate anion-binding catalysts.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Biochemistry & Molecular Biology
Clement Lemaitre, Stefania Perulli, Ophelie Quinonero, Cyril Bressy, Jean Rodriguez, Thierry Constantieux, Olga Garcia Mancheno, Xavier Bugaut
Summary: Atropisomers are intriguing objects of study for chemists and have various applications in applied chemistry. Obtaining them in enantiopure form is still a challenging task, but there have been significant advancements in recent decades. Among these, oxidative aromatization with central-to-axial conversion of chirality has gained popularity. This review critically analyzes the research field, discussing its historical background, present state of the art, and potential future development directions.
Review
Chemistry, Multidisciplinary
Martin Aleksiev, OlgaGarcia Mancheno
Summary: Catalytic asymmetric dearomatization of heteroaromatic compounds has attracted significant attention as it enables the rapid expansion of chemical space by converting simple, flat molecules into complex, three-dimensional structures with added value. Among different approaches, organocatalytic dearomatization methods, especially anion-binding catalysis technology, have shown remarkable progress, providing new means for enantioselective dearomatization of heteroarenes through chiral contact ion pair formation by activating the electrophilic reaction partner. This article provides an overview of different methodologies and advances in anion-binding catalyzed dearomatization reactions of heteroarenes.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Lukas Schifferer, Leon Hoppmann, Robin Groeters, Christian Mueck-Lichtenfeld, Constantin G. Daniliuc, Olga Garcia Mancheno
Summary: A solvent-dependent, divergent synthesis of highly functionalized N,S-heterocycles, containing thiazoline and isoquinuclidine or tetrahydroisoquinoline scaffolds, has been reported. This synthesis involves cyclization reactions of isoquinolinium 1,4-zwitterionic thiolates and shows robustness and applicability as demonstrated by efficient upscaling of the reaction and derivatization of the resulting products.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Niklas Lohmann, Vesna Milovanovic, Dariusz G. Piekarski, Olga Garcia Mancheno
Summary: In this study, a highly efficient oxidative reaction using a TEMPO salt as a mild oxidant was reported for the conversion of cyclic benzylic amines to corresponding tetrazole compounds. This method enables direct functionalization of N-heterocycles and does not require acid additives, resulting in high yields of the desired products.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
