Article
Chemistry, Organic
Peter Langer
Summary: This article presents a personalized approach to synthesizing nitrogen heterocycles by combining regioselective Pd-catalyzed cross-coupling reactions and acid-mediated cycloisomerization reactions. The resulting products exhibit new heterocyclic core structures and display interesting optical and electronic properties.
Article
Chemistry, Organic
Peter Langer
Summary: The present article discusses the personalized Account on the synthesis of nitrogen heterocycles through domino C-N coupling/hydroamination reactions and related processes. The starting materials, 2-alkynyl-1-halohetarenes, are obtained regioselectively by Sonogashira reactions of various 1,2-dihalogenated heterocycles. The formation of more complex products is achieved through domino C-N coupling/hydroamination/C-H arylation reactions. These reactions result in the formation of new heterocyclic core structures with interesting pharmacological or fluorescence properties.
Article
Chemistry, Organic
Subhankar Ghosh, Shital K. Chattopadhyay
Summary: In this study, a single metal catalyst and air as the oxidant were used to achieve tandem C-H arylation and C-H amidation of cis-cinnamyl hydroxamates, leading to the regioselective formation of a 3-aryl-2-quinolone ring system. Under identical conditions, the corresponding trans-isomer resulted in a 4-aryl-2-quinolone derivative. The observed complementary regioselectivity during the tandem C-H arylation and C-H amidation of isomeric substrates is unusual and has potential applications.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Peter Langer
Summary: The combination of regioselective palladium-catalyzed C-C with twofold C-N couplings allows for the synthesis of a variety of heterocyclic ring systems, including complex polyheterocyclic systems, which are of pharmacological relevance or interesting in the field of material science.
Review
Chemistry, Multidisciplinary
Xinlan A. F. Cook, Antoine de Gombert, Janette McKnight, Loic R. E. Pantaine, Michael C. Willis
Summary: This review focuses on the methods developed for the challenging coupling of 2-pyridine nucleophiles with (hetero)aryl electrophiles, ranging from traditional cross-coupling processes to alternative nucleophilic reagents and novel main group approaches.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Sanghyup Seo, Donghyeon Kim, Hyunwoo Kim
Summary: The reductive cross-coupling of terminal alkenes and N-heterocyclic bromides was successfully demonstrated through ligand optimization of Pd and CuH catalysis. The optimized ligands for Pd and CuH catalysis, Briphos and DTB-DPPBz respectively, were further applied to gram-scale production of clathryimine B.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Christopher A. Wilhelmsen, Xuntong Zhang, Jesse A. Myhill, James P. Morken
Summary: Versatile beta tert-boryl amides were synthesized through conjunctive cross-coupling of alpha-substituted alkenyl boron ate complexes and carbamoyl chloride electrophiles. The use of a palladium catalyst in combination with MandyPhos enabled enantioselective synthesis. Additionally, the chemoselectivity of the reaction product was enhanced by the addition of water.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Chengqiang Cao, Yi Yang, Xin Li, Yunxia Liu, Hui Liu, Zengdian Zhao, Lei Chen
Summary: The reaction, catalyzed by palladium, efficiently constructs two new bonds with high yields, while the alkene group is easily functionalized, leading to the formation of products with a unique structure that is difficult to synthesize.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Christian Frabitore, Jerome Lepeule, Tom Livinghouse
Summary: Nitrogen-containing heterocycles are the main components of most FDA-approved small-molecule pharmaceuticals. This article describes a synthetic method to produce saturated N-heterocyclic drug scaffolds with an internal alkyne. By treating compounds and conducting reactions, products such as piperidines and pyrrolidines can be obtained.
Article
Chemistry, Multidisciplinary
Barry M. Trost, Zhijun Zuo
Summary: A novel Pd-0-catalyzed highly selective [3+2] spiroannulation reaction has been developed for rapid assembly of a new class of [5,5] spirocyclic carbo- and heterocycles. The regioselectivity of the reaction can be controlled by fine-tuning the Pd-pi-allyl intermediate, with excellent toleration of various coupling partners and enantioselectivities demonstrated through further transformations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Han-Jun Ai, Wangyang Lu, Xiao-Feng Wu
Summary: Thiocarbonylation of alkynes offers a versatile method for the synthesis of unsaturated thioesters, with the possibility of controlling the product structure by using different ligands and acid additives. This approach also demonstrates the first example of thiocarbonylation of internal alkynes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Ziyi Yang, Chaofan Sun, Xing Wei, Jian Lu, Ju-You Lu
Summary: A cascade deboronation/regioselective B-P coupling of closo-carboranes was achieved using palladium catalysts and nitrogen or phosphine-containing directing groups. The reaction can tolerate unsymmetric C-substituted closo-carboranes and is compatible with various other directing groups. Phosphine and arsenic can serve as effective coupling partners, and a catalytic amount of palladium salt mediates the regioselective B-H activation process. The use of readily available closo-carboranes allows for direct synthesis of functionalized nido-carboranes without intermediate purification.
Article
Chemistry, Multidisciplinary
Felipe Verdugo, Ricardo Rodino, Martin Calvelo, Jose Luis Mascarenas, Fernando Lopez
Summary: The reactivity of carbonyl-tethered alkylidenecyclopropanes (ACPs) can be directed towards tandem cycloisomerization/cross-coupling processes by using Pd-0 catalysts with phosphorus-based monodentate ligands. This allows for the synthesis of a wide variety of highly functionalized cyclic alcohols and amines through the formation of key pi-allyl oxapalladacyclic intermediates which are trapped with external nucleophilic partners.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Rajender Nallagonda, Djamaladdin G. Musaev, Rashad R. Karimov
Summary: Partially saturated nitrogen heterocycles are versatile building blocks that can be used to synthesize other nitrogen heterocycles. Coupling reactions between aryl iodides and pyridinium or other heteroarenium salts can produce a wide range of nitrogen heterocycle scaffolds. This method has high operability and good tolerance towards functional groups.
Article
Chemistry, Multidisciplinary
Andrew Whyte, Jonathan Bajohr, Ramon Arora, Alexa Torelli, Mark Lautens
Summary: An enantioselective consecutive cyclization/coupling process catalyzed by palladium was reported in this study. The stereoinduction was achieved through an enantioselective carbopalladation, leading to the generation of an intermediate that promotes a nucleopalladation step. This dual cyclization sequence was compatible with various nucleophiles and aryl iodides, producing numerous bisheterocycles in good yields and high regio- and enantioselectivities.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Noah Jeremias, Martin T. Peschel, Constantin Jaschke, Regina de Vivie-Riedle, Thorsten Bach
Summary: In this study, it was found that cyclopent-2-enones can undergo a photochemical rearrangement to form ketenes when substituted in the 5,5-position, accompanied by the formation of cyclopropane. By trapping the ketene intermediates with primary amines, efficient synthesis of 2,2-disubstituted cyclopropaneacetic amides was achieved.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Audrey Gilbert, Thorsten Bach
Summary: Photochemical cascade (domino) reactions can construct complex molecular architectures through consecutive reactions with high diastereoselectivity.
Article
Chemistry, Multidisciplinary
Roger Jan Kutta, Johannes Grosskopf, Nils van Staalduinen, Antonia Seitz, Philipp Pracht, Stefan Breitenlechner, Christoph Bannwarth, Patrick Nuernberger, Thorsten Bach
Summary: In the presence of a chiral benzophenone catalyst, a racemic mixture of a chiral imidazolidine-2,4-dione can be converted into the same compound with high enantiomeric excess through photochemical deracemization. Mechanistic experiments revealed that the catalyst binds the two enantiomers through hydrogen bonding and facilitates hydrogen atom transfer to the photoexcited benzophenone. Quantum chemical calculations showed that the back hydrogen atom transfer occurs to the oxygen atom of the hydantoin radical. The results provide insights into a synthetically useful photochemical deracemization reaction.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Johannes Hofer, Franziska Pecho, Thorsten Bach
Summary: Under visible light irradiation, cyclic 2-alk-4enyl-substituted 1,3-diketones undergo an intramolecular endo-addition onto the double bond, resulting in spirocyclic products with yields ranging from 62 to 92%. The reaction can be promoted by both an organic photocatalyst (thioxanthone, 20 mol%) and an organometallic Ir-based photocatalyst (5 mol%). The addition of triisopropylthiophenol is necessary to obtain high yields.
Article
Chemistry, Multidisciplinary
Johannes Grosskopf, Alexandra A. Heidecker, Thorsten Bach
Summary: Racemic 3-substituted oxindoles can be converted into enantiomerically pure or enriched material through photochemical deracemization process. Light energy compensates for the loss of entropy and enables predictable editing of the stereogenic center. The obtained oxindoles are valuable intermediates for further transformations with complete retention at the stereogenic center.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Editorial Material
Chemistry, Organic
Anat Milo, Takashi Ooi, Thorsten Bach
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Niklas Rauscher, Christian Jandl, Thorsten Bach
Summary: A recent photochemical cascade reaction has been developed to access diastereomeric pentacyclic products that possess the carbon skeleton of prezizane natural products. The minor diastereoisomer, with a 2 beta-Me configuration, was transformed into (+)-prezizaan-15-ol through 12 reaction steps. Similarly, the major diastereoisomer, with a 2 alpha-Me configuration, yielded (+)-jinkohol II in an analogous route and was further oxidized at C13 to yield (+)-jinkoholic acid. Total synthesis of these natural products helped clarify their configurations.
Article
Chemistry, Organic
Johanna Proessdorf, Christian Jandl, Thomas Pickl, Thorsten Bach
Summary: Naturally occurring sesquiterpenes with a protoilludane skeleton are frequently oxygenated at carbon atoms C4 and C8. Boronic acid pinacol esters (BPin) can serve as precursors for hydroxy groups at these positions and synthetic methods have been developed for their preparation. Introduction of a boronate at position C4 was achieved through Cu-catalyzed hydroboration of a photochemically generated cyclobutene precursor, while introduction of BPin at carbon atom C8 was accomplished through a photochemical transformation starting with an alkenyl boronate. Subsequent reactions showed the oxidative transformation of boronates into the respective alcohols.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Physical
Malte Leverenz, Hendrik Brockmann, Andreas Dreuw, Thorsten Bach, Golo Storch
Summary: A strong enantiodivergence was observed in the oxadi-x-methane rearrangement of 2,4cyclohexadienones, ranging from +92% ee to -45% ee. The stereochemical outcome is determined solely by the oxazaborolidine substituents. The change in enantioselectivity is linked to a change in substrate binding, and TDDFT studies in the S1 excited state provided further mechanistic insights.
Article
Chemistry, Multidisciplinary
Johannes Grosskopf, Manuel Plaza, Roger Jan Kutta, Patrick Nuernberger, Thorsten Bach
Summary: 2,5-Diketopiperazines are cyclic dipeptides with a wide range of applications, and their enantioselective preparation can be achieved through photochemical deracemization, allowing for stereochemical editing at a single position while maintaining other stereogenic centers unaffected. The chiral benzophenone catalyst in combination with irradiation at lambda=366 nm enables the establishment of configuration at the stereogenic carbon atom C6 at will.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Lilla Koser, Thorsten Bach
Summary: The first total synthesis of (-)-5-deoxyenterocin has been accomplished, starting from pentane-1,3,5-triol with a linear sequence of 16 steps and an overall yield of 0.2%. Key steps of the synthesis include aldol reactions, hydroxylation reactions, and an intramolecular aldol reaction. Despite attempts, a functionalization reaction at position C5 was unsuccessful.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Daniel P. Schwinger, Thomas Pickl, Thorsten Bach
Summary: Cyclohept-1-ene-1-carbaldehyde undergoes photoinduced E & RARR; Z isomerization at & lambda; =350 nm. The ring strain facilitates various reactions, including Diels-Alder cycloadditions, [3 + 2] cycloadditions, and enereactions. The products obtained are trans-fusedat the cycloheptane core and yield up to 82%. Single crystal X-ray analyses confirm the structure and relative configuration. In the presence of BF3 and 2,3-dimethylbuta-1,3-diene, cyclohept-1-ene-1-carbaldehyde undergoes a stereoselective rearrangement to form a tricyclic ketone (87%).
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Morgane de Robichon, Thilo Kratz, Frederike Beyer, Julian Zuber, Christian Merten, Thorsten Bach
Summary: Substituted bicyclo[1.1.0]butanes add enantioselectively to 2(1H)-quinolones upon irradiation, leading to the formation of products with a chiral bicyclo[2.1.1]hexane skeleton. A two-point hydrogen bond between the quinolone and the template is responsible for stereocontrol in the photocycloaddition reaction. The chiral template can be recovered and reused, and sensitization is a suitable tool for performing the reaction with visible light.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Chemistry, Multidisciplinary
Johannes Grosskopf, Thorsten Bach
Summary: Upon irradiation with a suitable chiral catalyst, racemic compounds can be converted into enantiopure compounds through a process called photochemical deracemization. This review comprehensively covers the research and current developments in this field, discussing the reactions and mechanistic details underlying the presented reaction. Photochemical deracemization offers a unique opportunity to directly obtain enantiopure compounds from racemates, and short-lived intermediates play a key role in determining the enantioselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Freya M. M. Harvey, Alexandra H. H. Heidecker, Christian Merten, Thorsten Bach
Summary: Allenes with different substituents at their terminal carbon atom exhibit axial chirality and can be obtained in enantiopure form through a photochemical deracemization protocol. This study investigates the conditions under which allenoic acid derivatives undergo a Diels-Alder reaction with 1,3-cyclopentadienes and the resulting products. Cyclic derivatives (lactams, lactones) exhibited an exo-selective reaction catalyzed by the Lewis acid Eu(fod)(3), while acyclic derivatives mainly produced endo-products (with EtAlCl2 as the preferred Lewis acid). The exocyclic double bond exhibited excellent diastereoselectivity and achieved near-perfect chirality transfer. The method was successfully applied to the synthesis of sesquiterpenes beta-santalol (1) and 10(E)-beta-santalic acid (13).
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)