Review
Chemistry, Organic
Claire Empel, Sripati Jana, Rene M. Koenigs
Summary: This review article summarizes the progress made on [1,2]-sigmatropic rearrangements using carbenes in the ylide formation step, highlighting the application of diazoalkanes as carbene precursors and the formation and application of various ylide species.
SYNTHESIS-STUTTGART
(2021)
Article
Chemistry, Multidisciplinary
Fang Li, Chao Pei, Rene M. Koenigs
Summary: Our studies on the reaction of organoselenium compounds with triazoles reveal two different cascade reactions, shedding light on the multiple roles of organoselenium compounds in rearrangement reactions and mediating a free ylide reaction mechanism. Theoretical and experimental studies were conducted to provide an understanding of the reaction mechanism.
Article
Chemistry, Multidisciplinary
Sripati Jana, Chao Pei, Claire Empel, Rene M. Koenigs
Summary: Controlling the reactivity of diaryl carbenes can be achieved by manipulating the electronic properties of the substituents, allowing for highly chemoselective carbene transfer reactions without the need for external additives. Photolysis of diazo compounds can readily access the free diaryl carbenes, which can then undergo various chemoselective reactions. Experimental and theoretical analyses confirm the involvement of different carbene spin states in rationalizing the observed reactivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Caroline R. Pharr, Brian J. Esselman, Robert J. McMahon
Summary: This study experimentally verified the specific chemical reaction process of 1-(3-thienyl)diazoethane through photolysis, exploring its relationship with hydrogen migration and quantum mechanical tunneling effects.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Lennard Kloene, Sripati Jana, Claire Empel, Rene M. Koenigs
Summary: Sigmatropic rearrangement reactions are widely used in drug discovery and natural product synthesis for constructing small complex molecules. In this study, we applied aryl/aryl diazoalkanes in rhodium-catalyzed sigmatropic rearrangement reactions of allyl sulfides, and achieved high yields of desired products with compatibility for various allyl sulfides and diazoalkanes.
AUSTRALIAN JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Organic
Jiwon Jang, Hanbyul Kim, Seunghoon Shin
Summary: This study reports a revised mechanism for the gold-catalyzed enantioselective thioallylation of propiolates, which delivers highly enantio-enriched alpha-allyl-beta-thioacrylates. The research reveals that the competitive binding of thioethers as nucleophiles to the catalytic site inhibits its activity. The revised mechanism suggests that the conjugate addition of thioethers is the slowest step, followed by a rapid rearrangement, indicating the efficacy of the sulfonium-based approach in accelerating Claisen rearrangement.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Natalia Guranova, Dmitry Dar'in, Grigory Kantin, Mikhail Krasavin
Summary: The formation of oxonium ylide species through Rh(II) catalysis using alpha-diazo glutaconimides with tetrahydrofuran and 1,4-dioxane resulted in low-yielding spirocycle formation with THF, while higher-yielding results were observed with 1,4-dioxane. Different solvents led to different reaction pathways and by-products.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Sripati Jana, Claire Empel, Thanh Vinh Nguyen, Rene M. Koenigs
Summary: The study demonstrates a multiple C-H functionalization reaction of carbazole heterocycles with diazoalkanes using gold catalysts, enabling the introduction of up to six carbene fragments or linking multiple carbazole units into a single molecule. A one-pot stepwise approach allows for the introduction of two different carbene fragments, facilitating orthogonal deprotection and straightforward derivatization.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Claire Empel, Chao Pei, Feifei He, Sripati Jana, Rene M. Koenigs
Summary: In this study, the reaction of diazoalkanes with alcohols was investigated through experimental and theoretical studies. A protonation-addition mechanism was proposed, and the method showed broad application in O-H functionalization reactions of alcohols with various functional groups.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Review
Chemistry, Multidisciplinary
Arturs Sperga, Janis Veliks
Summary: This review discusses the synthesis methods of monofluorinated compounds and their applications in the synthesis of organofluorine compounds. The use of monofluorinated carbenes and related reactive species allows for the formation of C-C or C-X bonds while introducing valuable fluorine atoms into the target structure.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Keigo Saito, Hiroshi Aoyama, Makoto Sako, Kenichi Murai, Mitsuhiro Arisaw
Summary: A double ring expansion strategy for constructing fused 3-benzazepines was developed. The strategy involved oxidative ring expansion of spiroamine compounds and subsequent ring expansion of ketiminium ion intermediates. Moreover, the synthesis of Dolby-Weinreb enamine, a key intermediate for harringtonine alkaloids and cephalotaxines, was achieved in only two steps using this method.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Hiroki Tashiro, Masahiro Terada, Itaru Nakamura
Summary: Gold-catalyzed reactions were used to synthesize 2H-azirines with sulfenyl and acyl groups at the 3-position, yielding good to excellent results. These reactions involved internal transfer of sulfinyl oxygen atom and carbene insertion into the N-S bond for ring construction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Duo Fu, Jiaxi Xu
Summary: A Halide-promoted pyridinylation reaction between alpha-acyl sulfonylmethylides and 2-halo-1-methylpyridinium iodides in a transition-metal-free protocol is described. This method offers a facile and practical approach for constructing methylthio- and pyridinoxyl-substituted vinylsulfones. The reaction involves the formation of a C-O bond and consecutive breaking of C-S, C-Cl and C-N bonds.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Sripati Jana, Yujing Guo, Rene M. Koenigs
Summary: Sigmatropic rearrangements, known for over a century, have recently been increasingly utilized in organic synthesis through carbene transfer reactions. These processes involve sigma-bond cleavage, formation of a new bond between pi-bond and negatively charged atom, and redistribution of pi-electrons. Recent advances in this research area have led to the development of metal-catalyzed enantioselective sigmatropic rearrangements, metal-free photochemical rearrangements, and novel reaction pathways utilizing ylide intermediates.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Organic
M. Pilar Romero-Fernandez, Pedro Cintas, Sergio Rojas-Buzo
Summary: This study revisits the reactivity of thiazol-3-ium-4-olates with alkynes, and demonstrates that the structural variation of mesoionic rings can influence the steric outcome, leading to the regioselective formation of either five- or six-membered heterocycles. Microwave activation is found to enhance reaction rates, and density functional theory calculations provide insights into the mechanism of the reaction.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Fang Li, Chao Pei, Rene M. Koenigs
Summary: The study describes a photocatalytic approach for accessing triplet carbene intermediates via energy transfer to conduct efficient gem-difluoroolefination reactions, with the key role played by tertiary amines. The research explores a wide substrate scope, ranging from simple olefins to pharmaceutically relevant building blocks.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Tuong Anh To, Chao Pei, Rene M. Koenigs, Thanh Vinh Nguyen
Summary: In this study, the promotion of carbonyl-olefin metathesis reactions by hydrogen-bonding-assisted Bronsted acid catalysis was investigated. The role of hexafluoroisopropanol (HFIP) solvent in assisting the pTSA Bronsted acid catalyst and the current limitations of the carbonyl-olefin metathesis reaction were revealed through experimental and computational mechanistic studies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Claire Empel, Chao Pei, Rene M. Koenigs
Summary: This article provides a concise overview of photolysis reactions of diazoalkanes in photochemistry. It covers the discoveries in physical organic chemistry, examples of singlet carbene intermediates in organic synthesis, advances in cascade reactions and unusual protonation reactions under photochemical conditions. It also discusses the electronic control of singlet and triplet carbene intermediates and the recent advances in using weakly colored diazoalkanes in dye-sensitized reactions to access radical or triplet carbene intermediates.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Bao-Gui Cai, Qian Li, Claire Empel, Lei Li, Rene M. Koenigs, Jun Xuan
Summary: In this study, we reported the visible light and N-heterocyclic carbene (NHC) jointly promoted multicomponent carbene transfer reactions. Two kinds of important hydroxamic acid esters were obtained in good yields under optimized reaction conditions depending on the reaction media used. The utility and practicality of this method were demonstrated through mild reaction conditions, excellent functional group tolerance, useful synthetic transformations, and successful modification of natural products and drug molecules.
Article
Chemistry, Organic
Yue Zhao, Claire Empel, Wenjing Liang, Rene M. Koenig, Frederic W. Patureau
Summary: In this study, an unprecedented gem-difluoroallylation reaction of aryl sulfonium salts formed by direct functionalization was described. The method showed mild reaction conditions, wide applicability, and excellent selectivity.
Article
Chemistry, Organic
Chao Pei, Claire Empel, Rene M. Koenigs
Summary: In this study, a photochemical, chemoselective reaction between aryldiazoacetates and allylic alcohols was reported. This reaction efficiently furnishes cyclopropane-fused lactone skeletons in one step. The diastereoselectivity of the reaction was precisely controlled, and chemoselective cyclopropanation of allylic alcohols followed by transesterification produced a series of bicyclic lactones in high yield without the formation of ether byproducts via typical O-H insertion reactions.
Article
Chemistry, Multidisciplinary
Claire Empel, Sripati Jana, Lukasz W. Ciszewski, Katarzyna Zawada, Chao Pei, Dorota Gryko, Rene M. Koenigs
Summary: In this paper, the photocatalytic reaction of ethyl diazoacetate with indole is reported, showing an unusual solvent dependency. C2-functionalization occurs under protic conditions, while aprotic solvents lead to exclusive C3-functionalization. The reaction mechanism involves a triplet carbene intermediate and a cationic [1,2]-alkyl radical migration.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Multidisciplinary Sciences
Luca De Angelis, Chao Pei, Ana L. Narro, Daniel Wherritt, Rene M. Koenigs, Michael P. Doyle
Summary: The synthesis and characterization of organic compounds with unique atom or functional group connectivity is a significant interest for chemists. Polycarbonyl compounds, in which multiple carbonyl groups are directly adjacent and influence each other's reactivity, have been extensively studied. However, little is known about 1,2,3,4-tetracarbonyl compounds. In this study, a synthesis strategy involving C-nitrosation of enoldiazoacetates is reported, which allows for the synthesis of 1,2,3,4-tetracarbonyl compounds where each carbonyl group is orthogonally masked.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Hao Fang, Claire Empel, Iuliana Atodiresei, Rene M. Koenigs
Summary: Palladium-catalyzed cross-coupling reactions are important transformations for building C-C or C-heteroatom bonds. Recently, the use of photochemical activation of palladium complexes has expanded the scope of palladium catalysis beyond conventional cross-coupling chemistry. In this study, the photoinduced palladium-catalyzed 1,2-difunctionalization reaction of electron-rich olefins was investigated. Mechanistic experiments and computational studies revealed that this reaction proceeds through the addition of an alkyl radical and oxidation of a radical intermediate to access carbocation intermediates. These carbocation intermediates can then participate in various secondary C-C or C-N bond-forming reactions, enabling the synthesis of densely functionalized unsymmetric 1,1-bis(heterocyclyl)alkanes.
Article
Chemistry, Multidisciplinary
Bao-Gui Cai, Claire Empel, Wei-Zhong Yao, Rene M. Koenigs, Jun Xuan
Summary: The azoxy functional group is an important structural motif, and its synthesis, especially unsymmetric azoxy compounds, remains underdeveloped. In this study, we designed a method using readily accessible nitroso compounds and iminoiodinanes to synthesize sulfonyl-protected azoxy compounds. Visible light irradiation was used to generate a triplet nitrene from iminoiodinanes, which then reacted with nitroso arenes. The resulting sulfonyl-protected azoxy compounds showed good substrate scope and functional group tolerance. We also demonstrated the use of these compounds as radical precursors in two synthesis applications without the need for photoredox catalysts and additives.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Bao-Gui Cai, Claire Empel, Sripati Jana, Jun Xuan, Rene M. Koenigs
Summary: In this study, the synthesis of gem-dialkyl cyclopropanes using in situ-generated dialkyl diazo compounds under Bamford-Stevens conditions is reported. A simple cobalt catalyst was found to be the optimal choice for achieving high yields. Experimental and computational studies suggest the involvement of a metalloradical reaction mechanism, which enables carbene transfer reactions and provides a one-step access to dialkyl-substituted cyclopropanes.
Article
Chemistry, Physical
Bao-Gui Cai, Claire Empel, Sripati Jana, Jun Xuan, Rene M. Koenigs
Summary: The synthesis of dialkyl-substituted cyclopropanes, which has applications in drug discovery and agrochemistry, is a challenging task. This study presents a method for synthesizing gem-dialkyl cyclopropanes using in situ-generated dialkyl diazo compounds under Bamford-Stevens conditions. The use of a simple cobalt catalyst was found to be optimal for achieving high yields. Both experimental and computational studies suggest that a metalloradical reaction mechanism facilitates the carbene transfer reactions, enabling the one-step synthesis of dialkyl-substituted cyclopropanes.
Article
Chemistry, Multidisciplinary
Lennard Kloene, Sripati Jana, Claire Empel, Rene M. Koenigs
Summary: Sigmatropic rearrangement reactions are widely used in drug discovery and natural product synthesis for constructing small complex molecules. In this study, we applied aryl/aryl diazoalkanes in rhodium-catalyzed sigmatropic rearrangement reactions of allyl sulfides, and achieved high yields of desired products with compatibility for various allyl sulfides and diazoalkanes.
AUSTRALIAN JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Bao-Gui Cai, Ye-Peng Bao, Chao Pei, Qian Li, Lei Li, Rene M. Koenigs, Jun Xuan
Summary: This paper reports on the photochemical reaction of diazoalkanes with azodicarboxylates, wherein a triplet species formed upon photoexcitation reacts with diazoalkanes to generate an azomethine ylide, followed by dipolar cycloaddition reaction with organic nitriles to form 1,2,4-triazoles. The reaction exhibits broad substrate scope and can be scaled up via flow chemistry and downstream transformations.
Article
Chemistry, Multidisciplinary
Fang Li, Siqi Zhu, Rene M. Koenigs
Summary: This study reports on the photocatalytic 1,2-difunctionalization reaction of styrenes with acceptor-only diazoalkanes. By using DABCO and tBuOOH, the carbene reactivity of diazoalkanes can be suppressed, allowing for a 1,2 oxo-alkylation reaction to occur with high yield (up to 94%), without the formation of cyclopropane by-products via radical intermediates from ethyl diazoacetate.
CHEMICAL COMMUNICATIONS
(2022)
