Transition Metal-catalyzed Reactions Research Articles

Transition Metal-Catalyzed Cross-Couplings of Benzylic Sulfone Derivatives.

In recent years, the use of organosulfones as a new class of cross-coupling partner in transition-metal catalyzed reactions has undergone significant advancement. In this personal account, our recent investigations into desulfonylative cross-coupling reactions of benzylic sulfone derivatives catalyzed by Pd, Ni, and Cu catalysis is described. Combined with the facile α-functionalizations of sulfones, our methods can be used to form valuable multiply-arylated structures such as di-, tri-, and, tetraarylmethanes from readily available substrates. The reactivity of sulfones can be increased by introducing electron-withdrawing substituents such as 3,5-bis(trifluoromethyl)phenyl and trifluoromethyl groups, which enable more challenging cross-coupling reactions. Reactive intermediates including Cu-carbene complexes were identified as key intermediates in sulfone activation, representing new types of C-SO2 bond activation processes. These results indicate sulfones are powerful functional groups, enabling new catalytic desulfonylative transformations.

The legacy of Ei-ichi Negishi: Eternal optimism and excellence

Ei-ichi Negishi will remain known for pioneering and promoting the development of transition-metal catalyzed reactions in organic synthesis as well as fostering excellence and critical thinking among his collaborators. During his lifetime, with his wife Sumire by his side, he conquered many continents: in the chemical world, his name is associated with cross-coupling, cascade reactions, carbopalladation, zirconocene chemistry, and asymmetric synthesis; in life, we remember him as a kind, generous, and approachable individual that mastered golfing, singing, and skiing, among other things.

Hang Shi.

"Chemistry is fun because you may get a surprise from your next reaction … My science 'heroes' are Robert Burns Woodward and Ernst Otto Fischer …" Find out more about Hang Shi in his Introducing … Profile.

Hang Shi

Angewandte ChemieVolume 133, Issue 40 p. 21790-21790 Introducing …Free Access Hang Shi First published: 07 August 2021 https://doi.org/10.1002/ange.202109583AboutSectionsPDF ToolsRequest permissionAdd to favorites ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract “Chemistry is fun because you may get a surprise from your next reaction … My science ‘heroes' are Robert Burns Woodward and Ernst Otto Fischer …” Find out more about Hang Shi in his Introducing … Profile. Hang Shi The author presented on this page has published his first article as a submitting corresponding author in Angewandte Chemie: “Catalytic SNAr Hydroxylation and Alkoxylation of Aryl Fluorides”: Q.-K. Kang, Y. Lin, Y. Li, L. Xu, K. Li, H. Shi, Angew. Chem. Int. Ed. 2021, 60, doi.org/10.1002/anie.202106440; Angew. Chem. 2021, 133, doi.org/10.1002/ange.202106440. Position: Assistant Professor, School of Science, Westlake University, Hangzhou (China) Homepage: hangshi.lab.westlake.edu.cn ORCID: orcid.org/0000-0002-3846-3698 Education: 2008 Bachelor degree, Hunan University (China) 2013 PhD supervised by Zhen Yang, Peking University (China) 2013–2015 Postdoc with Tobias Ritter, Harvard University (USA) 2015–2018 Postdoc with Jin-Quan Yu, Scripps Research Institute (USA) Research: Organic synthesis, catalysis Hobbies: Basketball, cartoon Chemistry is fun because you may get a surprise from your next reaction. My science “heroes” are Robert Burns Woodward and Ernst Otto Fischer. My first experiment was a Pauson–Khand reaction. I chose my current career path because I like to explore in unknown areas. A turning point in my current research project was when the reaction intermediate was successfully isolated and characterized. The most challenging part of my job is seeking a glimmer of hope from failed attempts and negative results. My favorite thing about my lab group is group trips and group meetings. I advise my students to always be patient and curious. I'm always in a good mood when I go into my lab. A good day at work starts with a cup of hot tea. If I had one year of paid leave I would travel around the world. When I was a kid I wanted to be a racing driver. My favorite molecule is bis(benzene)chromium, a sandwich compound. My favorite food is BBQ. My favorite music is pop. Behind the Science References 1Our research group aims to discover and understand new transition-metal catalyzed reactions. Given that an efficient conversion of aryl fluorides into phenols remains to be demonstrated, we started to investigate the feasibility by applying η6-coordination catalysis. In this Angewandte paper, we demonstrate a solution to prepare phenols from aryl fluorides by using a Rh catalyst. We have encountered two significant challenges: one is merging arene exchange and nucleophilic aromatic hydroxylation in one catalytic cycle; the other is tracing the elusive reaction intermediate. Google Scholar Volume133, Issue40September 27, 2021Pages 21790-21790 This is the German version of Angewandte Chemie. Note for articles published since 1962: Do not cite this version alone. Take me to the International Edition version with citable page numbers, DOI, and citation export. We apologize for the inconvenience. ReferencesRelatedInformation

Generative adversarial networks for transition state geometry prediction.

This work introduces a novel application of generative adversarial networks (GANs) for the prediction of starting geometries in transition state (TS) searches based on the geometries of reactants and products. The multi-dimensional potential energy space of a chemical reaction often complicates the location of a starting TS geometry, leading to the correct TS combining reactants and products in question. The proposed TS-GAN efficiently maps the space between reactants and products and generates reliable TS guess geometries, and it can be easily combined with any quantum chemical software package performing geometry optimizations. The TS-GAN was trained and applied to generate TS guess structures for typical chemical reactions, such as hydrogen migration, isomerization, and transition metal-catalyzed reactions. The performance of the TS-GAN was directly compared to that of classical approaches, proving its high accuracy and efficiency. The current TS-GAN can be extended to any dataset that contains sufficient chemical reactions for training. The software is freely available for training, experimentation, and prediction at https://github.com/ekraka/TS-GAN.

Synthesis, characterization and catalytic activity of a mononuclear nonheme copper(II)-iodosylbenzene adduct

Iodosylbenzene (PhIO) and its derivatives have attracted significant attention due to their various applications in organic synthesis and biomimetic studies. For example, PhIO has been extensively used for generating high-valent metal-oxo species that have been regarded as key intermediates in diverse oxidative reactions in biological system. However, recent studies have shown that metal-iodosylbenzene adduct, known as a precursor of metal-oxo species, plays an important role in transition metal-catalyzed oxidation reactions. During last few decades, extensive investigations have been conducted on the synthesis and reactivity studies of metal-iodosylbenzene adducts with early and middle transition metals including manganese, iron, cobalt. Nevertheless, metal-iodosylbenzene adducts with late transition metals such as nickel, copper and zinc, still remains elusive. Herein, we report a novel copper(II)-iodosylbenzene adduct bearing a linear ligand composed of two pyridine rings and an ethoxyethanol side-chain, [Cu(OIPh)(HN3O2)]2+ (1). The copper(II)-iodosylbenzene adduct was characterized by several spectroscopic methods including UV–vis spectroscopy, electrospray ionization mass spectrometer (ESI MS), and electron paramagnetic resonance (EPR) combined with theoretical calculations. Interestingly, 1 can carry out the catalytic sulfoxidation reaction. In sulfoxidation reaction with thioanisole under catalytic reaction condition, not only two-electron but also four-electron oxidized products such sulfoxide and sulfone were yielded, respectively. However, 1 was not an efficient oxidant towards CH bond activation and epoxidation reactions due to the steric hindrance created by the intramolecular H-bonding interaction between HN3O2 ligand and iodosylbenzene moiety.

Facile Approach to C-Glucosides by Using a Protecting-Group-Free Hiyama Cross-Coupling Reaction: High-Yielding Dapagliflozin Synthesis.

Invited for the cover of this issue is Kamil Parkan and co-workers at University of Chemistry and Technology and Institute of Organic Chemistry and Biochemistry, Prague. The cover graphic depicts a schematic representation of the assembly of aryl-C-glycosides based on a protecting-group-free Hiyama reaction. Read the full text of the article at 10.1002/chem.202101052.

Base-Catalyzed, Solvent-Free Synthesis of Rigid V-Shaped Epoxydibenzo[b,f][1,5]diazocines.

A novel method for the synthesis of epoxydibenzo[b,f][1,5]diazocines exhibiting a V-shaped molecular architecture is reported. The unique approach is based on unprecedented base-catalyzed, solvent-free autocondensation and cross-condensation of fluorinated o-aminophenones. The structure of the newly synthesized diazocines was confirmed independently by X-ray analysis and chiroptical methods. The rigidity of the diazocine scaffold allowed for the separation of the racemate into single enantiomers that proved to be thermally stable up to 140 °C. Furthermore, the inertness of the diazocine scaffold was demonstrated by performing a series of typical transformations, including transition metal-catalyzed reactions, proceeding without affecting the bis-hemiaminal subunit.

Copper-Catalyzed Ring-Opening/Borylation of Cyclopropenes

Copper-Catalyzed Ring-Opening/Borylation of Cyclopropenes

A Computational Mechanistic Study of Cp*Co(III)-Catalyzed Three-Component C-H Bond Addition to Terpenes and Formaldehydes: Insights into the Origins of Regioselectivity.

Transition metal-catalyzed three-component reactions of arenes, dienes, and carbonyls enable the convergent synthesis of homoallylic alcohols. Controlling regioselectivity is a central challenge for the difunctionalization of substituted 1,3-dienes in which multiple unbiased C═C bonds exist. Here, the mechanisms of Cp*Co(III)-catalyzed three-component C-H bond addition to terpenes and formaldehydes were investigated by density functional theory calculations. The reaction proceeds via sequential C(sp2)-H activation, migratory insertion, β-hydride elimination, hydride reinsertion, and C-C bond formation to yield the final product. The migratory insertion is the rate- and regioselectivity-determining step of the overall reaction. We employed an energy decomposition approach to quantitatively dissect the contributions of different types of interactions to regioselectivity. For the 2-alkyl substituted 1,3-dienes, the orbital interactions in the 3,4-insertion are intrinsically more favorable as compared to that in the 4,3-insertion, while the stronger steric effects between metallacycle and 1,3-diene override the intrinsic electronic preference. However, the steric effects failed to rationalize the unfavorable 1,2-insertion that is analogous to 4,3-insertion and even bears smaller steric effects. The donor-acceptor interaction analysis indicates that orbital interactions between σCo-C and πC═C decreased significantly in the 1,2-insertion transition state, which leads to higher activation energy barriers. These insights into the dominant effects controlling regioselectivity will enable rational design of new catalysts for selective functionalization of dienes.

Multiwavelets applied to metal-ligand interactions: Energies free from basis set errors.

Transition metal-catalyzed reactions invariably include steps where ligands associate or dissociate. In order to obtain reliable energies for such reactions, sufficiently large basis sets need to be employed. In this paper, we have used high-precision multiwavelet calculations to compute the metal-ligand association energies for 27 transition metal complexes with common ligands, such as H2, CO, olefins, and solvent molecules. By comparing our multiwavelet results to a variety of frequently used Gaussian-type basis sets, we show that counterpoise corrections, which are widely employed to correct for basis set superposition errors, often lead to underbinding. Additionally, counterpoise corrections are difficult to employ when the association step also involves a chemical transformation. Multiwavelets, which can be conveniently applied to all types of reactions, provide a promising alternative for computing electronic interaction energies free from any basis set errors.

Palladium-Catalyzed Three-Component Coupling Reaction via Benzylpalladium Intermediate.

Transition-metal catalyzed multi-component reactions have captured the attention of researchers in organic synthesis and drug synthesis due to their advantages of simple operation, easy availability of raw materials and without separation of intermediates. Among the multi-component reactions, the three-component processes have been developed into effective organic procedures. This personal account reviews our and other group's studies on the development of three-component coupling reaction for the rapid construction of two new chemical bonds simultaneously via benzylpalladium intermediates. Catalyst-switched three-component reactions of benzyl halides, activated olefins, and allyltributylstannane were successfully conducted to produce the corresponding benzylallylation products. Activation and conversion of carbon monoxide and carbon dioxide via π-benzylpalladium intermediates provide access to a wide range of unsaturated ketones and esters with excellent functional group tolerance. Meanwhile, other methods to produce benzylpalladium intermediates, including Heck insertion of alkenes into arylpalladium complexes, the oxidative addition of benzyl carbonate to palladium complexes and palladium-carbene migratory insertion, were also highlighted.

Programmed Multiple C-H Bond Functionalization of the Privileged 4-hydroxyquinoline Template.

The introduction of substituents on bare heterocyclic scaffolds can selectively be achieved by directed C-H functionalization. However, such methods have only occasionally been used, in an iterative manner, to decorate various positions of a medicinal scaffold to build chemical libraries. We herein report the multiple, site selective, metal-catalyzed C-H functionalization of a "programmed" 4-hydroxyquinoline. This medicinally privileged template indeed possesses multiple reactive sites for diversity-oriented functionalization, of which four were targeted. The C-2 and C-8 decorations were directed by an N-oxide, before taking benefit of an O-carbamoyl protection at C-4 to perform a Fries rearrangement and install a carboxamide at C-3. This also released the carbonyl group of 4-quinolones, the ultimate directing group to functionalize position 5. Our study highlights the power of multiple C-H functionalization to generate diversity in a biologically relevant library, after showing its strong antimalarial potential.

Copper-Catalyzed Carbonylative Coupling of Alkyl Halides.

Transition metal-catalyzed carbonylation reactions represent a direct and atom-economical approach to introduce oxygen functionality into organic compounds, with CO acting as an inexpensive and readily available C1 feedstock. Despite the long history of carbonylation catalysis, including many processes that have been industrialized at bulk scale, there remain several challenges to tackle. For example, noble metals such as Pd, Rh, and Ir are typically used as catalysts for carbonylation reactions, rather than earth-abundant alternatives. Additionally, while carbonylation of C(sp2)-hybridized substrates (e.g., aryl halides) is well-known, carbonylation of unactivated alkyl electrophiles, especially where β-hydride elimination can compete with desired CO migratory insertion at the catalyst site, remains challenging for many systems. Recently, base metal catalysis based on Mn, Co, and other metals has enabled advances in carbonylative coupling of alkyl electrophiles, though the nucleophiles are often limited to alcohols or amines to generate esters or amides as products. Thus, we have targeted base metal-catalyzed carbonylative C-C and C-E (E = N, H, Si, B) coupling reactions as a method for approaching diverse carbonyl compounds of synthetic importance.Initially, we designed a heterobimetallic catalyst platform for carbonylative C-C coupling of alkyl halides with arylboronic esters (i.e., carbonylative Suzuki-Miyaura coupling) to generate aryl alkyl ketones. Subsequently, we developed multicomponent carbonylation reactions of alkyl halides using NHC-Cu catalysts (NHC = N-heterocyclic carbene). These reactions operate by radical mechanisms, converting alkyl halides into either acyl radical or acyl halide intermediates that undergo subsequent C-C or C-E coupling at the Cu site. This mechanistic paradigm is relatively novel in the metal-catalyzed carbonylation area, allowing us to discover a previously unexplored chemical space in carbonylative coupling catalysis. We have successfully developed the following reactions: (a) hydrocarbonylative coupling of alkynes with alkyl halides; (b) borocarbonylative coupling of alkynes with alkyl halides; (c) reductive aminocarbonylation of alkyl halides with nitroarenes; (d) reductive carbonylation of alkyl halides; (e) carbonylative silylation of alkyl halides; (f) carbonylative borylation of alkyl halides. These reactions provide a broad range of valuable products including ketones, allylic alcohols, β-borylenones, amides, alcohols, acylsilanes, and acylborons in an efficient manner. Notably, the preparation of some of these products has previously required multistep syntheses, harsh conditions, or specialized reagents. By contrast, the multicomponent coupling platform that we have developed requires only readily available building blocks and rapidly increases molecular complexity in a single synthetic manipulation.

Transition metal-catalyzed reactions of N-sulfinyl imines

Transition metal-catalyzed reactions of N-sulfinyl imines with several substrates lead to the corresponding chiral amines with high yields and diastereo- or enantioselectivities. As metals, titanium, copper, ruthenium, rhodium, palladium and silver have been successfully used as catalysts in different carbon–carbon forming reactions as well as hydrogenations with molecular hydrogen or transfer hydrogenations with isopropanol as hydrogen source.

Recent Development of Aryl Diazonium Chemistry for the Derivatization of Aromatic Compounds

Aryl diazonium salts are versatile building blocks in organic synthesis. In light of the ever-increasing importance of aryl diazonium salts spanning most disciplines of the chemical sciences, we review the recent development of aryl diazonium chemistry over the past seven years (2013-2020). Special emphasis is put on various new transformations involving the generation of radical intermediates via thermal, photochemical, and electrochemical means. Recent advances in the development of transition metal-catalyzed reactions using aryl diazonium salts are also reviewed. Together, these newly developed transformations significantly expand the synthetic chemist's repertoire of aromatic carbon-carbon and carbon-heteroatom bond forming methods using aryl diazonium precursors, providing powerful tools for the synthesis and modification of complex molecular scaffolds.

Ruthenium-Catalyzed Enantioselective Propargylic Phosphinylation of Propargylic Alcohols with Phosphine Oxides.

The development of transition metal-catalyzed enantioselective propargylic substitution reactions has gained much progress in recent years, however, no successful example with phosphorus-centered nucleophiles has yet been reported until now. Herein, we report the first successful example of ruthenium-catalyzed enantioselective propargylic substitution reactions of propargylic alcohols with diarylphosphine oxides as phosphorus-centered nucleophiles. This synthetic approach provides a new method to prepare chiral phosphorus-containing organic compounds.

Aerobic Heterogeneous Palladium-Catalyzed Oxidative Allenic C−H Arylation: Benzoquinone as a Direct Redox Mediator between O 2 and Pd

Transition metal-catalyzed aerobic oxidative reactions using molecular oxygen as the terminal oxidant play a significant role in organic synthesis. Benzoquinone (BQ) has been widely used as an elec...

An Updated Coverage on the Synthesis of Benzo[b]thiophenes via Transition-metalcatalyzed Reactions: A Review

The benzo[b]thiophene nucleus is ubiquitous in biologically and pharmaceutically important compounds. These moieties are highly important in materials science. The synthesis of benzothiophene as a privileged structure has readily become a subject of great interest and actively pursued in recent years. This review focuses on facile and convenient methods of synthesis of benzo[b]thiophene based molecules through different transition metals catalyzed reactions.

Iridium-catalyzed Z-retentive asymmetric allylic substitution reactions.

Z-Olefins are challenging synthetic targets owing to their relative thermodynamic instability. Transition metal-catalyzed asymmetric allylic substitution reactions are well known for installing stereocenters adjacent to branched or E-linear olefins. However, analogous reactions for the synthesis of optically active Z-olefin products are rare. Here we report iridium-catalyzed asymmetric allylic substitution reactions that retain Z-olefin geometries while establishing an adjacent quaternary stereocenter. The formation of transient anti-π-allyl-iridium intermediates and their capture by external nucleophiles before isomerization to the thermodynamically more stable syn-π-allyl-iridium counterparts have been observed. These results provide a promising method for preparing chiral Z-olefinic compounds.