Medium and Large N-Heterocycle Formation via Allene Hydroamination with a Bimetallic Rh(I) Catalyst

We report the synthesis of a bimetallic Rh(I) complex containing a bridging CO ligand that facilitates Rh–Rh bond formation. This bimetallic complex enables intramolecular allene hydroamination to form seven to ten-member rings in high yield. Monometallic Rh complexes, in contrast, fail to achieve any product formation. We demonstrate a broad substrate scope for formation of a variety of N-heterocycles in good to excellent yields. Macrocyclization reactions that form eleven to fifteen-membered heterocycles are also demonstrated. Mechanistic studies show that the reaction likely proceeds via catalyst protonation by trifluoroacetic acid, followed by reversible allene insertion and C–N bond-forming reductive elimination. The difference in product selectivity observed with our bimetallic catalyst vs monometallic Rh complexes may result from cooperativity between the two metals.

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Cu(OTf)2-Mediated Ionizing Cross-Coupling of N(sp) and N(sp2) with Arylboronic Acids

10.26434/chemrxiv.13399307.v1 ◽

2020 ◽

Author(s):

Allan Watson ◽

Nicola Bell ◽

Chao Xu ◽

James Fyfe ◽

Julien Vantourout ◽

...

Keyword(s):

Late Stage ◽

Cross Coupling ◽

Reductive Elimination ◽

Subsequent Generation ◽

Mechanistic Studies ◽

Arylboronic Acids ◽

Bond Forming ◽

Drug Synthesis ◽

C And N ◽

Metal Catalyzed

Metal-catalyzed C–N cross-coupling generally forms C–N bonds by reductive elimination from metal complexes bearing covalent C- and N-ligands. We have identified a Cu-mediated C–N cross-coupling that uses a dative N-ligand in the bond forming event, which, in contrast to conventional methods, generates reactive cationic products. Mechanistic studies suggest the process operates via transmetalation of an aryl organoboron to a Cu(II) complex bearing neutral N-ligands, such as nitriles or N-heterocycles. Subsequent generation of a putative Cu(III) complex enables the oxidative C–N coupling to take place, delivering nitrilium intermediates and pyridinium products. The reaction is general for a range of N(sp) and N(sp2) precursors and can be applied to drug synthesis and late-stage N-arylation, and the limitations in the methodology are mechanistically evidenced.

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Palladium-Catalyzed C−P Bond Formation: Mechanistic Studies on the Ligand Substitution and the Reductive Elimination. An Intramolecular Catalysis by the Acetate Group in PdIIComplexes

Organometallics ◽

10.1021/om800641n ◽

2008 ◽

Vol 27 (22) ◽

pp. 5876-5888 ◽

Cited By ~ 61

Author(s):

Marcin Kalek ◽

Jacek Stawinski

Keyword(s):

Bond Formation ◽

Ligand Substitution ◽

Reductive Elimination ◽

Acetate Group ◽

Mechanistic Studies ◽

Intramolecular Catalysis ◽

Palladium Catalyzed

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Cu(OTf)2-Mediated Ionizing Cross-Coupling of N(sp) and N(sp2) with Arylboronic Acids

10.26434/chemrxiv.13399307 ◽

2020 ◽

Author(s):

Allan Watson ◽

Nicola Bell ◽

Chao Xu ◽

James Fyfe ◽

Julien Vantourout ◽

...

Keyword(s):

Late Stage ◽

Cross Coupling ◽

Reductive Elimination ◽

Subsequent Generation ◽

Mechanistic Studies ◽

Arylboronic Acids ◽

Bond Forming ◽

Drug Synthesis ◽

C And N ◽

Metal Catalyzed

Metal-catalyzed C–N cross-coupling generally forms C–N bonds by reductive elimination from metal complexes bearing covalent C- and N-ligands. We have identified a Cu-mediated C–N cross-coupling that uses a dative N-ligand in the bond forming event, which, in contrast to conventional methods, generates reactive cationic products. Mechanistic studies suggest the process operates via transmetalation of an aryl organoboron to a Cu(II) complex bearing neutral N-ligands, such as nitriles or N-heterocycles. Subsequent generation of a putative Cu(III) complex enables the oxidative C–N coupling to take place, delivering nitrilium intermediates and pyridinium products. The reaction is general for a range of N(sp) and N(sp2) precursors and can be applied to drug synthesis and late-stage N-arylation, and the limitations in the methodology are mechanistically evidenced.

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Radical Capture at Ni(II) Complexes: C-C, C-N, and C-O Bond Formation

10.26434/chemrxiv.8115860.v1 ◽

2019 ◽

Author(s):

Abolghasem (Gus) Bakhoda ◽

Stefan Wiese ◽

Christine Greene ◽

Bryan C. Figula ◽

Jeffery A. Bertke ◽

...

Keyword(s):

Functional Groups ◽

Bond Formation ◽

Dft Studies ◽

Bond Forming ◽

Aryl Amines ◽

Shed Light ◽

Competing Pathways

The dinuclear b-diketiminato NiIItert-butoxide {[Me3NN]Ni}2(μ-OtBu)2 (2), synthesized from [Me3NN]Ni(2,4-lutidine) (1) and di-tert-butylperoxide, is a versatile precursor for the synthesis of a series of NiIIcomplexes [Me3NN]Ni-FG to illustrate C-C, C-N, and C-O bond formation at NiII via radicals. {[Me3NN]Ni}2(μ-OtBu)2 reacts with nitromethane, alkyl and aryl amines, acetophenone, benzamide, ammonia and phenols to deliver corresponding mono- or dinuclear [Me3NN]Ni-FG species (FG = O2NCH2, R-NH, ArNH, PhC(O)NH, PhC(O)CH2, NH2and OAr). Many of these NiII complexes are capable of capturing the benzylic radical PhCH(•)CH3 to deliver corresponding PhCH(FG)CH3 products featuring C-C, C-N or C-O bonds. DFT studies shed light on the mechanism of these transformations and suggest two competing pathways that depend on the nature of the functional groups. These radical capture reactions at [NiII]-FG complexes outline key C-C, C-N, and C-O bond forming steps and suggest new families of nickel radical relay catalysts.

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Iridium-Catalyzed Silylation of C-H bonds in Unactivated Arenes: A Sterically-Encumbered Phenanthroline Ligand Accelerates Catalysis Enabling New Reactivity

10.26434/chemrxiv.7744175 ◽

2019 ◽

Author(s):

Caleb Karmel ◽

Zhewei Chen ◽

John Hartwig

Keyword(s):

High Activity ◽

Functional Group ◽

Activity Analysis ◽

High Reactivity ◽

High Yield ◽

Phen Ligand ◽

Mechanistic Studies ◽

Phenanthroline Ligand ◽

First Time ◽

New System

We report a new system for the silylation of aryl C-H bonds. The combination of [Ir(cod)(OMe)]2 and 2,9-Me2-phenanthroline (2,9-Me2phen) catalyzes the silylation of arenes at lower temperatures and with faster rates than those reported previously, when the hydrogen byproduct is removed, and with high functional group tolerance and regioselectivity. Inhibition of reactions by the H2 byproduct is shown to limit the silylation of aryl C-H bonds in the presence of the most active catalysts, thereby masking their high activity. Analysis of initial rates uncovered the high reactivity of the catalyst containing the sterically hindered 2,9-Me2phen ligand but accompanying rapid inhibition by hydrogen. With this catalyst, under a flow of nitrogen to remove hydrogen, electron-rich arenes, including those containing sensitive functional groups, undergo silylation in high yield for the first time, and arenes that underwent silylation with prior catalysts react over much shorter times with lower catalyst loadings. The synthetic value of this methodology is demonstrated by the preparation of key intermediates in the synthesis of medicinally important compounds in concise sequences comprising silylation and functionalization. Mechanistic studies demonstrate that the cleavage of the aryl C-H bond is reversible and that the higher rates observed with the 2,9-Me2phen ligand is due to a more thermodynamically favorable oxidative addition of aryl C-H bonds.

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Connecting Remote C–H Bond Functionalization and Decarboxylative Coupling Using Simple Amines

10.26434/chemrxiv.9863363.v1 ◽

2019 ◽

Author(s):

Francisco de Azambuja ◽

Ming-Hsiu Yang ◽

Alexander Bruecker ◽

Paul Cheong ◽

Ryan Altman

Keyword(s):

Organic Molecules ◽

Mechanistic Studies ◽

Bond Functionalization ◽

Bond Forming ◽

Decarboxylative Coupling

The manuscript describes a Pd-catalyzed reaction of benzylic electrophiles that gives para-substituted arene products. Mechanistic studies suggest a mechanism involving a dearomative C–C bond-forming step, followed by base-mediated rearomatization. This mechanism is uncommon and underappreciated in Pd-catalysis and further exploitation of this mechanism should enable access to other organic molecules.

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Design and Development of Fe-Catalyzed Intra- and Intermolecular Carbofunctionalization of Vinyl Cyclopropanes

10.26434/chemrxiv.9858500.v1 ◽

2019 ◽

Cited By ~ 1

Author(s):

Lei Liu ◽

Wes Lee ◽

Mingbin Yuan ◽

Chris Acha ◽

Michael B. Geherty ◽

...

Keyword(s):

Bond Formation ◽

Cross Coupling ◽

Alkyl Halides ◽

Grignard Reagents ◽

Mechanistic Studies ◽

Radical Intermediates ◽

Design And Implementation ◽

Solvent Cage ◽

Radical Cascade ◽

Radical Processes

Design and implementation of the first (asymmetric) Fe-catalyzed intra- and intermolecular difunctionalization of vinyl cyclopropanes (VCPs) with alkyl halides and aryl Grignard reagents has been realized via a mechanistically driven approach. Mechanistic studies support the diffusion of the alkyl radical intermediates out of the solvent cage to participate in an intra- or -intermolecular radical cascade with the VCP followed by re-entering the Fe radical cross-coupling cycle to undergo selective C(sp2)-C(sp3) bond formation. Overall, we provide new design principles for Fe-mediated radical processes and underscore the potential of using combined computations and experiments to accelerate the development of challenging transformations.

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Recent Advances on C-Se Bond-forming Reactions at Low and Room Temperature

Current Organic Chemistry ◽

10.2174/1385272823666191209111934 ◽

2020 ◽

Vol 23 (28) ◽

pp. 3206-3225 ◽

Cited By ~ 5

Author(s):

Amol D. Sonawane ◽

Mamoru Koketsu

Keyword(s):

Room Temperature ◽

Bond Formation ◽

Bond Forming ◽

Material Chemistry ◽

Recent Advances ◽

Bond Forming Reactions ◽

Bond Formation Reactions

: Over the last decades, many methods have been reported for the synthesis of selenium- heterocyclic scaffolds because of their interesting reactivities and applications in the medicinal as well as in the material chemistry. This review describes the recent numerous useful methodologies on C-Se bond formation reactions which were basically carried out at low and room temperature.

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Microwave-accelerated Carbon-carbon and Carbon-heteroatom Bond Formation via Multi-component Reactions: A Brief Overview

Current Microwave Chemistry ◽

10.2174/2213346107666200218124147 ◽

2020 ◽

Vol 7 (1) ◽

pp. 23-39 ◽

Cited By ~ 2

Author(s):

Kantharaju Kamanna ◽

Santosh Y. Khatavi

Keyword(s):

Organic Synthesis ◽

Bond Formation ◽

Cycloaddition Reaction ◽

Nanoparticle Synthesis ◽

Single Step ◽

Bioactive Molecules ◽

One Pot ◽

Bond Forming ◽

Material Interest ◽

Carbon Carbon Bond

Multi-Component Reactions (MCRs) have emerged as an excellent tool in organic chemistry for the synthesis of various bioactive molecules. Among these, one-pot MCRs are included, in which organic reactants react with domino in a single-step process. This has become an alternative platform for the organic chemists, because of their simple operation, less purification methods, no side product and faster reaction time. One of the important applications of the MCRs can be drawn in carbon- carbon (C-C) and carbon-heteroatom (C-X; X = N, O, S) bond formation, which is extensively used by the organic chemists to generate bioactive or useful material synthesis. Some of the key carbon- carbon bond forming reactions are Grignard, Wittig, Enolate alkylation, Aldol, Claisen condensation, Michael and more organic reactions. Alternatively, carbon-heteroatoms containing C-N, C-O, and C-S bond are also found more important and present in various heterocyclic compounds, which are of biological, pharmaceutical, and material interest. Thus, there is a clear scope for the discovery and development of cleaner reaction, faster reaction rate, atom economy and efficient one-pot synthesis for sustainable production of diverse and structurally complex organic molecules. Reactions that required hours to run completely in a conventional method can now be carried out within minutes. Thus, the application of microwave (MW) radiation in organic synthesis has become more promising considerable amount in resource-friendly and eco-friendly processes. The technique of microwaveassisted organic synthesis (MAOS) has successfully been employed in various material syntheses, such as transition metal-catalyzed cross-coupling, dipolar cycloaddition reaction, biomolecule synthesis, polymer formation, and the nanoparticle synthesis. The application of the microwave-technique in carbon-carbon and carbon-heteroatom bond formations via MCRs with major reported literature examples are discussed in this review.

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