Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

? C-H (hetero)arylation via Cu-catalyzed radical relay.

ABSTRACT: A Cu-catalyzed strategy has been developed that harnesses a radical relay mechanism to intercept a distal C-centered radical for C-C bond formation. This approach enables selective ? C-H (hetero)arylation of sulfonamides via intramolecular hydrogen atom transfer (HAT) by an N-centered radical. The radical relay is both initiated and terminated by a Cu catalyst, which enables incorporation of arenes and heteroarenes by cross-coupling with boronic acids. The broad scope and utility of this catalytic method for ? C-H arylation is shown, along with mechanistic probes for selectivity of the HAT mechanism. A catalytic, asymmetric variant is also presented, as well as a method for accessing 1,1-diaryl-pyrrolidines via iterative ? C-H functionalizations.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC6349054 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

δ C-H (hetero)arylation <i>via</i> Cu-catalyzed radical relay.

Zhang Zuxiao Z Stateman Leah M LM Nagib David A DA

Chemical science 20181109 4

A Cu-catalyzed strategy has been developed that harnesses a radical relay mechanism to intercept a distal C-centered radical for C-C bond formation. This approach enables selective δ C-H (hetero)arylation of sulfonamides <i>via</i> intramolecular hydrogen atom transfer (HAT) by an N-centered radical. The radical relay is both initiated and terminated by a Cu catalyst, which enables incorporation of arenes and heteroarenes by cross-coupling with boronic acids. The broad scope and utility of this ...[more]

PMID: 30774920

Similar Datasets

Identifying Radical Pathways for Cu(I)/Cu(II) Relay Catalyzed Oxygenation via Online Coupled EPR/UV-Vis/Near-IR Monitoring.

Project description:Copper-catalyzed C─H oxygenation has drawn considerable attention in mechanistic studies. However, a comprehensive investigation combining radical pathways with a metal-catalytic cycle is challenged by the intricate organic radicals and metallic intermediates. Herein, an online coupled EPR/UV-vis/near-IR detecting method is developed to simultaneously monitor both reactive radical species and copper complex intermediates during the reaction. Focusing on copper-catalyzed phenol oxygenation with cumene hydroperoxide, the short-lived alkylperoxyl radical (EPR signal at g = 2.0143) as well as the unexpected square planar Cu(II)-alkoxyl radical complex (near-IR signal at 833 nm) are unveiled during the reaction, in addition to the observable phenoxyl radical in EPR, quinone product in UV-vis, and Cu(II) center in EPR. With a comprehensive picture of diverse intermediates evolving over the same timeline, a novel Cu(I)/Cu(II) proposed relay-catalyzed sequential radical pathway. In this sequence, Cu(II) activates hydroperoxide through Cu(II)-OOR into the alkylperoxide radical, while the reaction between Cu(I) and hydroperoxide leads to Cu(II)(•OR)OH with high H-atom abstracting activity. These results provide a thorough understanding of the Cu(I)/Cu(II) relay catalysis for phenol oxygenation, setting the stage for mechanistic investigations into intricate radical reactions promoted by metallic complexes.

| S-EPMC11304242 | biostudies-literature

Copper-catalyzed carbo-difluoromethylation of alkenes via radical relay.

Project description:Organic molecules that contain alkyl-difluoromethyl moieties have received increased attention in medicinal chemistry, but their synthesis in a modular and late-stage fashion remains challenging. We report herein an efficient copper-catalyzed radical relay approach for the carbo-difluoromethylation of alkenes. This approach simultaneously introduces CF2H groups along with complex alkyl or aryl groups into alkenes with regioselectivity opposite to traditional CF2H radical addition. We demonstrate a broad substrate scope and a wide functional group compatibility. This scalable protocol is applied to the late-stage functionalization of complex molecules and the synthesis of CF2H analogues of bioactive molecules. Mechanistic studies and density functional theory calculations suggest a unique ligand effect on the reactivity of the Cu-CF2H species.

| S-EPMC8169770 | biostudies-literature

Intermolecular selective carboacylation of alkenes via nickel-catalyzed reductive radical relay.

Project description:The development of catalytic carboacylation of simple olefins, which would enable the rapid construction of ketones with high levels of complexity and diversity, is very challenging. To date, the vast majority of alkene carboacylation reactions are typically restricted to single- and two-component methodologies. Here we describe a three-component carboacylation of alkenes via the merger of radical chemistry with nickel catalysis. This reaction manifold utilizes a radical relay strategy involving radical addition to an alkene followed by alkyl radical capture by an acyl-nickel complex to forge two vicinal C-C bonds under mild conditions. Excellent chemoselectivity and regioselectivity have been achieved by utilizing a pendant weakly chelating group. This versatile protocol allows for facile access to a wide range of important ?-fluoroalkyl ketones from simple starting materials.

| S-EPMC6113317 | biostudies-literature

Enantioselective cyanation of benzylic C-H bonds via copper-catalyzed radical relay.

Project description:Direct methods for stereoselective functionalization of sp3-hybridized carbon-hydrogen [C(sp3)-H] bonds in complex organic molecules could facilitate much more efficient preparation of therapeutics and agrochemicals. Here, we report a copper-catalyzed radical relay pathway for enantioselective conversion of benzylic C-H bonds into benzylic nitriles. Hydrogen-atom abstraction affords an achiral benzylic radical that undergoes asymmetric C(sp3)-CN bond formation upon reaction with a chiral copper catalyst. The reactions proceed efficiently at room temperature with the benzylic substrate as limiting reagent, exhibit broad substrate scope with high enantioselectivity (typically 90 to 99% enantiomeric excess), and afford products that are key precursors to important bioactive molecules. Mechanistic studies provide evidence for diffusible organic radicals and highlight the difference between these reactions and C-H oxidations mediated by enzymes and other catalysts that operate via radical rebound pathways.

| S-EPMC5488708 | biostudies-literature

Palladium-Catalyzed Enantioselective Relay Heck Arylation of Enelactams: Accessing ?,?-Unsaturated ?-Lactams.

Project description:In this Communication, we describe the construction of chiral ?,?-unsaturated ?-lactams, widely used as pharmacophores, in high yields and excellent enantioselectivities using an oxidative relay Heck arylation reaction. This strategy also allows facile access to 7-substituted ?,?-unsaturated ?-lactam products and ?-lactams containing a tetrasubstituted nitrogen-bearing stereocenter.

| S-EPMC5993423 | biostudies-other

Copper-catalyzed oxidative benzylic C-H cyclization via iminyl radical from intermolecular anion-radical redox relay.

Project description:Base-promoted C-H cleavage without transition metals opens a practical alternative for the one based on noble metals or radical initiators. The resulting carbanion can pass through radical addition to unsaturated bonds like C-N or C-C triple bonds, in which stoichiometric oxidants are needed. When in situ C-H cleavage meets catalytic carbanion-radical relay, it turns to be challenging but has not been accomplished yet. Here we report the combination of base-promoted benzylic C-H cleavage and copper-catalyzed carbanion-radical redox relay. Catalytic amount of naturally abundant and inexpensive copper salt, such as copper(II) sulfate, is used for anion-radical redox relay without any external oxidant. By avoiding using N-O/N-N homolysis or radical initiators to generate iminyl radicals, this strategy realizes modular synthesis of N-H indoles and analogs from abundant feedstocks, such as toluene and nitrile derivatives, and also enables rapid synthesis of large scale pharmaceuticals.

| S-EPMC6385223 | biostudies-literature

Intramolecular arylation of benzimidazoles via Pd(II)/Cu(I) catalyzed cross-dehydrogenative coupling.

Project description:Electron poor benzimidazole substrates were arylated via an intramolecular cross-dehydrogenative coupling (CDC) reaction. These CDC reactions were catalyzed by a Pd(II)/Cu(I) catalyst system, capable of producing moderate yields on a large library of substrates. The substrate scope consisted of tethered arene-benzimidazoles that upon coupling, produced a fused polycyclic motif.

| S-EPMC3993984 | biostudies-literature

Pd(II)-Catalyzed C3-Selective Arylation of Pyridine with (Hetero)arenes.

Project description:Palladium catalyzed, nondirected C3-selective arylation of pyridines with arenes and heteroarenes in the presence of 1,10-phenanthroline as the ligand has been developed. The optimized conditions allow for a highly C3-selective arylation of pyridines, affording various 3,3'-bipyridines and 3-arylpyridines.

| S-EPMC4821414 | biostudies-literature

Pd-catalyzed γ-arylation of γ,δ-unsaturated O-carbamates via an unusual haptotropic rearrangement.

Project description:An unusual γ-selectivity was observed in the arylation of γ,δ-unsaturated O-carbamates involving directed lithiation, transmetallation to zinc and Negishi coupling, when a specific combination of aryl electrophile and phosphine ligand is employed. Mechanistic studies indicate that an unusual, stereospecific haptotropic rearrangement of the palladium-diene intermediate is involved.

| S-EPMC6385668 | biostudies-other

Palladium-Catalyzed Enantioselective Redox-Relay Heck Arylation of 1,1-Disubstituted Homoallylic Alcohols.

Project description:An enantioselective redox-relay oxidative Heck arylation of 1,1-disubstituted alkenes to construct β-stereocenters was developed using a new pyridyl-oxazoline ligand. Various 1,2-diaryl carbonyl compounds were readily obtained in moderate yield and good to excellent enantioselectivity. Additionally, analysis of the reaction outcomes using multidimensional correlations revealed that enantioselectivity is tied to specific electronic features of the 1,1-disubstituted alkenol and the extent of polarizability of the ligand.

| S-EPMC5039009 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data