Browse
Submit Data
Databases
API
Help

Dataset Information

43 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Radical cascade synthesis of azoles via tandem hydrogen atom transfer.

ABSTRACT: A radical cascade strategy for the modular synthesis of five-membered heteroarenes (e.g. oxazoles, imidazoles) from feedstock reagents (e.g. alcohols, amines, nitriles) has been developed. This double C-H oxidation is enabled by in situ generated imidate and acyloxy radicals, which afford regio- and chemo-selective β C-H bis-functionalization. The broad synthetic utility of this tandem hydrogen atom transfer (HAT) approach to access azoles is included, along with experiments and computations that provide insight into the selectivity and mechanism of both HAT events.

SUBMITTER: Chen AD

PROVIDER: S-EPMC8157396 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Radical cascade synthesis of azoles via tandem hydrogen atom transfer.

Chen Andrew D AD Herbort James H JH Wappes Ethan A EA Nakafuku Kohki M KM Mustafa Darsheed N DN Nagib David A DA

Chemical science 20200131 9

A radical cascade strategy for the modular synthesis of five-membered heteroarenes (e.g. oxazoles, imidazoles) from feedstock reagents (e.g. alcohols, amines, nitriles) has been developed. This double C-H oxidation is enabled by in situ generated imidate and acyloxy radicals, which afford regio- and chemo-selective β C-H bis-functionalization. The broad synthetic utility of this tandem hydrogen atom transfer (HAT) approach to access azoles is included, along with experiments ...[more]

PMID: 34084413

Similar Datasets

Factors Controlling Reactivity in the Hydrogen Atom Transfer and Radical Addition Steps of a Radical Relay Cascade.

Project description:DFT exploration of 1,5- and 1,6-hydrogen atom transfers (HAT), radical addition, and relay to alkene is reported. The reactivity of 1,5- and 1,6-HAT are similar. We also explored reactions involving a multiple radical transferring process. Initially generated radicals undergo a multiple HAT process to form multiple bonds in a "relay" fashion, provided by exquisitely balanced rates.

| S-EPMC6760911 | biostudies-literature

Ketyl radical reactivity via atom transfer catalysis.

Project description:Single-electron reduction of a carbonyl to a ketyl enables access to a polarity-reversed platform of reactivity for this cornerstone functional group. However, the synthetic utility of the ketyl radical is hindered by the strong reductants necessary for its generation, which also limit its reactivity to net reductive mechanisms. We report a strategy for net redox-neutral generation and reaction of ketyl radicals. The in situ conversion of aldehydes to α-acetoxy iodides lowers their reduction potential by more than 1 volt, allowing for milder access to the corresponding ketyl radicals and an oxidative termination event. Upon subjecting these iodides to a dimanganese decacarbonyl precatalyst and visible light irradiation, an atom transfer radical addition (ATRA) mechanism affords a broad scope of vinyl iodide products with high Z-selectivity.

| S-EPMC6504239 | biostudies-literature

Efficient Synthesis of α-Haloboronic Esters via Cu-Catalyzed Atom Transfer Radical Addition.

Project description:The synthesis of α-haloboronic esters via atom transfer radical addition (ATRA) is constrained due to its limited range of compatible substrates or the need to manipulate the olefin coupling partners. Herein, we present a novel approach for their synthesis via Cu-catalyzed ATRA to vinyl boronic esters. The catalyst is proposed to mediate a traditionally inefficient halogen atom transfer of the α-boryl radical intermediate, thus significantly expanding the range of participating substrates relative to established methods. The forty-eight examples illustrate that a wide range of radical precursors, including primary, secondary, and tertiary alkyl halides, readily add across both unsubstituted and α-substituted vinyl pinacol boronic esters. Further, a one-pot, two-step protocol is presented for direct access to an array of α-functionalized products. Finally, the synthetic utility of this methodology is demonstrated in the synthesis of an ixazomib analogue.

| S-EPMC10765605 | biostudies-literature

Synthesis of RNA-Amphiphiles via Atom Transfer Radical Polymerization in the Organic Phase.

Project description:The combination of hydrophobic polymers with nucleic acids is a fascinating way to engineer the self-assembly behavior of nucleic acids into diverse nanostructures such as micelles, vesicles, nanosheets, and worms. Here we developed a robust route to synthesize a RNA macroinitiator with protecting groups on the 2'-hydroxyl groups in the solid phase using an oligonucleotide synthesizer. The protecting groups successfully solubilized the RNA macroinitiator, enabling atom transfer radical polymerization (ATRP) of hydrophobic monomers. As a result, the RNA-polymer hybrids obtained by ATRP exhibited enhanced chemical stability by suppressing cleavage. In addition, we demonstrated evidence of controlled polymerization behavior as well as control over the molecular weight of the hydrophobic polymers grown from RNA. We envision that this methodology will expand the field of RNA-polymer conjugates while vastly enhancing the possibility to alter and engineer the properties of RNA-based polymeric materials.

| S-EPMC10389804 | biostudies-literature

Tandem chain walking polymerization and atom transfer radical polymerization for efficient synthesis of dendritic nanoparticles for bioconjugation.

Project description:A tandem polymerization methodology, chain walking polymerization (CWP) followed by atom transfer radical polymerization, was developed for efficient synthesis of nanoparticles for bioconjugation. Using the chain walking palladium-alpha-diimine catalyst (catalyst 1), dendritic polymers bearing multiple initiation sites were synthesized and used as macroinitiators for subsequent Cu(I)-mediated ATRP. Control of molecular weight and size of the water-soluble core-shell polymeric nanoparticles was achieved by tuning reaction conditions. Addition of an N-acryloyloxysuccinamide (NAS) monomer at the end of the ATRP afforded NHS-activated polymer nanoparticles. Conjugation with both small dye molecules and protein (ovalbumin) yielded nanoparticle conjugates with relatively high dye or protein per particle ratio. With the efficient synthesis and good biocompatibility, these nanoparticles may find many potential applications in bioconjugation.

| S-EPMC3375215 | biostudies-literature

Palladium-Catalyzed Atom-Transfer Radical Cyclization at Remote Unactivated C(sp3 )-H Sites: Hydrogen-Atom Transfer of Hybrid Vinyl Palladium Radical Intermediates.

Project description:A novel mild, visible-light-induced palladium-catalyzed hydrogen atom translocation/atom-transfer radical cyclization (HAT/ATRC) cascade has been developed. This protocol involves a 1,5-HAT process of previously unknown hybrid vinyl palladium radical intermediates, thus leading to iodomethyl carbo- and heterocyclic structures.

| S-EPMC5829020 | biostudies-literature

Mechanistic Studies of a Skatole-Forming Glycyl Radical Enzyme Suggest Reaction Initiation via Hydrogen Atom Transfer.

Project description:Gut microbial decarboxylation of amino acid-derived arylacetates is a chemically challenging enzymatic transformation which generates small molecules that impact host physiology. The glycyl radical enzyme (GRE) indoleacetate decarboxylase from Olsenella uli (Ou IAD) performs the non-oxidative radical decarboxylation of indole-3-acetate (I3A) to yield skatole, a disease-associated metabolite produced in the guts of swine and ruminants. Despite the importance of IAD, our understanding of its mechanism is limited. Here, we characterize the mechanism of Ou IAD, evaluating previously proposed hypotheses of: (1) a Kolbe-type decarboxylation reaction involving an initial 1-e- oxidation of the carboxylate of I3A or (2) a hydrogen atom abstraction from the α-carbon of I3A to generate an initial carbon-centered radical. Site-directed mutagenesis, kinetic isotope effect experiments, analysis of reactions performed in D2O, and computational modeling are consistent with a mechanism involving initial hydrogen atom transfer. This finding expands the types of radical mechanisms employed by GRE decarboxylases and non-oxidative decarboxylases, more broadly. Elucidating the mechanism of IAD decarboxylation enhances our understanding of radical enzymes and may inform downstream efforts to modulate this disease-associated metabolism.

| S-EPMC9248008 | biostudies-literature

Visible-Light-Mediated Energy Transfer Enables the Synthesis of β-Lactams via Intramolecular Hydrogen Atom Transfer.

Project description:The synthesis of 2-azetidinones (β-lactams) from simple acrylamide starting materials by visible-light-mediated energy transfer catalysis is reported. The reaction features a C(sp3 )-H functionalization via a variation of the Norrish-Yang photocyclization involving a carbon-to-carbon 1,5-hydrogen atom transfer (supported by deuterium labelling and DFT calculations) and can be used for the construction of a diverse range of β-lactam products.

| S-EPMC9828223 | biostudies-literature

Synthesis of Polymer Bioconjugates via Photoinduced Atom Transfer Radical Polymerization under Blue Light Irradiation.

Project description:A rapid blue-light-induced atom transfer radical polymerization (ATRP) was conducted in a biologically friendly environment. Well-controlled polymerization of oligo(ethylene oxide) methyl ether methacrylate (OEOMA) was successfully performed in aqueous media (1X PBS) under irradiation by blue LED strips. With 10.0 mW/cm2 intensity output at 450 nm, >90% conversion was achieved in 2 h in the presence of a system comprising glucose, glucose oxidase, and sodium pyruvate. Poly-(OEOMA) was synthesized with predetermined M n and low dispersities using low ppm of Cu catalysts. Importantly, secondary structures of proteins, as analyzed by circular dichroism (CD), were preserved under blue-light irradiation due to its lower energy output. The aqueous blue-light ATRP technique was applied to biological systems by synthesizing well-defined protein-polymer and DNA-polymer hybrids by the "grafting-from" method.

| S-EPMC6901285 | biostudies-literature

Challenges in Synthesis and Analysis of Asymmetrically Grafted Cellulose Nanocrystals via Atom Transfer Radical Polymerization.

Project description:When cellulose nanocrystals (CNCs) are isolated from cellulose microfibrils, the parallel arrangement of the cellulose chains in the crystalline domains is retained so that all reducing end-groups (REGs) point to one crystallite end. This permits the selective chemical modification of one end of the CNCs. In this study, two reaction pathways are compared to selectively attach atom-transfer radical polymerization (ATRP) initiators to the REGs of CNCs, using reductive amination. This modification further enabled the site-specific grafting of the anionic polyelectrolyte poly(sodium 4-styrenesulfonate) (PSS) from the CNCs. Different analytical methods, including colorimetry and solution-state NMR analysis, were combined to confirm the REG-modification with ATRP-initiators and PSS. The achieved grafting yield was low due to either a limited conversion of the CNC REGs or side reactions on the polymerization initiator during the reductive amination. The end-tethered CNCs were easy to redisperse in water after freeze-drying, and the shear birefringence of colloidal suspensions is maintained after this process.

| S-EPMC8382247 | biostudies-literature