Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Asymmetric benzylic C(sp³)-H acylation via dual nickel and photoredox catalysis.

ABSTRACT: Asymmetric C(sp³)-H functionalization is a persistent challenge in organic synthesis. Here, we report an asymmetric benzylic C-H acylation of alkylarenes employing carboxylic acids as acyl surrogates for the synthesis of α-aryl ketones via nickel and photoredox dual catalysis. This mild yet straightforward protocol transforms a diverse array of feedstock carboxylic acids and simple alkyl benzenes into highly valuable α-aryl ketones with high enantioselectivities. The utility of this method is showcased in the gram-scale synthesis and late-stage modification of medicinally relevant molecules. Mechanistic studies suggest a photocatalytically generated bromine radical can perform benzylic C-H cleavage to activate alkylarenes as nucleophilic coupling partners which can then engage in a nickel-catalyzed asymmetric acyl cross-coupling reaction. This bromine-radical-mediated C-H activation strategy can be also applied to the enantioselective coupling of alkylarenes with chloroformate for the synthesis of chiral α-aryl esters.

SUBMITTER: Huan L

PROVIDER: S-EPMC8192574 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Enantioselective benzylic C-H arylation via photoredox and nickel dual catalysis.

Project description:The asymmetric cross-coupling reaction is developed as a straightforward strategy toward 1,1-diaryl alkanes, which are a key skeleton in a series of natural products and bioactive molecules in recent years. Here we report an enantioselective benzylic C(sp3)-H bond arylation via photoredox/nickel dual catalysis. Sterically hindered chiral biimidazoline ligands are designed for this asymmetric cross-coupling reaction. Readily available alkyl benzenes and aryl bromides with various functional groups tolerance can be easily and directly transferred to useful chiral 1,1-diaryl alkanes including pharmaceutical intermediates and bioactive molecules. This reaction proceeds smoothly under mild conditions without the use of external redox reagents.

| S-EPMC6685991 | biostudies-literature

Thioetherification via Photoredox/Nickel Dual Catalysis.

Project description:Hypervalent alkylsilicates represent new and readily accessible precursors for the generation of alkyl radicals under photoredox conditions. Alkyl radicals generated from such silicates serve as effective hydrogen atom abstractors from thiols, furnishing thiyl radicals. The reactive sulfur species generated in this manner can be funneled into a nickel-mediated cross-coupling cycle employing aromatic bromides to furnish thioethers. The serendipitous discovery of this reaction and its utilization for the thioetherification of various aryl and heteroaryl bromides with a diverse array of thiols is described. The S-H selective H atom abstraction event enables a wide range of functional groups, including those bearing protic moieties, to be tolerated.

| S-EPMC4854196 | biostudies-literature

Single-Electron Transmetalation: Protecting-Group-Independent Synthesis of Secondary Benzylic Alcohol Derivatives via Photoredox/Nickel Dual Catalysis.

Project description:Protecting-group-independent cross-coupling of ?-alkoxyalkyl- and ?-acyloxyalkyltrifluoroborates with aryl and heteroaryl bromides is achieved through application of photoredox/nickel dual catalysis. Reactions occur under exceptionally mild conditions, with outstanding functional group compatibility and excellent observed tolerance of heteroarenes. This method offers expedient access to protected secondary benzylic alcohol motifs bearing benzyl, pivaloyl, and N,N-diisopropylcarbamoyl protecting groups.

| S-EPMC4900145 | biostudies-literature

Benzylic C-H acylation by cooperative NHC and photoredox catalysis.

Project description:Methods that enable site selective acylation of sp3 C-H bonds in complex organic molecules are not well explored, particularly if compared with analogous transformations of aromatic and vinylic sp2 C-H bonds. We report herein a direct acylation of benzylic C-H bonds by merging N-heterocyclic carbene (NHC) and photoredox catalysis. The method allows the preparation of a diverse range of benzylic ketones with good functional group tolerance under mild conditions. The reaction can be used to install acyl groups on highly functionalized natural product derived compounds and the C-H functionalization works with excellent site selectivity. The combination of NHC and photoredox catalysis offers options in preparing benzyl aryl ketones.

| S-EPMC8024347 | biostudies-literature

Direct Acylation of C(sp(3))-H Bonds Enabled by Nickel and Photoredox Catalysis.

Project description:Using nickel and photoredox catalysis, the direct functionalization of C(sp(3))-H bonds of N-aryl amines by acyl electrophiles is described. The method affords a diverse range of ?-amino ketones at room temperature and is amenable to late-stage coupling of complex and biologically relevant groups. C(sp(3))-H activation occurs by photoredox-mediated oxidation to generate ?-amino radicals which are intercepted by nickel in catalytic C(sp(3))-C coupling. The merger of these two modes of catalysis leverages nickel's unique properties in alkyl cross-coupling while avoiding limitations commonly associated with transition-metal-mediated C(sp(3))-H activation, including requirements for chelating directing groups and high reaction temperatures.

| S-EPMC4807873 | biostudies-literature

Catalytic asymmetric ?-acylation of tertiary amines mediated by a dual catalysis mode: N-heterocyclic carbene and photoredox catalysis.

Project description:Cross-coupling reactions are among the most widely utilized methods for C-C bond formation; however, the requirement of preactivated starting materials still presents a major limitation. Methods that take direct advantage of the inherent reactivity of the C-H bond offer an efficient alternative to these methods, negating the requirement for substrate preactivation. In this process, two chemically distinct activation events culminate in the formation of the desired C-C bond with loss of H(2) as the only byproduct. Herein we report the catalytic asymmetric ?-acylation of tertiary amines with aldehydes facilitated by the combination of chiral N-heterocyclic carbene catalysis and photoredox catalysis.

| S-EPMC3354013 | biostudies-literature

Dual catalysis. Merging photoredox with nickel catalysis: coupling of ?-carboxyl sp³-carbons with aryl halides.

Project description:Over the past 40 years, transition metal catalysis has enabled bond formation between aryl and olefinic (sp(2)) carbons in a selective and predictable manner with high functional group tolerance. Couplings involving alkyl (sp(3)) carbons have proven more challenging. Here, we demonstrate that the synergistic combination of photoredox catalysis and nickel catalysis provides an alternative cross-coupling paradigm, in which simple and readily available organic molecules can be systematically used as coupling partners. By using this photoredox-metal catalysis approach, we have achieved a direct decarboxylative sp(3)-sp(2) cross-coupling of amino acids, as well as ?-O- or phenyl-substituted carboxylic acids, with aryl halides. Moreover, this mode of catalysis can be applied to direct cross-coupling of C(sp³)-H in dimethylaniline with aryl halides via C-H functionalization.

| S-EPMC4296524 | biostudies-literature

Direct ?-Arylation/Heteroarylation of 2-Trifluoroboratochromanones via Photoredox/Nickel Dual Catalysis.

Project description:Utilizing photoredox/nickel dual catalysis, diverse flavanones have been synthesized by coupling novel 2-trifluoroboratochromanone building blocks with aryl and heteroaryl bromide partners. The newly reported trifluoroboratochromanones can be easily accessed from the corresponding chromones on multigram scale. This represents a general route for accessing natural and unnatural flavanones that were previously formed through a synthetically more restrictive ring closure route from chalcone precursors.

| S-EPMC5295361 | biostudies-literature

Benzylic C(sp<sup>3</sup>)-C(sp<sup>2</sup>) cross-coupling of indoles enabled by oxidative radical generation and nickel catalysis.

Project description:A mechanistically unique functionalization strategy for a benzylic C(sp3)-H bond has been developed based on the facile oxidation event of indole substrates. This novel pathway was initiated by efficient radical generation at the benzylic position of the substrate, with subsequent transition metal catalysis to complete the overall transformation. Ultimately, an aryl or an acyl group could be effectively delivered from an aryl (pseudo)halide or an acid anhydride coupling partner, respectively. The developed method utilizes mild conditions and exhibits a wide substrate scope for both substituted indoles and C(sp2)-based reaction counterparts. Mechanistic studies have shown that competitive hydrogen atom transfer (HAT) processes, which are frequently encountered in conventional methods, are not involved in the product formation process of the developed strategy.

| S-EPMC8179435 | biostudies-literature

Deaminative Reductive Arylation Enabled by Nickel/Photoredox Dual Catalysis.

Project description:Described is a cross-electrophilic, deaminative coupling strategy harnessing Katritzky salts as a new species of electrophile in Ni/photoredox dual catalytic reductive cross-coupling reactions. Distinguishing features of this arylation protocol include its mild reaction conditions, high chemoselectivity, and adaptability to a variety of complex substrates [i.e., pyridinium salts derived from amines and partners derived from (hetero)aryl bromides].

| S-EPMC6512806 | biostudies-literature