Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Direct phosphorylation of benzylic C-H bonds under transition metal-free conditions forming sp³C-P bonds.

ABSTRACT: Direct phosphorylation of benzylic C-H bonds was achieved in a biphasic system under transition metal-free conditions. A selective radical/radical sp³C-H/P(O)-H cross coupling was proposed, and various substituted toluenes were applicable. The transformation provided a promising method for constructing sp³C-P bonds.

SUBMITTER: Li Q

PROVIDER: S-EPMC9227801 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Direct phosphorylation of benzylic C-H bonds under transition metal-free conditions forming sp3C-P bonds.

Li Qiang Q Zhao Chang-Qiu CQ Chen Tieqiao T Han Li-Biao LB

RSC advances 20220624 29

Direct phosphorylation of benzylic C-H bonds was achieved in a biphasic system under transition metal-free conditions. A selective radical/radical sp3C-H/P(O)-H cross coupling was proposed, and various substituted toluenes were applicable. The transformation provided a promising method for constructing sp3C-P bonds. ...[more]

PMID: 35799919

Similar Datasets

Metal-free direct alkylation of unfunctionalized allylic/benzylic sp3 C-H bonds via photoredox induced radical cation deprotonation.

Project description:Despite notable recent efforts, a catalytic and convenient strategy for the direct alkylation of unactivated allylic or benzylic sp3 C-H bonds remains a formidable challenge facing the synthesis community. We herein report an unprecedented allylic/benzylic alkylation using only an organo-photoredox catalyst, which enables coupling of a broad scope of alkenes/arenes and electron-deficient alkenes in an atom- and redox-economic manner. A photoredox induced alkene/arene radical cation deprotonation is proposed to smoothly generate the key allylic and benzylic radical intermediates. It represents the first C-C bond formation via radical cation deprotonation under visible light conditions. The resulting products can be easily scaled up and directly converted to γ,δ-unsaturated or α,β-diaryl-acids, -esters, -amides, -pyrazoles, -isoxazoles, as well as lactones, which enables this mild and selective sp3 C-H alkylation to rapidly access complex bioactive molecules.

| S-EPMC5618257 | biostudies-literature

Metal-free oxidative cross-dehydrogenative coupling of quinones with benzylic C(sp3)-H bonds.

Project description:A metal-free cross-dehydrogenative coupling of quinones with toluene derivatives has been established. A series of quinones were subjected to reaction with toluene derivatives in the presence of di-tertbutyl peroxide (DTBP) for direct synthesis of benzylquinones. The method exhibits good functional group tolerance, and desired products were obtained in moderate to good yields. Meanwhile, a radical pathway was proposed to describe the cross-dehydrogenative coupling of quinones with toluene derivatives.

| S-EPMC9070767 | biostudies-literature

Transition metal-free direct dehydrogenative arylation of activated C(sp3)-H bonds: synthetic ambit and DFT reactivity predictions.

Project description:A transition metal-free dehydrogenative method for the direct mono-arylation of a wide range of activated C(sp3)-H bonds has been developed. This operationally simple and environmentally friendly aerobic arylation uses tert-BuOK as the base and nitroarenes as electrophiles to prepare up to gram quantities of structurally diverse sets (>60 examples) of α-arylated esters, amides, nitriles, sulfones and triaryl methanes. DFT calculations provided a predictive model, which states that substrates containing a C(sp3)-H bond with a sufficiently low pK a value should readily undergo arylation. The DFT prediction was confirmed through experimental testing of nearly a dozen substrates containing activated C(sp3)-H bonds. This arylation method was also used in a one-pot protocol to synthesize over twenty compounds containing all-carbon quaternary centers.

| S-EPMC6202766 | biostudies-literature

Electrochemical Benzylic C(sp3)-H Direct Amidation.

Project description:Amide bonds are ubiquitous and found in a myriad of functional molecules. Although formed in a reliable and robust fashion, alternative amide bond disconnections provide flexibility and synthetic control. Herein we describe an electrochemical method to form the non-amide C-N bond from direct benzylic C(sp3)-H amidation. Our approach is applied toward the synthesis of secondary amides by coupling secondary benzylic substrates with substituted primary benzamides. The reaction has been scaled up to a multigram scale in flow.

| S-EPMC10825869 | biostudies-literature

Multicomponent double Mannich alkylamination involving C(sp2)-H and benzylic C(sp3)-H bonds.

Project description:Alkylamines are ubiquitous in pharmaceuticals, materials and agrochemicals. The Mannich reaction is a well-known three-component reaction for preparing alkylamines and has been widely used in academic research and industry. However, the nucleophilic components in this process rely on C(sp2)-H and activated C(sp3)-H bonds while the unactivated C(sp3)-H bonds involved Mannich alkylamination is a long-standing challenge. Here, we report an unprecedented multicomponent double Mannich alkylamination for both C(sp2)-H and unactivated benzylic C(sp3)-H bonds. In this process, various 3-alkylbenzofurans, formaldehyde and alkylamine hydrochlorides assemble efficiently to furnish benzofuran-fused piperidines. Mechanistic studies and density functional theory (DFT) calculations revealed a distinctive pathway that a multiple Mannich reaction and retro-Mannich reaction of benzofuran and dehydrogenation of benzylic C(sp3)-H bonds were key steps to constitute the alkylamination. This protocol furnishes a Mannich alkylamine synthesis from unusual C-H inputs to access benzofuran-fused piperidines with exceptional structural diversity, molecular complexity and drug-likeness. Therefore, this work opens a distinctive vision for the alkylamination of unactivated C(sp3)-H bonds, and provides a powerful tool in diversity-oriented synthesis (DOS) and drug discovery.

| S-EPMC8782832 | biostudies-literature

Electrochemical Benzylic C(sp3)-H Acyloxylation.

Project description:The development of sustainable C(sp3)-H functionalization methods is of great interest to the pharmaceutical and agrochemical industries. Anodic oxidation is an efficient means of producing benzylic cations that can undergo subsequent in situ nucleophilic attack to afford functionalized benzylic products. Herein, we demonstrate the suitability of carboxylic acids as nucleophiles to yield benzylic esters. This method employs a series of secondary benzylic substrates and functionalized carboxylic acids and is demonstrated on a gram scale in flow.

| S-EPMC9315976 | biostudies-literature

Enantioselective Hydroxylation of Benzylic C(sp3)-H Bonds by an Artificial Iron Hydroxylase Based on the Biotin-Streptavidin Technology.

Project description:The selective hydroxylation of C-H bonds is of great interest to the synthetic community. Both homogeneous catalysts and enzymes offer complementary means to tackle this challenge. Herein, we show that biotinylated Fe(TAML)-complexes (TAML = Tetra Amido Macrocyclic Ligand) can be used as cofactors for incorporation into streptavidin to assemble artificial hydroxylases. Chemo-genetic optimization of both cofactor and streptavidin allowed optimizing the performance of the hydroxylase. Using H2O2 as oxidant, up to ∼300 turnovers for the oxidation of benzylic C-H bonds were obtained. Upgrading the ee was achieved by kinetic resolution of the resulting benzylic alcohol to afford up to >98% ee for (R)-tetralol. X-ray analysis of artificial hydroxylases highlights critical details of the second coordination sphere around the Fe(TAML) cofactor.

| S-EPMC7332155 | biostudies-literature

Site-selective amination and/or nitrilation via metal-free C(sp2)-C(sp3) cleavage of benzylic and allylic alcohols.

Project description:Benzylic/allylic alcohols are converted via site-selective C(sp2)-C(sp3) cleavage to value-added nitrogenous motifs, viz., anilines and/or nitriles as well as N-heterocycles, utilizing commercial hydroxylamine-O-sulfonic acid (HOSA) and Et3N in an operationally simple, one-pot process. Notably, cyclic benzylic/allylic alcohols undergo bis-functionalization with attendant increases in architectural complexity and step-economy.

| S-EPMC9067586 | biostudies-literature

Aminodealkenylation: Ozonolysis and copper catalysis convert C(sp3)-C(sp2) bonds to C(sp3)-N bonds.

Project description:Great efforts have been directed toward alkene π bond amination. In contrast, analogous functionalization of the adjacent C(sp3)-C(sp2) σ bonds is much rarer. Here we report how ozonolysis and copper catalysis under mild reaction conditions enable alkene C(sp3)-C(sp2) σ bond-rupturing cross-coupling reactions for the construction of new C(sp3)-N bonds. We have used this unconventional transformation for late-stage modification of hormones, pharmaceutical reagents, peptides, and nucleosides. Furthermore, we have coupled abundantly available terpenes and terpenoids with nitrogen nucleophiles to access artificial terpenoid alkaloids and complex chiral amines. In addition, we applied a commodity chemical, α-methylstyrene, as a methylation reagent to prepare methylated nucleosides directly from canonical nucleosides in one synthetic step. Our mechanistic investigation implicates an unusual copper ion pair cooperative process.

| S-EPMC10753956 | biostudies-literature

1H NMR is not a proof of hydrogen bonds in transition metal complexes.

Project description: Not available

| S-EPMC6456571 | biostudies-literature