Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ligand-Enabled Auxiliary-Free meta-C-H Arylation of Phenylacetic Acids.

ABSTRACT: The meta-C-H arylation of free phenylacetic acid was realized using 2-carbomethoxynorbornene (NBE-CO2 Me) as a transient mediator. Both the modified norbornene and the mono-protected 3-amino-2-hydroxypyridine type ligand are crucial for this auxiliary-free meta-C-H arylation reaction. A series of phenylacetic acids, including mandelic acid and phenylglycine, react smoothly with various aryl iodides to provide the meta-arylated products in high yields.

SUBMITTER: Li GC

PROVIDER: S-EPMC5535739 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Ligand-Enabled Auxiliary-Free meta-C-H Arylation of Phenylacetic Acids.

Li Gen-Cheng GC Wang Peng P Farmer Marcus E ME Yu Jin-Quan JQ

Angewandte Chemie (International ed. in English) 20170509 24

The meta-C-H arylation of free phenylacetic acid was realized using 2-carbomethoxynorbornene (NBE-CO<sub>2</sub> Me) as a transient mediator. Both the modified norbornene and the mono-protected 3-amino-2-hydroxypyridine type ligand are crucial for this auxiliary-free meta-C-H arylation reaction. A series of phenylacetic acids, including mandelic acid and phenylglycine, react smoothly with various aryl iodides to provide the meta-arylated products in high yields. ...[more]

PMID: 28485900

Similar Datasets

Ligand-enabled ?-C-H arylation of ?-amino acids using a simple and practical auxiliary.

Project description:Pd-catalyzed ?-C-H functionalizations of carboxylic acid derivatives using an auxiliary as a directing group have been extensively explored in the past decade. In comparison to the most widely used auxiliaries in asymmetric synthesis, the simplicity and practicality of the auxiliaries developed for C-H activation remains to be improved. We previously developed a simple N-methoxyamide auxiliary to direct ?-C-H activation, albeit this system was not compatible with carboxylic acids containing ?-hydrogen atoms. Herein we report the development of a pyridine-type ligand that overcomes this limitation of the N-methoxyamide auxiliary, leading to a significant improvement of ?-arylation of carboxylic acid derivatives, especially ?-amino acids. The arylation using this practical auxiliary is applied to the gram-scale syntheses of unnatural amino acids, bioactive molecules, and chiral bis(oxazoline) ligands.

| S-EPMC4432912 | biostudies-literature

Pd-catalysed ligand-enabled carboxylate-directed highly regioselective arylation of aliphatic acids.

Project description:?-amino acids bearing aromatic side chains are important synthetic units in the synthesis of peptides and natural products. Although various ?-C-H arylation methodologies for amino acid derivatives involving the assistance of directing groups have been extensively developed, syntheses that directly employ N-protected amino acids as starting materials remain rare. Herein, we report an N-acetylglycine-enabled Pd-catalysed carboxylate-directed ?-C(sp3)-H arylation of aliphatic acids. In this way, various non-natural amino acids can be directly prepared from phthaloylalanine in one step in good to excellent yields. Furthermore, a series of aliphatic acids have been shown to be amenable to this transformation, affording ?-arylated propionic acid derivatives in moderate to good yields. More importantly, this ligand-enabled direct ?-C(sp3)-H arylation could be easily scaled-up to 10?g under reflux conditions, highlighting the potential utility of this synthetic method.

| S-EPMC5384235 | biostudies-literature

Ligand-Enabled Meta-C-H Alkylation and Arylation Using a Modified Norbornene.

Project description:2-Carbomethoxynorbornene is identified as a more effective transient mediator to promote a Pd(II)-catalyzed meta-C(sp(2))-H alkylation of amides with various alkyl iodides as well as arylation with previously incompatible aryl iodides. The use of a tailor-made quinoline ligand is also crucial for this reaction to proceed.

| S-EPMC4573956 | biostudies-other

Ligand-Enabled ?-C-H Arylation of ?-Amino Acids Without Installing Exogenous Directing Groups.

Project description:Herein we report acid-directed ?-C(sp3 )-H arylation of ?-amino acids enabled by pyridine-type ligands. This reaction does not require the installation of an exogenous directing group, is scalable, and enables the preparation of Fmoc-protected unnatural amino acids in three steps. The pyridine-type ligands are crucial for the development of this new C(sp3 )-H arylation.

| S-EPMC5302090 | biostudies-literature

Ligand-Enabled ?-C(sp3 )-H Olefination of Free Carboxylic Acids.

Project description:We report the ligand-enabled C-H activation/olefination of free carboxylic acids in the ?-position. Through an intramolecular Michael addition, ?-lactones are obtained as products. Two distinct ligand classes are identified that enable the challenging palladium-catalyzed activation of free carboxylic acids in the ?-position. The developed protocol features a wide range of acid substrates and olefin reaction partners and is shown to be applicable on a preparatively useful scale. Insights into the underlying reaction mechanism obtained through kinetic studies are reported.

| S-EPMC7496353 | biostudies-literature

Ligand-Enabled Arylation of ?-C-H Bonds.

Project description:Pd(II) -catalyzed arylation of ?-C(sp(3) )-H bonds of aliphatic acid-derived amides was developed by using quinoline-based ligands. Various ?-aryl-?-amino acids were prepared from natural amino acids using this method. The influence of ligand structure on reactivity was also systematically investigated.

| S-EPMC4821162 | biostudies-literature

Ligand-Enabled meta-Selective C-H Arylation of Nosyl-Protected Phenethylamines, Benzylamines, and 2-Aryl Anilines.

Project description:A Pd-catalyzed, meta-selective C-H arylation of nosyl-protected phenethylamines and benzylamines is disclosed using a combination of norbornene and pyridine-based ligands. Subjecting nosyl protected 2-aryl anilines to this protocol led to meta-C-H arylation at the remote aryl ring. A diverse range of aryl iodides are tolerated in this reaction, along with select heteroaryl iodides. Select aryl bromides bearing ortho-coordinating groups can also be utilized as effective coupling partners in this reaction. The use of pyridine ligands has allowed the palladium loading to be reduced to 2.5 mol %. Furthermore, a catalytic amount of 2-norbornene (20 mol %) to mediate this meta-C-H activation process is demonstrated for the first time. Utilization of a common protecting group as the directing group for meta-C-H activation of amines is an important feature of this reaction in terms of practical applications.

| S-EPMC5497681 | biostudies-other

Ligand-enabled ortho-C-H olefination of phenylacetic amides with unactivated alkenes.

Project description:Although chelation-assisted C-H olefination has been intensely investigated, Pd(ii)-catalyzed C-H olefination reactions are largely restricted to acrylates and styrenes. Here we report a quinoline-derived ligand that enables the Pd(ii)-catalyzed olefination of the C(sp2)-H bond with simple aliphatic alkenes using a weakly coordinating monodentate amide auxiliary. Oxygen is used as the terminal oxidant with catalytic copper as the co-oxidant. A variety of functional groups in the aliphatic alkenes are tolerated. Upon hydrogenation, the ortho-alkylated product can be accessed. The utility of this reaction is also demonstrated by the late-stage diversification of drug molecules.

| S-EPMC5887099 | biostudies-literature

Synthesis of amino acids and peptides with bulky side chains via ligand-enabled carboxylate-directed ?-C(sp3)-H arylation.

Project description:Amino acids and peptides with bulky side chains are of significant importance in organic synthesis and modern medicinal chemistry. The efficient synthesis of these molecules with full enantiocontrol and high diversity remains challenging. Herein we report a Pd-catalyzed ligand-enabled ?-C(sp3)-H arylation of tert-leucine and its derived peptides without using an external directing group (DG) via a less favored six-membered palladacycle. Structurally diverse bulky side chain amino acids and peptides were accessed in a step-economic fashion and the reaction could be conducted on a gram scale with retention of chirality. The resulting amino acids can be used as chiral ligands in Co(iii)-catalyzed enantioselective C(sp3)-H amidation. It is worth noting that the weakly coordinating carboxylate DG outcompetes the strongly coordinating bidentate DG of the peptide backbone, providing the products of ?-C(sp3)-H arylation of Tle residue exclusively. This protocol represents the first example of late stage C(sp3)-H functionalization of peptides using a weakly coordinating directing group.

| S-EPMC7021191 | biostudies-literature

Ligand-Enabled, Palladium-Catalyzed ?-C(sp3)-H Arylation of Weinreb Amides.

Project description:We report the development of Pd(II)-catalyzed C(sp3)-H arylation of Weinreb amides. This work demonstrates the first example of using Weinreb amide as a directing group for transition metal-catalyzed C(sp3)-H activation. Both the inductive effect and the potential bidentate coordination mode of the Weinreb amides pose a unique challenge for this reaction development. A pyridinesulfonic acid ligand is designed to accommodate the weak, neutral coordinating property of Weinreb amides via preserving the cationic character of Pd center through zwitterionic assembly of Pd/ligand complexes. DFT studies of the C-H cleavage step indicate that the superior reactivity of 3-pyridinesulfonic acid ligand compared to pyridine, Ac-Gly-OH, and ligandless conditions originates from the stabilization of overall substrate-bound Pd species.

| S-EPMC6586421 | 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