Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enantioselective radical process for synthesis of chiral indolines by metalloradical alkylation of diverse C(sp3)-H bonds.

ABSTRACT: A new C-C bond formation strategy based on enantioselective radical alkylation of C(sp3)-H bonds via Co(ii)-based metalloradical catalysis has been demonstrated for stereoselective synthesis of chiral indolines. The Co(ii)-based system enables activation of aryldiazomethanes as radical precursors at room temperature for enantioselective intramolecular radical alkylation of broad types of C-H bonds, constructing 2-substituted indolines in high yields with excellent enantioselectivities. In addition to chemoselectivity and regioselectivity, this Co(ii)-catalyzed alkylation features tolerance to functional groups and compatibility with heteroaryl substrates. Detailed mechanistic studies provide insight into the underlying stepwise radical pathway.

SUBMITTER: Wen X

PROVIDER: S-EPMC5994879 | biostudies-other | 2018 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Enantioselective radical process for synthesis of chiral indolines by metalloradical alkylation of diverse C(sp3)-H bonds.

Wen Xin X Wang Yong Y Zhang X Peter XP

Chemical science 20180514 22

A new C-C bond formation strategy based on enantioselective radical alkylation of C(sp3)-H bonds via Co(ii)-based metalloradical catalysis has been demonstrated for stereoselective synthesis of chiral indolines. The Co(ii)-based system enables activation of aryldiazomethanes as radical precursors at room temperature for enantioselective intramolecular radical alkylation of broad types of C-H bonds, constructing 2-substituted indolines in high yields with excellent enantioselect ...[more]

PMID: 29938039

Similar Datasets

Catalytic Radical Process for Enantioselective Amination of C(sp3 )-H Bonds.

Project description:A new catalytic radical system involving CoII -based metalloradical catalysis is effective in activating sulfamoyl azides for enantioselective radical 1,6-amination of C(sp3 )-H bonds, affording six-membered chiral heterocyclic sulfamides in high yields with excellent enantioselectivities. The CoII -catalyzed C-H amination features an unusual degree of functional-group tolerance and chemoselectivity. The unique reactivity and stereoselectivity is attributed to the underlying stepwise radical pathway. The resulting optically active cyclic sulfamides can be readily converted into synthetically useful chiral 1,3-diamine derivatives without loss in enantiopurity.

| S-EPMC6339699 | biostudies-literature

Chiral Bronsted base-promoted nitroalkane alkylation: enantioselective synthesis of sec-alkyl-3-substituted indoles.

Project description:A Brønsted base-catalyzed reaction of nitroalkanes with alkyl electrophiles provides indole heterocycles substituted at C3 bearing a sec-alkyl group with good enantioselectivity (up to 90% ee). Denitration by hydrogenolysis provides a product with equally high ee. An indolenine intermediate is implicated in the addition step, and surprisingly, water cosolvent was found to have a beneficial effect in this step, leading to a one-pot protocol for elimination/enantioselective addition using PBAM, a bis(amidine) chiral nonracemic base.

| S-EPMC3005818 | biostudies-literature

Ligand-promoted alkylation of C(sp3)-H and C(sp2)-H bonds.

Project description:9-Methylacridine was identified as a generally effective ligand to promote a Pd(II)-catalyzed C(sp(3))-H and C(sp(2))-H alkylation of simple amides with various alkyl iodides. This alkylation reaction was applied to the preparation of unnatural amino acids and geometrically controlled tri- and tetrasubstituted acrylic acids.

| S-EPMC4183600 | biostudies-literature

Asymmetric Radical Process for General Synthesis of Chiral Heteroaryl Cyclopropanes.

Project description:A highly efficient catalytic method has been developed for asymmetric radical cyclopropanation of alkenes with in situ-generated α-heteroaryldiazomethanes via Co(II)-based metalloradical catalysis (MRC). Through fine-tuning the cavity-like environments of newly-synthesized D2-symmetric chiral amidoporphyrins as the supporting ligand, the optimized Co(II)-based metalloradical system is broadly applicable to α-pyridyl and other α-heteroaryldiazomethanes for asymmetric cyclopropanation of wide-ranging alkenes, including several types of challenging substrates. This new catalytic methodology provides a general access to valuable chiral heteroaryl cyclopropanes in high yields with excellent both diastereoselectivities and enantioselectivities. Combined computational and experimental studies further support the underlying stepwise radical mechanism of the Co(II)-based olefin cyclopropanation involving α- and γ-metalloalkyl radicals as the key intermediates.

| S-EPMC8399893 | biostudies-literature

Auxiliary-assisted palladium-catalyzed arylation and alkylation of sp2 and sp3 carbon-hydrogen bonds.

Project description:We have developed a method for auxiliary-directed, palladium-catalyzed beta-arylation and alkylation of sp(3) and sp(2) C-H bonds in carboxylic acid derivatives. The method employs a carboxylic acid 2-methylthioaniline- or 8-aminoquinoline amide substrate, aryl or alkyl iodide coupling partner, palladium acetate catalyst, and an inorganic base. By employing 2-methylthioaniline auxiliary, selective monoarylation of primary sp(3) C-H bonds can be achieved. If arylation of secondary sp(3) C-H bonds is desired, 8-aminoquinoline auxiliary may be used. For alkylation of sp(3) and sp(2) C-H bonds, 8-aminoquinoline auxiliary affords the best results. Some functional group tolerance is observed and amino- and hydroxy-acid derivatives can be functionalized. Preliminary mechanistic studies have been performed. A palladacycle intermediate has been isolated, characterized by X-ray crystallography, and its reactions have been studied.

| S-EPMC2841226 | biostudies-literature

Enantioselective cyanation via radical-mediated C-C single bond cleavage for synthesis of chiral dinitriles.

Project description:Ring-opening reaction via selective cleavage of C-C bond is known as a powerful strategy for construction of complex molecules. Complementary to the ionic process focusing on mostly small ring systems, radical-mediated C-C bond cleavage offers a solution for further diverse enantioselective functionalization benefited from its mild conditions, whereas such asymmetric transformations are still limited to three-membered rings so far. Herein, we describe radical-mediated ring-opening and enantioselective cyanation of four- and five-membered cycloketone oxime esters to access chiral 1,5- and 1,6-dinitriles. Employment of dual photoredox/copper catalysis is essential for the asymmetric ring-opening cyanation of cyclopentanone oxime esters. Both reactions proceed under mild conditions giving chiral dinitriles in high yields and enantioselectivity with low catalyst loading and broad substrate scope. The products dinitriles can be converted to valuable optically active diamides and diamines. Mechanistic studies indicate that the benzylic radical generated via C-C single bond cleavage is involved in the catalytic cycle.

| S-EPMC6879615 | biostudies-literature

Synthesis of chiral malonates by α-alkylation of 2,2-diphenylethyl tert-butyl malonates via enantioselective phase-transfer catalysis

Project description:An efficient synthetic approach for chiral malonates was established via enantioselective phase transfer catalysis. The α-alkylation of 2,2-diphenylethyl tert-butyl α-methylmalonates with (S,S)-3,4,5-trifluorophenyl-NAS bromide as a phase-transfer catalyst under phase-transfer catalytic conditions successfully produced corresponding α-methyl-α-alkylmalonates; these compounds are versatile chiral building blocks containing a quaternary carbon center in high chemical yields (up to 99%) with excellent enantioselectivities (up to 98% ee). α,α-Dialkylmalonates were selectively hydrolyzed to the corresponding chiral malonic monoacids under basic (KOH/MeOH) and acidic conditions (TFA/CH2Cl2), showing the practicality of the method.

| S-EPMC10285525 | biostudies-literature

Access to P-chiral phosphine oxides by enantioselective allylic alkylation of bisphenols.

Project description:A novel biscinchona alkaloid-catalyzed highly enantioselective desymmetrization reaction of bisphenol compounds with achiral Morita-Baylis-Hillman carbonate agents was developed. Through the asymmetric allylic alkylation strategy, a broad range of optically active P-stereogenic phosphine oxides were generated with excellent to good yields (up to 99%) and high enantioselectivities (up to 98.5 : 1.5 e.r.). The reaction was further investigated by the linear free energy relationship (LFER) analysis. A possible transition state was proposed and furthered verified by theoretical calculations.

| S-EPMC6499109 | biostudies-literature

Enantioselective Borylation of Aromatic C-H Bonds with Chiral Dinitrogen Ligands.

Project description:The borylation of C-H bonds catalyzed by transition metals has been investigated extensively in the past two decades, but no iridium-catalyzed enantioselective borylation of C-H bonds has been reported. We report a set of iridium-catalyzed enantioselective borylations of aromatic C-H bonds. This reaction relies on a set of newly developed chiral quinolyl oxazoline ligands. This process proceeds under mild conditions with good to excellent enantioselectivity, and the borylated products can be converted to enantioenriched derivatives containing new C-O, C-C, C-Cl, or C-Br bonds.

| S-EPMC5852249 | biostudies-literature

Highly enantioselective catalytic synthesis of chiral pyridines.

Project description:General methods to prepare chiral pyridine derivatives are greatly sought after due to their significance in medicinal chemistry. Here, we report highly enantioselective catalytic transformations of poorly reactive ?-substituted alkenyl pyridines to access a wide range of alkylated chiral pyridines. The simple methodology involves reactivity enhancement via Lewis acid (LA) activation, the use of readily available and highly reactive Grignard reagents, and a copper-chiral diphosphine ligand catalyst. Apart from allowing the introduction of different linear, branched, cyclic, and functionalised alkyl chains at the ?-position of alkenyl pyridines, the catalytic system also shows high functional group tolerance.

| S-EPMC5727103 | biostudies-other