Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Light-Driven Carbene Catalysis for the Synthesis of Aliphatic and α-Amino Ketones.

ABSTRACT: Single-electron N-heterocyclic carbene (NHC) catalysis has gained attention recently for the synthesis of C-C bonds. Guided by density functional theory and mechanistic analyses, we report the light-driven synthesis of aliphatic and α-amino ketones using single-electron NHC operators. Computational and experimental results reveal that the reactivity of the key radical intermediate is substrate-dependent and can be modulated through steric and electronic parameters of the NHC. Catalyst potential is harnessed in the visible-light driven generation of an acyl azolium radical species that undergoes selective coupling with various radical partners to afford diverse ketone products. This methodology is showcased in the direct late-stage functionalization of amino acids and pharmaceutical compounds, highlighting the utility of single-electron NHC operators.

SUBMITTER: Bay AV

PROVIDER: S-EPMC8338790 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Light-Driven Carbene Catalysis for the Synthesis of Aliphatic and α-Amino Ketones.

Bay Anna V AV Fitzpatrick Keegan P KP González-Montiel Gisela A GA Farah Abdikani Omar AO Cheong Paul Ha-Yeon PH Scheidt Karl A KA

Angewandte Chemie (International ed. in English) 20210714 33

Single-electron N-heterocyclic carbene (NHC) catalysis has gained attention recently for the synthesis of C-C bonds. Guided by density functional theory and mechanistic analyses, we report the light-driven synthesis of aliphatic and α-amino ketones using single-electron NHC operators. Computational and experimental results reveal that the reactivity of the key radical intermediate is substrate-dependent and can be modulated through steric and electronic parameters of the NHC. Catalyst potential ...[more]

PMID: 34097802

Similar Datasets

Combined Photoredox and Carbene Catalysis for the Synthesis of γ-Aryloxy Ketones.

Project description:N-heterocyclic carbenes (NHCs) have emerged as catalysts for the construction of C-C bonds in the synthesis of substituted ketones under single-electron processes. Despite these recent reports, there still remains a need to increase the utility and practicality of these reactions by exploring new radical coupling partners. Herein, we report the synthesis of γ-aryloxyketones via combined NHC/photoredox catalysis. In this reaction, an α-aryloxymethyl radical is generated via oxidation of an aryloxymethyl potassium trifluoroborate salt, which is then added into styrene derivatives to provide a stabilized benzylic radical. Subsequent radical-radical coupling reaction with an azolium radical affords the γ-aryloxy ketone products.

| S-EPMC9012476 | biostudies-literature

Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids.

Project description:As a key element in the construction of complex organic scaffolds, the formation of C-C bonds remains a challenge in the field of synthetic organic chemistry. Recent advancements in single-electron chemistry have enabled new methods for the formation of various C-C bonds. Disclosed herein is the development of a novel single-electron reduction of acyl azoliums for the formation of ketones from carboxylic acids. Facile construction of the acyl azolium in situ followed by a radical-radical coupling was made possible merging N-heterocyclic carbene (NHC) and photoredox catalysis. The utility of this protocol in synthesis was showcased in the late-stage functionalization of a variety of pharmaceutical compounds. Preliminary investigations using chiral NHCs demonstrate that enantioselectivity can be achieved, showcasing the advantages of this protocol over alternative methodologies.

| S-EPMC7250732 | biostudies-literature

Enantioselective Synthesis of D-α-Amino Amides from Aliphatic Aldehydes.

Project description:Peptides consisting of D-amino amides are highly represented among both biologically active natural products and non-natural small molecules used in therapeutic development. Chemical synthesis of D-amino amides most often involves approaches based on enzymatic resolution or fractional recrystallization of their diastereomeric amine salts, techniques that produce an equal amount of the L-amino acid. Enantioselective synthesis, however, promises selective and general access to a specific α-amino amide, and may enable efficient peptide synthesis regardless of the availability of the corresponding α-amino acid. This report describes the use of a cinchona alkaloid-catalyzed aza-Henry reaction using bromonitromethane, and the integration of its product with Umpolung Amide Synthesis. The result is a straightforward 3-step protocol beginning from aliphatic aldehydes that provides homologated peptides bearing an aliphatic side chain at the resulting D-α-amino amide.

| S-EPMC4378585 | biostudies-literature

Synergistic Visible-Light Photoredox/Nickel-Catalyzed Synthesis of Aliphatic Ketones via N-C Cleavage of Imides.

Project description:An electrophilic, imide-based, visible-light-promoted photoredox/Ni-catalyzed cross-coupling reaction for the synthesis of aliphatic ketones has been developed. This protocol proceeds through N-C(O) bond activation, made possible through the lower activation energy for metal insertion into this bond due to delocalization of the lone pair of electrons on the nitrogen by electron-withdrawing groups. The operationally simple and mild cross-coupling reaction is performed at ambient temperature and exhibits tolerance for a variety of functional groups.

| S-EPMC5423445 | biostudies-literature

Palladium-catalyzed oxidative cross-coupling for the synthesis of α-amino ketones.

Project description:A novel oxidative cross-coupling reaction for the synthesis of α-aryl α-amino ketones in the presence of palladium catalysts using T+BF4 - as an oxidant has been developed. This transformation was achieved by direct C-H oxidation of α-aminocarbonyl compounds and arylation. The mild reaction has a broad reaction scope and gives desired α-aryl α-amino ketones in moderate to excellent yields.

| S-EPMC9072988 | biostudies-literature

Enantioselective synthesis of α-amino ketones through palladium-catalyzed asymmetric arylation of α-keto imines.

Project description:Chiral α-amino ketones are common structural motifs in natural products and pharmaceuticals, as well as important synthons in organic synthesis. Thus, establishing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor in synthetic chemistry. Herein we disclose a new catalytic asymmetric approach for the synthesis of chiral α-amino ketones through a chiral palladium-catalyzed arylation reaction of in situ generated challenging α-keto imines from previously unreported C-acyl N-sulfonyl-N,O-aminals, with arylboronic acids. The current reaction offers a straightforward approach to the asymmetric synthesis of acyclic α-amino ketones in a practical and highly stereocontrolled manner. Meanwhile, the multiple roles of the chiral Pd(ii) complex catalyst in the reaction were also reported.

| S-EPMC8966749 | biostudies-literature

Asymmetric Mannich synthesis of α-amino esters by anion-binding catalysis.

Project description:We report a scalable, one-pot Mannich route to enantioenriched α-amino esters by direct reaction of α-chloroglycine ester as a practical imino ester surrogate. The reaction is promoted by a chiral aminothiourea, which is proposed to operate cooperatively by generating an iminium ion by chloride abstraction and an enolate by deprotonation, followed by highly stereoselective C-C bond formation between both reactive intermediates associated non-covalently within the catalyst framework.

| S-EPMC4183616 | biostudies-literature

Stereoselective synthesis of unnatural α-amino acid derivatives through photoredox catalysis.

Project description:A protocol for stereoselective C-radical addition to a chiral glyoxylate-derived N-sulfinyl imine was developed through visible light-promoted photoredox catalysis, providing a convenient method for the synthesis of unnatural α-amino acids. The developed protocol allows the use of ubiquitous carboxylic acids as radical precursors without prior derivatization. The protocol utilizes near-stoichiometric amounts of the imine and the acid radical precursor in combination with a catalytic amount of an organic acridinium-based photocatalyst. Alternative mechanisms for the developed transformation are discussed and corroborated by experimental and computational studies.

| S-EPMC8179686 | biostudies-literature

Efficient synthesis of ?'-amino-?,?-unsaturated ketones.

Project description:A general and simple procedure to access chiral ?'-amino-?,?-enones, in seven steps, from an ?,? unsaturated ester has been described. The use of a Horner-Wadsworth-Emmons reaction as a key step for generating the ?'-amino-?,?-enones, permits access to a range of substrates under mild conditions and in moderate to high yield.

| S-EPMC3596044 | biostudies-other

Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling.

Project description:An enantioselective carbene-catalyzed radical-radical coupling of acyl imidazoles and racemic Hantzsch esters is disclosed. This method involves the coupling of an N-heterocyclic carbene-derived ketyl radical and a secondary sp3 -carbon radical and allows access to chiral α-aryl aliphatic ketones in moderate-to-good yields and enantioselectivities without any competitive epimerization. The utility of this protocol is highlighted by the late-stage functionalization of various pharmaceutical compounds and is further demonstrated by the transformation of the enantioenriched products to biologically relevant molecules. Computational investigations reveal the N-heterocyclic carbene controls the double-facial selectivity of the ketyl radical and the alkyl radicals, respectively.

| S-EPMC10841513 | 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