Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regio- and Enantioselective N-Heterocyclic Carbene-Catalyzed Annulation of Aminoindoles Initiated by Friedel-Crafts Alkylation.

ABSTRACT: Chiral indoles annulated on the benzene ring are unique and significant in natural and medicinal compounds. However, accessing these enantioenriched molecules has often been overlooked. The present study introduces an organocatalytic protocol to access these compounds efficiently, demonstrated by substrate scope, functional group tolerance, and using only 1 mol % of a chiral conjugated acid catalyst. Additionally, the study explores regioselectivity, gram-scale reactions, and follow-up transformations, underscoring the method's potential.

SUBMITTER: Docekal V

PROVIDER: S-EPMC11348421 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Regio- and Enantioselective <i>N</i>-Heterocyclic Carbene-Catalyzed Annulation of Aminoindoles Initiated by Friedel-Crafts Alkylation.

Dočekal Vojtěch V Niderer Yaroslava Y Kurčina Adam A Císařová Ivana I Veselý Jan J

Organic letters 20240808 33

Chiral indoles annulated on the benzene ring are unique and significant in natural and medicinal compounds. However, accessing these enantioenriched molecules has often been overlooked. The present study introduces an organocatalytic protocol to access these compounds efficiently, demonstrated by substrate scope, functional group tolerance, and using only 1 mol % of a chiral conjugated acid catalyst. Additionally, the study explores regioselectivity, gram-scale reactions, and follow-up transform ...[more]

PMID: 39115978

Similar Datasets

Tandem Friedel-Crafts-Alkylation-Enantioselective-Protonation by Artificial Enzyme Iminium Catalysis.

Project description:The incorporation of organocatalysts into protein scaffolds holds the promise of overcoming some of the limitations of this powerful catalytic approach. Previously, we showed that incorporation of the non-canonical amino acid para-aminophenylalanine into the non-enzymatic protein scaffold LmrR forms a proficient and enantioselective artificial enzyme (LmrR_pAF) for the Friedel-Crafts alkylation of indoles with enals. The unnatural aniline side-chain is directly involved in catalysis, operating via a well-known organocatalytic iminium-based mechanism. In this study, we show that LmrR_pAF can enantioselectively form tertiary carbon centres not only during C-C bond formation, but also by enantioselective protonation, delivering a proton to one face of a prochiral enamine intermediate. The importance of various side-chains in the pocket of LmrR is distinct from the Friedel-Crafts reaction without enantioselective protonation, and two particularly important residues were probed by exhaustive mutagenesis.

| S-EPMC9313897 | biostudies-literature

Lewis Acid-Catalyzed Enantioselective Friedel-Crafts Alkylation of Pyrrole in Water.

Project description:Highly enantioselective Friedel-Crafts alkylation of pyrroles with 2-enoyl-pyridine N-oxides in water/chloroform (10:1) was developed under catalysis of Lewis acid. The Friedel-Crafts alkylation products can be obtained in high yields and excellent enantioselectivities. Moreover, several control experiments were carried out to study the reaction mechanism.

| S-EPMC7271029 | biostudies-literature

N-Heterocyclic carbene-catalyzed enantioselective hetero-[10 + 2] annulation.

Project description:Higher-order cycloadditions are a powerful strategy for the construction of polycycles in one step. However, an efficient and concise version for the induction of asymmetry is lacking. N-heterocyclic carbenes are widely used organocatalysts for asymmetric synthesis and could be an ideal choice for enantioselective higher-order cycloadditions. Here, we report an enantioselective [10 + 2] annulation between catalytically formed aza-benzofulvene intermediates and trifluoromethyl ketone derivatives. This protocol exhibits a wide scope, high yields, and good ee values, reflecting a robust and efficient higher-order cycloaddition. Density functional theory calculations provide an accurate prediction of the reaction enantioselectivity, and in-depth insight to the origins of stereocontrol.

| S-EPMC9814252 | biostudies-literature

Enantioselective N-heterocyclic carbene catalyzed annulation reactions with imidazolidinones.

Project description:Add acetic acid: A highly stereoselective N-heterocyclic carbene (NHC)-catalyzed formal [4+2] annulation between α,β-unsaturated aldehydes and imidazolidinones for the synthesis of imidazoles has been developed. Acetic acid serves as a key additive to achieve high chemoselectivity for the formal [4+2] annulation product.

| S-EPMC3905989 | biostudies-literature

Friedel-Crafts Alkylation of Indoles with Trichloroacetimidates.

Project description:Substituted indole scaffolds are often utilized in medicinal chemistry as they regularly possess significant pharmacological activity. Therefore the development of simple, inexpensive and efficient methods for alkylating the indole heterocycle continues to be an active research area. Reported are reactions of trichloroacetimidate electrophiles and indoles to address the challenges of accessing alkyl decorated indole structures. These alkylations perform best when either the indole or the imidate is functionalized with electron withdrawing groups to avoid polyalkylation.

| S-EPMC6720118 | biostudies-literature

Tandem Friedel-Crafts annulation to novel perylene analogues.

Project description:Novel dialkyloxy- and dihydroxyoctahydroperylenes are regioselectively available via a new tandem Friedel-Crafts alkylation of tetrahydronaphthalene precursors followed by oxidative aromatization. Heating of 5-alkyloxy-1-tetralol with p-toluenesulfonic acid in sulfolane gave the corresponding octahydroperylenes in moderate yields. Studies with Lewis acids and tetralin-1,5-diol in acetonitrile at room temperature provided the 4,10-dihydroxy analogue cleanly, albeit in reduced yields. Examples of these new series of perylene analogues were partially oxidized to the corresponding contiguously aromatic, anthracene core products or fully aromatized to 3,9-dialkyloxyperylenes in good yields.

| S-EPMC4780845 | biostudies-literature

Artificial Metalloenzymes based on TetR Proteins and Cu(II) for Enantioselective Friedel-Crafts Alkylation Reactions.

Project description:The supramolecular approach is among the most convenient methodologies for creating artificial metalloenzymes (ArMs). Usually this approach involves the binding of a transition metal ion complex to a biomolecular scaffold via its ligand, which also modulates the catalytic properties of the metal ion. Herein, we report ArMs based on the proteins CgmR, RamR and QacR from the TetR family of multidrug resistance regulators (MDRs) and Cu2+ ions, assembled without the need of a ligand. These ArMs catalyze the enantioselective vinylogous Friedel-Crafts alkylation reaction with up to 75 % ee. Competition experiments with ethidium and rhodamine 6G confirm that the reactions occur in the chiral environment of the hydrophobic pocket. It is proposed that the Cu2+-substrate complex is bound via a combination of electrostatic and π-stacking interactions provided by the second coordination sphere. This approach constitutes a fast and straightforward way to assemble metalloenzymes and may facilitate future optimization of the protein scaffolds via mutagenesis or directed evolution approaches.

| S-EPMC7319431 | biostudies-literature

The enantioselective construction of tetracyclic diterpene skeletons with Friedel-Crafts alkylation and palladium-catalyzed cycloalkenylation reactions.

Project description:Due to the profound extent to which natural products inspire medicinal chemists in drug discovery, there is demand for innovative syntheses of these often complex materials. This article describes the synthesis of tricarbocyclic natural product architectures through an extension of the enantioselective Birch-Cope sequence with intramolecular Friedel-Crafts alkylation reactions. Additionally, palladium-catalyzed enol silane cycloalkenylation of the tricarbocyclic structures afforded the challenging bicyclo[3.2.1]octane C/D ring system found in the gibberellins and the ent-kauranes, two natural products with diverse medicinal value. In the case of the ent-kaurane derivative, an unprecedented alkene rearrangement converted four alkene isomers to one final product.

| S-EPMC4334740 | biostudies-literature

N-Heterocyclic Carbene Catalyzed Enantioselective Annulation of Benzothiazolyl Ethyl Acetates with 2-Bromoenals.

Project description:An N-heterocyclic carbene catalyzed enantioselective [3+3] annulation of benzothiazolyl acetates with 2-bromoenals has been developed. The protocol provides a direct asymmetric synthesis of dihydro-1H-benzothiazolopyridinones in good to very good yields and medium ee values. In many cases, the virtually enantiopure heterocycles are available through a single recrystallization (99% ee).

| S-EPMC4702349 | biostudies-literature

Electrifying Friedel-Crafts Intramolecular Alkylation toward 1,1-Disubstituted Tetrahydronaphthalenes.

Project description:In this work, we successfully employed electrochemical conditions to promote a Hofer-Moest, intramolecular Friedel-Crafts alkylation sequence. The reaction proceeds under mild conditions, employing carboxylic acids as starting materials. Notably, the electrochemical process performed in batch was adapted to a continuous flow electrolysis apparatus to provide a significant improvement. This catalyst-free, electrochemical approach produces an array of tetrahydronaphthalenes that could be used for API synthesis.

| S-EPMC10729024 | 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