Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Copper-catalyzed direct alkylation of heteroarenes.

ABSTRACT: An efficient and broadly applicable process is reported for the direct alkylation of C-H bonds in heteroarenes, privileged scaffolds in many areas of science. This reaction is based on the copper-catalyzed addition of alkyl radicals generated from activated secondary and tertiary alkyl bromides to a wide range of arenes, including furans, thiophenes, pyrroles, and their benzo-fused derivatives, as well as coumarins and quinolinones.

SUBMITTER: Theunissen C

PROVIDER: S-EPMC5418647 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Copper-catalyzed direct alkylation of heteroarenes.

Theunissen Cédric C Wang Jianjun J Evano Gwilherm G

Chemical science 20170320 5

An efficient and broadly applicable process is reported for the direct alkylation of C-H bonds in heteroarenes, privileged scaffolds in many areas of science. This reaction is based on the copper-catalyzed addition of alkyl radicals generated from activated secondary and tertiary alkyl bromides to a wide range of arenes, including furans, thiophenes, pyrroles, and their benzo-fused derivatives, as well as coumarins and quinolinones. ...[more]

PMID: 28507718

Similar Datasets

Visible Light-Mediated Direct C-H Aroylation and Alkylation of Heteroarenes.

Project description:Herein, we describe the photocatalytic generation of nucleophilic aroyl radicals from simple aroyl chlorides as a universal and efficient cross-coupling strategy for the direct aroylation of heteroarenes. Furthermore, visible light-mediated direct alkylation of heteroarenes has also been achieved using unactivated bromoalkanes as radical precursors. These two strategies feature high functional group tolerance, exclusive regioselectivity for reaction at the more electrophilic position of heteroarenes, easily accessible substrates, and mild reaction conditions. Moreover, mechanism studies of two reactions are carried out to support our hypotheses.

| S-EPMC6714600 | biostudies-literature

Direct alkylation of heteroarenes with unactivated bromoalkanes using photoredox gold catalysis.

Project description:Although visible light photoredox catalysis has emerged as a powerful tool for the construction of C-C bonds, common catalysts and/or their photoexcited states suffer from low redox potentials, limiting their applicability to alkyl radical generation from substrates with activated carbon-halogen bonds. Radicals derived from these activated compounds, being highly electrophilic or stabilized, do not undergo efficient addition to heteroarenes. Herein we describe the photocatalytic generation of nucleophilic alkyl radicals from unactivated bromoalkanes as part of a universal and efficient cross-coupling strategy for the direct alkylation of heteroarenes using a dimeric gold(i) photoredox catalyst, [Au2(bis(diphenylphosphino)methane)2]Cl2. The method proves to be efficient for alkylation of arenes under mild conditions in the absence of directing groups.

| S-EPMC6016576 | biostudies-literature

Copper-catalyzed electrophilic amination of heteroarenes and arenes by C-H zincation.

Project description:Direct amination of heteroarenes and arenes has been achieved in a one-pot C?H zincation/copper-catalyzed electrophilic amination procedure. This amination method provides an efficient and rapid approach to access a diverse range of heteroaromatic and aromatic amines including those previously inaccessible using C?H amination methods. The mild reaction conditions and good functional-group compatibility demonstrate its great potential for the synthesis of important and complex amines.

| S-EPMC4668583 | biostudies-literature

The photochemical alkylation and reduction of heteroarenes.

Project description:The functionalization of heteroarenes has been integral to the structural diversification of medicinally active molecules such as quinolines, pyridines, and phenanthridines. Electron-deficient heteroarenes are electronically compatible to react with relatively nucleophilic free radicals such as hydroxyalkyl. However, the radical functionalization of such heteroarenes has been marked by the use of transition-metal catalyzed processes that require initiators and stoichiometric oxidants. Herein, we describe the photochemical alkylation of quinolines, pyridines and phenanthridines, where through direct excitation of the protonated heterocycle, alcohols and ethers, such as methanol and THF, can serve as alkylating agents. We also report the discovery of a photochemical reduction of these heteroarenes using only iPrOH and HCl. Mechanistic studies to elucidate the underlying mechanism of these transformations, and preliminary results on catalytic methylations are also reported.

| S-EPMC5674141 | biostudies-literature

Copper-Catalyzed Alkylation of Nitroalkanes with ?-Bromonitriles: Synthesis of ?-Cyanonitroalkanes.

Project description:Copper catalysis now enables the efficient C-alkylation of nitroalkanes with ?-bromonitriles. Using a simple and inexpensive catalyst, this process provides access to ?-cyanonitroalkanes. The method is highly tolerant of various functional groups and substitution patterns. These functionally dense products serve as orthogonally masked 1,3-diamines, which can be revealed selectively for access to differentially substituted diamines. These products can also be exploited for the formation of complex cyanoalkenes and 5-aminoisoxazoles.

| S-EPMC4927086 | biostudies-literature

Iridium-catalyzed enantioselective direct vinylogous allylic alkylation of coumarins.

Project description:The first iridium-catalyzed enantioselective vinylogous allylic alkylation of coumarins is presented. Using easily accessible linear allylic carbonates as the allylic electrophile, this reaction installs unfunctionalized allyl groups at the ?-position of 4-methylcoumarins in an exclusively branched-selective manner generally in high yields with an excellent level of enantioselectivity (up to 99?:?1 er).

| S-EPMC6050583 | biostudies-literature

Site-Selective Copper-Catalyzed Amination and Azidation of Arenes and Heteroarenes via Deprotonative Zincation.

Project description:Arene amination is achieved by site-selective C-H zincation followed by copper-catalyzed coupling with O-benzoylhydroxylamines under mild conditions. Key to this success is ortho-zincation mediated by lithium amidodiethylzincate base that is effective for a wide range of arenes, including nonactivated arenes bearing simple functionalities such as fluoride, chloride, ester, amide, ether, nitrile, and trifluoromethyl groups as well as heteroarenes including indole, thiophene, pyridine, and isoquinoline. An analogous C-H azidation is also accomplished using azidoiodinane for direct introduction of a useful azide group onto a broad scope of arenes and heteroarenes. These new transformations offer rapid access to valuable and diverse chemical space of aminoarenes. Their broad applications in organic synthesis and drug discovery are demonstrated in the synthesis of novel analogues of natural product (-)-nicotine and antidepressant sertraline by late-stage amination and azidation reactions.

| S-EPMC5685551 | biostudies-literature

Copper-Catalyzed Enantioselective Allylic Alkylation with a ?-Butyrolactone-Derived Silyl Ketene Acetal.

Project description:Herein, we report a Cu-catalyzed enantioselective allylic alkylation using a ?-butyrolactone-derived silyl ketene acetal. Critical to the development of this work was the identification of a novel mono-picolinamide ligand with the appropriate steric and electronic properties to afford the desired products in high yield (up to 96?%) and high ee (up to 95?%). Aryl, aliphatic, and unsubstituted allylic chlorides bearing a broad range of functionality are well-tolerated. Spectroscopic studies reveal that a CuI species is likely the active catalyst, and DFT calculations suggest ligand sterics play an important role in determining Cu coordination and thus catalyst geometry.

| S-EPMC7051182 | biostudies-literature

Metal-free C-H alkylation of heteroarenes with alkyltrifluoroborates: a general protocol for 1°, 2° and 3° alkylation.

Project description:A photoredox-catalyzed C-H functionalization of heteroarenes using a variety of primary, secondary, and tertiary alkyltrifluoroborates is reported. Using Fukuzumi's organophotocatalyst and a mild oxidant, conditions amenable for functionalizing complex heteroaromatics are described, providing a valuable tool for late-stage derivatization. The reported method addresses the three major limitations of previously reported photoredox-mediated Minisci reactions: (1) use of superstoichiometric amounts of a radical precursor, (2) capricious regioselectivity, and (3) incorporation of expensive photocatalysts. Additionally, a number of unprecedented, complex alkyl radicals are used, thereby increasing the chemical space accessible to Minisci chemistry. To showcase the application in late-stage functionalization, quinine and camptothecin analogues were synthesized. Finally, NMR studies were conducted to provide a rationalization for the heteroaryl activation that permits the use of a single equivalent of radical precursor and also leads to enhanced regioselectivity. Thus, by 1H and 13C NMR a distinct heteroaryl species was observed in the presence of acid catalyst and BF3.

| S-EPMC5418733 | biostudies-literature

General electrochemical Minisci alkylation of <i>N</i>-heteroarenes with alkyl halides.

Project description:Herein, we report, a general, facile and environmentally friendly Minisci-type alkylation of N-heteroarenes under simple and straightforward electrochemical conditions using widely available alkyl halides as radical precursors. Primary, secondary and tertiary alkyl radicals have been shown to be efficiently generated and coupled with a large variety of N-heteroarenes. The method presents a very high functional group tolerance, including various heterocyclic-based natural products, which highlights the robustness of the methodology. This applicability has been further proved in the synthesis of various interesting biologically valuable building blocks. In addition, we have proposed a mechanism based on different proofs and pieces of electrochemical evidence.

| S-EPMC9172443 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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