Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A radical approach to the copper oxidative addition problem: Trifluoromethylation of bromoarenes.

ABSTRACT: Transition metal-catalyzed arene functionalization has been widely used for molecular synthesis over the past century. In this arena, copper catalysis has long been considered a privileged platform due to the propensity of high-valent copper to undergo reductive elimination with a wide variety of coupling fragments. However, the sluggish nature of oxidative addition has limited copper's capacity to broadly facilitate haloarene coupling protocols. Here, we demonstrate that this copper oxidative addition problem can be overcome with an aryl radical-capture mechanism, wherein the aryl radical is generated through a silyl radical halogen abstraction. This strategy was applied to a general trifluoromethylation of aryl bromides through dual copper-photoredox catalysis. Mechanistic studies support the formation of an open-shell aryl species.

SUBMITTER: Le C

PROVIDER: S-EPMC6607890 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A radical approach to the copper oxidative addition problem: Trifluoromethylation of bromoarenes.

Le Chip C Chen Tiffany Q TQ Liang Tao T Zhang Patricia P MacMillan David W C DWC

Science (New York, N.Y.) 20180601 6392

Transition metal-catalyzed arene functionalization has been widely used for molecular synthesis over the past century. In this arena, copper catalysis has long been considered a privileged platform due to the propensity of high-valent copper to undergo reductive elimination with a wide variety of coupling fragments. However, the sluggish nature of oxidative addition has limited copper's capacity to broadly facilitate haloarene coupling protocols. Here, we demonstrate that this copper oxidative a ...[more]

PMID: 29853683

Similar Datasets

Copper-mediated radical trifluoromethylation of unsaturated potassium organotrifluoroborates.

Project description:Copper-mediated trifluoromethylation of unsaturated organotrifluoroborates with the Langlois reagent (NaSO2CF3) and TBHP allows the introduction of trifluoromethyl groups into a variety of organic substructures. The reactions are easy to set up, the conditions are mild and general, and the process provides access to trifluoromethylated alkynes, alkenes, arenes, and heteroarenes in fair to good yields.

| S-EPMC3886853 | biostudies-literature

Room temperature aryl trifluoromethylation via copper-mediated oxidative cross-coupling.

Project description:A method for the room temperature copper-mediated trifluoromethylation of aryl and heteroaryl boronic acids has been developed. This protocol is amenable to normal benchtop setup and reactions typically require only 1-4 h. Proceeding under mild conditions, the method tolerates a range of functional groups, allowing access to a variety of trifluoromethylarenes.

| S-EPMC3093444 | biostudies-literature

A simple method for asymmetric trifluoromethylation of N-acyl oxazolidinones via Ru-catalyzed radical addition to zirconium enolates.

Project description:A Ru-catalyzed direct thermal trifluoromethylation and perfluoroalkylation of N-acyloxazolidinones has been developed. The reaction is experimentally simple and requires inexpensive reagents while providing good yields of products with good levels of stereocontrol. Preliminary studies have shown notable compatibility with functional groups, aromatics, and certain heteroaromatic substituents. The described method provides a useful alternative for the synthesis of fluorinated materials in an experimentally convenient manner.

| S-EPMC3375393 | biostudies-literature

Copper-catalyzed remote C(sp<sup>3</sup>)-H azidation and oxidative trifluoromethylation of benzohydrazides.

Project description:The Hofmann-Löffler-Freytag (HLF) reaction is a prototypical example of radical-based remote functionalization of unactivated C(sp3)-H bond. While 1,5-hydrogen atom transfer (1,5-HAT) of the amidyl radical is thermodynamically favorable and is well-established, the method for the subsequent functionalization of the translocated carbon radical is still limited. We report herein two catalytic remote C(sp3)-H functionalization protocols. Cu(MeCN)4PF6-catalyzed reaction of 2-alkyl benzohydrazides 3 with TMSN3 in the presence of MeCO2OtBu affords the ?-azido amides 4, while CuCl-catalyzed reaction of 3 with Togni's reagent provides 2-(?-trifluoromethylvinyl)benzamides 5 via an oxidative ?-trifluoromethylation of the alkyl group. Mechanistic studies suggest that the ?-azidation of benzohydrazides 3 goes through 1,5-HAT followed by a Cu-mediated azido transfer cascade, while the oxidative ?-trifluoromethylation of 3 proceeds via, after 1,5-HAT process, a radical-polar crossover mechanism.

| S-EPMC6377619 | biostudies-literature

Copper-Catalyzed Trifluoromethylation of Alkoxypyridine Derivatives.

Project description:The trifluoromethylation of aromatic and heteroaromatic cores has attracted considerable interest in recent years due to its pharmacological relevance. We studied the extension of a simple copper-catalyzed trifluoromethylation protocol to alkoxy-substituted iodopyridines and their benzologs. The trifluoromethylation proceeded smoothly in all cases, and the desired compounds were isolated and characterized. In the trifluoromethylation of 3-iodo-4-methoxyquinoline, we observed a concomitant O-N methyl migration, resulting in the trifluoromethylated quinolone as a product. Overall, the described procedure should facilitate the broader use of copper-catalyzed trifluoromethylation in medicinal chemistry.

| S-EPMC7587554 | biostudies-literature

Copper-Catalyzed Trifluoromethylation of Alkyl Bromides.

Project description:Copper oxidative addition into organohalides is a challenging two-electron process. In contrast, formal oxidative addition of copper to Csp2 carbon-bromine bonds can be accomplished by employing latent silyl radicals under photoredox conditions. This novel paradigm for copper oxidative addition has now been applied to a Cu-catalyzed cross-coupling of Csp3-bromides. Specifically, a copper/photoredox dual catalytic system for the coupling of alkyl bromides with trifluoromethyl groups is presented. This operationally simple and robust protocol successfully converts a variety of alkyl, allyl, benzyl, and heterobenzyl bromides into the corresponding alkyl trifluoromethanes.

| S-EPMC7557108 | biostudies-literature

A scalable and operationally simple radical trifluoromethylation.

Project description:The large number of reagents that have been developed for the synthesis of trifluoromethylated compounds is a testament to the importance of the CF3 group as well as the associated synthetic challenge. Current state-of-the-art reagents for appending the CF3 functionality directly are highly effective; however, their use on preparative scale has minimal precedent because they require multistep synthesis for their preparation, and/or are prohibitively expensive for large-scale application. For a scalable trifluoromethylation methodology, trifluoroacetic acid and its anhydride represent an attractive solution in terms of cost and availability; however, because of the exceedingly high oxidation potential of trifluoroacetate, previous endeavours to use this material as a CF3 source have required the use of highly forcing conditions. Here we report a strategy for the use of trifluoroacetic anhydride for a scalable and operationally simple trifluoromethylation reaction using pyridine N-oxide and photoredox catalysis to affect a facile decarboxylation to the CF3 radical.

| S-EPMC4533119 | biostudies-literature

Copper-catalyzed decarboxylative trifluoromethylation of allylic bromodifluoroacetates.

Project description:The development of new synthetic fluorination reactions has important implications in medicinal, agricultural, and materials chemistries. Given the prevalence and accessibility of alcohols, methods to convert alcohols to trifluoromethanes are desirable. However, this transformation typically requires four-step processes, specialty chemicals, and/or stoichiometric metals to access the trifluoromethyl-containing product. A two-step copper-catalyzed decarboxylative protocol for converting allylic alcohols to trifluoromethanes is reported. Preliminary mechanistic studies distinguish this reaction from previously reported Cu-mediated reactions.

| S-EPMC3867938 | biostudies-literature

Copper-Catalyzed Decarboxylative Trifluoromethylation of Propargyl Bromodifluoroacetates.

Project description:The development of efficient methods for accessing fluorinated functional groups is desirable. Herein, we report a two-step method that utilizes catalytic Cu for the decarboxylative trifluoromethylation of propargyl bromodifluoroacetates. This protocol affords a mixture of propargyl trifluoromethanes and trifluoromethyl allenes.

| S-EPMC4185158 | biostudies-literature

Copper-mediated 1,2-bis(trifluoromethylation) of arynes.

Project description:We herein describe an unprecedented 1,2-bis(trifluoromethylation) of arynes with [CuCF3] in the presence of an oxidant DDQ. The method allows the rapid construction of a new class of 1,2-bis(trifluoromethyl)arenes in one-step from aryne precursors under mild conditions. Its synthetic utility has been demonstrated in the preparation of bis(trifluoromethylated) molecules with potential pharmaceutical and materials science applications. Mechanistic studies indicated the presence of an o-trifluoromethyl aryl radical intermediate via CF3 group transfer from [CuCF3] to the aryne.

| S-EPMC6296300 | 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