Browse
Submit Data
Databases
API
Help

Dataset Information

6 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Oxidation of difluorocarbene and subsequent trifluoromethoxylation.

ABSTRACT: As a versatile intermediate, difluorocarbene is an electron-deficient transient species, meaning that its oxidation would be challenging. Herein we show that the oxidation of difluorocarbene could occur smoothly to generate carbonyl fluoride. The oxidation process is confirmed by successful trifluoromethoxylation, 18O-trifluoromethoxylation, the observation of AgOCF3 species, and DFT calculations.

SUBMITTER: Yu J

PROVIDER: S-EPMC6877537 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Oxidation of difluorocarbene and subsequent trifluoromethoxylation.

Yu Jiao J Lin Jin-Hong JH Yu Donghai D Du Ruobing R Xiao Ji-Chang JC

Nature communications 20191125 1

As a versatile intermediate, difluorocarbene is an electron-deficient transient species, meaning that its oxidation would be challenging. Herein we show that the oxidation of difluorocarbene could occur smoothly to generate carbonyl fluoride. The oxidation process is confirmed by successful trifluoromethoxylation, <sup>18</sup>O-trifluoromethoxylation, the observation of AgOCF<sub>3</sub> species, and DFT calculations. ...[more]

PMID: 31767850

Similar Datasets

Nucleophilic trifluoromethoxylation of alkyl halides without silver.

Project description:The biological properties of molecules containing the trifluoromethoxy group have made these compounds important targets in pharmaceuticals and agrochemicals, yet their preparation is still a substantial challenge. Herein, we present a practical nucleophilic trifluoromethoxylation of alkyl halides with (E)-O-trifluoromethyl-benzaldoximes (TFBO) as a trifluoromethoxylation reagent in the absence of silver under mild reaction conditions. The trifluoromethoxylation reagent TFBO is easily prepared and thermally stable, and can release CF3O- species in the presence of a base. Furthermore, broad scope and good functional group compatibility are demonstrated by application of the method to the late-stage trifluoromethoxylation of alkyl halides in complex small molecules.

| S-EPMC7005179 | biostudies-literature

Difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines.

Project description:2-Fluoroindoles as an important structural scaffold are widely existing in many bioactive or therapeutic agents. Despite their potential usefulness, efficient constructions of 2-fluoroindole derivatives are very sparce. The development of straightforward synthetic approaches to access 2-fluoroindoles is highly desirable for studying their fundamental properties and applications. Herein, we report an efficient and general strategy for the construction of 2-fluoroindoles in which a wide variety of 2-fluoroindoles were accessed with high efficiency and chemoselectivity. Instead of starting from indole skeletons, our strategy constructs indole scaffolds alongside the incorporation of fluorine atom on C2 position in a formal [4+1] cyclization from readily accessible ortho-vinylanilines and difluorocarbene. In our protocol, commercially accessible halodifluoroalkylative reagents provide one carbon and one fluorine atom by cleaving one C-N tertiary bond and forming one C-N bond and one C-C double bond with ortho-vinylanilines. Downstream transformations on 2-fluoroindoles lead to various valuable bioactive molecules which demonstrated significant synthetic advantages over previous reports. And mechanistic studies suggest that the reaction undergoes a cascade difluorocarbene-trapping and intramolecular Michael addition reaction followed by Csp3-F bond cleavage.

| S-EPMC8371155 | biostudies-literature

Catalytic C-H Trifluoromethoxylation of Arenes and Heteroarenes.

Project description:The intermolecular C-H trifluoromethoxylation of arenes remains a long-standing and unsolved problem in organic synthesis. Herein, we report the first catalytic protocol employing a novel trifluoromethoxylating reagent and redox-active catalysts for the direct (hetero)aryl C-H trifluoromethoxylation. Our approach is operationally simple, proceeds at room temperature, uses easy-to-handle reagents, requires only 0.03?mol?% of redox-active catalysts, does not need specialized reaction apparatus, and tolerates a wide variety of functional groups and complex structures such as sugars and natural product derivatives. Importantly, both ground-state and photoexcited redox-active catalysts are effective. Detailed computational and experimental studies suggest a unique reaction pathway where photoexcitation of the trifluoromethoxylating reagent releases the OCF3 radical that is trapped by (hetero)arenes. The resulting cyclohexadienyl radicals are oxidized by redox-active catalysts and deprotonated to form the desired products of trifluoromethoxylation.

| S-EPMC6105550 | biostudies-literature

Deconstructive Functionalizations of Unstrained Carbon-Nitrogen Cleavage Enabled by Difluorocarbene.

Project description:Transition-metal- or oxidant-promoted deconstructive functionalizations of noncyclic carbon-nitrogen bonds are well established, usually only leaving one moiety functionalized toward the final product. In contrast, concomitant C- and N-functionalizations via the unstrained C(sp3)-N bond under metal- and oxidant-free conditions are very rare, which would favorably confer versatility and product diversity. Disclosed herein is the first difluorocarbene-induced deconstructive functionalizations embodying successive C(sp3)-N bond cleavage of cyclic amines and synchronous functionalization of both constituent atoms which would be preserved in the eventual molecular outputs under transition-metal-free and oxidant-free conditions. Correspondent access to deuterated formamides with ample isotopic incorporation was demonstrated by a switch to heavy water which is conceivably useful in pharmaceutical sciences. The current strategy remarkably administers a very convenient, operationally simple and novel method toward molecular diversity from readily available starting materials. Therefore, we project that these findings would be of broad interest to research endeavors encompassing fluorine chemistry, carbene chemistry, C-N bond activation, as well as medicinal chemistry.

| S-EPMC7596867 | biostudies-literature

Difluorocarbene-Derived Trifluoromethylthiolation and [(18)F]Trifluoromethylthiolation of Aliphatic Electrophiles.

Project description:The first trifluoromethylthiolation and [(18)F]trifluoromethylthiolation of alkyl electrophiles with in situ generated difluorocarbene in the presence of elemental sulfur and external (radioactive) fluoride ion is described. This transition-metal-free approach is high yielding, compatible with a variety of functional groups, and operated under mild reaction conditions. The conceptual advantage of this exogenous-fluoride-mediated transformation enables unprecedented syntheses of [(18)F]CF3S-labeled molecules from most commonly used [(18)F]fluoride ions. The rapid radiochemical reaction time (≤1 min) and high functional-group tolerance allow access to a variety of aliphatic [(18)F]CF3S compounds in high yields.

| S-EPMC4692268 | biostudies-literature

Silver-mediated trifluoromethoxylation of aryl stannanes and arylboronic acids.

Project description:A silver-mediated cross-coupling of trifluoromethoxide with aryl stannanes and arylboronic acids to give aryl trifluoromethyl ethers is reported. This is the first report of a transition-metal-mediated C(aryl)-OCF(3) bond formation.

| S-EPMC3218431 | biostudies-literature

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow.

Project description:The first example of photocatalytic trifluoromethoxylation of arenes and heteroarenes under continuous-flow conditions is described. Application of continuous-flow microreactor technology allowed to reduce the residence time up to 16 times in comparison to the batch procedure, while achieving similar or higher yields. In addition, the use of inorganic bases was demonstrated to increase the reaction yield under batch conditions.

| S-EPMC7308607 | biostudies-literature

Ring-opening functionalizations of unstrained cyclic amines enabled by difluorocarbene transfer.

Project description:Chemical synthesis based on the skeletal variation has been prolifically utilized as an attractive approach for modification of molecular properties. Given the ubiquity of unstrained cyclic amines, the ability to directly alter such motifs would grant an efficient platform to access unique chemical space. Here, we report a highly efficient and practical strategy that enables the selective ring-opening functionalization of unstrained cyclic amines. The use of difluorocarbene leads to a wide variety of multifaceted acyclic architectures, which can be further diversified to a range of distinctive homologative cyclic scaffolds. The virtue of this deconstructive strategy is demonstrated by successful modification of several natural products and pharmaceutical analogues.

| S-EPMC7506026 | biostudies-literature

Selective C-H trifluoromethoxylation of (hetero)arenes as limiting reagent.

Project description:Methods for direct C-H trifluoromethoxylation of arenes and heteroarenes are rare, despite the importance of trifluoromethoxylated compounds for pharmaceuticals, agrochemicals, and material sciences. Especially selective C-H trifluoromethoxylation of pyridines remains a formidable challenge. Here we show a general late-stage C-H trifluoromethoxylation of arenes and heteroarenes as limiting reagent with trifluoromethoxide anion. The reaction is mediated by silver salts under mild reaction conditions, exhibiting broad substrate scope and wide functional-group compatibility. In addition, ortho-position selective C-H trifluoromethoxylation of pyridines is observed. The method is not only applicable to the gram-scale synthesis of trifluoromethoxylated products but also allows efficient late-stage C-H trifluoromethoxylation of marketed small-molecule drugs, common pharmacophores and natural products.

| S-EPMC7244481 | biostudies-literature

Radical C-H Trifluoromethoxylation of (Hetero)arenes with Bis(trifluoromethyl)peroxide.

Project description:Trifluoromethoxylated (hetero)arenes are of great interest for several disciplines, especially in agro- and medicinal chemistry. Radical C-H trifluoromethoxylation of (hetero)arenes represents an attractive approach to prepare such compounds, but the high cost and low atom economy of existing . OCF3 radical sources make them unsuitable for the large-scale synthesis of trifluoromethoxylated building blocks. Herein, we introduce bis(trifluoromethyl)peroxide (BTMP, CF3 OOCF3 ) as a practical and efficient trifluoromethoxylating reagent that is easily accessible from inexpensive bulk chemicals. Using either visible light photoredox or TEMPO catalysis, trifluoromethoxylated arenes could be prepared in good yields under mild conditions directly from unactivated aromatics. Moreover, TEMPO catalysis allowed for the one-step synthesis of valuable pyridine derivatives, which have been previously prepared via multi-step approaches.

| S-EPMC8457207 | 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