Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Urea-Catalyzed Vinyl Carbocation Formation Enables Mild Functionalization of Unactivated C-H Bonds.

ABSTRACT: Herein we report the 3,5-bistrifluoromethylphenyl urea-catalyzed functionalization of unactivated C-H bonds. In this system, the urea catalyst mediates the formation of high-energy vinyl carbocations that undergo facile C-H insertion and Friedel-Crafts reactions. We introduce a new paradigm for these privileged scaffolds where the combination of hydrogen-bonding motifs and strong bases affords highly active Lewis acid catalysts capable of ionizing strong C-O bonds. Despite the highly Lewis-acidic nature of these catalysts that enables triflate abstraction from sp² carbons, these newly found reaction conditions allow for the formation of heterocycles and tolerate highly Lewis-basic heteroaromatic substrates. This strategy showcases the potential utility of dicoordinated vinyl carbocations in organic synthesis.

SUBMITTER: Bagdasarian AL

PROVIDER: S-EPMC8448122 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Urea-Catalyzed Vinyl Carbocation Formation Enables Mild Functionalization of Unactivated C-H Bonds.

Bagdasarian Alex L AL Popov Stasik S Wigman Benjamin B Wei Wenjing W Lee Woojin W Nelson Hosea M HM

Organic letters 20200619 20

Herein we report the 3,5-bistrifluoromethylphenyl urea-catalyzed functionalization of unactivated C-H bonds. In this system, the urea catalyst mediates the formation of high-energy vinyl carbocations that undergo facile C-H insertion and Friedel-Crafts reactions. We introduce a new paradigm for these privileged scaffolds where the combination of hydrogen-bonding motifs and strong bases affords highly active Lewis acid catalysts capable of ionizing strong C-O bonds. Despite the highly Lewis-acidi ...[more]

PMID: 32558583

Similar Datasets

Anaerobic functionalization of unactivated C-H bonds.

Project description:The functionalization of alkanes was once thought to lie strictly within the domain of enzymes that activate dioxygen in order to generate an oxidant with suitable potency to cleave inert C-H bonds. The emergence of the radical SAM superfamily of enzymes-those which use S-adenosyl-l-methionine as a precursor to a 5'-deoxyadenosyl 5'-radical-has kindled a renaissance in the study of radical-dependent enzymatic reactions, and is ushering in a wealth of new and intriguing chemistry that remains to be elucidated. This review will focus on a special subclass of radical SAM enzymes that functionalize inert C-H bonds, highlighting the functional groups and the chemistry that leads to their insertion. Within this class are first, enzymes that catalyze sulfur insertion, the prototype of which is biotin synthase; second, enzymes that catalyze P-methylation or C-methylation, such as P-methylase or Fom3; third, enzymes that catalyze oxygen insertion, such as the anaerobic magnesium protoporphyrin-IX oxidative cyclase (BchE); and fourth, enzymes that functionalize n-hexane or other alkanes as the first step in the metabolism of these inert compounds by certain bacteria. In addition to surveying reactions that have been studied at various levels of detail, this review will speculate on the mechanisms of other types of reactions that this chemistry lends itself to.

| S-EPMC2762545 | biostudies-literature

Azolation of Benzylic C-H Bonds via Photoredox-Catalyzed Carbocation Generation.

Project description:A visible-light photoredox-catalyzed method is reported that enables the coupling between benzylic C-H substrates and N-H azoles. Classically, medicinally relevant N-benzyl azoles are produced via harsh substitution conditions between the azole and a benzyl electrophile in the presence of strong bases at high temperatures. Use of C-H bonds as the alkylating partner streamlines the preparation of these important motifs. In this work, we report the use of N-alkoxypyridinium salts as a critically enabling reagent for the development of a general C(sp3)-H azolation. The platform enables the alkylation of electron-deficient, -neutral, and -rich azoles with a range of C-H bonds, most notably secondary and tertiary partners. Moreover, the protocol is mild enough to tolerate benzyl electrophiles, thus offering an orthogonal approach to existing SN2 and cross-coupling methods.

| S-EPMC10409882 | biostudies-literature

Enantioselective functionalization of unactivated C(sp<sup>3</sup>)-H bonds through copper-catalyzed diyne cyclization by kinetic resolution.

Project description:Site- and stereoselective C-H functionalization is highly challenging in the synthetic chemistry community. Although the chemistry of vinyl cations has been vigorously studied in C(sp3)-H functionalization reactions, the catalytic enantioselective C(sp3)-H functionalization based on vinyl cations, especially for an unactivated C(sp3)-H bond, has scarcely explored. Here, we report an asymmetric copper-catalyzed tandem diyne cyclization/unactivated C(sp3)-H insertion reaction via a kinetic resolution, affording both chiral polycyclic pyrroles and diynes with generally excellent enantioselectivities and excellent selectivity factors (up to 750). Importantly, this reaction demonstrates a metal-catalyzed enantioselective unactivated C(sp3)-H functionalization via vinyl cation and constitutes a kinetic resolution reaction based on diyne cyclization. Theoretical calculations further support the mechanism of vinyl cation-involved C(sp3)-H insertion reaction and elucidate the origin of enantioselectivity.

| S-EPMC10933314 | biostudies-literature

Heteroarylation of unactivated C-H bonds suitable for late-stage functionalization.

Project description:The late-stage introduction of diverse heterocycles onto complex small molecules enables efficient access to new medicinally relevant compounds. An attractive approach to such a transformation would utilize the ubiquitous aliphatic C-H bonds of a complex substrate. Herein, we report a system that enables direct C-H heteroarylation using a stable, commercially available O-alkenylhydroxamate with heterocyclic sulfone partners. The C-H heteroarylation proceeds efficiently with a range of aliphatic substrates and common heterocycles, and is a rare example of heteroarylation of strong C-H bonds. Importantly, the present approach is amenable to late-stage functionalization as the substrate is the limiting reagent in all cases.

| S-EPMC9580477 | biostudies-literature

Catalytic functionalization of unactivated primary C-H bonds directed by an alcohol.

Project description:New synthetic methods for the catalytic functionalization of C-H bonds have the potential to revolutionize the synthesis of complex molecules. However, the realization of this synthetic potential requires the ability to functionalize selectively one C-H bond in a compound containing many such bonds and an array of functional groups. The site-selective functionalization of aliphatic C-H bonds is one of the greatest challenges that must be met for C-H bond functionalization to be used widely in complex-molecule synthesis, and processes catalysed by transition-metals provide the opportunity to control selectivity. Current methods for catalytic, aliphatic C-H bond functionalization typically rely on the presence of one inherently reactive C-H bond, or on installation and subsequent removal of directing groups that are not components of the desired molecule. To overcome these limitations, we sought catalysts and reagents that would facilitate aliphatic C-H bond functionalization at a single site, with chemoselectivity derived from the properties of the catalyst and site-selectivity directed by common functional groups contained in both the reactant and the desired product. Here we show that the combination of an iridium-phenanthroline catalyst and a dihydridosilane reagent leads to the site-selective γ-functionalization of primary C-H bonds controlled by a hydroxyl group, the most common functional group in natural products. The scope of the reaction encompasses alcohols and ketones bearing many substitution patterns and auxiliary functional groups; this broad scope suggests that this methodology will be suitable for the site-selective and diastereoselective functionalization of complex natural products.

| S-EPMC11620535 | biostudies-literature

C-H bond functionalization via hydride transfer: direct coupling of unactivated alkynes and sp(3) C-H bonds catalyzed by platinum tetraiodide.

Project description:We report a catalytic intramolecular coupling between terminal unactivated alkynes and sp(3) C-H bonds via through-space hydride transfer (HT-cyclization of alkynes). This method enables one-step preparation of complex heterocyclic compounds by alpha-alkenylation of readily available cyclic ethers and amines. We show that PtI(4) is an effective Lewis acid catalyst for the activation of terminal alkynes for hydride attack and subsequent C-C bond formation. In addition, we have shown that the activity of neutral platinum salts (PtX(n)) can be modulated by the halide ligands. This modulation in turn allows for fine-tuning of the platinum center reactivity to match the reactivity and stability of selected substrates and products.

| S-EPMC2971677 | biostudies-literature

Palladium(0)-catalyzed intermolecular amination of unactivated C(sp³)-H bonds.

Project description: Not available

| S-EPMC3413323 | biostudies-literature

Iridium-Catalyzed, Hydrosilyl-Directed Borylation of Unactivated Alkyl C-H Bonds.

Project description:We report the iridium-catalyzed borylation of primary and secondary alkyl C-H bonds directed by a Si-H group to form alkylboronate esters site selectively. The reactions occur with high selectivity at primary C-H bonds γ to the hydrosilyl group to form primary alkyl bisboronate esters. In the absence of such primary C-H bonds, the borylation occurs selectively at a secondary C-H bond γ to the hydrosilyl group, and these reactions of secondary C-H bonds occur with high diastereoselectivity. The hydrosilyl-containing alkyl boronate esters formed by this method undergo transformations selectively at the carbon-boron or carbon-silicon bonds of these products under distinct conditions to give the products of amination, oxidation, and arylation.

| S-EPMC4809204 | biostudies-literature

Directed copper-catalyzed C-H functionalization of unactivated olefins with azodicarbonamide compounds.

Project description:The copper-catalyzed strategy employing the 8-aminoquinoline directing group has proven to be a highly advantageous approach for functionalizing C-H bonds. In this study, we present the successful application of this strategy to accomplish Heck-type coupling reactions and construct β-lactam skeletons, simultaneously introducing a unique cyano functional group. The resulting Heck-type coupling products demonstrate good stereo- and region-selectivity. Initial mechanistic investigations indicate that the reaction proceeds via a radical coupling mechanism, exhibiting a wide substrate scope and delivering good yields.

| S-EPMC11359497 | biostudies-literature

Cobalt catalyzed carbonylation of unactivated C(sp<sup>3</sup>)-H bonds.

Project description:A general efficient regioselective cobalt catalyzed carbonylation of unactivated C(sp3)-H bonds of aliphatic amides was demonstrated using atmospheric (1-2 atm) carbon monoxide as a C1 source. This straightforward approach provides access to α-spiral succinimide regioselectively in a good yield. Cobalt catalyzed sp3 C-H bond carbonylation is reported for the first time including the functionalization of (β)-C-H bonds of α-1°, 2°, 3° carbons and even internal (β)-C-H bonds. Our initial mechanistic investigation reveals that the C-H activation step is irreversible and will possibly be the rate determining step.

| S-EPMC5369400 | 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