Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

General Co-catalytic Hydrothiolation of gem-Difluoroalkenes.

ABSTRACT: Regioselective functionalization of gem-difluoroalkenes enables convergent late-stage access to fluorinated functional groups, though most functionalization reactions proceed through defluorinative functionalization processes that deliver mono-fluorovinyl products. In contrast, fewer reactions undergo net hydrofunctionalization to generate difluorinated products. Herein, we report a photocatalytic hydrothiolation of gem-difluoroalkenes that enables access to a broad spectrum of α,α-difluoroalkylthioethers. Notably, the reaction successfully couples nonactivated substrates, which expands the scope of accessible molecules relative to previously reported reactions involving organo- or photocatalytic strategies. Further, this reaction successfully couples biologically relevant molecules under aqueous conditions, highlighting potential applications in both late-stage and biorthogonal functionalizations.

SUBMITTER: Sorrentino JP

PROVIDER: S-EPMC9772298 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

General Co-catalytic Hydrothiolation of gem-Difluoroalkenes.

Sorrentino Jacob P JP Herrick Ryan M RM Abd El-Gaber Mohammed K MK Abdelazem Ahmed Z AZ Kumar Ankit A Altman Ryan A RA

The Journal of organic chemistry 20221205 24

Regioselective functionalization of gem-difluoroalkenes enables convergent late-stage access to fluorinated functional groups, though most functionalization reactions proceed through defluorinative functionalization processes that deliver mono-fluorovinyl products. In contrast, fewer reactions undergo net hydrofunctionalization to generate difluorinated products. Herein, we report a photocatalytic hydrothiolation of gem-difluoroalkenes that enables access to a broad spectrum of α,α ...[more]

PMID: 36469658

Similar Datasets

Arylation of gem-difluoroalkenes using a Pd/Cu Co-catalytic system that avoids β-fluoride elimination.

Project description:PdII/CuI co-catalyze an arylation reaction of gem-difluoroalkenes using arylsulfonyl chlorides to deliver α,α-difluorobenzyl products. The reaction proceeds through a β,β-difluoroalkyl-Pd intermediate that typically undergoes unimolecular β-F elimination to deliver monofluorinated alkene products in a net C-F functionalization reaction. However to avoid β-F elimination, we offer the β,β-difluoroalkyl-Pd intermediate an alternate low-energy route involving β-H elimination to ultimately deliver difluorinated products in a net arylation/isomerization sequence. Overall, this reaction enables exploration of new reactivities of unstable fluorinated alkyl-metal species, while also providing new opportunities for transforming readily available fluorinated alkenes into more elaborate substructures.

| S-EPMC8179108 | biostudies-literature

Organocatalytic Strategy for Hydrophenolation of Gem-Difluoroalkenes.

Project description:Gem-difluoroalkenes are an easily accessed fluorinated functional group, and a useful intermediate for elaborating into more complex fluorinated compounds. Currently, most functionalization reactions of gem-difluoroalkenes, with or without a transition metal-based catalyst system, involve the addition or removal of a fluorine atom to generate trifluorinated or monofluorinated products, respectively. In contrast, we present a complementary "fluorine-retentive" reaction that exploits an organocatalytic strategy to add phenols across gem-difluoroalkenes to deliver β,β-difluorophenethyl arylethers. The products are produced in good to moderate yields and selectivities, thus providing a range of compounds that are underrepresented in the synthetic and medicinal chemistry literature.

| S-EPMC7043310 | biostudies-literature

Catalytic Hydrothiolation: Counterion-Controlled Regioselectivity.

Project description:In this Article, we expand upon the catalytic hydrothiolation of 1,3-dienes to afford either allylic or homoallylic sulfides with high regiocontrol. Mechanistic studies support a pathway in which regioselectivity is dictated by the choice of counterion associated with the Rh center. Non-coordinating counterions, such as SbF6-, allow for η4-diene coordination to Rh complexes and result in allylic sulfides. In contrast, coordinating counterions, such as Cl-, favor neutral Rh complexes in which the diene binds η2 to afford homoallylic sulfides. We propose mechanisms that rationalize a fractional dependence on thiol for the 1,2-Markovnikov hydrothiolation while accounting for an inverse dependence on thiol in the 3,4- anti-Markovnikov pathway. Through the hydrothiolation of an essential oil (β-farnesene), we achieve the first enantioselective synthesis of (-)-agelasidine A.

| S-EPMC6563821 | biostudies-literature

Cobalt-Catalyzed Selective Unsymmetrical Dioxidation of gem-Difluoroalkenes.

Project description:gem-Difluoroalkenes represent valuable synthetic handles for organofluorine chemistry; however, most reactions of this substructure proceed through reactive intermediates prone to eliminate a fluorine atom and generate monofluorinated products. Taking advantage of the distinct reactivity of gem-difluoroalkenes, we present a cobalt-catalyzed regioselective unsymmetrical dioxygenation of gem-difluoroalkenes using phenols and molecular oxygen, which retains both fluorine atoms and provides β-phenoxy-β,β-difluorobenzyl alcohols. Mechanistic studies suggest that the reaction operates through a radical chain process initiated by Co(II)/O2/phenol and quenched by the Co-based catalyst. This mechanism enables the retention of both fluorine atoms, which contrasts most transition-metal-catalyzed reactions of gem-difluoroalkenes that typically involve defluorination.

| S-EPMC7442739 | biostudies-literature

Addition of Carboxylic Acids to gem-Difluoroalkenes for the Synthesis of gem-Difluoromethylenated Compounds.

Project description:We herein describe a straightforward protocol for the synthesis of carboxylic esters containing a gem-difluoromethylene unit. Readily available carboxylic acids can act as nucleophiles to add regioselectively to tetrasubstituted or trisubstituted β,β-difluoroacrylates (formal hydroacetoxylation) for the construction of RCO2-CF2 bonds. Thermal conditions are sufficient without the use of catalysts or additives.

| S-EPMC10877607 | biostudies-literature

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides.

Project description:Here, we report the first transition-metal-free defluorinative cycloaddition of gem-difluoroalkenes with organic azides in morpholine as a solvent to construct fully decorated morpholine-substituted 1,2,3-triazoles. Mechanistic studies revealed the formation of an addition-elimination intermediate of morpholine and gem-difluoroalkenes prior to the triazolization reaction via two plausible pathways. Attractive elements include the regioselective and straightforward direct synthesis of fully substituted 1,2,3-triazoles, which are otherwise difficult to access, from readily available starting materials.

| S-EPMC10562644 | biostudies-literature

Stereodivergent Palladium-Catalyzed C-F Bond Functionalization of gem-Difluoroalkenes.

Project description:We herein describe a stereodivergent C-F bond functionalization of gem-difluoroalkenes. Using trisubstituted β,β-difluoroacrylates, both E and Z monofluoroalkene products can be obtained with excellent diastereoselectivities. The design of two different reaction manifolds, i.e., Pd(II)- versus Pd(0)-catalyzed cross-coupling of boronic acids, is the key to stereocontrol.

| S-EPMC11250036 | biostudies-literature

Peroxide-Initiated Hydrophosphinylation of gem-Difluoroalkenes.

Project description:The installation of fluorine and fluorinated functional groups into drug-like scaffolds can perturb the physicochemical, pharmacokinetic, and pharmacodynamic properties of compounds. However, some potentially useful fluorinated substructures reside predominantly outside the realm of the current synthetic methodologies. One such substructure, the α,α-difluorophosphine oxide, might be convergently prepared by the reaction of a gem-difluorinated alkene with a P-H bond, though such nucleophilic reactions instead proceed through a C-F substitution pathway that delivers monofluorovinyl products. In contrast, we report a peroxide-initiated hydrophosphinylation reaction of gem-difluoroalkenes that avoids C-F substitution and produces a wide range of α,α-difluorophosphine oxides and functions using readily available reagents and green solvents.

| S-EPMC10591976 | biostudies-literature

Selective C-F bond carboxylation of gem-difluoroalkenes with CO2 by photoredox/palladium dual catalysis.

Project description:The catalytic C-F bond carboxylation of organofluorines with CO2 gas remains a challenging problem in synthetic chemistry. Here, we describe a selective defluorinative carboxylation of gem-difluoroalkenes through photoredox/palladium dual catalysis. The C-F bond activation is enabled by single electron reduction through photoredox catalysis to generate a fluorovinyl radical, which subsequently participates in an unprecedented palladium-catalyzed carboxylation. This novel C-F functionalization proved applicable to a wide range of substituted gem-difluoroalkenes, providing a rapid access to valuable α-fluoroacrylic acids.

| S-EPMC6625485 | biostudies-literature

Acid-Catalyzed Hydrothiolation of gem-Difluorostyrenes to Access α,α-Difluoroalkylthioethers.

Project description:The substitution of hydrogen atoms with fluorine in bioactive molecules can greatly impact physicochemical, pharmacokinetic, and pharmacodynamic properties. However, current synthetic methods cannot readily access many fluorinated motifs, which impedes utilization of these groups. Thus, the development of new methods to introduce fluorinated functional groups is critical for developing the next generation of biological probes and therapeutic agents. The synthesis of one such substructure, the α,α-difluoroalkylthioether, typically requires specialized conditions that necessitate early-stage installation. A late-stage and convergent approach to access α,α-difluoroalkylthioethers could involve nucleophilic addition of thiols across gem-difluorostyrenes. Unfortunately, under basic conditions, nucleophilic addition to gem-difluorostyrenes generates an anionic intermediate that can undergo facile elimination of fluoride to generate α-fluorovinylthioethers. To overcome this decomposition, we herein exploit an acid-based catalyst system to facilitate simultaneous nucleophilic addition and protonation of the unstable intermediate. Ultimately, the optimized mild conditions afford the desired α,α-difluoroalkylthioethers in high selectivity and moderate to excellent yields. These α,α-difluoroalkylthioethers are less nucleophilic and more oxidatively stable relative to nonfluorinated thioethers, suggesting the potential application of this unexplored functional group in biological probes and therapeutic agents.

| S-EPMC7869866 | biostudies-literature