Redox-neutral photocatalytic hydrodealkenylation of aryl olefins.

Carbon-carbon bond cleavage is a transformative strategy in chemical synthesis, particularly for modifying complex molecules. While the cleavage of C(sp²)=C(sp²) π-bonds is relatively straightforward, the selective cleavage of unpolarized C(sp²)-C(sp³) σ-bonds remains a significant challenge. In this study, we present a redox-neutral approach for hydrodealkenylation, enabling the selective cleavage of C(sp²)-C(sp³) σ-bonds in aryl olefins.

Radiofluorination of 2-Arylquinolin-4-yl Oxypropanamide Derivatives for TSPO Imaging in Neuroinflammatory Murine, Nonhuman Primates, and Human Brain Autoradiography with Insensitivity to the rs6971 Polymorphism.

The 18 kDa translocator protein (TSPO) is a critical target for PET imaging of neuroinflammation in central nervous system (CNS) disorders; however, many clinical TSPO PET tracers are limited by sensitivity to rs6971 polymorphism. In this study, three novel fluorine-containing oxypropanamide ligands were developed, with (LW1, = 0.07 nM) and (LW2, = 0.

Facile synthesis of 1-silaacenaphthenes by transition metal-catalyzed intramolecular C(sp)-H silylation.

We report a general strategy for synthesizing novel fused aromatic 1-silaacenaphthenes by iridium or rhodium-catalyzed intramolecular C(sp)-H silylation. Both methods showed similar activity and broad substrate scope, producing a variety of 1-silaacenaphthenes with high functional group tolerance. We found that C-H cleavage was not the rate-determining step and that the reaction was first-order with respect to the initial concentrations of substrate, catalyst and ligand.

Enantioselective Synthesis of Acenaphthene-Type Monohydrosilanes.

Acenaphthene and its analogues are privileged frameworks in medicinal chemistry and material science. However, the properties of silicon-substituted acenaphthene-type scaffolds are poorly understood. Here, we report a rhodium-catalyzed intramolecular C(sp)-H silylation for enantioselective synthesis of acenaphthene-type scaffolds with excellent enantioselectivity and broad substrate scope.

Elucidating Binding Selectivity in Cyclin-Dependent Kinases 4, 6, and 9: Development of Highly Potent and Selective CDK4/9 Inhibitors.

CDK4/6 inhibitors are effective in treating HR/HER2 breast cancer but face limitations due to therapeutic resistance and hematological toxicity, particularly from strong CDK6 inhibition. To address these challenges, designing selective inhibitors targeting specific cyclin-dependent kinases (CDK) members could offer clinical advantages and broaden CDK inhibitor indications. However, the highly conserved binding pockets of CDKs complicate selective targeting.

Troglitazone Reduction of Intracellular Mycobacterium tuberculosis Survival Via Macrophage Autophagy Through LKB1-AMPKα Signaling.

Tuberculosis caused by Mycobacterium tuberculosis (Mtb), results in significant disease and death worldwide. Host-directed therapy, including conventional drugs, is a promising antituberculosis strategy that shows synergistic antibacterial effects when combined with antituberculosis drugs. Here, the mycobactericidal effect of 3 antidiabetic drugs was examined.

Three-component modular synthesis of chiral 1,3-dioxoles a Rh-catalyzed carbenic olefination cascade.

The advance of organic synthesis and the discovery of novel chemical transformations are often propelled by the rational programming of various bond-forming mechanisms and sequences that involve delicate reactive intermediates. In this study, we present an innovative Rh(ii)-catalyzed asymmetric three-component cascade reaction involving I/P-hybrid ylides, aldehydes, and carboxylic acids for the synthesis of 1,3-dioxoles with moderate to good yields and high enantioselectivity. This method utilizes I/P-hybrid ylides as carbene precursors to form α-P-Rh-carbenes, which initiate the formation of carbonyl ylides, followed by stereoselective cyclization with carboxylate anions and an intramolecular Wittig olefination cascade, ultimately resulting in the modular assembly of chiral 1,3-dioxoles.

N-Heterocyclic Carbene-Catalyzed Asymmetric S2 Alkylation via Noncovalent Activation.

The field of asymmetric catalysis has been developed by exploring noncovalent interactions, particularly within N-heterocyclic carbene-mediated processes. Despite challenges due to the limited number of compatible electrophiles (predominantly π-acceptors), this study introduces the first asymmetric α-alkylation of 3-aryl oxindoles using C electrophiles. The innovative protocol integrates diverse oxindoles and alkyl, allyl, and propargyl electrophiles, achieving high yields and enantioselectivities.

Water mediated redox-neutral cleavage of arylalkenes via photoredox catalysis.

Cleavage of carbon-carbon bonds remains a challenging task in organic synthesis. Traditional methods for splitting C=C bonds into two halves typically involve non-redox (metathesis) or oxidative (ozonolysis) mechanisms, limiting their synthetic potential. Disproportionative deconstruction of alkenes, which yields one reduced and one oxidized fragment, remains an unexplored area.

Photochemical three-component assembly of tri-substituted oxazoles through a carbenic phosphorus-nitrile hybrid ylide formation/trapping cascade.

Construction of complex molecular skeletons with ubiquitous chemical feedstocks in a single transformation is highly appealing in organic synthesis. We report a novel visible-light-induced three-component reaction for the construction of complex 2,4,5-trisubstituted oxazoles, which are valuable in medicinal chemistry, from simple and readily available iodonium-phosphonium hybrid ylides, carboxylic acids, and nitriles. This reaction features a carbenic phosphorus-nitrile hybrid ylide formation/trapping cascade, in which a photo-generated α-phosphonium carbene acts as a sequence trigger.

Amide C-N bonds activation by A new variant of bifunctional N-heterocyclic carbene.

We report an organocatalyst that combines a triazolium N-heterocyclic carbene (NHC) with a squaramide as a hydrogen-bonding donor (HBD), which can effectively catalyze the atroposelective ring-opening of biaryl lactams via a unique amide C-N bond cleavage mode. The free carbene species attacks the amide carbonyl, forming an axially chiral acyl-azolium intermediate. Various axially chiral biaryl amines can be accessed by this methodology with up to 99% ee and 99% yield.

Enantioselective S 2 Alkylation of Homoenolates by N-Heterocyclic Carbene Catalysis.

The functionalization of the β-carbon of enals with electrophiles is a signature umpolung reactivity of N-heterocyclic carbene (NHC) derived homoenolates. However, only a limited number of electrophiles are shown to be compatible, with most of them being π-electrophiles. In this study, the successful enantioselective β-alkylation of homoenolates is reported using C electrophiles through an S 2 strategy.

Photoredox Cleavage of a C-C Bond in Aromatic Hydrocarbons.

Functionalizing molecules through the selective cleavage of carbon-carbon bonds is an attractive approach in synthetic chemistry. Despite recent advances in both transition-metal catalysis and radical chemistry, the selective cleavage of inert C-C bonds in hydrocarbon feedstocks remains challenging. Examples reported in the literature typically involve substrates containing redox functional groups or highly strained molecules.

The thiol-sulfoxonium ylide photo-click reaction for bioconjugation.

Visible-light-mediated methods were heavily studied as a useful tool for cysteine-selective bio-conjugation; however, many current methods suffer from bio-incompatible reaction conditions and slow kinetics. To address these challenges, herein, we report a transition metal-free thiol-sulfoxonium ylide photo-click reaction that enables bioconjugation under bio-compatible conditions. The reaction is highly cysteine-selective and generally finished within minutes with naturally occurring riboflavin derivatives as organic photocatalysts.

A Thioether-Catalyzed Cross-Coupling Reaction of Allyl Halides and Arylboronic Acids.

C(sp )-C(sp ) cross-coupling reactions are an indispensable tool for organic synthesis. In these reactions transition metals have been extensively employed to promote the formation of valuable carbon-carbon bonds. Herein, we report our recent discovery of a designer thioether as a highly active organocatalyst for reactions between an allyl bromide and an arylboronic acid.

An NHC-catalyzed [3+2] cyclization of β-disubstituted enals with benzoyl cyanides.

The NHC-catalyzed asymmetric [3+2] cyclization of benzoyl cyanides to homoenolate generated from enals was reported. This methodology leads to the efficient construction of a series of chiral cyclic compounds bearing vicinal quaternary stereocenters under mild reaction conditions. Additionally, the representative large-scale and derivatization reactions of the chiral cyclic products reveal the potential synthetic utility of this protocol.

Enantioselective synthesis of acyclic monohydrosilanes by steric hindrance assisted C-H silylation.

Herein, a rhodium-catalyzed desymmetrization of dihydrosilanes with heterocyclic compounds intermolecular dehydrogenative C-H silylation is developed. The strategy tolerates a variety of thianaphthene and thiophene derivatives, giving rise to a wide range of silicon-stereogenic acyclic monohydrosilanes. Several rare skeletons featuring bis-silicon-stereogenic centers were also designed to enhance the library's diversity further.

Enantioselective Seleno-Michael Addition Reactions Catalyzed by a Chiral Bifunctional N-Heterocyclic Carbene with Noncovalent Activation.

The Michael reaction is a conjugate addition and is one of the most powerful methods with which to prepare functional molecules with a β-stereogenic center. Despite its success in the formation of various asymmetric carbon-carbon and carbon-heteroatom bonds, enantioselective seleno-Michael addition remains essentially unexplored. We report here a highly enantioselective Michael addition reaction of alkyl selenols to enones.

N-Heterocyclic Carbene-Catalyzed 1,4-Alkylacylation of 1,3-Enynes.

The radical relay coupling reaction recently emerged as a powerful synthetic strategy for producing tetrasubstituted allenes. However, bond-forming processes involving the allenyl radical intermediate are mostly limited to those promoted by transition metals. In this report, we describe that a ketyl radical generated from single-electron oxidation of the Breslow intermediate is an excellent coupling partner of allenyl radicals.

Photo-induced energy transfer relay of N-heterocyclic carbene catalysis: an asymmetric α-fluorination/isomerization cascade.

The geometric configuration of olefin products is often driven by thermodynamic control in synthesis. Methods enabling switching of cis/trans selectivity are rare. Recently, photosensitized approaches have emerged as a powerful tool for accomplishing this task.

Direct Synthesis of Bicyclic Acetals via Visible Light Catalysis.

Polysubstituted bicyclic acetals are a class of privileged pharmacophores with a unique 3D structure and an adjacent pair of hydrogen bond acceptors. The key, fused acetal functionality is often assembled, via intramolecular cyclization, from linear substrates that are not readily available. Herein, we report a formal cycloaddition between cinnamyl alcohols and cyclic enol ethers under ambient photoredox catalysis conditions.