Photoinduced, Redox-Neutral Decyanative and Defluorinative Phosphination of (Hetero)Arenes.

Triarylphosphines play a crucial role in organic synthesis as versatile components serving as ligands, catalysts, and reactants. This study introduces a metal-free, visible-light-induced method for the cross-coupling of cyanopyridines or polyfluoroarenes with diarylphosphines. This approach facilitates the formation of C(sp2)-P bonds through redox-neutral decyanative or defluorinative process, enabling the convenient synthesis of diverse triarylphosphines.

The Substituent Effects of Suzuki Coupling in Aqueous Micelles.

The Suzuki coupling in aqueous micelles has received much attention, but few attempts focus on its substituent effects. In view of the significant substituent effects on this reaction, it is necessary and practical to investigate its substituent effects. Herein, the substituent effects of Suzuki coupling in aqueous micelles are well established through Hammett plots and kinetic studies. In the cases of aryl halides, the rate-determining step of the reaction will shift from the oxidation addition step to the transmetalation step as the substituents' electron withdrawing ability increases, so aryl halides with weak electron-withdrawing groups exhibit better reactivity than ones containing strong electron-withdrawing or electron-donating groups. For arylboronic acids, the electron donating groups are beneficial to the Suzuki reaction, while the electron withdrawing group is unfavorable for the reaction. The Suzuki reactions of substituent exchange between arylboronic acids and aryl halides further confirm these substituent effects.

Recent advances in electrochemically enabled construction of indoles from non-indole-based substrates.

Indole motifs are important heterocycles found in natural products, pharmaceuticals, agricultural chemicals, and materials. Although there are well-established classical name reactions for indole synthesis, these transformations often require harsh reaction conditions, have a limited substrate scope, and exhibit poor regioselectivity. As a result, organic synthesis chemists have been exploring efficient and practical methods, leading to numerous strategies for synthesizing a variety of functionalized indoles. In recent years, electrochemistry has emerged as an environmentally friendly and sustainable synthetic tool, with widespread applications in organic synthesis. This technology allows for elegant synthetic routes to be developed for the construction of indoles under external oxidant-free conditions. This feature article specifically focuses on recent advancements in indole synthesis from non-indole-based substrates, as well as the mechanisms underlying these transformations.

Radical Ring-Opening Fluorosulfonylation of Methylenecyclobutanols via Electron Donor-Acceptor Photoactivation.

A visible-light-mediated catalyst- and additive-free method for radical ring-opening fluorosulfonylation of methylenecyclobutanols is reported. Sulfuryl chlorofluoride acts as a FSO2 radical precursor as well as an electron acceptor to form electron donor-acceptor complexes with various methylenecyclobutanol substrates. This method shows fully regioselective and (E)-stereoselective ring-opening processes, providing a variety of FSO2-functionalized γ,δ-unsaturated carbonyls in 38-77% yields. A selection of product diversifications has been studied to demonstrate the versatility of these sulfonyl fluoride products.

Selective Hydrodeoxygenation of Lignin-Derived Phenolic Monomers to Cyclohexanol over Tungstated Zirconia Supported Ruthenium Catalysts.

The selective hydrodeoxygenation (HDO) of lignin-derived methoxyphenols to cyclohexanol is one of the most significant transformation in biomass conversion since cyclohexanol is an important industrial raw material. This study has disclosed a series of tungstated zirconia with different Zr/W ratio supported Ru catalysts (Ru/xZrW, x means the molar ration of Zr/W) for the hydrodeoxygenation (HDO) of guaiacol to cyclohexanol. Among these catalysts, Ru/16ZrW has the best catalytic activity, which can achieve 92 % yield of cyclohexanol under the conditions of 180 °C and 1 MPa H2 pressure for 2 h (TOF 231 h-1). Compared with Ru/ZrO2, Ru/16ZrW has smaller particles, more dispersed and electron-rich Ru species, significant hydrogen spillover and more acid sites, which are the main reason for its excellent performance on this reaction. Apart from guaiacol, other methoxy substitution phenols and organosolv lignin can also be converted into cyclohexanol via hydrodeoxygenation reactions over this catalyst.

Photoredox-Enabled Deconstructive [5 + 1] Annulation Approach to Isoquinolones from Indanones in Water.

We disclose a deconstructive [5 + 1] annulation protocol for the synthesis of isoquinolones through a nitrogen insertion into abundant indanones. This method exploits photoredox-catalyzed ring-opening of oxime esters. The reaction proceeds smoothly with water as the reaction medium and tolerates a range of functional groups on diverse thiophenols, amines, or indanones. Moreover, the representative isoquinolones exhibit promising antifungal activities.

Fluorosulfonyl Arylation of Alkynes via Electron Donor-Acceptor Photoactivation.

A radical fluorosulfonyl arylation of alkynes with sulfuryl chlorofluoride as the FSO2 radical precursor via electron donor-acceptor photoactivation driven by daylight or a blue light-emitting diode is disclosed. A series of valuable benzo-fused carbocycles and heterocycles have been produced with simple operation under mild conditions in the absence of any external catalysts or additives. The synthetic potential of this protocol has further demonstrated excellent scalability, as well as diverse postderivatizations, including SuFEx reactions and other useful cascade reactions.

Radical Hydro-Fluorosulfonylation of Propargylic Alcohols via Electron Donor-Acceptor Photoactivation.

A radical hydro-fluorosulfonylation of propargyl alcohols with FSO2Cl is presented based on the photoactivation of the electron donor-acceptor (EDA) complex. The reaction avoids the requirement for photocatalysts, bases, hydrogen donor reagents, any other additives, and harsh conditions, enabling the facile synthesis of various functionalized γ-hydroxy (E)-alkenylsulfonyl fluorides. These multifunctional sulfonyl fluorides can be further diversified, providing access to various privileged molecules of biological relevance.

Cathodically Coupled Electrolysis to Access Biheteroaryls.

An electrochemical approach to biheteroaryls through the coupling of diverse N-heteroarenes with heteroaryl phosphonium salts is reported. The reaction features pH and redox-neutral conditions and excellent regioselectivity, as well as exogenous air or moisture tolerance. Additionally, a one-pot, two-step protocol can be established to realize formal C-H/C-H coupling of heteroarenes, thereby greatly expanding the substrate availability. The utility of this method is demonstrated through late-stage functionalization, the total synthesis of nitraridine, and antifungal activity studies.

Cereblon-based Bifunctional Degrader of SOS1, BTX-6654, Targets Multiple KRAS Mutations and Inhibits Tumor Growth.

Mutations within the oncogene KRAS drive an estimated 25% of all cancers. Only allele-specific KRAS G12C inhibitors are currently available and are associated with the emergence of acquired resistance, partly due to upstream pathway reactivation. Given its upstream role in the activation of KRAS, son of sevenless homolog 1 (SOS1), has emerged as an attractive therapeutic target. Agents that target SOS1 for degradation could represent a potential pan-KRAS modality that may be capable of circumventing certain acquired resistance mechanisms. Here, we report the development of two SOS1 cereblon-based bifunctional degraders, BTX-6654 and BTX-7312, cereblon-based bifunctional SOS1 degraders. Both compounds exhibited potent target-dependent and -specific SOS1 degradation. BTX-6654 and BTX-7312 reduced downstream signaling markers, pERK and pS6, and displayed antiproliferative activity in cells harboring various KRAS mutations. In two KRAS G12C xenograft models, BTX-6654 degraded SOS1 in a dose-dependent manner correlating with tumor growth inhibition, additionally exhibiting synergy with KRAS and MEK inhibitors. Altogether, BTX-6654 provided preclinical proof of concept for single-agent and combination use of bifunctional SOS1 degraders in KRAS-driven cancers.

Electrochemical Ring-Opening of Cyclopropylamides with Alcohols toward the Synthesis of 1,3-Oxazines.

An electrochemical method is presented to construct 1,3-oxazines by the oxidative ring-opening of cyclopropylamides with alcohols. This method avoids the use of external oxidants and thus shows good functional group tolerance. The substrate scope covers primary, secondary, and tertiary alcohols as well as (hetero)aryl amide-substituted cyclopropanes.

Electroreductive hydroxy fluorosulfonylation of alkenes.

An electroreductive strategy for radical hydroxyl fluorosulfonylation of alkenes with sulfuryl chlorofluoride and molecular oxygen from air is described. This mild protocol displays excellent functional group compatibility, broad scope, and good scalability, providing convenient access to diverse ß-hydroxy sulfonyl fluorides. These ß-hydroxy sulfonyl fluoride products can be further converted to valuable aliphatic sulfonyl fluorides, ß-keto sulfonyl fluorides, and ß-alkenyl sulfonyl fluorides. Further, some of these products showed excellent inhibitory activity against Botrytis cinerea or Bursaphelenchus xylophilus, which could be useful for potent agrochemical discovery. Preliminary mechanistic studies indicate that this transformation is achieved through rapid O2 interception by the alkyl radical and subsequent reduction of the peroxy radical, which outcompete other side reactions such as chlorine atom transfer, hydrogen atom transfer, and Russell fragmentation.

Synthesis of Aryl Thioalkynes Enabled by Electrophilic Sulfenylation of Alkynes and the Following Elimination.

An unexpected deprotonative process of thiirenium ions is presented, which provides a new synthesis of aryl thioalkynes directly from terminal alkynes via the electrophilic activation of the carbon-carbon triple bonds. The conditions are well compatible with various functional-group-substituted aryl alkynes. The direct elimination from the thiirenium ion intermediate, or its tautomer, benzyl vinyl carbocation, is supported by control experiments and labeling reaction.

Fluorosulfonylvinylation of Unactivated C(sp3)-H via Electron Donor-Acceptor Photoactivation.

An electron donor-acceptor (EDA) complex photoactivation strategy for radical fluorosulfonylation is disclosed for the first time. Simply upon blue light irradiation, the FSO2 radical can be generated efficiently under catalyst-free, base-free, and additive-free conditions, which enables facile access to 6-keto alkenylsulfonyl fluorides from readily available propargyl alcohols and FSO2Cl. The 6-keto alkenylsulfonyl fluoride motif has been showcased as a versatile SuFEx hub with diverse follow-up derivatizations.

Gold-Catalyzed Cascade Reaction of Diynamides with Allylic Alcohols: A Versatile Platform to Allenamide, 2-Aminofuran and Bridged [2.2.2]Octadiene Derivatives.

Transition metal-catalyzed divergent synthesis through alternation of the catalyst is appealing, as it provides an operationally simple way to access different valuable products, while using the same reactants as starting materials. Herein, a gold-catalyzed cascade reaction of conjugated diynamides with allylic alcohols is described. By variation of the catalysts, substituted allenes and furans could be obtained selectively. Mechanistic studies indicate that, after the addition of allylic alcohol to gold-activated diynamide, a [3,3]-sigmatropic rearrangement would take place and lead to the formation of a common reactive intermediate, which would further convert to the final products selectively. Further variation of the structure of diynamides has unveiled an additional reaction sequence involving intramolecular Himbert arene/allene Diels-Alder cycloaddition to afford a series of dearomatized products bearing bicyclo[2,2,2]octadiene core.

SO2ClF: A Reagent for Controllable Chlorination and Chlorooxidation of Simple Unprotected Indoles.

Sulfuryl chlorofluoride was first employed as a versatile reagent for controllable chlorination and chlorooxidation of simple unprotected indoles. Three types of products including 3-chloro-indoles, 3-chloro-2-oxindoles, and 3,3-dichloro-2-oxindoles could be selectively obtained in good to excellent yields by switching the reaction solvents. The present method features easy-to-operate, broad substrate scope, and mild reaction conditions.

Electrochemical Oxidative Cleavage of Alkynes to Carboxylic Acids.

A sustainable method for converting terminal alkynes into their corresponding carboxylic acids is reported using synthetic electrolysis in an undivided cell at room temperature. This protocol, avoiding transition metal catalysis and stoichiometric chemical oxidants, tolerates a variety of aryl, heteroaryl, and alkyl akynes. Preliminary mechanistic studies demonstrate that sodium nitrite serves a triple role as the electrolyte, nitryl radical precursor, and a nitrosating reagent.

Chromene-based BioAIEgens: 'in-water' synthesis, regiostructure-dependent fluorescence and ER-specific imaging.

Exploration of artificial aggregation-induced emission luminogens (AIEgens) has garnered extensive interest in the past two decades. In particular, AIEgens possessing natural characteristics (BioAIEgens) have received more attention recently due to the advantages of biocompatibility, sustainability and renewability. However, the extremely limited number of BioAIEgens extracted from natural sources have retarded their development. Herein, a new class of BioAIEgens based on the natural scaffold of chromene have been facilely synthesized via green reactions in a water system. These compounds show regiostructure-, polymorphism- and substituent-dependent fluorescence, which clearly illustrates the close relationship between the macroscopic properties and hierarchical structure of aggregates. Due to the superior biocompatibility of the natural scaffold, chromene-based BioAIEgens can specifically target the endoplasmic reticulum (ER) via the introduction of tosyl amide. This work has provided a new chromene scaffold for functional BioAIEgens on the basis of green and sustainable 'in-water' synthesis, applicable regiostructure-dependent fluorescence, and effective ER-specific imaging.

Regio- and Stereoselective Synthesis of ß-Methylthio Vinyl Triflates.

Vinyl triflates are commonly employed as electrophilic vinyl sources in complex synthesis. The triflation of enolates is commonly required for the preparation of vinyl triflates, generally under strongly basic conditions. Herein, the reaction between alkynes and dimethyl(methylthio)sulfonium trifluoromethanesulfonate is presented, which leads to the development of a facile synthesis of ß-methylthio vinyl triflates in a chemo-, regio-, and stereoselective manner under neutral and extremely simple conditions.

Synthesis of Pyrrole via Formal Cycloaddition of Allyl Ketone and Amine under Metal-Free Conditions.

A new metal-free synthesis of pyrrole from allyl ketone and amine has been established. The reaction proceeds via an thiolative activation of the C-C double bond with dimethyl(methylthio)sulfonium trifluoromethanesulfonate, followed by a nucleophilic ring-opening addition of primary amine to the generated episulfonium intermediate, and then an internal condensation and aromatization. This mild procedure provides a novel strategy to the construction of substituted pyrroles through a formal [4 + 1] cycloaddition reaction.