Aryl Boronic Research Articles

CuCl‐Catalyzed Conversion of Aryl Boronic Acids and Carbon Dioxide to Carboxylate Esters

AbstractThe CuCl‐catalyzed reaction of aryl boronic acid with carbon dioxide to form carboxylate ester after treatment with CH3I has been developed. The procedure featured mild conditions and good functional group tolerances. A diverse range of aryl boronic acids were effectively converted into carboxylate esters. Even those bearing sensitive groups such as carbonyl, ester, and amide could produce the desired products in good yields.

A Fruitful Decade of Organofluorine Chemistry: New Reagents and Reactions

A Fruitful Decade of Organofluorine Chemistry: New Reagents and Reactions

Dearomatization of Heteroarenium Salts with ArBpin Reagents. Application to the Total Synthesis of a Nuphar Alkaloid.

Rhodium-catalyzed enantioselective addition of aryl and heteroaryl boron pinacol esters to pyridinium and quinolinium salts is developed for the synthesis of enantioenrichred dihydroheteroarenes. The methodology has enabled the synthesis of 2-heteroaryl-substituted dihydropyridines in high yield and ee, which provided efficient synthetic access to a nuphar alkaloid.

Enhancing Metalating Efficiency of the Sodium Amide NaTMP in Arene Borylation Applications.

Though LiTMP (TMP=2,2′,6,6′‐tetramethylpiperidide) is a commonly used amide, surprisingly the heavier NaTMP has hardly been utilised. Here, by mixing NaTMP with tridentate donor PMDETA (N,N,N′,N′′,N′′‐pentamethyldiethylenetriamine), we provide structural, and mechanistic insights into the sodiation of non‐activated arenes (e.g. anisole and benzene). While these reactions are low yielding, adding B(OiPr)3 has a profound effect, not only by intercepting the CAr‐Na bond, but also by driving the metalation reaction towards quantitative formation of more stabilized sodium aryl boronates. Demonstrating its metalating power, regioselective C2‐metalation/borylation of naphthalene has been accomplished contrasting with single‐metal based protocols which are unselective and low yielding. Extension to other arenes allows for in situ generation of aryl boronates which can then directly engage in Suzuki–Miyaura couplings, furnishing a range of biaryls in a selective and efficient manner.

Enhancing Metalating Efficiency of the Sodium Amide NaTMP in Arene Borylation Applications

AbstractThough LiTMP (TMP=2,2′,6,6′‐tetramethylpiperidide) is a commonly used amide, surprisingly the heavier NaTMP has hardly been utilised. Here, by mixing NaTMP with tridentate donor PMDETA (N,N,N′,N′′,N′′‐pentamethyldiethylenetriamine), we provide structural, and mechanistic insights into the sodiation of non‐activated arenes (e.g. anisole and benzene). While these reactions are low yielding, adding B(OiPr)3 has a profound effect, not only by intercepting the CAr‐Na bond, but also by driving the metalation reaction towards quantitative formation of more stabilized sodium aryl boronates. Demonstrating its metalating power, regioselective C2‐metalation/borylation of naphthalene has been accomplished contrasting with single‐metal based protocols which are unselective and low yielding. Extension to other arenes allows for in situ generation of aryl boronates which can then directly engage in Suzuki–Miyaura couplings, furnishing a range of biaryls in a selective and efficient manner.

Pd-Catalyzed Difluoromethylations of Aryl Boronic Acids, Halides, and Pseudohalides with ICF2 H Generated ex Situ.

An expedient ex‐situ generation of difluoroiodomethane (DFIM) and its immediate use in a Pd‐catalyzed difluoromethylation of aryl boronic acids and ester derivatives in a two‐chamber reactor is reported. Heating a solution of bromodifluoroacetic acid with sodium iodide in sulfolane proved to be effective for the generation of near stoichiometric amounts of DFIM for the ensuing catalytic coupling step. A two‐step difluoromethylation of aryl (pseudo)halides with tetrahydroxydiboron as a low‐cost reducing agent, both promoted by Pd catalysis, proved effective to install this fluorine‐containing C1 group onto several pharmaceutically relevant molecules. Finally, the method proved adaptable to deuterium incorporation by simply adding D2O to the DFIM‐generating chamber.

Aryl Boronic Esters Are Stable on Silica Gel and Reactive under Suzuki-Miyaura Coupling Conditions.

A wide range of aryl boronic 1,1,2,2-tetraethylethylene glycol esters [ArB(Epin)s] were readily synthesized. Purifying aryl boronic esters by conventional silica gel chromatography is generally challenging; however, these introduced derivatives are easily purified on silica gel and isolated in excellent yields. We subjected the purified ArB(Epin) to Suzuki-Miyaura couplings, which provided higher yields of the desired biaryl products than those obtained using the corresponding aryl boronic acids or pinacol esters.

Chromium-Catalyzed Selective Borylation of Vinyl Triflates and Unactivated Aryl Carboxylic Esters with Pinacolborane.

The use of pinacolborane to borylate abundant vinyl triflates and unactivated aryl carboxylic esters was enabled by chromium catalysis via the selective formation of vinyl and aryl boronate esters. The competing hydrided reduction or allylic borylation proceeds sluggishly or does not occur, therefore providing a selective strategy for the incorporation of boronate into olefins and arenes. Mechanistic studies indicate that the σ-bond metathesis or oxidative addition mechanism may be considered to be responsible for the cleavage of ester scaffolds.

A general strategy for in situ assembly of light-up fluorophores via bioorthogonal Suzuki-Miyaura cross-coupling

Herein we presented a general strategy for in situ assembly of intramolecular charge-transfer (ICT)-based light-up fluorophores via bioorthogonal Suzuki-Miyaura cross-coupling reaction. By introducing iodo group at the appropriate position, five fluorophores with different scaffolds including naphthalimide, coumarin, naphthalene sulfonate, nitrobenzoxadiazole, and acetonaphthone, were designed as bioorthogonal multicolor fluorogenic probes, which could produce significant fluorescence enhancement and high fluorescence quantum yield after Suzuki-Miyaura reaction with aryl boronic acid or boronate. Manipulating the substituents and π scaffold in the fluorophores allows fine-tuning of their photophysical properties. With this strategy, we succeeded in peptide conjugation, no-wash fluorogenic protein labeling, and mitochondria-selective bioorthogonal imaging in live cells.

Potassium Trimethylsilanolate-Promoted, Anhydrous Suzuki-Miyaura Cross-Coupling Reaction Proceeds via the "Boronate Mechanism": Evidence for the Alternative Fork in the Trail.

Previous studies have shown that the critical transmetalation step in the Suzuki-Miyaura cross-coupling proceeds through a mechanism wherein an arylpalladium hydroxide complex reacts with an aryl boronic acid, termed the oxo-palladium pathway. Moreover, these same studies have established that the reaction between an aryl boronate and an arylpalladium halide complex (the boronate pathway) is prohibitively slow. Herein, studies on isolated intermediates, along with kinetic analysis, have demonstrated that the Suzuki-Miyaura reaction promoted by potassium trimethylsilanolate (TMSOK) proceeds through the boronate pathway, in contrast with other, established systems. Furthermore, an unprecedented, binuclear palladium(I) complex containing a μ-phenyl bridging ligand was characterized by NMR spectroscopy, mass spectrometry, and computational methods. Density functional theory (DFT) calculations suggest that the binuclear complex exhibits an open-shell ground electronic state, and reaction kinetics implicate the complex in the catalytic cycle. These results expand the breadth of potential mechanisms by which the Suzuki-Miyaura reaction can occur, and the novel binuclear palladium complex discovered has broad implications for palladium-mediated cross-coupling reactions of aryl halides.

Nickel-Catalyzed Enantioselective C(sp 3 )–H Arylation of Ketones with Aryl Ethers via Selective C Ar –O Cleavage to Construct All-Carbon Quaternary Stereocenters

Nickel-Catalyzed Enantioselective C(sp ³ )–H Arylation of Ketones with Aryl Ethers via Selective C _Ar –O Cleavage to Construct All-Carbon Quaternary Stereocenters

Photoinduced radical polymerization by methyl fluoresceins under visible light and the application to signal amplification of hydrogen peroxide

We investigate visible‒light‒induced radical polymerization initiated by methyl fluorescein and its derivatives (e.g., methyl ether of fluorescein, methyl ether ester of fluorescein, and methyl ester of fluorescein), which act as photoredox catalysts. The structural alterations of fluorescein noticeably affect their photoredox catalytic performance, which increases in the following order: methyl ether of fluorescein < methyl ether ester of fluorescein < methyl ester of fluorescein ≤ fluorescein. Particularly, the methylation on the phenolic hydroxyl group reduces their performance mainly due to the restraint of tautomerization. Based on this systematic investigation, we synthesize methyl ether fluorescein, bearing aryl boronate as an H2O2−selective photoredox catalyst and use it to amplify the signal of H2O2 through the photoinduced radical polymerization. In the presence of H2O2, this photoredox catalyst successfully initiates the polymerization of poly(ethylene glycol) diacrylate and N-vinylpyrrolidone, forming a polymeric hydrogel in 1 min under visible‒light irradiation. For the naked-eye detection of H2O2, 10 μM of the catalyst allows a successful detection of H2O2 down to 20 μM. We envision that our strategy will be highlighted by mechanistic elucidation of photoredox catalysis and synthesis of multifunctional photoredox catalysts. Other benefits include biomedical applications such as colorimetric sensing of a target analyte, cell surface engineering, and cell therapy.

Preparation of Synthetic and Natural Derivatives of Flavonoids Using Suzuki-Miyaura Cross-Coupling Reaction.

Herein, we report the use of the Suzuki–Miyaura cross-coupling reaction for the preparation of a library of synthetic derivatives of flavonoids for biological activity assays. We have investigated the reactivity of halogenated flavonoids with aryl boronates and with boronyl flavonoids. This reaction was used to prepare new synthetic derivatives of flavonoids substituted at C-8 with aryl, heteroaryl, alkyl, and boronate substituents. The formation of flavonoid boronate enabled a cross-coupling reaction with halogenated flavones yielding biflavonoids connected at C-8. This method was used for the preparation of natural compounds including C-8 prenylated compounds, such as sinoflavonoid NB. Flavonoid boronates were used for the preparation of rare C-8 hydroxyflavonoids (natural flavonoids gossypetin and hypolaetin). A series of previously unknown derivatives of quercetin and luteolin were prepared and fully characterized.

Merging Halogen-Atom Transfer (XAT) and Copper Catalysis for the Modular Suzuki-Miyaura-Type Cross-Coupling of Alkyl Iodides and Organoborons.

We report here a mechanistically distinct approach to achieve Suzuki–Miyaura-type cross-couplings between alkyl iodides and aryl organoborons. This process requires a copper catalyst but, in contrast with previous approaches based on palladium and nickel systems, does not utilizes the metal for the activation of the alkyl electrophile. Instead, this strategy exploits the halogen-atom-transfer ability of α-aminoalkyl radicals to convert secondary alkyl iodides into the corresponding alkyl radicals that then are coupled with aryl, vinyl, alkynyl, benzyl, and allyl boronate species. These novel coupling reactions feature a simple setup and conditions (1 h at room temperature) and facilitate access to privileged motifs targeted by the pharmaceutical sector.

Photochemical and electrochemical C-N borylation of arylhydrazines.

The C-N borylation of arylhydrazine hydrochlorides with bis(pinacolato)diboron was achieved under photochemical and electrochemical conditions, respectively. This novel and scalable transformation provides two efficient and mild transition-metal-free synthetic routes towards aryl boronate esters from easily available arylhydrazines.

NHC induced radical formation via homolytic cleavage of B-B bonds and its role in organic reactions.

New borylation methodologies have been reported recently, wherein diboron(4) compounds apparently participate in free radical couplings via the homolytic cleavage of the B–B bond. We report herein that bis-NHC adducts of the type (NHC)2·B2(OR)4, which are thermally unstable and undergo intramolecular ring expansion reactions (RER), are sources of boryl radicals of the type NHC–BR2˙, exemplified by Me2ImMe·Bneop˙ 1a (Me2ImMe = 1,3,4,5-tetramethyl-imidazolin-2-ylidene, neop = neopentylglycolato), which are formed by homolytic B–B bond cleavage. Attempts to apply the boryl moiety 1a in a metal-free borylation reaction by suppressing the RER failed. However, based on these findings, a protocol was developed using Me2ImMe·B2pin23 for the transition metal- and additive-free boryl transfer to substituted aryl iodides and bromides giving aryl boronate esters in good yields. Analysis of the side products and further studies concerning the reaction mechanism revealed that radicals are likely involved. An aryl radical was trapped by TEMPO, an EPR resonance, which was suggestive of a boron-based radical, was detected in situ, and running the reaction in styrene led to the formation of polystyrene. The isolation of a boronium cation side product, [(Me2ImMe)2·Bpin]+I−7, demonstrated the fate of the second boryl moiety of B2pin2. Interestingly, Me2ImMe NHC reacts with aryl iodides and bromides generating radicals. A mechanism for the boryl radical transfer from Me2ImMe·B2pin23 to aryl iodides and bromides is proposed based on these experimental observations.

Oxidative Coupling of Aryl Boronic Acids with Aryl- and Alkylamines Via Cooperative Photoredox and Copper Catalysis

Oxidative Coupling of Aryl Boronic Acids with Aryl- and Alkylamines Via Cooperative Photoredox and Copper Catalysis

Transition-Metal-Free Synthesis of an Aryl Boronate Ester through Base-Mediated Boryl Substitution of an Aryl Halide with a Silylborane

Transition-Metal-Free Synthesis of an Aryl Boronate Ester through Base-Mediated Boryl Substitution of an Aryl Halide with a Silylborane

Nickel/Tio2-Catalyzed Suzuki–Miyaura Cross-Coupling (Smr) of Aryl Boronic Acids with Aryl Halides in Meoh/H2o

Nickel/Tio2-Catalyzed Suzuki–Miyaura Cross-Coupling (Smr) of Aryl Boronic Acids with Aryl Halides in Meoh/H2o

Cobalt‐Catalyzed Redox‐Neutral Sulfonylative Coupling from (Hetero)aryl Boronic Acids, Ammonium Salts and Potassium Metabisulfite

AbstractAn efficient cobalt‐catalyzed redox‐neutral sulfonylative coupling to afford (hetero)aryl alkyl sulfones from boronic acids, ammonium salts and potassium metabisulfite has been realized. Commercially available and air‐stable CoCl2, in combination with phenanthroline ligand, is sufficient to achieve rapid and high‐yielding conversion of the reactants into the corresponding sulfones. This practical transformation proceeds smoothly through C−N bond cleavage under redox‐neutral catalytic conditions and shows broad functional‐group tolerance. Other carbon based electrophiles, including diaryliodonium salts, heteroaryl halides, and carbonates were compatible. Further transformation of aryl alkyl sulfones then allows conversion into olefins, alkenyl sulfones and halogenated sulfones, respectively, in a one‐pot process.