镍催化的芳基硼酸偕二氟炔丙基化反应

偕二氟炔丙基取代的芳烃是一类非常重要的化合物, 但传统合成该类化合物的方法却存在很大局限性. 以过渡金属催化直接向芳烃偕二氟炔丙基化是一种高效简洁制备上述化合物的方法. 以廉价易得的Ni(NO₃)₂·6H₂O为催化剂, 首次实现了镍催化下芳基硼酸与α,α-二氟炔丙基溴的偶联反应. 该反应不仅温和高效、原料廉价易得、官能团兼容性良好, 而且还能进行克量级放大和对生物活性分子的后期氟修饰, 从而为新药研发提供了一种有效手段.     

Interactions of Night Blue with Nucleic Acids and Determination of Nucleic Acids Using Resonance Light Scattering Technique

The noncovalent interactions of night blue (NB) with several nucleic acids in buffer medium of Britton‐Robinson at pH 4.1 have been studied by spectroscopic methods. It is shown that the binding of NB with nucleic acids involves the J‐aggregation of NB molecules on the surface of nucleic acids. The aggregation was encouraged by polyanions nucleic acids, in which nucleic acids served for acting templates. In this connection, a new method of nucleic acids with sensitivity at nanogram level is proposed based on the measurement of enhanced resonance light scattering (RLS). The linear range of ctDNA, fsDNA and yRNA is 0.01—2.5, 0.03—2.5 and 0.04—1.0 μg/mL, respectively, and the corresponding detection limits (3s?) are 9.4, 7.3 and 5.7 ng/mL at 2.5 × 10–⁵mol/L of NB. Synthetic and real samples were analyzed with satisfactory results.     

Reversible Lysine Modification on Proteins by Using Functionalized Boronic Acids

Iminoboronates have been utilized to successfully install azide and alkyne bioorthogonal functions on proteins, which may then be further reacted with their bioorthogonal counterparts. These constructs were also used to add polyethylene glycol (PEG) to insulin, a modification which has been shown to be reversible in the presence of fructose. Finally, iminoboronates were used to assemble a folic acid/paclitaxel small‐molecule/drug conjugate in situ with an IC₅₀ value of 20.7 nM against NCI‐H460 cancer cells and negligible cytotoxicity against the CRL‐1502 noncancer cells.     

Decarboxylative Conjunctive Cross‐coupling of Vinyl Boronic Esters using Metallaphotoredox Catalysis

The synthesis of complex alkyl boronic esters through conjunctive cross‐coupling of vinyl boronic esters with carboxylic acids and aryl iodides is described. The reaction proceeds under mild metallaphotoredox conditions and involves an unprecedented decarboxylative radical addition/cross‐coupling cascade of vinyl boronic esters. Excellent functional‐group tolerance is displayed, and application of a range of carboxylic acids, including secondary α‐amino acids, and aryl iodides provides efficient access to highly functionalized alkyl boronic esters. The decarboxylative conjunctive cross‐coupling was also applied to the synthesis of sedum alkaloids.     

The Development of Boronic Acids as Sensors and Separation Tools

Synthetic receptors for diols that incorporate boronic acid motifs have been developed as new sensors and separation tools. Utilizing the reversible interactions of diols with boronic acids to form boronic esters under new binding regimes has provided new hydrogel constructs that have found use as dye‐displacement sensors and electrophoretic separation tools; similarly, molecular boronic‐acid‐containing chemosensors were constructed that offer applications in the sensing of diols. This review provides a somewhat‐personal perspective of developments in boronic‐acid‐mediated sensing and separation, placed in the context of the seminal works of others in the area, as well as offering a concise summary of the contributions of the co‐authors in the area. DOI 10.1002/tcr.201200006     

Rhodium-Catalyzed Addition of Aryl Boronic Acids to 2,2-Disubstituted Malononitriles

β-Ketonitriles bearing a quaternary carbon at the 2-position were prepared through Rh-catalyzed addition of aryl boronic acids to 2,2-disubstituted malononitriles. In contrast to the previously described transnitrilative cyanation of aryl boronic acids with dialkylmalononitriles, the present reaction avoids retro-Thorpe collapse of the intermediate addition product through the use of a milder base. The reaction was amenable to a variety of aryl boronic acids and disubstituted malononitriles, providing a diverse array of β-ketonitriles. The products could be further derivatized to valuable chiral α,α-disubstituted-β-aminonitriles through addition reactions to the corresponding N-tert-butanesulfinyl imines.     

Palladium‐Catalyzed Aminocarbonylation of N‐Chloroamines with Boronic Acids

Aryl (pseudo)halide‐based (C?X) carbonylation reactions have been extensively studied during the past few decades. From both academic and synthetic points of view, the carbonylative transformation of N?X bonds represents an interesting and attractive area of investigation. In light of this, the first carbonylative cross‐coupling between N‐chloroamines and organoboronic acids has been developed. This new type of aminocarbonylation proceeds at mild temperatures (45–55 °C) with 2 mol % Pd/C (10 wt %) as the ligand‐free catalyst. Not only arylboronic acids, but also alkenyl‐ and alkylboronic acids can be applied as the substrates and bromide and iodide substituents in the substrates are well tolerated. Initial mechanistic investigations have also been performed.     

Stereoselective Csp3–Csp2 Bond‐Forming Reactions by Transition‐Metal‐Free Reductive Coupling of Cyclic Tosylhydrazones with Boronic Acids

The reactions between alkenylboronic acids and tosylhydrazones derived from substituted cyclohexanones lead to the construction of disubstituted cyclohexanes with total regio‐ and stereoselectivity. In these transition‐metal‐free processes, a Csp³?Csp² and Csp³?H bond are formed on the same carbon atom. The stereoselective reaction is general for 2‐, 3‐, and 4‐substituted cyclohexanone tosylhydrazones, as well as for 2‐substituted cyclopentanones. However, no stereoselectivity is observed for acyclic derivatives. DFT computational modeling suggests that the stereoselectivity of the reaction is determined by the approach of the boronic acid to the diazocyclohexane on its most stable chair conformation through an equatorial trajectory.     

Probing the Lewis Acidity of Boronic Acids through Interactions with Arene Substituents

Boronic acids are Lewis acids that exist in equilibrium with boronate forms in aqueous solution. Here we experimentally and computationally investigated the Lewis acidity of 2,6-diarylphenylboronic acids; specially designed phenylboronic acids that possess two flanking aromatic rings with tunable aromatic character. Hammett analysis of 2,6-diarylphenylboronic acids reveals that their Lewis acidity remains unchanged upon the introduction of EWG/EDG at the distant para position of the flanking aromatic rings. Structural and computational studies demonstrate that polar-π interactions and solvation effects contribute to the stabilization of boronic acids and boronate forms by aromatic rings. Our physical-organic chemistry work highlights that boronic acids and boronates can be stabilized by aromatic systems, leading to an important molecular knowledge for rational design and development of boronic acid-based catalysts and inhibitors of biomedically important proteins.     

Nickel‐Catalyzed Cross‐Coupling of Functionalized Difluoromethyl Bromides and Chlorides with Aryl Boronic Acids: A General Method for Difluoroalkylated Arenes

Transition‐metal‐catalyzed difluoroalkylation of aromatics remains challenging despite the importance of difluoroalkylated arenes in medicinal chemistry. Herein, the first successful example of nickel‐catalyzed difluoroalkylation of aryl boronic acids is described. The reaction allows access to a variety of functionalized difluoromethyl bromides and chlorides, and paves the way to highly cost‐efficient synthesis of a wide range of difluoroalkylated arenes. The notable features of this protocol are its high generality, excellent functional‐group compatibility, low‐cost nickel‐catalyst, and practicality for gram‐scale production, thus providing a facile method for applications in drug discovery and development.     

Boronic Acids as Bioorthogonal Probes for Site‐Selective Labeling of Proteins

Over the past two decades, bioorthogonal chemistry has become a preferred tool to achieve site‐selective modifications of proteins. However, there are only a handful of commonly applied bioorthogonal reactions and they display some limitations, such as slow rates, use of unstable or cytotoxic reagents, and side reactions. Hence, there is significant interest in expanding the bioorthogonal chemistry toolbox. In this regard, boronic acids have recently been introduced in bioorthogonal chemistry and are exploited in three different strategies: 1) boronic ester formation between a boronic acid and a 1,2‐cis diol; 2) iminoboronate formation between 2‐acetyl/formyl‐arylboronic acids and hydrazine/hydroxylamine/semicarbazide derivatives; 3) use of boronic acids as transient groups in a Suzuki–Miyaura cross‐coupling or other reactions that leave the boronyl group off the conjugation product. In this Review, we summarize progress made in the use of boronic acids in bioorthogonal chemistry to enable site‐selective labeling of proteins and compare these methods with the most commonly utilized bioorthogonal reactions.     

Correlating the Surface Basicity of Metal Oxides with Photocatalytic Hydroxylation of Boronic Acids to Alcohols

Photoredox catalysis provides opportunities in harnessing clean and green resources such as sunlight and O₂, while the acid and base surface sites of metal oxides are critical for industrial catalysis such as oil cracking. The contribution of metal oxide surfaces towards photocatalytic aerobic reactions was elucidated, as demonstrated through the hydroxylation of boronic acids to alcohols. The strength and proximity of the surface base sites appeared to be two key factors in driving the reaction; basic and amphoteric oxides such as MgO, TiO₂, ZnO, and Al₂O₃ enabled high alcohol yields, while acidic oxides such as SiO₂ and B₂O₃ gave only low yields. The reaction is tunable to different irradiation sources by merely selecting photosensitizers of compatible excitation wavelengths. Such surface complexation mechanisms between reactants and earth abundant materials can be effectively utilized to achieve a wider range of photoredox reactions.     

Copper-Catalyzed Homocoupling of Boronic Acids: A Focus on B-to-Cu and Cu-to-Cu Transmetalations

Controlling and understanding the Cu-catalyzed homocoupling reaction is crucial to prompt the development of efficient Cu-catalyzed cross-coupling reactions. The presence of a coordinating base (hydroxide and methoxide) enables the B-to-Cu(II) transmetalation from aryl boronic acid to Cu^IICl₂ in methanol, through the formation of mixed Cu-(μ-OH)-B intermediates. A second B-to-Cu transmetalation to form bis-aryl Cu(II) complexes is disfavored. Instead, organocopper(II) dimers undergo a coupled transmetalation-electron transfer (TET) allowing the formation of bis-organocopper(III) complexes readily promoting reductive elimination. Based on this mechanism some guidelines are suggested to control the undesired formation of homocoupling product in Cu-catalyzed cross-coupling reactions.     

超声条件下制备单取代硼酸

本文报道以硼酸三丁酯为原料与卤代烃,金属镁粉在室温下经超声辐射制备单取代硼酸的结果。该方法操作简单,反应速度快,并得到满意的产率,有一定的应用价值。     

Aryl Boronic Acids in Columnar Stacked Co-crystalline Materials: Key-Factors Governing the Assembly with Quinones

The assembly of aryl boronic acids B with quinones Q into columnar mixed stacked materials, as previously observed in the solid-state, has been here subjected to a detailed theoretical analysis focusing on the properties of the isolated synthons (HOMO-LUMO energies, electron affinity, ionization potential, reorganization hole/electron energies, partial Hirshfeld atomic charges and conformation stabilities) as well as those of the 1 : 1 adducts (Hirshfeld analysis, IRI surfaces, Hirshfeld atomic charges, hydrogen bond and slipped stacked π-π contributions). The overall picture obtained throught this study shows an intricate pattern of interconnected factors contributing to the formation and stability of the B _x Q _y adducts, and it unveils the importance of parameters such as HOMO-LUMO gap, polarization and charge transfer, in addition to the more evident hydrogen bond and slipped-stacked π-π interactions in the formation of 1 : 1 adducts. An explanation has been also given for the presence in some B _x Q _y adducts of the rare anti-anti conformation for the BO−H group with respect to the most studied and common anti-syn conformation.     

Synthesis of Biaryls via Pd-Catalyzed Decarboxylative Coupling of Substituted Benzoic Acids with Phenylboronic Acids

A Pd-catalyzed decarboxylative coupling of substituted benzoic acids with phenylboronic acid has been developed. Under the optimized conditions, a variety of substituted benzoic acids were found to undergo decarboxylative coupling with various phenylboronic acids to give the desired unsymmetrical biaryls in good yields.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Pd-Catalyzed Difluoromethylations of Aryl Boronic Acids,Halides, and Pseudohalides with ICF2H 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.     

Boronic Acid Catalysis for Mild and Selective [3+2] Dipolar Cycloadditions to Unsaturated Carboxylic Acids

Herein, the concept of boronic acid catalysis (BAC) for the activation of unsaturated carboxylic acids is applied in several classic dipolar [3+2] cycloadditions involving azides, nitrile oxides, and nitrones as partners. These cycloadditions can be used to produce pharmaceutically interesting, small heterocyclic products, such as triazoles, isoxazoles, and isoxazolidines. These cycloadducts are formed directly and include a free carboxylic acid functionality that can be employed for further transformations, thereby avoiding prior masking or functionalization. In all cases, BAC provides faster reactions, under milder conditions, with much improved product yields and regioselectivities. In some instances, such as triazole formation from the reaction of azides with 2‐alkynoic acids, catalysis with ortho‐nitrophenylboronic acid circumvents the undesirable product decarboxylation observed when using thermal activation. By using NMR spectroscopic studies, the boronic acid catalyst was shown to provide activation by a LUMO‐lowering effect in the unsaturated carboxylic acid, likely via a monoacylated hemiboronic ester intermediate.