Organoboron Research Articles

A Facile and General Oxidative Hydroxylation of Organoboron Compounds: Citric Acid as an Efficient Catalyst in Water to Access Phenolic and Alcoholic Motifs

An efficient and convenient method for the synthesis of phenols and aliphatic alcohols is described in this paper. The oxidative hydroxylation reaction of various organoboron compounds proceeded smoothly by employing H2O2 as the oxidant and citric acid as the catalyst in water at room temperature to produce phenols and aliphatic alcohols in satisfactory to excellent yields (up to 99% yield). Various synthetically useful functional groups, such as halogen atom, cyano, and nitro groups, remain intact during the oxidative hydroxylation. The developed catalytic system also could accommodate phenylboronic pinacol ester and potassium phenyltrifluoroborate to give the target product good yields.

The Cracked Potential of Boron-containing Compounds in Alzheimer's Disease.

Alzheimer's disease (AD) is a relevant neurodegenerative disease worldwide. Its relevancy is mainly due to its high prevalence and high global burden. Metalloids have attracted attention as their serum levels seem to differ between affected patients and healthy individuals. On the other hand, atoms of some metalloids have been included in bioactive molecules, exerting some interesting effects, mainly due to their ameliorative effects in neurodegeneration. In this sense, boron-containing compounds (BCC) have been explored to regulate or prevent neurodegeneration. As an example, boric acid has been reported as a compound with antioxidant, anti-inflammatory and neurotrophic effects. Other natural BCCs have also shown amelioration of metabolic conditions often related to increased risk of neurodegenerative maladies. However, in recent years, additional organoboron compounds have been reported as active in several processes linked to neurodegeneration and especially attractive as regulators of the origin and progression of AD. In this mini-review, some data are collected suggesting that some natural BCC could be used as preventive agents, but also the potential of some BODIPYs as tools for diagnosis and some other BCC (particularly boronic acids and pinacol boronic esters) for acting as promising therapeutic agents for AD.

Recent Advances in Pd‐Catalyzed Suzuki‐Miyaura Cross‐Coupling Reactions with Triflates or Nonaflates

The Pd‐catalyzed Suzuki‐Miyaura (SM) cross‐coupling of organo halides with organoboron compounds is a widely used tool in organic synthesis for the construction of C‐C bonds. Alternative methods using pseudohalides, such as triflates or nonaflates, are also suitable for this transformation. These substrates offer the advantages of simple access from readily available phenols (or enolizable ketones) and possible use for chemodivergent sequential SM couplings using electronically differentiated leaving groups. This review aims to give an overview about the current strategies of Suzuki‐Miyaura cross‐couplings with triflates or nonaflates as leaving groups. In particular, it aims to give a better understanding about the development of new efficient catalyst systems over the last decade overcoming the limitations of the standard catalyst Pd(PPh3)4. The hydrolysis of triflates as a common side reaction and its prevention will be discussed, as well as the possible transformation of triflates into halides as a strategic alternative. A matrix table is provided to guide the practitioners to find suitable reaction conditions for the various combinations of aryl/enol triflate substrates and arylboronic acids with differing electronic character.

Organoboron chemistry towards controlled and precise polymer synthesis

Organoboron chemistry towards controlled and precise polymer synthesis

Formation of C-B, C-C, and C-X Bonds from Nonstabilized Aryl Radicals Generated from Diaryl Boryl Radicals.

With the development of organoboron chemistry, boron-centered radicals have become increasingly attractive. However, their synthetic applications remain limited in that they have been used only as substrates for addition reactions or as initiators for catalytic reactions. We have achieved a new reaction pathway in which tetraarylborate salts are used as precursors for aryl radicals via boron radicals, by introducing a simple activation reagent. In addition, we carried out a diverse array of transformations involving these aryl radical precursors, which allowed the construction of new C-B, C-C, and C-X bonds in the presence of visible light.

A Binary Silicon‐Centered Organoboron Catalyst with Superior Performance to That of Its Bifunctional Analogue

AbstractThis work reported that a silicon‐centered alkyl borane/ammonium salt binary (two‐component) catalyst exhibits much higher activity than its bifunctional analogue (one‐component) for the ring‐opening polymerization of propylene oxide, showing 7.3 times the activity of its bifunctional analogue at a low catalyst loading of 0.01 mol %, and even 15.3 times the activity at an extremely low loading of 0.002 mol %. By using 19F NMR spectroscopy, control experiments, and theoretical calculation we discovered that the central silicon atom displays appropriate electron density and a larger intramolecular cavity, which is useful to co‐activate the monomer and to deliver propagating chains, thus leading to a better intramolecular synergic effect than its bifunctional analogue. A unique two‐pathway initiation mode was proposed to explain the unusual high activity of the binary catalytic system. This study breaks the traditional impression of the binary Lewis acid/nucleophilic catalyst with poor activity because of the increase in entropy.

A Binary Silicon-Centered Organoboron Catalyst with Superior Performance to That of Its Bifunctional Analogue.

This work reported that a silicon-centered alkyl borane/ammonium salt binary (two-component) catalyst exhibits much higher activity than its bifunctional analogue (one-component) for the ring-opening polymerization of propylene oxide, showing 7.3 times the activity of its bifunctional analogue at a low catalyst loading of 0.01 mol %, and even 15.3 times the activity at an extremely low loading of 0.002 mol %. By using 19 F NMR spectroscopy, control experiments, and theoretical calculation we discovered that the central silicon atom displays appropriate electron density and a larger intramolecular cavity, which is useful to co-activate the monomer and to deliver propagating chains, thus leading to a better intramolecular synergic effect than its bifunctional analogue. A unique two-pathway initiation mode was proposed to explain the unusual high activity of the binary catalytic system. This study breaks the traditional impression of the binary Lewis acid/nucleophilic catalyst with poor activity because of the increase in entropy.

Stereoselective Unsymmetrical 1,1-Diborylation of Alkynes with a Neutral sp2 -sp3 Diboron Reagent.

The incorporation of two distinct boryl groups at the same carbon center in organic molecules has attracted growing research interest due to its potential for facilitating controlled, precise synthesis through stepwise dual carbon-boron bond transformations. Here we report a method to access unsymmetrical 1,1-diborylalkene (UDBA) stereoselectively via the reaction of readily available alkynes with a neutral sp2 -sp3 diboron reagent (NHC)BH2 -Bpin (NHC=N-heterocyclic carbene). Attributing to the chemically easily distinguishable nature of the sp2 and sp3 boryl moieties, controllable stepwise derivatization of the resultant UDBAs is realized. This process leads to various multifunctionalized olefins and organoborons, such as acylboranes, which are difficult to prepare by other methods.

Photoelectrochemical oxidative C(sp3)−H borylation of unactivated hydrocarbons

Organoboron compounds are of high significance in organic synthesis due to the unique versatility of boryl substituents to access further modifications. The high demand for the incorporation of boryl moieties into molecular structures has witnessed significant progress, particularly in the C(sp3)−H borylation of hydrocarbons. Taking advantage of special characteristics of photo/electrochemistry, we herein describe the development of an oxidative C(sp3)−H borylation reaction under metal- and oxidant-free conditions, enabled by photoelectrochemical strategy. The reaction exhibits broad substrate scope (>57 examples), and includes the use of simple alkanes, halides, silanes, ketones, esters and nitriles as viable substrates. Notably, unconventional regioselectivity of C(sp3)−H borylation is achieved, with the coupling site of C(sp3)−H borylation selectively located in the distal methyl group. Our method is operationally simple and easily scalable, and offers a feasible approach for the one-step synthesis of high-value organoboron building blocks from simple hydrocarbons, which would provide ample opportunities for drug discovery.

Metal-free C-H Borylation and Hydroboration of Indoles.

The C-H borylation and hydroboration reactions have emerged as promising synthetic tools to construct organoboron compounds. Organoboron compounds of N-heterocycles, particularly indole derivatives, have found widespread application in a variety of fields. As a result, considerable advancement in the area of C-H borylation and hydroboration reactions of indoles was observed in the last few decades. Among the various synthetic methods applied, the metal-free approach has received special attention. This mini-review discusses the recent progress in the area of C-H borylation and hydroboration reactions of indoles under metal-free conditions, their scope, and brief mechanistic studies.

Theoretical Understanding on the Facilitated Photoisomerization of a Carbonyl Supported Borane System.

Boron compound BOMes2 containing an internal B-O bond undergoes highly efficient photoisomerization, followed by sequential structural transformations, resulting in a rare eight-membered B, O-heterocycle (S. Wang, et al. Org. Lett.2019, 21, 5285-5289). In this work, the detailed reaction mechanisms of such a unique carbonyl-supported tetracoordinate boron system in the first excited singlet (S1) state and the ground (S0) state were investigated by using the complete active space self-consistent field and its second-order perturbation (MS-CASPT2//CASSCF) method combined with time-dependent density functional theory (TD-DFT). Moreover, an imine-substituted tetracoordinated organic boron system (BNMes2) was selected for comparative study to explore the intrinsic reasons for the difference in reactivity between the two types of compounds.Steric factorwasfound to influence the photoisomerization activity of BNMes2 and BOMes2. These results rationalize the experimental observations and can provide helpful insights into understanding the excited-state dynamics of heteroatom-doped tetracoordinate organoboron compounds, which facilitates the rational design of boron-based materials with superior photoresponsive performances.

Conjugate Addition of Organoboron Compounds to α,β-Unsaturated Ketones Catalyzed by Nickelacycles

AbstractThe catalytic activity of nickelacycles in the conjugate addition of arylboronates to α,β-unsaturated ketones was investigated. Nickelacycles afforded β-arylated ketones in moderate to high yields, whereas an analogous palladacycle did not catalyze the reaction. Studies on the time course of the reaction confirmed that the nickelacycles act as active species in the conjugate addition reaction.

Recent Expedition in Pd- and Rh-Catalyzed C(Ar) -B Bond Formations and Their Applications in Modern Organic Syntheses.

Transition metal-catalyzed borylation has emerged as a powerful and versatile strategy for synthesizing organoboron compounds. These compounds have found widespread applications in various aspects, including organic synthesis, materials science, and medicinal chemistry. This review provides a concise summary of the recent advances in palladium- and rhodium-catalyzed borylation from 2013 to 2023. The review covers the representative examples of catalysts, substrates scope and reaction conditions, with particular emphasis on the development of catalyst systems, such as phosphine ligands, NHC-carbene, and more. The diverse array of borylative products obtained for further applications in Suzuki-Miyaura coupling, and other transformations, are also discussed. Future directions in this rapidly evolving field, with the goal of designing more efficient, selective borylation methodologies are highlighted, too.

Recent Advances in Borylation via Electron Donor–Acceptor Complex Photoactivation

AbstractPhotoinduced borylation is becoming a fascinating and growing research field in synthetic chemistry. On the other hand, electron donor–acceptor (EDA) complex photoactivation has emerged as an alternative strategy to generate active open‐shell species without the need for photosensitizers. Suitable organoboron compounds can serve as the electron donor or acceptor to form the corresponding electron donor–acceptor complexes, which then undergo photoinduced intracomplex single electron transfer (SET) to generate carbon‐ or boron‐centered radicals for the construction of new C−B bonds. In this Concept paper, we review recent advances in photoinduced borylation via the EDA complex photoactivation strategy surveying the relevant literature until December 2022.

Decaborane: From Alfred Stock and Rocket Fuel Projects to Nowadays.

The review covers more than a century of decaborane chemistry from the first synthesis by Alfred Stock to the present day. The main attention is paid to the reactions of the substitution of hydrogen atoms by various atoms and groups with the formation of exo-polyhedral boron-halogen, boron-oxygen, boron-sulfur, boron-nitrogen, boron-phosphorus, and boron-carbon bonds. Particular attention is paid to the chemistry of conjucto-borane anti-[B18H22], whose structure is formed by two decaborane moieties with a common edge, the chemistry of which has been intensively developed in the last decade.

MIDA- and TIDA-Boronates Stabilize α-Radicals Through B-N Hyperconjugation.

Multifunctional organoboron compounds increasingly enable the simple generation of complex, Csp3 -rich small molecules. The ability of boron-containing functional groups to modify the reactivity of α-radicals has also enabled a myriad of chemical reactions. Boronic esters with vacant p-orbitals have a significant stabilizing effect on α-radicals due to delocalization of spin density into the empty orbital. The effect of coordinatively saturated derivatives, such as N-methyliminodiacetic acid (MIDA) boronates and counterparts, remains less clear. Herein, we demonstrate that coordinatively saturated MIDA and TIDA boronates stabilize secondary alkyl α-radicals via σB-N hyperconjugation in a manner that allows site-selective C-H bromination. DFT calculated radical stabilization energies and spin density maps as well as LED NMR kinetic analysis of photochemical bromination rates of different boronic esters further these findings. This work clarifies that the α-radical stabilizing effect of boronic esters does not only proceed via delocalization of radical character into vacant boron p-orbitals, but that hyperconjugation of tetrahedral boron-containing functional groups and their ligand electron delocalizing ability also play a critical role. These findings establish boron ligands as a useful dial for tuning reactivity at the α-carbon.

MIDA‐ and TIDA‐Boronates Stabilize α‐Radicals Through B−N Hyperconjugation

AbstractMultifunctional organoboron compounds increasingly enable the simple generation of complex, Csp3‐rich small molecules. The ability of boron‐containing functional groups to modify the reactivity of α‐radicals has also enabled a myriad of chemical reactions. Boronic esters with vacant p‐orbitals have a significant stabilizing effect on α‐radicals due to delocalization of spin density into the empty orbital. The effect of coordinatively saturated derivatives, such as N‐methyliminodiacetic acid (MIDA) boronates and counterparts, remains less clear. Herein, we demonstrate that coordinatively saturated MIDA and TIDA boronates stabilize secondary alkyl α‐radicals via σB‐N hyperconjugation in a manner that allows site‐selective C−H bromination. DFT calculated radical stabilization energies and spin density maps as well as LED NMR kinetic analysis of photochemical bromination rates of different boronic esters further these findings. This work clarifies that the α‐radical stabilizing effect of boronic esters does not only proceed via delocalization of radical character into vacant boron p‐orbitals, but that hyperconjugation of tetrahedral boron‐containing functional groups and their ligand electron delocalizing ability also play a critical role. These findings establish boron ligands as a useful dial for tuning reactivity at the α‐carbon.

Transition-Metal-Free Insertion of Diazo Compounds, N-Arylsulfonylhydrazones or Ylides into Organoboronic Acids or Their Derivatives

AbstractInsertion reactions of carbenes or ylides with organoboronic acids or their derivatives have emerged as valuable methods for coupling or homologation of organoboron compounds under metal-free conditions. The crucial steps of these reactions are coordination of the electron-rich carbon centers of the carbene precursors or ylides to the electron-poor boron center, followed by 1,2-migration of the corresponding tetracoordinated boron intermediates. This type of unique transformation provides an efficient method for the construction of C–C or C–X (X = H, B) bonds. Moreover, the C–B bonds generated by such transformations can be utilized as a handle for further derivatization or iterative homologations. In this Account, we summarize the developments in this arena according to the reactive diazo compound, N-arylsulfonylhydrazone or ylide species involved.1 Introduction2 Reactions with Diazo Compounds3 Reactions with N-Arylsulfonylhydrazones4 Reactions with Ylides5 Conclusion

Boron-Methylated Dipyrromethene as a Green Light Activated Type I Photoinitiator for Rapid Radical Polymerizations.

Unimolecular (Type I) radical photoinitiators (PIs) have transformed the chemical manufacturing industry by enabling (stereo)lithography for microelectronics and emergent 3D printing technologies. However, the reliance on high energy UV-violet light (≤420 nm) restricts the end-use applications. Herein, boron-methylated dipyrromethene (methylated-BODIPY) is shown to act as a highly efficient Type I radical PI upon irradiation with low energy green light. Using a low intensity (∼4 mW/cm2) light emitting diode centered at 530 nm and a low PI concentration (0.3 mol %), acrylic-based resins were polymerized to maximum conversion in ∼10 s. Under equivalent conditions (wavelength, intensity, and PI concentration), state-of-the-art visible light PIs Ivocerin and Irgacure 784 show no appreciable polymerization. Spectroscopic characterization suggests that homolytic β-scission at the boron-carbon bond results in radical formation, which is further facilitated by accessing long-lived triplet excited states through installment of bromine. Alkylated-BODIPYs represent a new modular visible light PI platform with exciting potential to enable next generation manufacturing and biomedical applications where a spectrally discrete, low energy, and thus benign light source is required.

Harnessing Supported Gold Nanoparticle as a Single‐Electron Transfer Catalyst for Decarboxylative Cross‐Coupling

AbstractWe found that gold nanoparticles function as single‐electron transfer catalysts to promote decarboxylative cross‐coupling between N‐hydroxy phthalimide esters and disilanes or diborons. A variety of disilanes coupled with alkyl radicals could be generated from N‐hydroxy phthalimide esters via single‐electron reduction by active carbon‐supported gold nanoparticle catalysts to afford diverse alkylsilanes without the need for external bases. Furthermore, the present gold catalytic system was also effective for decarboxylative carbon‐boron coupling to afford alkyl boronates. A detailed mechanistic investigation revealed that single‐electron transfer mediated by supported gold nanoparticles enabled the generation of alkyl radical and silyl radical, thereby enabling radical cross‐coupling. The reusability and environmentally‐friendly nature of supported gold catalyst as well as the scalability of the reaction system enable the practical transformation of carboxylic acid derivatives into value‐added organosilicon and organoboron compounds.