Organoboron Research Articles

Low-Temperature Borylation of C(sp3)-O Bonds of Alkyl Ethers by Gold-Metal Oxide Cooperative Catalysis.

Since ether moieties are often found not only in petrochemical products but also in natural organic molecules, the development of methods for manipulating C-O bonds of ethers is important for expanding the range of compound libraries synthesized from biomass resources, which should contribute to the goal of carbon neutrality. We report herein that gold nanoparticles supported on Lewis acidic metal oxides, namely α-Fe2O3, showed excellent catalytic activity for the reaction of dialkyl ethers and diborons, which enables the conversion of unactivated C(sp3)-O bonds to C(sp3)-B bonds at around room temperature. Various acyclic and cyclic ethers as well as a series of diborons participated in the heterogeneous gold-catalyzed borylation of unactivated C(sp3)-O bonds, to give a series of alkylboronates in high yields. Mechanistic studies corroborated that the present borylation of C(sp3)-O bonds of dialkyl ethers proceeded at the interface between gold nanoparticles and Lewis acidic metal oxides. Furthermore, adsorption IR measurements supported the notion that strong Lewis acid sites were generated at the boron atom of diborons adsorbed at the interface between Lewis acidic metal oxides and gold nanoparticles, which enabled us to ensure that the cooperation of gold nanoparticles and Lewis acidic metal oxides was responsible for the efficient transformation of unactivated C(sp3)-O bonds in ethers under mild conditions. This novel reaction technology which is specific to heterogeneous catalysts enables the activation of stable C(sp3)-O bonds of oxygenated chemical feedstock, which is beneficial for the sustainable synthesis of value-added organoboron compounds.

Electrophilic Cyanation Using Lewis Acidity of Organoboron Compounds

Electrophilic Cyanation Using Lewis Acidity of Organoboron Compounds

Direct synthesis of α-functionalized amides via heteroatom–hydrogen insertion reactions using amide-sulfoxonium ylides

α-Functionalized Si-, Ge-, B-, Se-, and S-amide moieties are present in many medicinally active molecules, but their synthesis remains challenging. Here, we demonstrate a high-throughput synthesis using amide-sulfoxonium ylides as carbene precursors in a Si–H, Ge–H, B–H, Se–H, and S–H insertion reactions to target a wide range of α-silyl, α-geryl, α-boryl, α-selenyl, and α-sulfur (hetero)amides. The process is featured as simple operation, mild conditions, broad substrate scope, high functional group compatibility, and excellent chemoselectivity. Both experimental and computational studies are conducted to explore the mechanisms underlying the formation of C–Si/Ge/B/Se/S bond. This research highlights the use of highly selective X–H insertion reactions with amide-sulfoxonium ylide-derived carbenes, paving the way for the preparation of diverse functional organosilane, organogermane, organoboron, organoselenium, and organosulfur compounds from accessible and bench-stable precursors.

Highly Sensitive Solid Ratiometric Luminescent Thermometer Based on N,C-Chelating Four-Coordinate Organoboron Compounds.

Realizing ratiometric thermometers using single-component organic solid-state luminophores is attractive but challenging. Here, we synthesized a series of N,C-chelated tetra-coordinated organoboron compounds and characterized their structures. Among them, sample BN2Br can be used as a luminescent thermometer and exhibits a high temperature sensitivity (3.67% K-1), a wide response range of 120-280 K, and good reversibility, which is mainly due to the temperature-dependent intermolecular stacking effect in the solid state. The proposed ratiometric thermometry protocol may provide new insights for developing photonic thermometers.

Interception of Alkynyl Tetracoordinate Borons with Sulfur Electrophiles beyond the Zweifel Pathway

AbstractZweifel reaction is a powerful strategy to construct olefins from alkenyl tetracoordinate borons in organoboron chemistry, however, it usually only involves one functional group migration and then undergoes an elimination process affording alkenes or alkynes exclusively. Herein, we disclose several intriguing interception of alkynyl tetracoordinate borons with sulfur electrophiles. Wherein, the substituted benzothiophenes are accessed by consecutive 1,2‐migrations and intramolecular electrophilic substitution, meanwhile, the challenging and elusive five/four‐membered boracycles are easily assembled, and an approach to alkenyl sulfides with good stereoselectivity was developed as well. Moreover, by adding readily available deuterium sources, the tetrasubstituted deuterated alkenyl sulfides with high deuteration rates are constructed. These protocols not only improve atom economy by prohibiting the elimination of Zweifel intermediate, but also enrich the reaction modes of alkynyl tetracoordinate borons achieving versatile value‐added sulfur‐containing molecules. Mechanistic investigations illustrate that dichlorosulfoxide (SOCl2) and dialkylaminosulfur trifluoride‐type reagents (DAST‐type) as surfur sources could promote dual 1,2‐aryl migration of alkynyl tetracoordinate borons, which are distinct from traditional Zweifel reaction, and the regulation of steric hindrance could also make four‐membered boracycles and alkenyl sulfides feasible. And these transformations feature novel reaction modes and unusual reaction mechanisms with valuable products in high efficiency.

Interception of Alkynyl Tetracoordinate Borons with Sulfur Electrophiles beyond the Zweifel Pathway.

Zweifel reaction is a powerful strategy to construct olefins from alkenyl tetracoordinate borons in organoboron chemistry, however, it usually only involves one functional group migration and then undergoes an elimination process affording alkenes or alkynes exclusively. Herein, we disclose several intriguing interception of alkynyl tetracoordinate borons with sulfur electrophiles. Wherein, the substituted benzothiophenes are accessed by consecutive 1,2-migrations and intramolecular electrophilic substitution, meanwhile, the challenging and elusive five/four-membered boracycles are easily assembled, and an approach to alkenyl sulfides with good stereoselectivity was developed as well. Moreover, by adding readily available deuterium sources, the tetrasubstituted deuterated alkenyl sulfides with high deuteration rates are constructed. These protocols not only improve atom economy by prohibiting the elimination of Zweifel intermediate, but also enrich the reaction modes of alkynyl tetracoordinate borons achieving versatile value-added sulfur-containing molecules. Mechanistic investigations illustrate that dichlorosulfoxide (SOCl2) and dialkylaminosulfur trifluoride-type reagents (DAST-type) as surfur sources could promote dual 1,2-aryl migration of alkynyl tetracoordinate borons, which are distinct from traditional Zweifel reaction, and the regulation of steric hindrance could also make four-membered boracycles and alkenyl sulfides feasible. And these transformations feature novel reaction modes and unusual reaction mechanisms with valuable products in high efficiency.

Co-Catalyzed Suzuki-Miyaura Coupling of Organoboronic Acids and Alkynyl Chlorides Using Potassium Bicarbonate as Base.

Organoboronic acids, some of the most common and widely used organoboron compounds, have not yet been used in the cobalt-catalyzed cross coupling reactions, despite cobalt demonstrating good reactivity with zinc reagents, Grignard reagents, and metal organoborates that are formed by n-butyl lithium or alkaline metal alkoxide salts and organoboron esters. Herein, a highly efficient and practical cobalt-catalyzed coupling reaction of aryl/alkenyl boronic acids and alkynyl chloride under mild reaction conditions is reported. The advantages of the organoboronic acids, along with a broad functional group compatibility and the reaction's tolerance to moisture and air, enable this reaction to be a synthetically useful protocol for the construction of a C(sp2)-C(sp) bond. Lastly, the synthesis of two natural products and a key intermediate of roxadustat was effectively accomplished using the methodology to construct the critical alkynyl-aryl bond.

Enantioselective Borylative Functionalization of Internal Alkenes: A Platform for Constructing Vicinal Stereocenters†

Comprehensive SummaryVicinal stereogenic centers are ubiquitous structural scaffolds in both natural products and synthetic compounds, yet their enantioselective construction remains a significant challenge in organic synthesis. Organoboron compounds are of paramount importance in synthetic chemistry due to their ability to undergo facile transformations, yielding diverse essential chemical bonds such as carbon‐carbon, carbon‐oxygen, carbon‐nitrogen, and carbon‐halogen bonds. Transition‐metal‐catalyzed asymmetric borylative functionalizations of internal alkenes offer a promising strategy for the enantioselective installation of two adjacent chiral centers across carbon‐carbon bonds. By leveraging the versatile transformations of the newly introduced boryl unit, this approach holds great potential for expanding the structural diversity of vicinal stereogenic scaffolds. In this concise review, we aim to highlight recent advancements in transition‐metal‐catalyzed asymmetric borylative functionalizations of internal alkenes, underscore their utility as a versatile approach for constructing vicinal stereogenic centers, and discuss unsolved challenges and future directions in this field. Key Scientists

Recent Advances in the Development of Targeted Activation Strategies for Organoboron Prodrugs

AbstractElevated levels of reactive oxygen species (ROS) are a hallmark of varieties of diseases such as cancer, inflammation, and neurodegenerative disorders. Inspired by the discrepancy of ROS concentrations between pathological tissues and the normal counterparts, an increasing number of ROS‐responsive theragnostic prodrugs are developed in past years, with particularly high proportions of organoboron‐based prodrugs that can respond to H2O2. Unfortunately, increasing studies have demonstrated that the intrinsic ROS (H2O2) levels in most pathological tissue are only slightly higher than normal tissues and are not adequate to activate organoboron prodrugs; in contrast, several organoboron compounds have been clinically approved in which boronic acid acts as electrophilic warhead. To this end, developing more robust and universal approaches for boronic acid‐prodrug activation becomes highly attractive. In this context, we discuss the recently reported activation strategies for boron‐caged prodrugs with a particular focus on their design principles and activation mechanisms. The perspectives on the future directions for this important research area are discussed as well.

Enantioconvergent Cross-Nucleophile Coupling: Copper-Catalyzed Deborylative Cyanation.

Organoboron compounds are widely utilized in organic synthesis for their diverse reactivity, modular preparation, and stability compared to other classes of organometallic reagents. While organoboron species are commonly employed as nucleophiles in cross-coupling reactions, their potential as racemic building blocks in enantioconvergent transformations remains largely untapped. Herein, we demonstrate the direct utilization of alkylboronic pinacol esters in intermolecular enantioconvergent transformations. Specifically, this work describes the development and mechanistic study of an enantioconvergent deborylative cyanation enabled by Cu catalysis. This method imparts a high degree of enantioselectivity and tolerates a wide range of common functional groups and heterocycles. The reaction is proposed to proceed through a radical-relay mechanism. Aniline-assisted homolysis of the carbon-boron bond results in prochiral alkyl radicals that are functionalized by in situ generated Cu(II)(CN)2 species in an enantioselective fashion. The Cu(II)(CN)2 intermediate was characterized by electron paramagnetic resonance (EPR) spectroscopy, and its electronic structure was probed using density functional theory (DFT) calculations. Computational studies were carried out to corroborate the proposed radical-relay mechanism.

Enantioconvergent Cross‐Nucleophile Coupling: Copper‐Catalyzed Deborylative Cyanation

AbstractOrganoboron compounds are widely utilized in organic synthesis for their diverse reactivity, modular preparation, and stability compared to other classes of organometallic reagents. While organoboron species are commonly employed as nucleophiles in cross‐coupling reactions, their potential as racemic building blocks in enantioconvergent transformations remains largely untapped. Herein, we demonstrate the direct utilization of alkylboronic pinacol esters in intermolecular enantioconvergent transformations. Specifically, this work describes the development and mechanistic study of an enantioconvergent deborylative cyanation enabled by Cu catalysis. This method imparts a high degree of enantioselectivity and tolerates a wide range of common functional groups and heterocycles. The reaction is proposed to proceed through a radical‐relay mechanism. Aniline‐assisted homolysis of the carbon–boron bond results in prochiral alkyl radicals that are functionalized by in situ generated Cu(II)(CN)2 species in an enantioselective fashion. The Cu(II)(CN)2 intermediate was characterized by electron paramagnetic resonance (EPR) spectroscopy, and its electronic structure was probed using density functional theory (DFT) calculations. Computational studies were carried out to corroborate the proposed radical‐relay mechanism.

Carbenoids with Sulfinate as Nucleofuge for Matteson-Type Homologation: Direct Insertion of Oxygen- and Nitrogen-Substituted Units into Carbon-Boron Bonds.

Carbenoid insertion into boronate carbon-boron bonds, namely the Matteson-type homologation, has been recognized as a powerful tool for constructing carbon-carbon bonds. However, some limitations and inconvenience still exist with the carbenoids currently employed, such as the use of highly cryogenic and basic conditions. Herein, we report a new class of stable carbenoids with sulfinate as nucleofuge for Matteson-type homologations, which directly introduce O- and N-substituted methylenes into carbon-boron bonds. Enabled by oxazaborolidines as the boronic substrates, the reaction is operatable at 0 °C or room temperature with weaker bases. Broad functional groups, including acidic C-H bonds, can be tolerated. The synthetic utility of this method has been demonstrated in the gram-scale synthesis and iterative insertion of various carbenoids.

Iron‐Catalyzed Regioselective Borobenzylation of Vinyl Arenes

AbstractHerein, catalytic difunctionalization of vinyl arenes is reported using an iron salt as a catalyst without ligands. A series of substituted alkylboronic acid esters was obtained as a single regioisomer from vinyl arenes at 50 °C. This multicomponent protocol enabled the formation of C−C and C−B bonds to produce boroalkylated products in a single process. A non‐radical pathway is proposed for the reaction in contrast to the radical pathways of iron‐catalyzed hydroalkylation reactions. The organoboron compounds generated from this reaction were further utilized for diverse functional group conversions.

Organoboron catalysis for direct amide/peptide bond formation.

Amides and peptides are ubiquitous functional groups found in several natural and artificial materials, and they are essential for the advancement of life and material sciences. In particular, their relevance in clinical medicine and drug discovery has increased in recent years. Dehydrative condensation of readily available carboxylic acids with amines is the most "direct" method for amide synthesis; however, this methodology generally requires a stoichiometric amount of condensation agent (coupling reagent). Catalytic direct dehydrative amidation has become an "ideal" methodology for synthesizing amides from the perspective of green chemistry, with water as the only byproduct in principle, high atom efficiency, environmentally friendly, energy saving, and safety. Conversely, organoboron compounds, such as boronic acids, which are widely used in various industries as coupling reagents for Suzuki-Miyaura cross-coupling reactions or pharmaceutical structures, are environmentally friendly molecules that have low toxicity and are easy to handle. Based on the chemical properties of organoboron compounds, they have potential Lewis acidity and the ability to form reversible covalent bonds with dehydration, making them attractive as catalysts. This review explores studies on the development of direct dehydrative amide/peptide bond formation reactions from carboxylic acids using organoboron catalysis, classifying them based on chemical bonding and catalysis over approximately 25 years, from the early developmental days to 2023.

Recent Advances in Photoinduced Borylation via N-Heterocyclic Carbene Boryl Radicals

AbstractOrganoboron compounds are recognized as essential synthetic intermediates in organic chemistry and have found broad applications in pharmaceutical and materials science. In recent years, the development of novel boronating reagents has opened new avenues for the synthesis of organoboron compounds. Among these, N-heterocyclic carbene boranes (NHC-boranes), with their unique advantages, have garnered sustained interest and have evolved into important precursors for boron-centered radicals, participating in a diverse array of visible-light-induced borylation reactions. This short review primarily focuses on visible-light-induced radical borylation reactions involving NHC-boranes, summarizing the latest advancements in the field and offering inspiration for subsequent research.1 Introduction2 Photoinduced Borylation via NHC-Boryl Radicals2.1 Photoinduced Borylation of Polyfluoroarenes2.2 Photoinduced Borylation of Arenes2.3 Photoinduced Borylation of Alkenes2.4 Photoinduced Borylation of Alkynes2.5 Photoinduced Borylation of Other Substrates3 Conclusion and Future Prospects

Activity of Organoboron Compounds against Biofilm-Forming Pathogens.

Bacteria have evolved and continue to change in response to environmental stressors including antibiotics. Antibiotic resistance and the ability to form biofilms are inextricably linked, requiring the continuous search for alternative compounds to antibiotics that affect biofilm formation. One of the latest drug classes is boron-containing compounds. Over the last several decades, boron has emerged as a prominent element in the field of medicinal chemistry, which has led to an increasing number of boron-containing compounds being considered as potential drugs. The focus of this review is on the developments in boron-containing organic compounds (BOCs) as antimicrobial/anti-biofilm probes and agents.

The current utility and future potential of multiborylated alkanes.

Organoboron chemistry has become a cornerstone of modern synthetic methodology. Most of these reactions use an organoboron starting material that contains just one C(sp2)-B or C(sp3)-B bond; however, there has been a recent and accelerating trend to prepare multiborylated alkanes that possess two or more C(sp3)-B bonds. This is despite a lack of general reactivity, meaning many of these compounds currently offer limited downstream synthetic value. This Review summarizes recent advances in the exploration of multiborylated alkanes, including a discussion on how these products may be elaborated in further synthetic manipulations.

Asymmetric dihydroboration of allenes enabled by ligand relay catalysis

Catalytic asymmetric hydroboration of unsaturated bonds has been recognized as the most straightforward method for the construction of chiral organoboron compounds. Although catalytic asymmetric hydroboration of alkenes has been well-developed, enantioselective hydroboration of allenes still remains rare probably due to the challenges in controlling the enantio-, stereo-, and regioselectivity. Additionally, the hydroboration products might go through over-borohydride, making the catalytic asymmetric dihydroboration of allenes challenging. Here, we report a cobalt-catalyzed asymmetric dihydroboration of allenes using a ligand relay strategy with two simple ligands. This protocol shows excellent enantio-, stereo-, and regioselectivity with positive functional group compatibilities in the construction of chiral 1,4-diboronate products. The applications of this reaction are demonstrated by various product derivatizations, gram-scale reactions, and the preparation of artigenin analogues. Mechanistic studies indicate that the achiral ligand controls the first hydroboration of allenes, and the chiral oxazoline iminopyridine ligand is responsible for the subsequent isomerization and asymmetric hydroboration.

Manganese(III) Triacetate-Mediated Cross Coupling of Organoboron Compounds with Trichloroethylene (TCE): Synthesis of 1,1-Dichloroalkenes.

Herein, we report an efficient method for the synthesis of 1,1-dichloroalkenes from organoboron compounds. This reaction proceeds in the presence of manganese(III) triacetate using trichloroethylene (TCE) as the vinylation reagent. This reaction can tolerate various types of organoboron compounds and various functional groups. The yields are moderate to good. Surprisingly, this transformation could even be achieved in the presence of manganese(II) acetate. Furthermore, this synthetic strategy could be applied to the synthesis of 1,1,2-trichloro-, 1-chloro-, and 2-chloroalkenes.

Post‐Functionalization of Organoboranes by Cu‐Catalyzed Azide Alkyne [3+2]‐Cycloaddition Reaction

AbstractThe copper‐catalyzed azide alkyne [3+2]‐cycloaddition (CuAAC) reaction of organoboranes represents an attractive area of research within the field of click chemistry, with diverse applications in organic synthesis, medicinal chemistry, or materials science. Despite the potential issues caused by the copper insertion into the carbon‐boron bond, significant progress has been made to harness the reactivity of organoboron compounds in CuAAC. This review provides an overview of the catalytic methods reported for CuAAC with various organoboranes, discussing the stability of the boron group and highlighting recent advancements in this area.