Bond Borylation Research Articles

Nickel-Catalyzed Secondary Benzylic C-O Bond Borylation.

A remote steric hindrance ligand (m-tBu)2C6H3PCy2 (L1) was synthesized to promote Ni-catalyzed C-O bond activation. The reaction achieved high yields for secondary benzylic C(sp3)-O borylation in non-π-extended systems under mild conditions. Mechanistic studies indicate that the nickel complex containing 1 equiv of L1 serves as the active catalyst, while increased loading of L1 gives the inactive bisligated Ni species. Acetanilide is crucial for the cross-coupling reaction, which facilitates generation of the monoligated nickel species.

Optimization of Metal-Support Cooperation for Boosting the Performance of Supported Gold Catalysts for the Borylation of C-O and C-N Bonds.

The cooperation of multiple catalytic components is a powerful tool for intermolecular bond formation, specifically, cross-coupling reactions. Supported metal catalysts have interfacial sites between metal nanoparticles and their supports where multiple catalytic elements can work in cooperation to efficiently promote intermolecular reactions. Hence, the establishment of novel guidelines for designing active interfacial sites of supported metal catalysts is indispensable for heterogeneous catalysts which enable efficient cross-coupling reactions. In this article, we performed kinetic and theoretical studies to elucidate the effect of metal-support cooperation for the borylation of C-O bonds by supported gold catalysts and revealed that the Lewis acid density of the supports determined the number of active sites at which metal nanoparticles (NPs) and Lewis acid at the surface of the supports work in cooperation. Furthermore, DFT calculations revealed that strong adsorption of diborons at the interface between Au NPs and supports and a decrease in the LUMO level of adsorbed diboron were responsible for efficient C-O bond borylation. Supported Au catalysts with the optimized metal-metal oxide cooperation sites, namely, Au/α-Fe2O3 catalyst, showed excellent activity for C-O bond borylation, and also enabled the synthesis of organoboron compounds by using continuous-flow reactions. Furthermore, Au/α-Fe2O3 showed high activity for direct C-N bond borylation without the transformation of amino groups to ammonium cations. The results described herein suggest that the optimization of metal-metal oxide cooperation is beneficial for taking full advantage of the potential performance of supported metal catalysts for intermolecular reactions.

Photoinduced Site-Selective Aryl C-H Borylation with Electron-Donor-Acceptor Complex Derived from B2Pin2 and Isoquinoline.

Due to boron's metalloid properties, aromatic boron reagents are prevalent synthetic intermediates. The direct borylation of aryl C-H bonds for producing aromatic boron compounds offers an appealing, one-step solution. Despite significant advances in this field, achieving regioselective aryl C-H bond borylation using simple and readily available starting materials still remains a challenge. In this work, we attempted to enhance the reactivity of the electron-donor-acceptor (EDA) complex by selecting different bases to replace the organic base (NEt3) used in our previous research. To our delight, when using NH4HCO3 as the base, we have achieved a mild visible-light-mediated aromatic C-H bond borylation reaction with exceptional regioselectivity (rr > 40:1 to single isomers). Compared with our previous borylation methodologies, this protocol provides a more efficient and broader scope for aryl C-H bond borylation through the use of N-Bromosuccinimide. The protocol's good functional-group tolerance and excellent regioselectivity enable the functionalization of a variety of biologically relevant compounds and novel cascade transformations. Mechanistic experiments and theoretical calculations conducted in this study have indicated that, for certain arenes, the aryl C-H bond borylation might proceed through a new reaction mechanism, which involves the formation of a novel transient EDA complex.

Trialkoxysilane-Induced Iridium-Catalyzed para-Selective C–H Bond Borylation of Arenes

An ideal approach for the construction of aryl boron compounds is to selectively replace a C–H bond in arenes with a C–B bond, and controlling regioselectivity is one of the most challenging aspects of these transformations. Herein, we report an iridium-catalyzed trialkoxysilane protecting group-assisted regioselective C–H borylation of arenes, including derivatives of benzaldehydes, acetophenones, benzoic acids, benzyl alcohols, phenols, aryl silanes, benzyl silanes, and multi-functionalized aromatic rings are all well tolerated and gave the para -selective C–H borylation products in a short time without the requirement of inert gases atmosphere. The site-selective C–H borylation can be adjustable by installing the developed trialkoxysilane protecting group on different functional groups on one aromatic ring. Importantly, the preparation process of the trialkoxychlorosilane is efficient and scalable. Mechanistic and computational studies reveal that the steric hindrance of the trialkoxysilane protecting group plays a key role in dictating the para-selectivity.

Diversification of NH‐Aryl Sulfoximines through Iridium‐Catalyzed ortho‐ and meta‐Selective C−H Borylation

AbstractHerein, the selective ortho‐ and meta‐C−H bond borylation of NH‐aryl sulfoximines is reported. Regioselectivity is achieved by the choice of commercially available ligands giving fast excess to valuable borylated aryl sulfoximine building blogs. The utility of the borylated products is demonstrated for the formation of C−O, C−C, C−N, C−D, and C−I bonds.

Palladium-Catalyzed Stereoselective Defluoroborylation of gem-Difluoroalkenes with Unsymmetrical Diboron: Access to Tetrasubstituted Monofluorinated Vinyl-B(dan) Derivatives.

The stereoselective C-F bond borylation of tetrasubstituted β,β-difluoroacrylates has been achieved. In contrast to the previously used B2pin2 reagent, which only led to dimerization products, this work employs the unsymmetrical diboron reagent (pin)B-B(dan) under the palladium(0)-catalyzed conditions to access novel boronamides containing the monofluorinated vinyl-B(dan) functionality. These compounds can cross-couple directly with gem-difluoroalkenes without reactivation in Suzuki-Miyaura reactions to afford vincinal difluoro 1,3-dienes with modular control of the substituents.

Fast and Selective β-C–H Borylation of N-Heterocycles with a Supramolecular Iridium Catalyst: Circumventing Deactivation Pathways and Mechanistic Insights

Selective iridium-catalyzed C–H bond borylations of unbiased or directing-group-free substrates typically occur under long reaction times and mild temperatures in order to avoid unselective processes including catalyst deactivation. Herein, we describe a supramolecular approach that enables the C–H bond borylation of challenging pyiridines and imidazoles in very short reaction times (up to 2 h) with a negligible incubation period for catalyst activation. The catalyst is based on a highly rigid zinc–porphyrin substrate-recognition site in the secondary coordination sphere and a triazolopyridine chelating fragment attached to the first coordination sphere at iridium. The borylation occurs at the C–H bond from the substrate located at four chemical bonds apart from the molecular recognition site with the selectivity being exclusively imposed by the distance between the active site and the molecular recognition site regardless of the nature of the N,N-chelating fragment coordinating to iridium as further supported by density functional theory (DFT) calculations. Additional studies (control experiments, nuclear magnetic resonance, and single-crystal X-ray diffraction) unraveled key catalyst deactivation pathways in which up to three different partners (water, methoxide ligands from the iridium precursor, and the triazolopyridine fragment) compete with the N-heterocycle substrate for binding to the molecular recognition site of the supramolecular catalyst. This fundamental understanding made possible the identification of a supramolecular catalyst featuring a 4-methyl substitution pattern in the first coordination sphere at iridium that provides a suitable balance of steric and electronic effects in both primary and secondary coordination spheres, thereby bypassing the manifold catalyst deactivation pathways. DFT calculations further indicated the importance of noncovalent interactions beyond the molecular recognition site on the stabilization of the different intermediates and transition sates.

Iron‐Catalysed C(sp2)‐H Borylation with Expanded Functional Group Tolerance†

Comprehensive SummaryArene C(sp2)‐H bond borylation offers direct and efficient access to aryl boronic esters. Using in situ catalyst activation and photoirradiation, the iron‐catalysed C(sp2)‐H borylation reaction of carboarenes, pyrroles, and indoles has been developed using only bench‐stable pre‐catalysts and reagents. Good functional group tolerance was observed including those not reported using previous methods (ArNH2, ArOH, ArSiR3, ArP(O)(OR)2, ArC(O)NR2). Mechanistic studies revealed iron‐catalysed reductive deoxygenation, C—F protodefluorination, and a demethylation of aryl methyl ethers by C—O sigma bond hydroboration.

Unravelling Enzymatic Features in a Supramolecular Iridium Catalyst by Computational Calculations.

Non-biological catalysts following the governing principles of enzymes are attractive systems to disclose unprecedented reactivities. Most of those existing catalysts feature an adaptable molecular recognition site for substrate binding that are prone to undergo conformational selection pathways. Herein, we present a non-biological catalyst that is able to bind substrates via the induced fit model according to in-depth computational calculations. The system, which is constituted by an inflexible substrate-recognition site derived from a zinc-porphyrin in the second coordination sphere, features destabilization of ground states as well as stabilization of transition states for the relevant iridium-catalyzed C-H bond borylation of pyridine. In addition, this catalyst appears to be most suited to tightly bind the transition state rather than the substrate. Besides these features, which are reminiscent of the action modes of enzymes, new elementary catalytic steps (i. e. C-B bond formation and catalyst regeneration) have been disclosed owing to the unique distortions encountered in the different intermediates and transition states.

Directed C–H borylation: From metal catalysis to metal free

<p indent="0mm">Organoborons play a highly important role in many science fields, range from synthetic chemistry to materials science to medicinal chemistry. The C−H borylation strategy has made significant development in recent decades, and its reaction system is changing from noble-metal catalysis to more environmentally friendly metal-free systems. Typically, an organic molecule contains multiple C−H bonds with subtle difference in activation barrier. Therefore, controlling the positional selectivity represents a key challenge in complex molecules. To override this intrinsic selectivity, introducing a directing group in molecules can exhibit different site-selectivity. This review focuses on the development of ortho-selective borylation of (hetero)arenes by various directing groups, including: (1) Metal-catalyzed directed C−H borylation; and (2) metal-free directed C−H borylation. The directed C−H borylation is shifting from noble metals to metal-free systems, breaking through the dependence of traditional means on metal catalysts and broadening the concept of C–H functionalization. In the first section, the development of transition metal catalysts for directed C−H<italic> </italic>borylation is summarized. Among various catalysts, the iridium complexes have proven to be most active toward C−H borylation. The 16e intermediate <sc>[Ir(dtbpy)(Bpin)₃] </sc>(dtbpy=4,4′-di-tert-butyl-2,2′-bipyridine, Bpin = 4,4,5,5-tetramethyl-1,3,2-dioxaborolane) has been proved to be the catalytically active species in the [Ir(X)(cod)]₂/dtbpy (X=OMe or Cl, cod=1,5-cyclooctadiene) catalyzed directed C−H borylation. Three different strategies have been developed for the direct regioselective C−H bond borylation: Chelate directed, relay directed, and outer-sphere directed. Notably, dimethylsilyl can be employed as the directing group in Ir-catalyzed ortho-borylation of arenes. In addition to iridium, the use of other transition metal catalysts including rhodium and palladium has met some success as well. The second section first analyses the disadvantages of traditional C−H<italic> </italic>borylation by transition metal catalysts. The requirement of precious metals and metal residues in the final product will limit the application of these processes, especially in large-scale synthesis. Alternatively, some novel metal-free electrophilic borylations of arenes have been reported which proceed via borenium or boronium species, but stoichiometric quantities of by-products are formed at the same time. Therefore, the development of simpler and efficient metal-free C−H bond borylation is highly desirable. Then we show our discovery on the development of a talent approach for the C−H bond borylation of (hetero)arenes including indoles, pyrroles and amides using the readily available BBr₃ without any additive. Other groups also reported some similar examples after our discovery. The concluding section of this review discusses the significance of the directed C−H<italic> </italic>borylation under metal-free conditions, and limitations of the known approaches in this field. The additional breakthroughs required to further advance the metal-free C−H functionalization are described in the concluding section of this review. We hope that this review will not only present the most exciting new discoveries for the C–H borylation of feedstock chemicals into valuable organoboron products, but also provide valuable guidance for researchers, especially in drug and natural product research, facilitating the continued development of synthetic chemistry.

Cobalt-Catalyzed Formation of Grignard Reagents via C-O or C-S Bond Activation.

C(aryl)-OMe bond functionalization catalyzed by cobalt(II) chloride in combination with a nacnac-type ligand and magnesium as a reductant is reported. Borylation and benzoylation of aryl methoxides are demonstrated, and C(aryl)-SMe bond borylation can be achieved under similar conditions. This is the first example of achieving these transformations using cobalt catalysis. Mechanistic studies suggest that a Grignard reagent is generated as an intermediate in a rare example of a magnesiation via a C-O bond activation reaction. Indeed, an organomagnesium species could be directly observed by electrospray ionization mass spectroscopic analysis. Kinetic experiments indicate that a heterogeneous cobalt catalyst performs the C-O bond activation.

Undirected, Asymmetric Alkyl Group Functionalizations through Alkane Dehydrogenation.

Direct asymmetric alkyl group functionalizations can potentially convert abundant and inexpensive hydrocarbon feedstocks into value-added chiral fine chemicals. Here, we report a one-pot, dehydrogenation-based strategy for enantioselective formal benzylic C(sp3)-H bond borylation. Dehydrogenation of alkylarenes by a pincer-Ir complex produces aryl alkenes via a tandem dehydrogenation/alkene-isomerization catalysis. The subsequent Cu-catalyzed asymmetric alkene hydroboration affords benzylic boronate esters with excellent site- and enantioselectivity. The generality of this strategy has been further demonstrated by asymmetric alkyl group amination.

Photoinduced metal-free borylation of aryl halides catalysed by an in situ formed donor-acceptor complex.

Organoboron compounds are very important building blocks which can be applied in medicinal, biological and industrial fields. However, direct borylation in a metal free manner has been very rarely reported. Herein, we described the successful direct borylation of haloarenes under mild, operationally simple, catalyst-free conditions, promoted by irradiation with visible light. Mechanistic experiments and computational investigations indicate the formation of an excited donor–acceptor complex with a −3.12 V reduction potential, which is a highly active reductant and can facilitate single-electron-transfer (SET) with aryl halides to produce aryl radical intermediates. A two-step one-pot method was developed for site selective aromatic C–H bond borylation. The protocol's good functional group tolerance enables the functionalization of a variety of biologically relevant compounds, representing a new application of aryl radicals merged with photochemistry.

Rücktitelbild: Enzyme‐like Supramolecular Iridium Catalysis Enabling C−H Bond Borylation of Pyridines with meta‐Selectivity (Angew. Chem. 33/2021)

Wie ein Enzym beschreibt am besten den supramolekularen Katalysator, über den Rafael Gramage-Doria et al. in ihrem Forschungsartikel auf S. 18154 berichten. Die entfernt lokalisierten Zn⋅⋅⋅N-Wechselwirkungen in einem Iridium-Borylierungskatalysator sind für die einzigartige Selektivität und Reaktivität verantwortlich, die für die Funktionalisierung der C-H-Bindung von Pyridin beobachtet wurde. Das Pyridin nähert sich der Substrat-Erkennungstasche wie eine Sternschnuppe aus den Perseiden. Grafik: Romain Baloche.

An Introductory Overview of C–H Bond Activation/ Functionalization Chemistry with Focus on Catalytic C(sp3)–H Bond Borylation

The direct and selective functionalization of C–H bonds provides novel disconnections and innovative strategies to streamline the synthesis of molecules with diverse complexities. However, despite the significant advances in the elaboration of techniques for C–H activation, the utilization of unactivated C(sp3)–H bonds remains challenging. In particular, asymmetric transformation of C(sp3)–H bonds is underdeveloped owing to the lack of catalytic systems that can competently discriminate among ubiquitous C–H bonds in organic molecules. This short review aims to outline the challenges and strategies for the catalytic functionalization of C(sp3)–H bonds giving a general and non-exhaustive explanatory approach. Current strategies on the basis of the substrates and reaction mechanisms are summarized in Section 1. Examples of enantioselective C–H bond transformations are then given in Section 2. Finally, in Section 3, an outline of current methodologies towards the direct borylation of C(sp3)–H bonds is described to showcase the importance of developing techniques for catalytic C–H bond chemistry. While we try to cover all excellent reports available in the literature on this topic, any omissions are unintentional, taking note of the most representative examples available.

Tetracoordinate Boron Intermediates Enable Unconventional Transformations.

ConspectusOrganoboron compounds are a class of multifunctional reagents for the construction of carbon-carbon and carbon-heteroatom bonds in modern synthetic chemistry. The transformations of organoboron compounds are usually carried out through tetracoordinate boron intermediates and mainly include additions to unsaturated bonds, rearrangement reactions, transmetalation reactions, and so on. Although great progress has been achieved in improving tetracoordinate boron intermediates, there are still shortcomings, such as sparse activation modes, a paucity of reaction strategies and difficulties in stereoselective control. In this Account, we mainly discuss our recent advances in the development of unconventional transformations of organoboron compounds based on the design of tetracoordinate boron intermediates, including the following three topics: (1) the construction of C-B bonds; (2) the construction of C-C bonds; (3) the design and application of chiral tetracoordinate boron.The development of new strategies to build C-B bonds is of great interest for chemists. We have developed tandem reactions involving multiple tetracoordinate boron intermediates for the selective borylations of alkynes and the synthesis of stable tetracoordinate boron, including a domino-borylation-protodeboronation (DBP) strategy for selective borylations of alkynes, highly regio-, stereo-, and chemoselective Cu-catalyzed diborylation of β-CF3-1,3-enynes and cascade B-Cl/C-B cross-metathesis and C-H bond borylation for the synthesis of tetracoordinate triarylboranes. We have also developed novel strategies involving tetracoordinate boron intermediates to form C-C bonds because the formation of C-C bonds is an enduring theme of organic chemistry. We disclosed long distance or multiple migration reactions and novel coupling partners in transmetalation reactions, such as long distance 1,4-migrations of tetracoordinate nitrile oxide boron and nitrilium boron intermediates, multiple migrations of tetracoordinate isocyanide boron intermediate, palladium-catalyzed Suzuki-Miyaura coupling of thioureas or thioamides, copper-catalyzed atroposelective Michael-type addition, and a palladium-catalyzed atroposelective Catellani reaction. Moreover, in terms of stereoselective control of the tetracoordinate boron intermediate, we found that a chiral tricoordinate boron complex could activate water to form a chiral tetracoordinate boron complex with Brønsted acidity, which has been successfully applied with high enantioselectivity to the asymmetric catalytic reduction of challenging indoles.This Account summarizes our recent efforts using unconventional transformations of organoboron compounds for the design of tetracoordinate boron intermediates, which not only achieved the precise construction of a wide range of diverse C-B bonds and C-C bonds but also developed a novel chiral Brønsted acid for the asymmetric catalytic reduction of challenging indoles.

Advances in Nitrogen-Directed Aromatic Compound ortho-C—H Bond Borylation Catalyzed by Transition Metals

Advances in Nitrogen-Directed Aromatic Compound <i>ortho</i>-C—H Bond Borylation Catalyzed by Transition Metals

Frustrated Lewis Pairs: Discovery and Overviews in Catalysis

Frustrated Lewis Pairs (FLPs) are derived from simple combinations of Lewis acids (electron acceptors) and Lewis bases (electron donors), in which steric demands prevent from forming classical Lewis acid‐base adducts. Since 2006, FLP chemistry has emerged as a novel strategy for the design and application of main‐group chemistry and development of new metal‐free catalytic processes. This strategy has been applied to stoichiometric reactivity and then extended to catalysis. In this review, we briefly summarize the representative discoveries and developments of FLP chemistry in the field of catalysis, including hydrogenation, hydrosilylation, reduction of CO2, transformations of alkynes to organic derivatives, C—H bond borylation and polymerization.

Revisiting Polyfluoroarenes as Radical Acceptors: Radical C-F Bond Borylation of Polyfluoroarenes with N-Heterocyclic Carbene Boranes and Synthesis of Borane-Containing Liquid Crystals.

Polyfluoroarenes work as good radical acceptors in the thermal radical reaction with N-heterocyclic carbene boranes (NHC-boranes) in the presence of di-tert-butyl peroxide. In this reaction, a C-F bond of polyfluoroarenes is substituted with an NHC-boryl group to provide B-aryl NHC-borane derivatives. The developed synthetic method was applied to the synthesis of novel borane-containing liquid crystalline molecules having highly thermal stability.

Iron-Catalysed C(sp2)-H Borylation Enabled by Carboxylate Activation.

Arene C(sp2)-H bond borylation reactions provide rapid and efficient routes to synthetically versatile boronic esters. While iridium catalysts are well established for this reaction, the discovery and development of methods using Earth-abundant alternatives is limited to just a few examples. Applying an in situ catalyst activation method using air-stable and easily handed reagents, the iron-catalysed C(sp2)-H borylation reactions of furans and thiophenes under blue light irradiation have been developed. Key reaction intermediates have been prepared and characterised, and suggest two mechanistic pathways are in action involving both C-H metallation and the formation of an iron boryl species.