Boryl Group Research Articles

Stereodefined polymetalloid alkenes synthesis via stereoselective boron-masking of polyborylated alkenes

Polyborylated-alkenes are valuable polymetalloid reagents in modern organic synthesis, providing access to a wide array of transformations, including the construction of multiple C–C and C–heteroatom bonds. However, because they contain similar boryl groups, many times their transformation faces the main challenge in controlling the chemo-, regio- and stereoselectivity. One way to overcome these limitations is by installing different boron groups that can provide an opportunity to tune their reactivity toward better chemo-, regio- and stereoselectivity. Yet, the preparation of polyborylated-alkenes containing different boryl groups has been rare. Herein we report concise, highly site-selective, and stereoselective boron-masking strategies of polyborylated alkenes. This is achieved by designed stereoselective trifluorination and MIDA-ation reactions of readily available starting polyborylated alkenes. Additionally, the trifluoroborylated-alkenes undergo a stereospecific interconversion to Bdan-alkenes. These transition-metal free reactions provide a general and efficient method for the conversion of polyborylated alkenes to access 1,1-di-, 1,2-di-, 1,1,2-tris-(borylated) alkenes containing BF3M, Bdan, and BMIDA, a family of compounds that currently lack efficient synthetic access. Moreover, tetraborylethene undergoes the metal-free MIDA-ation reaction to provide the mono BMIDA tetraboryl alkene selectively. The mixed polyborylalkenes are then demonstrated to be useful in selective C–C and C–heteroatom bond-forming reactions. Given its simplicity and versatility, these stereoselective boron-masking approaches hold great promise for organoboron synthesis and will result in more transformations.

Zwitterionic Bergman cyclization triggered polymerization gives access to metal-graphene nanoribbons using a boron metal couple

With the rapid growth in artificial intelligence, designing high-speed and low-power semiconducting materials is of utmost importance. This investigation provides a theoretical basis to access covalently bonded transition metal-graphene nanoribbon (TM-GNR) hybrid semiconductors whose DFT-computed bandgaps were much narrower than the commonly used pentacene. Systematic optimization of substrates containing remotely placed boryl groups and the transition metals produced the zwitterions via ionic Bergman cyclization (i-BC) and unlocked the polymerization of metal-substituted polyenynes. Aside from i-BC, the subsequent steps were barrierless, which involved structureless transition regions. Multivariate analysis revealed the strong dependence of activation energy and the cyclization mode on the electronic nature of boron and Au(I). Consequently, three regions corresponding to radical Bergman (r-BC), ionic Bergman (i-BC), and ionic Schreiner-Pascal (i-SP) cyclizations were identified. The boundaries between these regions corresponded to the mechanistic shift induced by the three-center-three-electron (3c-3e) hydrogen bond, three-center-four-electron (3c-4e) hydrogen bond, and vacant p-orbital on boron. The ideal combination for cascade polymerization was observed near the boundary between i-BC and i-SP.

Boryl Radical-Promoted Dehydroxylative Alkylation of 3-Hydroxyoxindole Derivatives

A boryl radical-promoted dehydroxylative alkylation of 3-hydroxy-oxindole derivatives is achieved. The reaction starts from addition of 4-dimethylaminopyridine (DMAP)-boryl radical to the amide carbonyl oxygen atom, which induces a spin-center shift process to promote the C-O bond cleavage. The elimination of a hydroxide anion from a free hydroxy group is also accomplished. Capture of the generated carbon radical with alkenes furnishes a variety of C-3 alkylated oxindoles. This method features a simple operation and broad substrate scope.

Transition‐Metal‐Free Radical Borylation Reactions

AbstractOrganoboron compounds are versatile synthons in synthetic chemistry, materials science, and medicinal chemistry. The preparation of them often requires either reactive organometallic reagents or transition metals. In recent years, transition‐metal‐free borylation methodologies using radical chemistry for C−B bond formation have attracted much attention and developed rapidly, which circumvents the use of preformed organometallic reagents. Various successful approaches from different radical precursors (such as carboxylic acids, amines and alcohols, which are abundant in nature) through either thermochemical, photochemical or electrochemical pathways have been developed. Therefore, in this review, we hope to provide an overview of recent advances in the discovery, development, and mechanistic study of transition‐metal‐free radical borylation processes.

Electrooxidative Activation of B−B Bond in B2cat2: Access to gem‐Diborylalkanes via Paired Electrolysis

AbstractThis report describes the unprecedented electrooxidation of a solvent (e.g., DMF)‐ligated B2cat2 complex, whereby a solvent‐stabilized boryl radical is formed via quasi‐homolytic cleavage of the B−B bond in a DMF‐ligated B2cat2 radical cation. Cyclic voltammetry and density functional theory provide evidence to support this novel B−B bond activation strategy. Furthermore, a strategy for the electrochemical gem‐diborylation of gem‐bromides via paired electrolysis is developed for the first time, affording a range of versatile gem‐diborylalkanes, which are widely used in synthetic society. Notably, this reaction approach is scalable, transition‐metal‐free, and requires no external activator.

Electrooxidative Activation of B-B Bond in B2 cat2 : Access to gem-Diborylalkanes via Paired Electrolysis.

This report describes the unprecedented electrooxidation of a solvent (e.g., DMF)-ligated B2 cat2 complex, whereby a solvent-stabilized boryl radical is formed via quasi-homolytic cleavage of the B-B bond in a DMF-ligated B2 cat2 radical cation. Cyclic voltammetry and density functional theory provide evidence to support this novel B-B bond activation strategy. Furthermore, a strategy for the electrochemical gem-diborylation of gem-bromides via paired electrolysis is developed for the first time, affording a range of versatile gem-diborylalkanes, which are widely used in synthetic society. Notably, this reaction approach is scalable, transition-metal-free, and requires no external activator.

C-C and C-N Bond Activation, Lewis-Base Coordination and One- and Two-Electron Oxidation at a Linear Aminoborylene.

A cyclic alkyl(amino)carbene (CAAC)-stabilized dicoordinate aminoborylene is synthesized by the twofold reduction of a [(CAAC)BCl2 (TMP)] (TMP=2,6-tetramethylpiperidyl) precursor. NMR-spectroscopic, X-ray crystallographic and computational analyses confirm the cumulenic nature of the central C=B=N moiety. Irradiation of [(CAAC)B(TMP)] (2) resulted in an intramolecular C-C bond activation, leading to a doubly-fused C10 BN heterocycle, while the reaction with acetonitrile resulted in an aryl migration from the CAAC to the acetonitrile nitrogen atom, concomitant with tautomerization of the latter to a boron-bound allylamino ligand. One-electron oxidation of 2 with CuX (X=Cl, Br) afforded the corresponding amino(halo)boryl radicals, which were characterized by EPR spectroscopy and DFT calculations. Placing 2 under an atmosphere of CO afforded the tricoordinate (CAAC,CO)-stabilized aminoborylene. Finally, the twofold oxidation of 2 with chalcogens led, in the case of N2 O and sulfur, to the splitting of the B-CCAAC bond and formation of the 2,4-diamino-1,3,2,4-dichalcogenadiboretanes and CAAC-chalcogen adducts, whereas with selenium a monomeric boraselenone was isolated, which showed some degree of B-Se multiple bonding.

Highly Stereoselective Syntheses of α,α-Disubstituted (E)- and (Z)-Crotylboronates

We report herein stereoselective syntheses of α,α-disubstituted (E)- and (Z)-crotylboronates. Starting from α-boryl (E)- or (Z)-crotylboronate, base-mediated alkylation occurred exclusively at the position α to the boryl groups to give targeted boronates while retaining the geometries of the alkenes in the starting crotylboronates. Under proper conditions, the resulting α,α-disubstituted crotylboronates underwent aldehyde addition to give allylated products with high stereoselectivities.

Hydroalkylation of Olefins Mediated by Photochemically Generated NHC-Ligated Boryl Radicals

Hydroalkylation of Olefins Mediated by Photochemically Generated NHC-Ligated Boryl Radicals

Dearomative triple elementalization of quinolines driven by visible light

Organoboron and organosilicon compounds are used not only as synthetic building blocks but also as functional materials and pharmaceuticals, and compounds with multiple boryl and silyl groups are beginning to be used for these purposes. Especially in drug discovery, methodology providing easy stereoselective access to aliphatic nitrogen heterocycles bearing multiple boryl or silyl groups from readily available aromatic nitrogen heterocycles would be attractive. However, such transformations remain challenging, and available reactions have been mostly limited to dearomative hydroboration or hydrosilylation reactions. Here, we report the dearomative triple elementalization (carbo-sila-boration) of quinolines via the addition of organolithium followed by photo-boosted silaboration, affording the desired products with complete chemo-, regio-, and stereoselectivity. The reaction proceeds via the formation of silyl radicals instead of silyl anions. We also present preliminary studies to illustrate the potential of silaboration products as synthetic platforms.

Ir-Catalyzed Regioselective Dihydroboration of Thioalkynes toward Gem-Diboryl Thioethers.

While 1,1-diboryl (gem-diboryl) compounds are valuable synthetic building blocks, currently, related studies have mainly focused on those 1,1-diboryl alkanes without a hetero functional group in the α-position. gem-Diboryl compounds with an α-hetero substituent, though highly versatile, have been limitedly accessible and thus rarely utilized. Herein, we have developed the first α-dihydroboration of heteroalkynes leading to the efficient construction of gem-diboryl, hetero-, and tetra-substituted carbon centers. This straightforward, practical, mild, and atom-economic reaction is an attractive complement to the conventional multistep synthetic strategy relying on deprotonation of gem-diborylmethane by a strong base. Specifically, [Ir(cod)(OMe)]2 was found to be uniquely effective for this process of thioalkynes, leading to excellent α-regioselectivity when delivering the two boryl groups, which is remarkable in view of the many competitive paths including monohydroboration, 1,2-dihydroboration, dehydrodiboration, triboration, tetraboration, etc. Control experiments combined with DFT calculations suggested that this process involves two sequential hydroboration events. The second hydroboration requires a higher energy barrier due to severe steric repulsion in generating the highly congested α-sulfenyl gem-diboryl carbon center, a structural motif that was almost unknown before.

Copper(I)-Catalyzed Regio- and Stereoselective Silaboration of Terminal Allenes.

Organic compounds bearing both silyl and boryl groups are important building blocks in organic synthesis because of the adequate reactivity of the silyl and boryl groups and high stereospecificity in their derivatization reactions. The difference in reactivity between the silyl and boryl groups enables stepwise derivatization of these groups to afford complex molecules. Here, we report the copper(I)-catalyzed silaboration of terminal allenes to produce multisubstituted allylic boronates embedded with an alkenyl silane structure. The reaction can proceed with a variety of allenes and silylboranes. Furthermore, the silyl and boryl groups were successfully converted into other functional groups, while retaining the stereochemistry of the alkene moiety.

Selective Mono- and Di-deuterodefluorination of Trifluoroacetamides Promoted by Boryl Radicals

Selective Mono- and Di-deuterodefluorination of Trifluoroacetamides Promoted by Boryl Radicals

Visible light induced boryl radical and its application in reduction of unsaturated XO (X = C, N, S) bonds

A boryl radical is generated by 4-cyanopyridine and B2cat2 and illustrated a ketyl radical by visible light, furtherly reduced unsaturated double bond XO (X = C, N, S). The reaction mechanism is confirmed by spectroscopy and calculation studies.

Programmable synthesis of difluorinated hydrocarbons from alkenes through a photocatalytic linchpin strategy.

The introduction of difluoromethylene moieties into organic molecules has garnered significant attention due to their profound influence on the physicochemical and biological properties of compounds. Nonetheless, the existing approaches for accessing difluoroalkanes from readily available feedstock chemicals remain limited. In this study, we present an efficient and modular protocol for the synthesis of difluorinated compounds from alkenes, employing the readily accessible reagent, ClCF2SO2Na, as a versatile "difluoromethylene" linchpin. By means of an organophotoredox-catalysed hydrochlorodifluoromethylation of alkenes, followed by a ligated boryl radical-facilitated halogen atom transfer (XAT) process, we have successfully obtained various difluorinated compounds, including gem-difluoroalkanes, gem-difluoroalkenes, difluoromethyl alkanes, and difluoromethyl alkenes, with satisfactory yields. The practical utility of this linchpin strategy has been demonstrated through the successful preparation of CF2-linked derivatives of complex drugs and natural products. This method opens up new avenues for the synthesis of structurally diverse difluorinated hydrocarbons and highlights the utility of ligated boryl radicals in organofluorine chemistry.

Selective multifunctionalization of N-heterocyclic carbene boranes via the intermediacy of boron-centered radicals.

The selective difunctionalization of N-heterocyclic carbene (NHC) boranes with alkenes has been achieved via decatungstate and thiol synergistic catalysis. The catalytic system also allows stepwise trifunctionalization, leading to complex NHC boranes with three different functional groups which are challenging to prepare by other methods. The strong hydrogen-abstracting ability of the excited decatungstate enables the generation of boryl radicals from mono- and di-substituted boranes for realizing borane multifunctionalization. This proof-of-principle research provides a new chance for fabricating unsymmetrical boranes and developing boron-atom-economic synthesis.

Photoinduced catalyst-free borylation of alkenyl triflates with Lewis base complexes of boranes

Herein, a direct radical borylation of alkenyl triflates with Lewis base-ligated boranes (LB-BH3) was accomplished, affording a series of α-boryl carbonyl compounds.

Chloroacetyl boronate N-tosylhydrazone as a versatile synthetic building block.

Chloroacetyl boronate N-tosylhydrazone (CABT) has been synthesized as a reagent to generate a diverse range of molecular skeletons. CABT can undergo a series of transformations involving nucleophilic substitution of the chloride and coupling of the N-tosylhydrazones, followed by boryl group functionalization. We further demonstrated that this CABT reagent could enable a diversity-oriented synthesis.

Photoinduced Halogen-Atom Transfer by N-Heterocyclic Carbene-Ligated Boryl Radicals for C(sp3)-C(sp3) Bond Formation.

Herein, we present a comprehensive study on the use of N-heterocyclic carbene (NHC)-ligated boryl radicals to enable C(sp3)-C(sp3) bond formation under visible-light irradiation via Halogen-Atom Transfer (XAT). The methodology relies on the use of an acridinium dye to generate the boron-centered radicals from the corresponding NHC-ligated boranes via single-electron transfer (SET) and deprotonation. These boryl radicals subsequently engage with alkyl halides in an XAT step, delivering the desired nucleophilic alkyl radicals. The present XAT strategy is very mild and accommodates a broad scope of alkyl halides, including medicinally relevant compounds and biologically active molecules. The key role of NHC-ligated boryl radicals in the operative reaction mechanism has been elucidated through a combination of experimental, spectroscopic, and computational studies. This methodology stands as a significant advancement in the chemistry of NHC-ligated boryl radicals, which had long been restricted to radical reductions, enabling C-C bond formation under visible-light photoredox conditions.

Lewis Base-Boryl Radicals Enabled Borylation Reactions and Selective Activation of Carbon-Heteroatom Bonds.

ConspectusThe past decades have witnessed tremendous progress on radical reactions. However, in comparison with carbon, nitrogen, oxygen, and other main group element centered radicals, the synthetic chemistry of boron centered radicals was less studied, mainly due to the high electron-deficiency and instability of such 3-center-5-electron species. In the 1980s, Roberts and co-workers found that the coordination of a Lewis base (amines or phosphines) with the boron center could form 4-center-7-electron boryl radicals (Lewis base-boryl radicals, LBRs) that are found to be more stable. However, only limited synthetic applications were developed. In 2008, Curran and co-workers achieved a breakthrough with the discovery of N-heterocyclic carbene (NHC) boryl radicals, which could enable a range of radical reduction and polymerization reactions. Despite these exciting findings, more powerful and valuable synthetic applications of LBRs would be expected, given that the structures and reactivities of LBRs could be easily modulated, which would provide ample opportunities to discover new reactions. In this Account, a summary of our key contributions in LBR-enabled radical borylation reactions and selective activation of inert carbon-heteroatom bonds will be presented.Organoboron compounds have shown versatile applications in chemical society, and their syntheses rely principally on ionic borylation reactions. The development of mechanistically different radical borylation reactions allows synthesizing products that are inaccessible by traditional methods. For this purpose, we progressively developed a series of NHC-boryl radical mediated chemo-, regio-, and stereoselective radical borylation reactions of alkenes and alkynes, by which a wide variety of structurally diverse organoboron molecules were successfully prepared. The synthetic utility of these borylated products was also demonstrated. Furthermore, we disclosed a photoredox protocol for oxidative generation of NHC-boryl radicals, which enabled useful defluoroborylation and arylboration reactions.Selective bond activation is an ideal way to convert simple starting materials to value-added products, while the cleavage of inert chemical bonds, in particular the chemoselectivity control when multiple identical bonds are present in similar chemical environments, remains a long-standing challenge. We envisaged that finely tuning the properties of LBRs might provide a new solution to address this challenge. Recently, we disclosed a 4-dimethylaminopyridine (DMAP)-boryl radical promoted sequential C-F bond functionalization of trifluoroacetic acid derivatives, in which the α-C-F bonds were selectively snipped via a spin-center shift mechanism. This strategy enables facile conversion of abundantly available trifluoroacetic acid to highly valuable mono- and difluorinated molecules. Encouraged by this finding, we further developed a boryl radical enabled three-step sequence to construct all-carbon quaternary centers from a range of trichloromethyl groups, where the three C-Cl bonds were selectively cleaved by the rational choice of suitable boryl radical precursors in each step. Furthermore, a boryl radical promoted dehydroxylative alkylation of α-hydroxy carboxylic acid derivatives was achieved, allowing for the efficient conversion of some biomass platform molecules to high value products.