The metal-catalyzed intermolecular C-H borylation of arenes is an extremely powerful C-H functionalization methodology. However, to date it is effectively restricted to forming organo-boronate esters (Aryl-B(OR)2) with its application to form other organoboranes rarely explored. Herein, we report a catalytic intermolecular heteroarene C-H borylation method using the commercial hydroborane 9-borabicyclo-[3.3.1]-nonane, (H-BBN)2. This process is effective for mono- and di-borylation to form a range of heteroaryl-BBN compounds using either NacNacAl or NacNacZn (NacNac = {(2,6-iPr2C6H3)N(CH3)C}2CH) based catalysts. Notably, mechanistic studies indicated a highly unusual σ-bond metathesis process between NacNacZn-Aryl and the dimeric hydroborane, with first order kinetics in the hydroborane dimer ((H-BBN)2). Our calculated metathesis pathway involves ligand non-innocence and addition of both H-BBN units in (H-BBN)2 to the NacNacZn-heteroaryl complex. This is in contrast to the conventional σ-bond metathesis mechanism using other hydroboranes which invariably proceeds by reaction of one equivalent of a monomeric hydroborane (e.g., H-B(OR)2) with a M-C unit. Overall, this work demonstrates the potential of extending catalytic arene C-H borylation beyond boronate esters, while highlighting that the σ-bond metathesis reaction can be mechanistically more complex when utilizing dimeric hydroboranes such as (H-BBN)2.

C-H zincation is an efficient route to useful organozinc compounds. To date, most approaches effect aryl C-H zincation with selectivity controlled by substrate pKa. Herein, we report a heteroaryl C-H zincation method that uses an easy to access (β-diketiminate)Zn-Me complex and [(R3N)H][Anion] and proceeds under electronic control. This catalytic process is anion dependent; the less coordinating anion [B(C6F5)4]- proved superior to [CHB11H5Br6]-, with the latter forming the intimate ion pair [(β-diketiminate)Zn(CHB11H5Br6)]. The Zn-Me complex and the [(R3N)H]+ salt can also initiate catalytic C-H borylation. A key requirement for a viable transfer zincation is a low barrier protonolysis reaction between the zinc-alkyl and [(R3N)H]+. This study found significant differences between the zinc-methyl and zinc-ethyl systems which stem from increased steric crowding in the zinc-ethyl congener. For the latter, the SE2(open) protonolysis transition state is forced to proceed through a sub-optimal non-linear Zn⋯Cα⋯HNR3 orientation which increases the energy of this barrier (vs. that for the Zn-Me analogue). While the scope of this initial process is limited, this work demonstrates that catalytic electrophilic transfer zincation is feasible and also highlights the sensitivity of a key transition state to small changes in the steric environment.

Organofluorine compounds are vital across multiple sectors, hence highly selective methods to install fluorine are of considerable importance. The deoxyfluorination of alcohols is a key approach to prepare organofluorine compounds, however, a highly secondary (2°)-selective deoxyfluorination of alcohols has not been realized to date. Herein, we report that borane-mediated deoxyfluorination results in high 2°-selectivity in inter- and intra-molecular competition reactions versus primary (1°), tertiary (3°) and even benzylic (Bn) alcohols. This is an operationally simple method using only commercial reagents (e.g., Et3N ⋅ 3HF) that starts from the alcohol which is converted to the O-alkyl-N-H-isourea in situ. The origin of the high 2°-selectivity was elucidated to be due to the relative barriers to carbodiimide elimination from the O-alkyl-N-(BR2)-isoureas. As the selectivity controlling step does not involve fluoride, this borane-mediated approach can be applied to other nucleophiles, as demonstrated by 2°-selective deoxychlorination using HCl occurring in preference to substitution of 1° and Bn analogues. This borane-mediated nucleophilic substitution therefore provides a new approach to circumvent the selectivity limitations inherent in classical SN2 and SN1 type reactions.

2,6-Di-tert-butyl substituted pyridines (tBu2-py) are widely used non-nucleophilic Brønsted bases. Their ubiquity is due to their highly hindered basic site and chemically robust nature. Herein we report that simple M2X6 Lewis acids (M═Al or Ga, X═Cl, Br or I) effect intermolecular sp3C─H metalation of tBu2-py bases under mild conditions. The sp3C─H metalated products can be converted in situ into ─BPin, ─iodo, ─bromo and ─hydroxy derivatives for further elaboration. Mechanistic investigations indicate that: i) a frustrated Lewis pair effects sp3C─H heterolysis to form the C─M bond and a protonated pyridine; ii) C─H metalation requires singly halide-bridged super-electrophilic M2X6 dimers for sufficiently low barriers. Finally, sp3C─H metalation using M2X6 is not limited to tBu2-py bases. Thus, it is important to be aware of this facile sp3C─H functionalisation when using a range of non-nucleophilic Brønsted bases.

Oxoboranes (R-BO) are transient species that rapidly trimerise to form boroxines. To date, the only method used to stabilise oxoboranes is to add a Lewis base, but this forms a three-coordinate at boron oxoborane that has a different bonding/reactivity profile. Herein we report a base-free, two-coordinate oxoborane that is isolated as a Lewis adduct with AlCl3. This species, Mes*BO-AlCl3 (Mes*=2,4,6-tBu-C6H2), has a ν11ΒΟ stretching frequency of 1843 cm-1, indicating a strong BO bond. Computational analysis indicates this is due to a highly polarised BO bonding interaction combined with modest BO multiple bond character. While the polarisation of the BO bond on AlCl3 coordination enhances the Lewis acidity at boron it also reduces the basicity at oxygen and the latter is key to accessing a base-free oxoborane. Finally, this oxoborane reacts with PhN3 in a unique way to form an unprecedented boron heterocycle.

N-directed 2-fold bromoboration reactions of diynes with BBr3 have been developed, allowing the access to novel internally BN-doped polycyclic aromatic hydrocarbons from readily available precursors under mild conditions. Computational investigations identified three potential reaction mechanisms, each involving either BBr3 or [BBr4](-), with low activation barriers (Delta G(double dagger) < 16 kcal/mol) for all pathways. The resulting brominated products can be further functionalized through various cross-coupling protocols, enabling the synthesis of highly luminescent emitters with quantum yield exceeding 90.

C−H metalation is the most efficient method to prepare aryl–zinc and –aluminum complexes that are highly useful nucleophiles. Virtually all C–H metalation routes to form Al or Zn organometallic reagents require stoichiometric, strong Brønsted bases with no base-catalyzed reactions reported, to our knowledge. Herein we present a catalytic C–H metalation process to form aryl-zinc and aryl-aluminum complexes that uses only simple amine bases (e.g., Et3N) in sub-stoichiometric quantity (10 mol%). Key to this approach is coupling an endergonic C–H metalation step using a [(-diketiminate)MNR3]+ (M = Zn or Al–Me) electrophile with a sufficiently exergonic dehydrocoupling step between the acidic ammonium salt by-product of C–H metalation ([(R3N)H]+) and a Zn–H or Al–Me containing complex. This step, forming H2/MeH, makes the overall cycle exergonic while also generating more of the key cationic metal electrophile. Mechanistic studies supported by DFT calculations revealed metal-specific dehydrocoupling pathways, with the divergent reactivity shown to be due to the different metal valency (which impacts the accessibility of amine-free cationic complexes) and steric environment. Notably, dehydrocoupling in the zinc system proceeds through a ligand-mediated pathway involving protonation of the -diketiminate C position. In this step the magnitude of the key barrier is dependent on the steric bulk of the spectator ligand, with bulkier ligands actually affording lower barriers. This catalytic approach to arene C−H metalation has the potential to be applicable to other main group metals and ligands, thus will facilitate the synthesis of these important organometallic compounds.

[(NacNac)Zn(DMT)][B(C6F5)4], 1, (NacNac = {(2,6- i Pr2H3C6)N(CH3)C}2CH), DMT = N,N-dimethyl-4-toluidine), was synthesized via two routes starting from either (NacNac)ZnEt or (NacNac)ZnH. Complex 1 is an effective (pre)catalyst for the C-H borylation of (hetero)arenes using catecholborane (CatBH) with H2 the only byproduct. The scope included weakly activated substrates such as 2-bromothiophene and benzothiophene. Computational studies elucidated a plausible reaction mechanism that has an overall free energy span of 22.4 kcal/mol (for N-methylindole borylation), consistent with experimental observations. The calculated mechanism starting from 1 proceeds via the displacement of DMT by CatBH to form [(NacNac)Zn(CatBH)]+, D, in which CatBH binds via an oxygen to zinc which makes the boron center much more electrophilic based on the energy of the CatB-based LUMO. Combinations of D and DMT act as a frustrated Lewis pair (FLP) to effect C-H borylation in a stepwise process via an arenium cation that is deprotonated by DMT. Subsequent B-H/[H-DMT]+ dehydrocoupling and displacement from the coordination sphere of zinc of CatBAr by CatBH closes the cycle. The calculations also revealed a possible catalyst decomposition pathway involving hydride transfer from boron to zinc to form (NacNac)ZnH which reacts with CatBH to ultimately form Zn(0). In addition, the key rate-limiting transition states all involve the base, thus fine-tuning of the steric and electronic parameters of the base enabled a further minor enhancement in the C-H borylation activity of the system. Outlining the mechanism for all steps of this FLP-mediated process will facilitate the development of other main group FLP catalysts for C-H borylation and other transformations.

Herein we report the synthesis, isolation and polymerisation activity of two new zinc compounds based on a 2,6-diisopropylphenyl (Dipp) β-diiminate (NacNac) ligand framework with zinc also ligated by an amidate (2-pyridonate or 6-methyl-2-pyridonate) unit. The compounds crystallised as either monomeric (6-Me-2-pyridonate derivative) or dimeric (2-pyridonate) species, although both were found to be monomeric in solution via1H DOSY NMR spectroscopy, which was supported by DFT calculations. These observations suggest that both complexes initiate ring-opening polymerisation (ROP) through a single-site monometallic mechanism. High molecular weight poly ε-caprolactone (PCL) was achieved via exogenous initiator-free ROP conditions with both catalysts. An increase in the 2-pyridonate initiator steric bulk (6-Me- vs. 6-H-) resulted in an improved catalytic activity, facilitating complete monomer conversion within 1 h at 60 °C. Pyridonate end-groups were observed by MALDI-ToF mass spectrometry, contrasting with previous observations for DippNacNac-Zn acetate complexes (where no acetate end groups are observed), instead this more closely resembles the reactivity of DippNacNac-Zn alkoxide complexes in ROP (where RO end groups are observed). Additional major signals in the MALDI-ToF spectra were consistent with cyclic PCL species, which are attributed to back-biting ring-closing termination steps occuring in a process facilitated by the pyridonate unit being an effective leaving group. To the best of our knowledge, these complexes represent the first examples of pyridonate, and indeed amidate, initated ROP.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

ADVERTISEMENT RETURN TO ISSUEPREVViewpointNEXTMain Group Catalyzed Arene Borylation: Challenges and OpportunitiesMichael J. Ingleson*Michael J. InglesonEaStCHEM School of Chemistry, University of Edinburgh, Edinburgh EH9 3FJ, United Kingdom*Email: [email protected]More by Michael J. Inglesonhttps://orcid.org/0000-0001-9975-8302Cite this: ACS Catal. 2023, 13, 11, 7691–7697Publication Date (Web):May 23, 2023Publication History Received12 April 2023Published online23 May 2023Published inissue 2 June 2023https://doi.org/10.1021/acscatal.3c01668Copyright © 2023 The Author. Published by American Chemical SocietyRIGHTS & PERMISSIONSACS AuthorChoiceCC: Creative CommonsBY: Credit must be given to the creatorArticle Views1701Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (3 MB) Get e-AlertscloseSUBJECTS:Borylation,Electrophiles,Frustrated Lewis pairs,Functionalization,Hydrocarbons Get e-Alerts

Given the current interest in materials containing 1,4-azaborine units, the development of new routes to these structures is important. Carbonyl directed electrophilic borylation using BBr3 is a facile method for the ortho-borylation of N,N-diaryl-amide derivatives. Subsequent addition of Et3SiH results in carbonyl reduction and then formation of 1,4-azaborines that can be protected in situ using a Grignard reagent. Overall, borylation-reduction-borylation is a one-pot methodology to access 1,4-azaborines from simple precursors.

Doubly electrophilic pyrazabole derivatives (pyrazabole = [H2B(μ-C3N2H3)]2) combined with one equiv. of base effect the ortho-borylation of N-alkyl anilines. Initial studies found that the bis(trifluoromethane)sulfonimide ([NTf2]−) pyrazabole derivative, [H(NTf2)B(μ-C3N2H3)]2, is highly effective for ortho-borylation, with this process proceeding through N–H borylation and then ortho C–H borylation. The activation of pyrazabole by I2 was developed as a cheaper and simpler alternative to using HNTf2 as the activator. The addition of I2 forms mono or ditopic pyrazabole electrophiles dependent on stoichiometry. The ditopic electrophile [H(I)B(μ-C3N2H3)]2 was also effective for the ortho-borylation of N-alkyl-anilines, with the primary C–H borylation products readily transformed into pinacol boronate esters (BPin) derivatives. Comparison of borylation reactions using the di-NTf2-and the diiodo-pyrazabole congeners revealed that more forcing conditions are required with the latter. Furthermore, the presence of iodide leads to competitive formation of side products, including [HB(μ-C3N2H3)3BH]+, which are not active for C–H borylation. Using [H(I)B(μ-C3N2H3)]2 and 0.2 equiv. of [Et3NH][NTf2] combines the higher yields of the NTf2 system with the ease of handling and lower cost of the iodide system generating an attractive process applicable to a range of N-alkyl-anilines. This methodology represents a metal free and transiently directed C–H borylation approach to form N-alkyl-2-BPin-aniline derivatives.

Bromo-functionalized B1-polycyclic aromatic hydrocarbons (PAHs) with LUMOs of less than -3.0 eV were synthesized and used in cross-couplings to form donor-acceptor materials. These materials spanned a range of S1 energies, with a number showing thermally activated delayed fluorescence and significant emission in the near-infrared region of the spectrum. These B1-PAHs represent a useful family of acceptors that can be readily synthesized and functionalized.

Benzoxaborinines are intermediates en-route to bicyclic boronates that are important active pharmaceutical ingredients (APIs). Herein, the haloboration of o-alkynyl-phenols using BX3 (X=Cl or Br) is disclosed as a route to form C4-X-benzoxaborinines with good functional group tolerance. Computational studies indicated that there are two similar in barrier mechanisms: (i) double alkyne haloboration followed by retro-haloboration; (ii) concerted trans-haloboration involving an exogenous chloride source. The C4-halide in these benzoxaborinines is useful, with a one-pot haloboration-Negishi cross coupling protocol effective to form benzoxaborinines with an alkyl or an aryl at C4. Therefore this method is a useful addition to the toolbox for synthesising bicyclic-boronates that are attracting increasing attention as APIs.

Amide directed C-H borylation using ≥two equiv. of BBr3 forms borenium cations containing a R2N(R')C[double bond, length as m-dash]O→B(Ar)Br unit which has significant Lewis acidity at the carbonyl carbon. This enables reduction of the amide unit to an amine using hydrosilanes. This approach can be applied sequentially in a one-pot electrophilic borylation-reduction process, which for phenyl-acetylamides generates ortho borylated compounds that can be directly oxidised to the 2-(2-aminoethyl)-phenol. Other substrates amenable to the C-H borylation-reduction sequence include mono and diamino-arenes and carbazoles. This represents a simple method to make borylated molecules that would be convoluted to access otherwise (e.g. N-octyl-1-BPin-carbazole). Substituent variation is tolerated at boron as well as in the amide unit, with diarylborenium cations also amenable to reduction. This enables a double C-H borylation-reduction-hydrolysis sequence to access B,N-polycyclic aromatic hydrocarbons (PAHs), including an example where both the boron and nitrogen centres contain functionalisable handles (N-H and B-OH). This method is therefore a useful addition to the metal-free borylation toolbox for accessing useful intermediates (ArylBPin) and novel B,N-PAHs.

A simple, regioselective synthesis of di‐indole sulfides by electrophilic aromatic substitution of the C3‐position of indoles was achieved using Xtalfluor‐E as the sulfenylating reagent. The addition of amine bases was found to have a significant effect on the reaction outcome, with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) switching off the reactivity of XtalFluor‐E, while the hindered base 2,6‐di tert butyl‐4‐methylpyridine (DBP) led to the formation of two di‐indole‐sulfur containing products, one S(II) and one S(IV). The optimal base for accessing the di‐indole sulfides in high yield proved to be Hünigs base, EtN i Pr 2 . While this amine formed a Lewis adduct with XtalFluor‐E, adduct formation did not completely quench electrophilic reactivity indicating reversible coordination to the sulfur center. This is the first report utilizing XtalFluor‐E in electrophilic aromatic substitution to form C−S bonds to our knowledge, and this process is applicable to a wide range of functionalized indoles and does not require N1‐protection.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Pyrazabole ( 1 ) is a readily accessible diboron compound that can be transformed into ditopic electrophiles. In 1 (and derivatives), the B⋅⋅⋅B separation is ca. 3 Å, appropriate for one boron centre bonding to N and one to the C7 of indoles and indolines. This suitable B⋅⋅⋅B separation enables double E−H (E=N/C) functionalisation of indoles and indolines. Specifically, the activation of 1 with HNTf 2 generates an electrophile that transforms N−H indoles and indolines into N/C7-diborylated indolines, with N−H borylation directing subsequent C7−H borylation. Indole reduction to indoline occurs before C−H borylation and our studies indicate this proceeds via hydroboration—C3-protodeboronation to produce an intermediate that then undergoes C7 borylation. The borylated products can be converted in situ into C7-BPin-N-H-indolines. Overall, this represents a transient directed C−H borylation to form useful C7-BPin-indolines.

Helicenes are chiral polycyclic aromatic hydrocarbons (PAHs) of significant interest e.g. in supramolecular chemistry, materials science and asymmetric catalysis. Herein an enhanced N-directed electrophilic C-H borylation methodology has been developed that provides access to azaborine containing helicenes (BN-helicenes). This borylation process proceeds via protonation of an aminoborane with bistriflimidic acid. DFT calculations reveal the borenium cation formed by protonation to be more electrophilic than the product derived from aminoborane activation with BBr3. The synthesised helicenes include BN-analogues of archetypal all carbon [5]- and [6]helicenes. The replacement of a CC with a BN unit (that has a longer bond) on the outer helix increases the strain in the BN congeners and the racemization half-life for a BN-[5]helicene relative to the all carbon [5]helicene. BN incorporation also increases the fluorescence efficency of the helicenes, a direct effect of BN incorporation altering the distribution of the key frontier orbitals across the helical backbone relative to carbo-helicenes.