Transition Metal-Free Catalytic C-H Zincation and Alumination.

C-H metalation is the most efficient method to prepare aryl-zinc and -aluminium complexes that are ubiquitous nucleophiles. Virtually all C-H metalation routes to form Al/Zn organometallics require stoichiometric, strong Brønsted bases with no base-catalyzed reactions reported. Herein we present a catalytic in amine/ammonium salt (Et3N/[(Et3N)H]+) C-H metalation process to form aryl-zinc and aryl-aluminium complexes. Key to this approach is coupling an endergonic C-H metalation step with a sufficiently exergonic dehydrocoupling step between the ammonium salt by-product of C-H metalation ([(Et3N)H]+) and a Zn-H or Al-Me containing complex. This step, forming H2/MeH, makes the overall cycle exergonic while generating more of the reactive metal electrophile. Mechanistic studies supported by DFT calculations revealed metal-specific dehydrocoupling pathways, with the divergent reactivity due to the different metal valency (which impacts the accessibility of amine-free cationic metal complexes) and steric environment. Notably, dehydrocoupling in the zinc system proceeds through a ligand-mediated pathway involving protonation of the ß-diketiminate Cγ position. Given this process is applicable to two disparate metals (Zn and Al), other main group metals and ligand sets are expected to be amenable to this transition metal-free, catalytic C-H metalation.

Haloboration of o-Alkynyl Phenols Generates Halogenated Bicyclic-Boronates.

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.

Two Directing Groups Used for Metal Catalysed Meta-C-H Functionalisation Only Effect Ortho Electrophilic C-H Borylation.

Two templates used in meta-directed C-H functionalisation under metal catalysis do not direct meta-C-H borylation under electrophilic borylation conditions. Using BCl3 only Lewis adduct formation with Lewis basic sites in the template is observed. While combining BBr3 and the template containing an amide linker only led to amide directed ortho C-H borylation, with no pyridyl directed meta borylation. The amide directed borylation is selective for the ortho borylation of the aniline derived unit in the template, with no ortho borylation of the phenylacetyl ring - which would also form a six membered boracycle - observed. In the absence of other aromatics amide directed ortho borylation on to phenylacetyl rings can be achieved. The absence of meta-borylation using two templates indicates a higher barrier to pyridyl directed meta borylation relative to amide directed ortho borylation and suggests that bespoke templates for enabling meta-directed electrophilic borylation may be required.

Borylation Directed Borylation of Indoles Using Pyrazabole Electrophiles: A One-Pot Route to C7-Borylated-Indolines.

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 HNTf2 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.

Borylative cyclisation of diynes using BCl3 and borocations.

The borylative cyclisation of 1,2-dialkynyl benzenes with BCl3 leads to dibenzopentalenes (via intramolecular SEAr) or benzofulvenes (via chloride addition) depending on substituents, with stabilised vinyl cation intermediates (e.g. with a p-MeO-C6H4-group) favouring the latter. The use of borocations leads to more selective dibenzopentalene formation, while other diyne frameworks undergo intramolecular SEAr selectively even with p-MeO groups.

Acyl-Directed ortho-Borylation of Anilines and C7 Borylation of Indoles using just BBr3.

Indoles are privileged heterocycles found in many biologically active pharmaceuticals and natural products. However, the selective functionalization of the benzenoid moiety in indoles in preference to the more reactive pyrrolic unit is a significant challenge. Herein we report that N-acyl directing groups enable the C7-selective C-H borylation of indoles using just BBr3 . This transformation shows some functional-group tolerance and notably proceeds with C6 substituted indoles. The directing group can be readily removed in situ and the products isolated as the pinacol boronate esters. Acyl-directed electrophilic borylation can be extended to carbazoles and anilines with excellent ortho selectivity. 4-amino-indoles are amenable to this process, with acyl group installation and directed electrophilic C-H borylation enabling selective formation of C5-BPin-indoles.

C-H Borylation/Cross-Coupling Forms Twisted Donor-Acceptor Compounds Exhibiting Donor-Dependent Delayed Emission.

Benzothiadiazole (BT) directed C-H borylation using BCl3 , followed by B-Cl hydrolysis and Suzuki-Miyaura cross-coupling enables facile access to twisted donor-acceptor compounds. A subsequent second C-H borylation step provides, on arylation of boron, access to borylated highly twisted D-A compounds with a reduced bandgap, or on B-Cl hydrolysis/cross-coupling to twisted D-A-D compounds. Photophysical studies revealed that in this series there is long lifetime emission only when the donor is triphenylamine. Computational studies indicated that the key factor in observing the donor dependent long lifetime emission is the energy gap between the S1 /T2 excited states, which are predominantly intramolecular charge-transfer states, and the T1 excited state, which is predominantly a local excited state on the BT acceptor moiety.

Selective Boryl-Anion Migration in a Vinyl sp2 -sp3 Diborane Induced by Soft Borane Lewis Acids.

An intramolecular 1,2-boryl-anion migration from boron to carbon has been achieved by selective activation of the π system in [(vinyl)B2 Pin2 )]- using "soft" BR3 electrophiles (BR3 =BPh3 or 9-aryl-BBN). The soft character is key to ensure 1,2-migration proceeds instead of oxygen coordination/B-O activation. The BR3 -induced 1,2-boryl-anion migration represents a triple borylation of a vinyl Grignard reagent using only B2 Pin2 and BR3 and forms differentially protected 1,1,2-triborylated alkanes. Notably, by increasing the steric bulk at the ß position of the vinyl Grignard reagent used to activate B2 Pin2 , 1,2-boryl-anion migration can be suppressed in favor of intermolecular {BPin}- transfer to BPh3 , thus enabling simple access to unsymmetrical sp2 -sp3 diboranes.

Synthesis, Characterization, and Functionalization of 1-Boraphenalenes.

1-Boraphenalenes have been synthesized by reaction of BBr3 with 1-(aryl-ethynyl)naphthalenes, 1-ethynylnaphthalene, and 1-(pent-1-yn-1-yl)naphthalene and they can be selectively functionalized at boron or carbon to form bench-stable products. All of these 1-boraphenalenes have LUMOs localized on the planar C12 B core that are closely comparable in character to isoelectronic phenalenyl cations. In contrast to the comparable LUMOs, the aromatic stabilization of the C5 B ring in 1-boraphenalenes is dramatically lower than the C6 rings in phenalenyl cations. This is due to the occupied orbitals of π symmetry being less delocalised in the 1-boraphenalenes.

Diboryldiborenes: π-Conjugated B4 Chains Isoelectronic to the Butadiene Dication.

B(sp2 )-B(sp3 ) diborane species based on bis(catecholato)diboron and N-heterocyclic carbenes (NHCs) underwent catechol/bromide exchange selectively at the sp3 -hybridized boron atom. The reduction of the resulting 1,1-dibromodiborane adducts led to reductive coupling and isolation of doubly NHC-stabilized 1,2-diboryldiborenes. These compounds are the first examples of molecules exhibiting π-electron delocalization over an all-boron chain.

Expanding Water/Base Tolerant Frustrated Lewis Pair Chemistry to Alkylamines Enables Broad Scope Reductive Aminations.

Lower Lewis acidity boranes demonstrate greater tolerance to combinations of water/strong Brønsted bases than B(C6 F5 )3 , this enables Si-H bond activation by a frustrated Lewis pair (FLP) mechanism to proceed in the presence of H2 O/alkylamines. Specifically, BPh3 has improved water tolerance in the presence of alkylamines as the Brønsted acidic adduct H2 O-BPh3 does not undergo irreversible deprotonation with aliphatic amines in contrast to H2 O-B(C6 F5 )3 . Therefore BPh3 is a catalyst for the reductive amination of aldehydes and ketones with alkylamines using silanes as reductants. A range of amines inaccessible using B(C6 F5 )3 as catalyst, were accessible by reductive amination catalysed by BPh3 via an operationally simple methodology requiring no purification of BPh3 or reagents/solvent. BPh3 has a complementary reductive amination scope to B(C6 F5 )3 with the former not an effective catalyst for the reductive amination of arylamines, while the latter is not an effective catalyst for the reductive amination of alkylamines. This disparity is due to the different pKa values of the water-borane adducts and the greater susceptibility of BPh3 species towards protodeboronation. An understanding of the deactivation processes occurring using B(C6 F5 )3 and BPh3 as reductive amination catalysts led to the identification of a third triarylborane, B(3,5-Cl2 C6 H3 )3 , that has a broader substrate scope being able to catalyse the reductive amination of both aryl and alkyl amines with carbonyls.

N-Methyl-Benzothiazolium Salts as Carbon Lewis Acids for Si-H σ-Bond Activation and Catalytic (De)hydrosilylation.

N-Me-Benzothiazolium salts are introduced as a new family of Lewis acids able to activate Si-H σ bonds. These carbon-centred Lewis acids were demonstrated to have comparable Lewis acidity towards hydride as found for the triarylboranes widely used in Si-H σ-bond activation. However, they display low Lewis acidity towards hard Lewis bases such as Et3 PO and H2 O in contrast to triarylboranes. The N-Me-benzothiazolium salts are effective catalysts for a range of hydrosilylation and dehydrosilylation reactions. Judicious selection of the C2 aryl substituent in these cations enables tuning of the steric and electronic environment around the electrophilic centre to generate more active catalysts. Finally, related benzoxazolium and benzimidazolium salts were found also to be active for Si-H bond activation and as catalysts for the hydrosilylation of imines.

Catalytic Electrophilic C-H Borylation Using NHC⋠Boranes and Iodine Forms C2-, not C3-, Borylated Indoles.

Activation of N-heterocyclic carbene boranes (NHC⋅BH3 ) by I2 enables the metal-free catalytic C-H borylation of heteroarenes with formation of H2 as the by-product in a process that uses only bench stable precursors. The borylation of indoles using NHC⋅BH3 /I2 produces C2-borylated indoles exclusively in contrast to other catalytic electrophilic C-H borylation methods. Mechanistic studies indicate that this is due to C3 to C2 boron migration facilitated by the absence of exogenous Brønsted bases. Thus this C-H borylation methodology proceeds under sufficiently Brønsted acidic conditions to enable the thermodynamic C2-borylated indole isomer to be formed instead of the C3 borylated-isomer. This demonstrates that electrophilic C-H borylation can be used to access a wider range of borylated regioisomers than reported to date.

A Zinc Catalyzed C(sp3 )-C(sp2 ) Suzuki-Miyaura Cross-Coupling Reaction Mediated by Aryl-Zincates.

The Suzuki-Miyaura (SM) reaction is one of the most important methods for C-C bond formation in chemical synthesis. In this communication, we show for the first time that the low toxicity, inexpensive element zinc is able to catalyze SM reactions. The cross-coupling of benzyl bromides with aryl borates is catalyzed by ZnBr2 , in a process that is free from added ligand, and is compatible with a range of functionalized benzyl bromides and arylboronic acid pinacol esters. Initial mechanistic investigations indicate that the selective in situ formation of triaryl zincates is crucial to promote selective cross-coupling reactivity, which is facilitated by employing an arylborate of optimal nucleophilicity.

BCl3 -Induced Annulative Oxo- and Thioboration for the Formation of C3-Borylated Benzofurans and Benzothiophenes.

BCl3 -induced borylative cyclization of aryl-alkynes possessing ortho-EMe (E=S, O) groups represents a simple, metal-free method for the formation of C3-borylated benzothiophenes and benzofurans. The dichloro(heteroaryl)borane primary products can be protected to form synthetically ubiquitous pinacol boronate esters or used in situ in Suzuki-Miyaura cross couplings to generate 2,3-disubstituted heteroarenes from simple alkyne precursors in one pot. In a number of cases alkyne trans-haloboration occurs alongside, or instead of, borylative cyclization and the factors controlling the reaction outcome are determined.

Frustrated Lewis Pair Mediated 1,2-Hydrocarbation of Alkynes.

Frustrated Lewis pair (FLP) chemistry enables a rare example of alkyne 1,2-hydrocarbation with N-methylacridinium salts as the carbon Lewis acid. This 1,2-hydrocarbation process does not proceed through a concerted mechanism as in alkyne syn-hydroboration, or through an intramolecular 1,3-hydride migration as operates in the only other reported alkyne 1,2-hydrocarbation reaction. Instead, in this study, alkyne 1,2-hydrocarbation proceeds by a novel mechanism involving alkyne dehydrocarbation with a carbon Lewis acid based FLP to form the new C-C bond. Subsequently, intermolecular hydride transfer occurs, with the Lewis acid component of the FLP acting as a hydride shuttle that enables alkyne 1,2-hydrocarbation.

A General Protocol for the Polycondensation of Thienyl N-Methyliminodiacetic Acid Boronate Esters To Form High Molecular Weight Copolymers.

Thienyl di-N-methyliminodiacetic acid (MIDA) boronate esters are readily synthesized by electrophilic C-H borylation producing bench stable crystalline solids in good yield and excellent purity. Optimal conditions for the slow release of the boronic acid using KOH as the base in biphasic THF/water mixtures enables the thienyl MIDA boronate esters to be extremely effective homo-bifunctionalized (AA-type) monomers in Suzuki-Miyaura copolymerizations with dibromo-heteroarenes (BB-type monomers). A single polymerization protocol is applicable for the formation of five alternating thienyl copolymers that are (or are close analogues of) state of the art materials used in organic electronics. The five polymers were produced in excellent yields and with high molecular weights comparable to those produced using Stille copolymerization protocols. Therefore, thienyl di-MIDA boronate esters represent bench stable and low toxicity alternatives to highly toxic di-trimethylstannyl AA-type monomers that are currently ubiquitous in the synthesis of these important alternating copolymers.

Highly Emissive Far Red/Near-IR Fluorophores Based on Borylated Fluorene-Benzothiadiazole Donor-Acceptor Materials.

Stille, Suzuki-Miyaura and Negishi cross-coupling reactions of bromine-functionalised borylated precursors enable the facile, high yielding, synthesis of borylated donor-acceptor materials that contain electron-rich aromatic units and/or extended effective conjugation lengths. These materials have large Stokes shifts, low LUMO energies, small band-gaps and significant fluorescence emission >700 nm in solution and when dispersed in a host polymer.

Room temperature ring expansion of N-heterocyclic carbenes and B-B bond cleavage of diboron(4) compounds.

We report the isolation and detailed structural characterization, by solid-state and solution NMR spectroscopy, of the neutral mono- and bis-NHC adducts of bis(catecholato)diboron (B2 cat2 ). The bis-NHC adduct undergoes thermally induced rearrangement, forming a six-membered -B-C=N-C=C-N-heterocyclic ring via C-N bond cleavage and ring expansion of the NHC, whereas the mono-NHC adduct is stable. Bis(neopentylglycolato)diboron (B2 neop2 ) is much more reactive than B2 cat2 giving a ring expanded product at room temperature, demonstrating that ring expansion of NHCs can be a very facile process with significant implications for their use in catalysis.