Lewis Acid Directed Regioselective Metalations of Pyridazine

Mono‐ or bidentate boron Lewis acids trigger a regioselective magnesiation or zincation of pyridazine in position C3 (ortho product) or C4 (meta product). The regioselectivity of the metalation was rationalized with the help of calculated pK_a values of both pyridazine and pyridazine/Lewis acid complexes.     

Electrophilic Fluorophosphonium Cations in Frustrated Lewis Pair Hydrogen Activation and Catalytic Hydrogenation of Olefins

The combination of phosphorus(V)‐based Lewis acids with diaryl amines and diaryl silylamines promotes reversible activation of dihydrogen and can be further exploited in metal‐free catalytic olefin hydrogenation. Combined experimental and density functional theory (DFT) studies suggest a frustrated Lewis pair type activation mechanism.     

Lewis Superacidic Tellurenyl Cation-Induced Electrophilic Activation of an Inert Carborane

The aryltellurenyl cation [2-(tBuNCH)C₆H₄Te]⁺, a Lewis super acid, and the weakly coordinating carborane anion [CB₁₁H₁₂]⁻, an extremely weak Brønsted acid (pK_a=131.0 in MeCN), form an isolable ion pair complex [2-(tBuNCH)C₆H₄Te][CB₁₁H₁₂], in which the Brønsted acidity (pK_a 7.4 in MeCN) of the formally hydridic B−H bonds is dramatically increased by more than 120 orders of magnitude. The electrophilic activation of B−H bonds in the carborane moiety gives rise to a proton transfer from boron to nitrogen at slightly elevated temperatures, as rationalized by the isolation of a mixture of the zwitterionic isomers 12- and 7-[2-(tBuN{H}CH)C₆H₄Te(CB₁₁H₁₁)] in ratios ranging from 62 : 38 to 80 : 20.     

Regioselective Magnesiation and Zincation Reactions of Aromatics and Heterocycles Triggered by Lewis Acids

Mixed TMP-bases (TMP=2,2,6,6-tetramethylpiperidyl), such as TMPMgCl ⋅ LiCl, TMP₂Mg ⋅ 2LiCl, TMPZnCl ⋅ LiCl and TMP₂Zn ⋅ 2LiCl, are outstanding reagents for the metalation of functionalized aromatics and heterocycles. In the presence of Lewis acids, such as BF₃ ⋅ OEt₂ or MgCl₂, the metalation scope of such bases was dramatically increased, and regioselectivity switches were achieved in the presence or absence of these Lewis acids. Furthermore, highly reactive lithium bases, such as TMPLi or Cy₂NLi, are also compatible with various Lewis acids, such as MgCl₂ ⋅ 2LiCl, ZnCl₂ ⋅ 2LiCl or CuCN ⋅ 2LiCl. Performing such metalations in continuous flow using commercial setups permitted practical and convenient reaction conditions.     

Structure and dynamic features of an intramolecular frustrated Lewis pair

Di(mesityl)cyclohexenylphosphine undergoes hydroboration with Piers' borane [HB(C₆F₅)₂] to yield the cyclohexylene‐anellated frustrated Lewis pair 5 . This P/B pair splits H₂ with the formation of the product 4 and adds to the C?O double bond of phenyl isocyanate to yield 6 . In the crystal, compound 5 features a puckered four‐membered heterocyclic core structure with a long P? B bond (av. 2.197(5) Å). The activation energy of the P? B cleavage of the frustrated Lewis pair 5 was determined by dynamic ¹⁹F NMR spectroscopy at ΔG^≠(298 K)=12.1±0.3 kcal mol^?1.     

Planar N‐Heterocyclic Carbene Diarylborenium Ions: Synthesis by Cationic Borylation and Reactivity with Lewis Bases

The NHC–borane adduct (IBn)BH₃ ( 1 ) (NHC= N‐heterocyclic carbene; IBn=1,3‐dibenzylimidazol‐2ylidene) reacts with [Ph₃C][B(C₆F₅)₄] through sequential hydride abstraction and dehydrogenative cationic borylation(s) to give singly or doubly ring closed NHC–borenium salts 2 and 3 . The planar doubly ring closed product [C₃H₂(NCH₂C₆H₄)₂B][B(C₆F₅)₄] is resistant to quaternization at boron by Et₂O coordination, but forms classical Lewis acid–base adducts with the stronger donors Ph₃P, Et₃PO, or 1,4‐diazabicyclo[2.2.2]octane (DABCO). Treatment of 3 with tBu₃P selectively yields the unusual oligomeric borenium salt trans‐[(C₃H₂(NCH₂C₆H₄)₂B)₂(C₃H₂(NCHC₆H₄)₂B)][B(C₆F₅)₄] ( 7 ).     

Functionalization of Intramolecular Frustrated Lewis Pairs by 1,1‐Carboboration with Conjugated Enynes

The vicinal P/B frustrated Lewis pair (FLP) Mes₂PCH₂CH₂B(C₆F₅)₂ undergoes 1,1‐carboboration reactions with the Me₃Si‐substituted enynes to give ring‐enlarged functionalized C₃‐bridged P/B FLPs. These serve as active FLPs in the activation of dihydrogen to give the respective zwitterionic [P]H⁺/[B]H^? products. One such product shows activity as a metal‐free catalyst for the hydrogenation of enamines or a bulky imine. The ring‐enlarged FLPs contain dienylborane functionalities that undergo “bora‐Nazarov”‐type ring‐closing rearrangements upon photolysis. A DFT study had shown that the dienylborane cyclization of such systems itself is endothermic, but a subsequent C₆F₅ migration is very favorable. Furthermore, substituted 2,5‐dihydroborole products are derived from cyclization and C₆F₅ migration from the photolysis reaction. In the case of the six‐membered annulation product, a subsequent stereoisomerization reaction takes place and the resultant compound undergoes a P/B FLP 1,2‐addition reaction with a terminal alkyne with rearrangement.     

Frustrated Lewis Pair Chemistry: Searching for New Reactions

Frustrated Lewis pair chemistry has taken a steep development in the recent years. It offers possibilities of developing new variants of known reactions and of finding new chemical transformations. This is demonstrated and described by the recently developed FLP‐formylborane chemistry, which has led to the formation of the unique (η²‐formylborane)FLP adducts and opened a way of preparing a genuine formylborane compound, which shows an interesting follow‐up chemistry. FLPs have helped finding phosphorus analogues of the enamine Stork reaction and the Claisen reaction. These reactions lead to new organophosphorus compounds and they make new phosphane/borane systems available. P/B FLPs add to a variety of small main group element oxides. They undergo 1,2‐addition reactions to CO₂, SO₂ and other heterocumulenes and they feature unique 1,1‐addition reactions to carbon monoxide, to isonitriles and even to nitric oxide (NO), the latter yielding examples of a new class of persistent nitroxide radicals, the FLPNO nitroxyls. Eventually, some remarkable radical reactions of FLPs and related compounds are briefly mentioned.     

Formylborane Formation with Frustrated Lewis Pair Templates

Boranes R₂BH react with carbon monoxide by forming the respective borane carbonyl compounds R₂BH(CO). The formation of (C₆F₅)₂BH(CO) derived from the Piers borane, HB(C₆F₅)₂, is a typical example. Subsequent CO‐hydroboration does not take place, since the formation of the formylborane is usually endothermic. However, an “η²‐formylborane” was formed by CO‐hydroboration with the Piers borane at vicinal phosphane/borane frustrated Lewis pair (FLP) templates. Subsequent treatment with pyridine liberated the intact formylborane from the FLP framework, and (pyridine)(C₆F₅)₂B? CHO was then isolated as a stable compound. This product underwent typical reactions of carbonyl compounds, such as Wittig olefination.     

Enhancing the Acceptor Character of Conjugated Organoborane Macrocycles: A Highly Electron-Deficient Hexaboracyclophane

We introduce a new boron-doped cyclophane, the hexabora[1₆]cyclophane B6-^FMes , in which six tricoordinate borane moieties alternate with short conjugated p-phenylene linkers. Exocyclic 2,4,6-tris(trifluoromethyl)phenyl (^FMes) groups serve not only to further withdraw electron density but at the same time sterically shield the boron atoms, resulting in a macrocycle that is both highly electron-deficient and stable. The optical and electronic properties are compared with those of related linear oligomers and the electronic structure is further evaluated by computational methods. The studies uncover unique properties of B6-^FMes , including a low-lying and extensively delocalized LUMO and a wide HOMO–LUMO gap, which arise from the combination of a cyclic π-system, strong electronic communication between the closely spaced borons, and the attachment of electron-deficient pendent groups. The binding of small anions to the electron-deficient macrocycle and molecular model compounds is investigated and emissive exciplexes are detected in aromatic solvents.     

Formation of Active Cyclic Five-membered Frustrated Phosphane/Borane Lewis Pairs and their Cycloaddition Reactions

The cyclic five-membered frustrated phosphane/borane Lewis pairs 11 a , b featuring the bulky octaethylhydrindacenyl- (Eind) substituent or its mono-bromo derivative (^BrEind) at phosphorus are monomeric at room temperature. The reactive frustrated Lewis pairs (FLPs) cleave dihydrogen. The cyclic FLP 11 b (^BrEind) undergoes 1,2-P/B addition to ethylene to give the zwitterionic heteronorbornane derivative 14 b . It reacts similarly with the carbon–carbon double bond of norbornene. With a variety of organic π-reagents, the cyclic FLP 11 b often undergoes reaction sequences reminiscent of the Alder–Rickert reaction: the cycloaddition reaction is followed by rapid cycloreversion to form new five-membered heterocyclic FLP products with extrusion of ethene. Reactions of 11 b with benzaldehyde or with acetylenes follow this reaction pattern.     

Enhancing the Acceptor Character of Conjugated Organoborane Macrocycles: A Highly Electron‐Deficient Hexaboracyclophane

We introduce a new boron‐doped cyclophane, the hexabora[1₆]cyclophane B6‐^FMes , in which six tricoordinate borane moieties alternate with short conjugated p‐phenylene linkers. Exocyclic 2,4,6‐tris(trifluoromethyl)phenyl (^FMes) groups serve not only to further withdraw electron density but at the same time sterically shield the boron atoms, resulting in a macrocycle that is both highly electron‐deficient and stable. The optical and electronic properties are compared with those of related linear oligomers and the electronic structure is further evaluated by computational methods. The studies uncover unique properties of B6‐^FMes , including a low‐lying and extensively delocalized LUMO and a wide HOMO–LUMO gap, which arise from the combination of a cyclic π‐system, strong electronic communication between the closely spaced borons, and the attachment of electron‐deficient pendent groups. The binding of small anions to the electron‐deficient macrocycle and molecular model compounds is investigated and emissive exciplexes are detected in aromatic solvents.     

α‐Hydroxymethylation of Pyridines at a Frustrated Lewis Pair Template

The “η²‐formylborane” moiety formed by CO reduction with HB(C₆F₅)₂ at a P/B frustrated Lewis pair template undergoes a hydroxymethylation reaction at the α‐position to nitrogen in pyridine or isoquinoline. The analogous reaction with pyrimidine revealed a mechanism related to the Tschitschibabin reaction.     

Frustrated Lewis Pair Chemistry of Chiral (+)‐Camphor‐Based Aminoboranes

Dimethylamino‐(+)‐camphorenamine reacted with an equimolar amount of Piers’ borane, HB(C₆F₅)₂, to give the corresponding iminium–hydroborate zwitterionic salt. Being in equilibrium with the parent enamine–HB(C₆F₅)₂ N–B pair, this salt was able to split hydrogen heterolytically, hydrogenating the iminium group in the molecule. Detailed studies revealed that the hydrogen splitting in this reaction proceeded through an intermolecular pathway leading to a bornylamine–HB(C₆F₅)₂ adduct. When the starting enamine is present in excess over HB(C₆F₅)₂, the produced bornylamine–HB(C₆F₅)₂ adduct breaks up, eliminating free bornylamine and forming the initial camphorenamine– HB(C₆F₅)₂ pair. This results in hydrogenation of the camphorenamine framework in a catalytic fashion.     

Coupling of Carbon Monoxide with Nitrogen Monoxide at a Frustrated Lewis Pair Template

Coupling of carbon monoxide with nitrogen monoxide was achieved at a frustrated Lewis pair template. This unique reaction uses hydride as an auxiliary, which reductively activates carbon monoxide at the frustrated Lewis pair. The CO/NO coupling reaction then takes place through a pathway involving a radical reaction in which the hydrogen atom auxiliary is eventually removed again.     

Direct Mannich‐Type Reactions Promoted by Frustrated Lewis Acid/Brønsted Base Catalysts

Direct Mannich‐type reactions that afford both α‐ and β‐amino esters by the reaction of a broad range of carbonyl compounds and aldimines are disclosed. The transformation is promoted by a sterically frustrated Lewis acid/Brønsted base pair, which is proposed to operate cooperatively: Within the catalyst complex, an enolate is generated that then reacts with a hydrogen‐bond‐activated imine. Noncovalent interactions between reactants and the catalyst provide selectivity and new opportunities for future catalyst design.     

Methylene Bridging Effect on the Structures,Lewis Acidities and Optical Properties of Semi-planar Triarylboranes

Three synthetic methods towards semi-planar triarylboranes with two aryl rings connected by a methylene bridge have been developed. The fine-tuning of their stereoelectronic properties and Lewis acidities was achieved by introducing fluorine, methyl, methoxy, n-butyl and phenyl groups either at their exocyclic or bridged aryl rings. X-ray diffraction analysis and quantum-chemical calculations provided quantitative information on the structural distortion experienced by the near planar hydro-boraanthracene skeleton during the association with Lewis bases such as NH₃ and F⁻. Though the methylene bridge between the ortho-positions of two aryl rings of triarylboranes decreased the Gibbs free energies of complexation with small Lewis bases by less than 5 kJ mol⁻¹ relative to the classical Lewis acid BAr₃, the steric shielding of the CH₂ bridge is sufficient to avoid the formation of Lewis adducts with larger Lewis bases such as triarylphosphines. A newly synthesized spirocyclic amino-borane with a long intramolecular B−N bond that could be dissociated under thermal process, UV-irradiation, or acidic conditions might be a potential candidate in Lewis pairs catalysis.     

Using the Secondary PH/BH Functional Groups of an Active Geminal Frustrated Lewis Pair for Carbon Monoxide Reduction and Reactions with Nitriles and Isonitriles

Reaction of the secondary alkynyl(Mes*)PH phosphane 2 with (Fmes)BH₂?SMe₂ gives the geminal PH/BH frustrated Lewis pair (FLP) 3 . The PH and the BH functions are jointly used in the reduction of carbon monoxide under mild reaction conditions to give the [P]‐CH₂‐O‐[B] product. A subsequent cycloaddition sequence results in the liberation of formaldehyde. The FLP 3 reacts with benzonitrile to give a P‐benzamidine, and it couples two isonitriles at the FLP framework.