Catalytic Regioselective Isomerization of 2,2-Disubstituted Oxetanes to Homoallylic Alcohols

The selective isomerization of strained heterocyclic compounds is an important tool in organic synthesis. An unprecedented regioselective isomerization of 2,2-disubstituted oxetanes into homoallylic alcohols is described. The use of tris(pentafluorophenyl)borane (B(C₆F₅)₃)_, a commercially available Lewis acid was key to obtaining good yields and selectivities since other Lewis acids afforded mixtures of isomers and substantial polymerization. The reaction took place under exceptionally mild reaction conditions and very low catalyst loading (0.5 mol %). DFT calculations disclose the mechanistic features of the isomerization and account for the high selectivity displayed by the B(C₆F₅)₃ catalyst. The synthetic applicability of the new reaction is demonstrated by the preparation of γ-chiral alcohols using iridium-catalyzed asymmetric hydrogenation.     

B(C6F5)3‐Catalyzed Transfer Hydrogenation of Imines and Related Heteroarenes Using Cyclohexa‐1,4‐dienes as a Dihydrogen Source

The strong boron Lewis acid tris(pentafluorophenyl)borane, B(C₆F₅)₃, is shown to abstract a hydride from suitably donor‐substituted cyclohexa‐1,4‐dienes, eventually releasing dihydrogen. This process is coupled with the FLP‐type (FLP=frustrated Lewis pair) hydrogenation of imines and nitrogen‐containing heteroarenes that are catalyzed by the same Lewis acid. The net reaction is a B(C₆F₅)₃‐catalyzed, i.e., transition‐metal‐free, transfer hydrogenation using easy‐to‐access cyclohexa‐1,4‐dienes as reducing agents. Competing reaction pathways with or without the involvement of free dihydrogen are discussed.     

The B(C6F5)3 Boron Lewis Acid Route to Arene‐Annulated Pentalenes

4,5‐Dimethyl‐1,2‐bis(1‐naphthylethynyl)benzene ( 12 ) undergoes a rapid multiple ring‐closure reaction upon treatment with the strong boron Lewis acid B(C₆F₅)₃ to yield the multiply annulated, planar conjugated π‐system 13 (50 % yield). In the course of this reaction, a C₆F₅ group was transferred from boron to carbon. Treatment of 12 with CH₃B(C₆F₅)₂ proceeded similarly, giving a mixture of 13 (C₆F₅‐transfer) and the product 15 , which was formed by CH₃‐group transfer. 1,2‐Bis(phenylethynyl)benzene ( 8 a ) reacts similarly with CH₃B(C₆F₅)₂ to yield a mixture of the respective C₆F₅‐ and CH₃‐substituted dibenzopentalenes 10 a and 16 . The reaction is thought to proceed through zwitterionic intermediates that exhibit vinyl cation reactivities. Some B(C₆F₅)₃‐substituted species ( 26 , 27 ) consequently formed by in situ deprotonation upon treatment of the respective 1,2‐bis(alkynyl)benzene starting materials ( 24 , 8 ) with the frustrated Lewis pair B(C₆F₅)₃/P(o‐tolyl)₃. The overall formation of the C₆F₅‐substituted products formally require HB(C₆F₅)₂ cleavage in an intermediate dehydroboration step. This was confirmed in the reaction of a thienylethynyl‐containing starting material 21 with B(C₆F₅)₃, which gave the respective annulated pentalene product 23 that had the HB(C₆F₅)₂ moiety 1,4‐added to its thiophene ring. Compounds 12 – 14 , 23 , and 26 were characterized by X‐ray diffraction.     

Borohydrides from Organic Hydrides: Reactions of Hantzsch’s Esters with B(C6F5)3

We report herein that the reaction between a series of Hantzsch’s ester analogues 1 a – d with the Lewis acidic species B(C₆F₅)₃ results in facile transfer of hydride to boron. The main products of this reaction are pyridinium borohydride salts 2 a – d , which are obtained in high to moderate yields. The N‐substituted substrates (N‐Me, N‐Ph) reacted in high yield 90–98 % and the connectivity of the products were confirmed by an X‐ray crystallographic analysis of the N‐Me borohydride salt 2 a . Unsubstituted Hanztsch’s ester 1 a reacted less effectively generating only 60 % of the corresponding borohydride salt, with the balance of the material sequestered as the ester‐bound Lewis acid–base adduct 3 a . Formation of the Lewis acid–base adduct could be minimized by increasing the steric bulk about the ester groups as in 1 d . The connectivity of the carbonyl‐bound adduct was confirmed by an X‐ray crystallographic analysis of 3 e the product of the reaction of methyl ketone 1 e with B(C₆F₅)₃. We also explored the generation of these pyridinium salts by employing frustrated Lewis pair methodology. However, the reaction of mixtures of the corresponding pyridine and B(C₆F₅)₃ with hydrogen gas only resulted in formation of trace amounts of the pyridinium borohydride, along with the Lewis acid–base adduct of the starting material and B(C₆F₅)₃. The 1,2‐dihydropyridine adduct was the final product of this reaction. This was ascribed to the low basicity of the pyridine nitrogen and the complicating formation of an ester bound Lewis acid–base adduct.     

Effects of tris(pentafluorophenyl)borane on the activation of a metal alkyl‐free Ni‐based catalyst in the polymerization of 1,3‐butadiene

The activation of a metal alkyl‐free Ni‐based catalyst with B(C₆F₅)₃ was investigated in the polymerization of 1,3‐butadiene. A catalyst of bis(1,5‐cyclooctadiene)nickel (Ni(COD)₂)/B(C₆F₅)₃ was found to have high catalytic activity and 1,4‐cis stereoregularity. The catalyst was also found to provide polybutadiene having a molecular weight (M_w) of up to 117,000, even in the absence of AlR₃ and MAO. Variations in the mol ratio of B(C₆F₅)₃ to Ni affected catalytic activity, 1,4‐cis stereoregularity, and the M_w of polybutadiene, while the molecular weight distribution (MWD) of polybutadiene showed little correlation with the mol ratio of B(C₆F₅)₃ to Ni. The use of other borane compounds such as B(C₆H₅)₃, BEt₃, and BF₃ etherate in place of B(C₆F₅)₃ clearly showed the two main functions of B(C₆F₅)₃ in the present catalyst. The high Lewis acidity of B(C₆F₅)₃ enabled it to activate catalytic complexes, thus inducing the polymerization. The steric bulkiness of B(C₆F₅)₃ suppressed chain transfer reactions, contributing to the production of polybutadiene with a high M_w. Kinetic studies showed that the catalyst had an induction period, possibly due to the time needed for the formation of catalytic complexes starting from Ni(COD)₂. A plot of ?ln (1?X), where X is the fractional conversion, as a function of time resulted in a linear relationship, showing that the present catalyst system followed first‐order kinetics with respect to monomer concentration. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1164–1173, 2004     

A Combined “Electrochemical–Frustrated Lewis Pair” Approach to Hydrogen Activation: Surface Catalytic Effects at Platinum Electrodes

Herein, we extend our “combined electrochemical–frustrated Lewis pair” approach to include Pt electrode surfaces for the first time. We found that the voltammetric response of an electrochemical–frustrated Lewis pair (FLP) system involving the B(C₆F₅)₃/[HB(C₆F₅)₃]^? redox couple exhibits a strong surface electrocatalytic effect at Pt electrodes. Using a combination of kinetic competition studies in the presence of a H atom scavenger, 6‐bromohexene, and by changing the steric bulk of the Lewis acid borane catalyst from B(C₆F₅)₃ to B(C₆Cl₅)₃, the mechanism of electrochemical–FLP reactions on Pt surfaces was shown to be dominated by hydrogen‐atom transfer (HAT) between Pt, [Pt?H] adatoms and transient [HB(C₆F₅)₃] ^? electrooxidation intermediates. These findings provide further insight into this new area of combining electrochemical and FLP reactions, and proffers additional avenues for exploration beyond energy generation, such as in electrosynthesis.     

Cyclisation versus 1,1‐Carboboration: Reactions of B(C6F5)3 with Propargyl Amides

A series of propargyl amides were prepared and their reactions with the Lewis acidic compound B(C₆F₅)₃ were investigated. These reactions were shown to afford novel heterocycles under mild conditions. The reaction of a variety of N‐substituted propargyl amides with B(C₆F₅)₃ led to an intramolecular oxo‐boration cyclisation reaction, which afforded the 5‐alkylidene‐4,5‐dihydrooxazolium borate species. Secondary propargyl amides gave oxazoles in B(C₆F₅)₃ mediated (catalytic) cyclisation reactions. In the special case of disubstitution adjacent to the nitrogen atom, 1,1‐carboboration is favoured as a result of the increased steric hindrance (1,3‐allylic strain) in the 5‐alkylidene‐4,5‐dihydrooxazolium borate species.     

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.     

Developing Phospha‐Stork Chemistry Induced by a Borane Lewis Acid

Bulky vinyl phosphanes undergo carbon–carbon coupling with aryl aldehydes with the help of the Lewis acid B(C₆F₅)₃ to give isolable methylene phosphonium products. Dimesityl(vinyl)phosphane undergoes a phospha‐Stork reaction with bulky enones efficiently catalyzed by B(C₆F₅)₃ to eventually yield the corresponding substituted cyclobutane products.     

Lewis Acid Coordination Redirects S‐Nitrosothiol Signaling Output

S‐Nitrosothiols (RSNOs) serve as air‐stable reservoirs for nitric oxide in biology. While copper enzymes promote NO release from RSNOs by serving as Lewis acids for intramolecular electron‐transfer, redox‐innocent Lewis acids separate these two functions to reveal the effect of coordination on structure and reactivity. The synthetic Lewis acid B(C₆F₅)₃ coordinates to the RSNO oxygen atom, leading to profound changes in the RSNO electronic structure and reactivity. Although RSNOs possess relatively negative reduction potentials, B(C₆F₅)₃ coordination increases their reduction potential by over 1 V into the physiologically accessible +0.1 V vs. NHE. Outer‐sphere chemical reduction gives the Lewis acid stabilized hyponitrite dianion trans‐[LA‐O‐N=N‐O‐LA]^2? [LA=B(C₆F₅)₃], which releases N₂O upon acidification. Mechanistic and computational studies support initial reduction to the [RSNO‐B(C₆F₅)₃] radical anion, which is susceptible to N?N coupling prior to loss of RSSR.     

B(C6F5)3/Chiral Phosphoric Acid Catalyzed Ketimine–Ene Reaction of 2‐Aryl‐3H‐indol‐3‐ones and α‐Methylstyrenes

The enantioselective ketimine–ene reaction is one of the most challenging stereocontrolled reaction types in organic synthesis. In this work, catalytic enantioselective ketimine–ene reactions of 2‐aryl‐3H‐indol‐3‐ones with α‐methylstyrenes were achieved by utilizing a B(C₆F₅)₃/chiral phosphoric acid (CPA) catalyst. These ketimine–ene reactions proceed well with low catalyst loading (B(C₆F₅)₃/CPA=2 mol %/2 mol %) under mild conditions, providing rapid and facile access to a series of functionalized 2‐allyl‐indolin‐3‐ones with very good reactivity (up to 99 % yield) and excellent enantioselectivity (up to 99 % ee). Theoretical calculations reveal that enhancement of the acidity of the chiral phosphoric acid by B(C₆F₅)₃ significantly reduces the activation free energy barrier. Furthermore, collective favorable hydrogen‐bonding interactions, especially the enhanced N?H???O hydrogen‐bonding interaction, differentiates the free energy of the transition states of CPA and B(C₆F₅)₃/CPA, thereby inducing the improvement of stereoselectivity.     

Exploring the Limits of Frustrated Lewis Pair Chemistry with Alkynes: Detection of a System that Favors 1,1‐Carboboration over Cooperative 1,2‐P/B‐Addition

The zirconocene complex [{(C₆F₅)₂B‐(CH₂)₃‐Cp}(Cp‐PtBu₂)ZrCl₂] ( 6 ; Cp=cyclo‐C₅H₄) was prepared by hydroboration of [(allyl‐Cp)(Cp‐PtBu₂)ZrCl₂] ( 5 ) with HB(C₆F₅)₂ (“Piers’ borane”). It represents a frustrated Lewis pair (FLP) in which both the Lewis acid and the Lewis base were attached at the metallocene framework. Its reaction with 1‐pentyne did not result in the 1,2‐addition of or deprotonation reaction by the FLP, but rather in the 1,1‐carboboration of the triple bond, thereby obtaining a Z/E mixture (1.2:1) of the respective organometallic substituted alkenes 7 . The analogous reaction of 1‐pentyne with the phosphorous‐free system [{(C₆F₅)₂B‐(CH₂)₃‐Cp)}CpZrCl₂] ( 9 ) gave the respective 1,1‐carboboration products ( Z‐10 / E‐10 ≈1.3:1).     

Synthesis of α-aryl nitriles through B(C6F5)3-catalyzed direct cyanation of α-aryl alcohols and thiols

Various α-aryl nitriles have been prepared in excellent yield from the corresponding α-aryl alcohols employing 3 mol % of B(C₆F₅)₃ (1) as Lewis acid catalyst and (CH₃)₃SiCN (TMSCN) as cyanide source. Cyano transfer from TMSCN to alcohol proceeds within short reaction time at rt. α-Aryl thiols also produce corresponding nitriles in good to excellent yield at reflux condition.     

Characterization of the Zwitterionic Intermediate in 1,1‐Carboboration of Alkynes

The reaction of a Lewis acidic borane with an alkyne is a key step in a diverse range of main group transformations. Alkyne 1,1‐carboboration, the Wrackmeyer reaction, is an archetypal transformation of this kind. 1,1‐Carboboration has been proposed to proceed through a zwitterionic intermediate. We report the isolation and spectroscopic, structural and computational characterization of the zwitterionic intermediates generated by reaction of B(C₆F₅)₃ with alkynes. The stepwise reactivity of the zwitterion provides new mechanistic insight for 1,1‐carboboration and wider B(C₆F₅)₃ catalysis. Making use of intramolecular stabilization by a ferrocene substituent, we have characterized the zwitterionic intermediate in the solid state and diverted reactivity towards alkyne cyclotrimerization.     

Reactivity of an Intramolecular Fluorophosphonium Fluoroborate

The reactions of the intramolecular frustrated Lewis pair‐adduct Ph₂PC(p‐Tol)?C(C₆F₅)B(C₆F₅)₂(CNtBu) with XeF₂ gave Ph₂P(F)C(p‐Tol)?C(C₆F₅)B(F)(C₆F₅)₂ ( 3 ). This species reacts with two equivalents of Al(C₆F₅)₃?C₇H₈ producing the salt, [Ph₂P(F)C(p‐Tol)?C(C₆F₅)B(C₆F₅)₂][F(Al(C₆F₅)₃)₂] ( 4 ), whereas reaction with HSiEt₃/B(C₆F₅)₃ gave Ph₂P(F)C(p‐Tol)?C(H)B(C₆F₅)₃ ( 5 ). The photolysis of 3 resulted in aromatization affording the phenanthralene derivative Ph₂P(F)C(p‐Tol(o‐C₆F₄))?CB(F)(C₆F₅)₂ ( 6 ).     

Methyl branching in polyethylene from homopolymerization of ethylene with N‐arylcyano‐β‐diketiminate methallyl nickel‐B(C6F5)3

N‐Arylcyano‐β‐diketiminate methallyl nickel complexes activated with B(C₆F₅)₃ were used in the polymerization of ethylene. The microstructure analysis of obtained polyethylene (PE) was done by differential scanning calorimetry and ¹³C nuclear magnetic resonance (NMR). The branched polymer structures produced by these catalysts were attributed to one step isomerization mechanism of the catalyst along the polymer chain. The ortho or para position of the cyano group with co‐ordinated B(C₆F₅)₃ in both methallyl nickel catalysts influenced the polymer molecular weight, branching, and consequently melting and crystallization temperatures. NMR spectroscopic studies showed predominantly the formation of methyl branches in the obtained PE. Catalysts under study gave linear low‐density PEs with good crystallinities at temperatures of reaction between 50 °C and 70 °C at moderate pressures (12.3 atm). A propylene–ethylene copolymer produced by the metallocene catalyst had the same concentration of branches as the PE synthesized from methallyl nickel/B(C₆F₅)₃. Comparing the two polyolefins with the same degree of branching, it was observed that the polymer obtained with the nickel catalyst proved to be twice more crystalline and had greater T_m. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 452–458     

1,1‐Hydroboration and a Borane Adduct of Diphenyldiazomethane: A Potential Prelude to FLP‐N2 Chemistry

Diphenyldiazomethane reacts with HB(C₆F₅)₂ and B(C₆F₅)₃, resulting in 1,1‐hydroboration and adduct formation, respectively. The hydroboration proceeds via a concerted reaction involving initial formation of the Lewis adduct Ph₂CN₂BH(C₆F₅)₂. The highly sensitive adduct Ph₂CN₂(B(C₆F₅)₃) liberates N₂ and generates Ph₂CB(C₆F₅)₃. DFT computations reveal that formation of Ph₂CN₂B(C₆F₅)₃ from carbene, N₂, and borane is thermodynamically favourable, suggesting steric frustration could preclude carbene–borane adduct formation and affect FLP‐N₂ capture.     

Autoinduced Catalysis and Inverse Equilibrium Isotope Effect in the Frustrated Lewis Pair Catalyzed Hydrogenation of Imines

The frustrated Lewis pair (FLP)‐catalyzed hydrogenation and deuteration of N‐benzylidene‐tert‐butylamine ( 2 ) was kinetically investigated by using the three boranes B(C₆F₅)₃ ( 1 ), B(2,4,6‐F₃‐C₆H₂)₃ ( 4 ), and B(2,6‐F₂‐C₆H₃)₃ ( 5 ) and the free activation energies for the H₂ activation by FLP were determined. Reactions catalyzed by the weaker Lewis acids 4 and 5 displayed autoinductive catalysis arising from a higher free activation energy (2 kcal mol^?1) for the H₂ activation by the imine compared to the amine. Surprisingly, the imine reduction using D₂ proceeded with higher rates. This phenomenon is unprecedented for FLP and resulted from a primary inverse equilibrium isotope effect.     

Stoichiometric and Catalytic C−C and C−H Bond Formation with B(C6F5)3 via Cationic Intermediates

This work showcases a new catalytic cyclization reaction using a highly Lewis acidic borane with concomitant C−H or C−C bond formation. The activation of alkyne‐containing substrates with B(C₆F₅)₃ enabled the first catalytic intramolecular cyclizations of carboxylic acid substrates using this Lewis acid. In addition, intramolecular cyclizations of esters enable C−C bond formation as catalytic B(C₆F₅)₃ can be used to effect formal 1,5‐alkyl migrations from the ester functional groups to unsaturated carbon–carbon frameworks. This metal‐free method was used for the catalytic formation of complex dihydropyrones and isocoumarins in very good yields under relatively mild conditions with excellent atom efficiency.     

Synthesis,Structure, and Reactivity of Diazene Adducts: Isolation of iso‐Diazene Stabilized as a Borane Adduct

This work describes the synthesis and full characterization of a series of GaCl₃ and B(C₆F₅)₃ adducts of diazenes R¹?N?N?R² (R¹=R²=Me₃Si, Ph; R¹=Me₃Si, R²=Ph). Trans‐Ph?N?N?Ph forms a stable adduct with GaCl₃, whereas no adduct, but instead a frustrated Lewis acid–base pair is formed with B(C₆F₅)₃. The cis‐Ph?N?N?Ph ? B(C₆F₅)₃ adduct could only be isolated when UV light was used, which triggers the isomerization from trans‐ to cis‐Ph?N?N?Ph, which provides more space for the bulky borane. Treatment of trans‐Ph?N?N?SiMe₃ with GaCl₃ led to the expected trans‐Ph?N?N?SiMe₃ ? GaCl₃ adduct but the reaction with B(C₆F₅)₃ triggered a 1,2‐Me₃Si shift, which resulted in the formation of a highly labile iso‐diazene, Me₃Si(Ph)N?N; stabilized as a B(C₆F₅)₃ adduct. Trans‐Me₃Si?N?N?SiMe₃ forms a labile cis‐Me₃Si?N?N?SiMe₃ ? B(C₆F₅)₃ adduct, which isomerizes to give the transient iso‐diazene species (Me₃Si)₂N?N ? B(C₆F₅)₃ upon heating. Both iso‐diazene species insert easily into one B?C bond of B(C₆F₅)₃ to afford hydrazinoboranes. All new compounds were fully characterized by means of X‐ray crystallography, vibrational spectroscopy, CHN analysis, and NMR spectroscopy. All compounds were further investigated by DFT and the bonding situation was assessed by natural bond orbital (NBO) analysis.