Palladium(0)‐Catalyzed Directed syn‐1,2‐Carboboration and ‐Silylation: Alkene Scope,Applications in Dearomatization,and Stereocontrol by a Chiral Auxiliary

We report the development of palladium(0)‐catalyzed syn‐selective 1,2‐carboboration and ‐silylation reactions of alkenes containing cleavable directing groups. With B₂pin₂ or PhMe₂Si‐Bpin as nucleophiles and aryl/alkenyl triflates as electrophiles, a broad range of mono‐, di‐, tri‐ and tetrasubstituted alkenes are compatible in these transformations. We further describe a directed dearomative 1,2‐carboboration of electron‐rich heteroarenes by employing this approach. Through use of a removable chiral directing group, we demonstrate the viability of achieving stereoinduction in Heck‐type alkene 1,2‐difunctionalization. This work introduces new avenues to access highly functionalized boronates and silanes with precise regio‐ and stereocontrol.     

A Stable but Highly Reactive Phosphine‐Coordinated Borenium: Metal‐free Dihydrogen Activation and Alkyne 1,2‐Carboboration

Borenium cations have been found to be valuable analogues of boranes as a result of their cationic character which imparts high electrophilicity. Herein, we report the synthesis, characterization, and reactivity of a new type of borenium cation employing a naphthyl bridge and a strong intramolecular P→B interaction. The cation reacts with H₂ in the presence of PtBu₃ (frustrated Lewis pair (FLP) approach) but also on its own. The mechanism of the reaction between the borenium cation and H₂ in the absence of PtBu₃ has been investigated using deuterium‐labeling experiments and DFT calculations. Both experiments and calculations imply the side‐on coordination of H₂ to the B center, followed by heterolytic splitting and B? C bond cleavage. An uncommon syn 1,2‐carboboration has also been observed upon reaction of the borenium ion with 3‐hexyne.     

Iron‐Catalyzed Diboration and Carboboration of Alkynes

An iron‐catalyzed diboration reaction of alkynes with bis(pinacolato)diboron (B₂pin₂) and external borating agents (MeOB(OR)₂) affords diverse symmetrical or unsymmetrical cis‐1,2‐diborylalkenes. The simple protocol for the diboration reaction can be extended to the iron‐catalyzed carboboration of alkynes with primary and, unprecedentedly, secondary alkyl halides, affording various tetrasubstituted monoborylalkenes in a highly stereoselective manner. DFT calculations indicate that a boryliron intermediate adds across the triple bond of an alkyne to afford an alkenyliron intermediate, which can react with the external trapping agents, borates and alkyl halides. In situ trapping experiments support the intermediacy of the alkenyl iron species using radical probe stubstrates.     

Copper/Palladium Synergistic Catalysis for the syn‐ and anti‐Selective Carboboration of Alkenes

A method for the diastereoselective carboboration of 1,2‐disubstituted styrenes with aryl/vinyl bromides and (Bpin)₂ is reported. High diastereoselectivities and yields are observed for the formation of either diastereomer of the product from a single alkene isomer. These reactions provide access to a diverse range of structures from simple starting materials.     

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).     

Preparation of Dithienylphospholes by 1,1‐Carboboration

In this study the scope of the 1,1‐carboboration reaction was extended to the preparation of mixed heterole‐based conjugated π‐systems. Two arylbis(alkynyl)phosphane starting materials 2 were synthesized bearing two thiophene isomers at the alkyne units and the bulky tipp‐substituent (tipp=2,4,6‐triisopropylphenyl) at the phosphorous atom. The bis(thienylethynyl)phosphanes 2 were converted into the corresponding 2,5‐thienyl‐substituted 3‐borylphospholes 4 in a double 1,1‐carboboration reaction sequence employing the strongly electrophilic B(C₆F₅)₃ reagent under mild reaction conditions. Subsequent Suzuki–Miyaura type cross‐coupling yielded the corresponding 3‐phenylphospholes 7 in a one‐pot procedure from phosphanes 2 in high yields. Phospholes 7 were converted into the respective phosphole oxides 8 . A photophysical characterization of derivatives 7 and 8 was carried out. The results presented here demonstrate the suitability of the 1,1‐carboboration reaction for the preparation of phosphole‐/thiophene‐based, light‐emitting systems.     

Synthesis and Reactivity of Cyclic Borane‐Amidine Conjugated Molecules Formed by Direct 1,2‐Carboboration of Carbodiimides with 9‐Borafluorenes

Efficient 1,2‐carboboration reactions to the C=N bond of carbodiimides with 9‐borafluorenes, which give rise to cyclic borane‐amidine conjugates with a seven‐membered BNC₅ ring, are reported. The resulting cyclic borane‐amidine conjugates can be hydrolyzed into an acyclic bifunctional biaryl compound carrying both boronic acid and amidine groups, rendering the utility of the two‐step protocol for the synthesis of multi‐functionalized molecular systems with a potential as a supramolecular building block. Furthermore, the conjugated structure of the cyclic boron‐amidine compounds can be changed upon alkylation of the boron atom that increases the coordination number of boron. The combination of Lewis acid (borane) and conjugated base (amidine) provides rich structural diversity of heteroatom‐containing π‐conjugated systems.     

Copper‐Catalyzed Cross‐Coupling of Boronic Esters with Aryl Iodides and Application to the Carboboration of Alkynes and Allenes

Copper‐catalyzed Suzuki–Miyaura‐type cross‐coupling and carboboration processes are reported. The cross‐couplings function well with a variety of substituted aryl iodides and aryl boronic esters and allows for orthogonal reactivity compared to palladium‐catalyzed processes. The carboboration method includes both alkynes and allenes and provides access to highly substituted and stereodefined vinyl boronic esters. The alkyne carboboration method is highlighted in the simple one‐pot synthesis of Tamoxifen.     

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.     

A 1,1‐Carboboration Route to Bora‐Nazarov Systems

Hydroboration of the conjugated enynes 1 a and 1 b with Piers’ borane [HB(C₆F₅)₂] gave the respective dienylboranes trans‐ 2 c and trans‐ 2 d . Their photolysis resulted in the formation of the dihydroborole products 3 c and 3 d . Both were converted to their pyridine adducts 5 c and 5 d , respectively. Compounds 3 c and 5 c,d were characterized by X‐ray diffraction. The reaction of the bis(enynyl)boranes 6 a and 6 b with B(C₆F₅)₃ resulted in the formation of the dihydroboroles 7 a and 7 b , respectively. This reaction is thought to proceed by 1,1‐carboboration of one of the enynyl substituents at boron to generate the dienylborane intermediates 8 a / 8 b , followed by thermally induced bora‐Nazarov ring‐closure and subsequent stabilizing 1,2‐pentafluorophenyl group migration from boron to carbon. Compound 7 a was characterized by X‐ray diffraction and solid‐state ¹¹B NMR spectroscopy.     

Copper‐Catalyzed 1,2‐Addition of α‐Carbonyl Iodides to Alkynes

β,γ‐Unsaturated ketones are an important class of organic molecules. Herein, copper catalysis has been developed for the synthesis of β‐γ‐unsaturated ketones through 1,2‐addition of α‐carbonyl iodides to alkynes. The reactions exhibit wide substrate scope and high functional group tolerance. The reaction products are versatile synthetic intermediates to complex small molecules. The method was applied for the formal synthesis of (±)‐trichostatin A, a histone deacetylase inhibitor.     

Carboboration Reactions of 1,2‐Bis[(diarylphosphino)ethynyl]benzenes with Tris(pentafluorophenyl)borane

The 1,2‐bis[(diarylphosphino)ethynyl]benzene derivatives 1a (R=Ph) and 1b (R=o‐tolyl) undergo 1,1‐carboboration at one of their acetylene units upon treatment with (C₆F₅)₃B at elevated temperature to give the products 5a and 5b , respectively. At room temperature, we observed the formation of the corresponding phosphireniumborate zwitterions, 7a and 7b , respectively, which may be intermediates of the 1,1‐carboboration reactions. The reaction of the more bulky 1,2‐bis[(dimesitylphosphino)ethynyl]benzene 1c with (C₆F₅)₃B takes a different course. At 110°, we observed the complete conversion to the benzopentafulvene derivative 8 which is probably formed in a typical carbocation rearrangement sequence after the initial (C₆F₅)₃B Lewis acid‐addition step. The compounds 5a, 5b, 7b , and 8 were characterized by X‐ray crystal‐structure analyses.     

1,2‐Dithioquadratato‐ und 1,2‐Dithiooxalatoindate(III)

Indium(III) chloride forms in water with potassium 1,2‐dithiooxalate (dto) and potassium 1,2‐dithiosquarate (dtsq) stable coordination compounds. Due to the higher bridging ability of the 1,2‐dithiooxalate ligand in all cases only thiooxalate bridged binuclear complexes were found. From 1,2‐dithioquadratate with an identical donor atom set mononuclear trischelates could be isolated. Five crystalline complexes, (BzlMe₃N)₄[(dto)₂In(dto)In(dto)₂] ( 1 ), (BzlPh₃P)₄[(dto)₂In(dto)In(dto)₂] ( 2 ), (BzlMe₃N)₃[In(dtsq)₃] ( 3 ), (Bu₄N)₃[In(dtsq)₃] ( 4 ) and (Ph₄P)[In(dtsq)₂(DMF)₂] ( 5 ), have been isolated and characterized by X‐ray analyses. Due to the type of the complex and the cations involved these compounds crystallize in different space groups with the following parameters: 1 , monoclinic in P2₁/c with a = 14.4035(5) Å, b = 10.8141(5) Å, c = 23.3698(9) Å, β = 124.664(2)°, and Z = 2; 2 , triclinic in P with a = 11.3872(7) Å, b = 13.6669(9) Å, c = 17.4296(10) Å, α = 88.883(5)°, β = 96.763(1)°, γ = 74.587(5)°, and Z = 1; 3 , hexagonal in R3 with a = 20.6501(16) Å, b = 20.6501(16) Å, c = 19.0706(13) Å and Z = 6; 4 , monoclinic in P2₁/c with a = 22.7650(15) Å, b = 20.4656(10) Å, c = 14.4770(9) Å, β = 101.095(5)°, and Z = 4; 5 , triclinic in P with a = 9.2227(6) Å, b = 15.3876(9) Å, c = 15.5298(9) Å, α = 110.526(1)°, β = 100.138(1)°, γ = 101.003(1)°, and Z = 2.     

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 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.     

Phosphine‐Catalyzed anti‐Carboboration of Alkynoates with 9‐BBN‐Based 1,1‐Diborylalkanes: Synthesis and Use of Multisubstituted γ‐Borylallylboranes

Trialkylphosphine organocatalysis has enabled the regioselective anti‐carboboration of alkynoates with 9‐BBN‐based 1,1‐diborylalkanes to produce secondary allylboranes with β‐alkoxycarbonyl and γ‐boryl substituents. The utility of the densely functionalized allylboranes was demonstrated by the highly diastereoselective allylation of N‐(trimethylsilyl)aldimines to produce homoallylamines containing tertiary allylborane and acrylate moieties.     

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.     

The Hydride‐Ion Affinity of Borenium Cations and Their Propensity to Activate H2 in Frustrated Lewis Pairs

A range of frustrated Lewis pairs (FLPs) containing borenium cations have been synthesised. The catechol (Cat)‐ligated borenium cation [CatB(PtBu₃)]⁺ has a lower hydride‐ion affinity (HIA) than B(C₆F₅)₃. This resulted in H₂ activation being energetically unfavourable in a FLP with the strong base PtBu₃. However, ligand disproportionation of CatBH(PtBu₃) at 100 °C enabled trapping of H₂ activation products. DFT calculations at the M06‐2X/6‐311G(d,p)/PCM (CH₂Cl₂) level revealed that replacing catechol with chlorides significantly increases the chloride‐ion affinity (CIA) and HIA. Dichloro–borenium cations, [Cl₂B(amine)]⁺, were calculated to have considerably greater HIA than B(C₆F₅)₃. Control reactions confirmed that the HIA calculations can be used to successfully predict hydride‐transfer reactivity between borenium cations and neutral boranes. The borenium cations [Y(Cl)B(2,6‐lutidine)]⁺ (Y=Cl or Ph) form FLPs with P(mesityl)₃ that undergo slow deprotonation of an ortho‐methyl of lutidine at 20 °C to form the four‐membered boracycles [(CH₂{NC₅H₃Me})B(Cl)Y] and [HPMes₃]⁺. When equimolar [Y(Cl)B(2,6‐lutidine)]⁺/P(mesityl)₃ was heated under H₂ (4 atm), heterolytic cleavage of dihydrogen was competitive with boracycle formation.     

1,2‐Bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile: Enol Ethers and Ketene Acetals as Cycloaddition Partners

(E)‐ and (Z)‐1,2‐bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile ((E)‐ and (Z)‐BTE, resp., =(E)‐ and (Z)‐2,3‐bis(trifluoromethyl)but‐2‐enedinitrile) were used as a stereochemical probe in studying (2+2) cycloadditions of acceptor with donor alkenes. The additions to methyl (E)‐ and (Z)‐propenyl ether gave rise to the eight conceivable cyclobutanes 8 , although in different ratios in reactions of (E)‐ and (Z)‐BTE. The ¹⁹F‐NMR data served the structural assignment and the quantitative analysis. The mechanistic discussion is based on rotations and ring closures of the assumed 1,4‐zwitterionic intermediates. Dimethylketene dimethyl acetal, methylketene dimethyl acetal, and ketene diethyl acetal show an increasing rate in their reactions with BTE as well as in the equilibration of the cycloadducts.