An Olefinic 1,2‐Boryl‐Migration Enabled by Radical Addition: Construction of gem‐Bis(boryl)alkanes

A series of in situ formed alkenyl diboronate complexes from alkenyl Grignard reagents (commercially available or prepared from alkenyl bromides and Mg) with B₂Pin₂ (bis(pinacolato)diboron) react with diverse alkyl halides by a Ru photocatalyst to give various gem‐bis(boryl)alkanes. Alkyl radicals add efficiently to the alkenyl diboronate complexes, and the adduct radical anions undergo radical‐polar crossover, specifically, a 1,2‐boryl‐anion shift from boron to the α‐carbon sp² center. This transformation shows good functional‐group compatibility and can serve as a powerful synthetic tool for late‐stage functionalization in complex compounds. Measurements of the quantum yield reveal that a radical‐chain mechanism is operative in which the alkenyl diboronates acts as reductive quencher for the excited state of the photocatalyst.     

Synthesis,Structure, and Reactivity of Anionic sp2–sp3 Diboron Compounds: Readily Accessible Boryl Nucleophiles

Lewis base adducts of tetra‐alkoxy diboron compounds, in particular bis(pinacolato)diboron (B₂pin₂), have been proposed as the active source of nucleophilic boryl species in metal‐free borylation reactions. We report the isolation and detailed structural characterization (by solid‐state and solution NMR spectroscopy and X‐ray crystallography) of a series of anionic adducts of B₂pin₂ with hard Lewis bases, such as alkoxides and fluoride. The study was extended to alternative Lewis bases, such as acetate, and other diboron reagents. The B(sp²)–B(sp³) adducts exhibit two distinct boron environments in the solid‐state and solution NMR spectra, except for [(4‐tBuC₆H₄O)B₂pin₂]^?, which shows rapid site exchange in solution. DFT calculations were performed to analyze the stability of the adducts with respect to dissociation. Stoichiometric reaction of the isolated adducts with two representative series of organic electrophiles—namely, aryl halides and diazonium salts—demonstrate the relative reactivities of the anionic diboron compounds as nucleophilic boryl anion sources.     

Four‐Component Borocarbonylation of Vinylarenes Enabled by Cooperative Cu/Pd Catalysis: Access to β‐Boryl Ketones and β‐Boryl Vinyl Esters

We report here a general four‐component synthetic procedure for the preparation of β‐boryl ketones and β‐boryl vinyl esters. Joint catalyzed by palladium and copper catalysts, borocarbonylative reaction between vinylarenes, aryl halides/triflates, B₂Pin₂, and carbon monoxide proceed successfully. A variety of synthetically useful β‐boryl ketones were synthesized in good to high yields by using aryl iodides as the substrates. It is noteworthy that when aryl triflates were applied as the starting materials, β‐boryl vinyl esters were synthesized in a similar manner and with broad functional group tolerance. A rational mechanism for this reaction was also proposed.     

Stereospecific 1,2‐Migrations of Boronate Complexes Induced by Electrophiles

The stereospecific 1,2‐migration of boronate complexes is one of the most representative reactions in boron chemistry. This process has been used extensively to develop powerful methods for asymmetric synthesis, with applications spanning from pharmaceuticals to natural products. Typically, 1,2‐migration of boronate complexes is driven by displacement of an α‐leaving group, oxidation of an α‐boryl radical, or electrophilic activation of an alkenyl boronate complex. The aim of this article is to summarize the recent advances in the rapidly expanding field of electrophile‐induced stereospecific 1,2‐migration of groups from boron to sp² and sp³ carbon centers. It will be shown that three different conceptual approaches can be utilized to enable the 1,2‐migration of boronate complexes: stereospecific Zweifel‐type reactions, catalytic conjunctive coupling reactions, and transition metal‐free sp²–sp³ couplings. A discussion of the reaction scope, mechanistic insights, and synthetic applications of the work described is also presented.     

N‐Heterocyclic Carbene Stabilized Boryl Radicals

The reaction of the 2‐(trimethylsilyl)imidazolium triflate 9 with diarylboron halides (4‐R‐C₆H₄)₂BX (R=H, X=Br; R=CH₃, X=Cl; R=CF₃, X=Cl) afforded the NHC‐stabilized borenium cations 10 a – c . Cyclic voltammetry revealed a linear correlation between the Hammett parameter σ _p of the para substituent and the half‐wave potential. Chemical reduction with decamethylcobaltocene, [(C₅Me₅)₂Co], furnished the corresponding radicals 11 a – c ; their characterization by EPR spectroscopy confirmed the paramagnetic character of 11 a – c , with large hyperfine coupling constants to the boron isotopes ¹¹B and ¹⁰B, while delocalization of the unpaired electron into the NHC is negligible. DFT calculations of the percentage of spin density distribution between the carbene (NHC) and the boryl fragments (BR₂) revealed for 11 a – c a spin density ratio (BR₂/NHC) of ca. 9:1, which underlines their distinct boryl radical character. The molecular structure of the most stable species 11 c was established by X‐ray diffraction analysis.     

Intermolecular Amination of Unactivated C(sp3)−H Bonds with Cyclic Alkylamines: Formation of C(sp3)−N Bonds through Copper/Oxygen‐Mediated C(sp3)−H/N−H Activation

The first example of intermolecular amination of unactivated C(sp³)?H bonds by cyclic alkylamines mediated by Cu(OAc)₂/O₂ is reported. This method avoids the use of benzoyloxyamines as the aminating reagent, which are normally prepared from alkylamines in extra steps. A variety of unnatural β^{2, 2}‐amino acid analogues are synthesized by this simple and efficient procedure. This approach offers a solution to the previous unmet challenge of C(sp³)?H/N?H activation for the formation of C(sp³)?N bonds.     

Mechanism of the Pd‐catalyzed Decarboxylative Allylation of α‐Imino Esters: Decarboxylation via Free Carboxylate Ion

The Pd‐catalyzed decarboxylative allylation of α‐(diphenylmethylene)imino esters ( 1 ) or allyl diphenylglycinate imines ( 2 ) is an efficient method to construct new C(sp³)? C(sp³) bonds. The detailed mechanism of this reaction was studied by theoretical calculations [ONIOM(B3LYP/LANL2DZ+p:PM6)] combined with experimental observations. The overall catalytic cycle was found to consist of three steps: oxidative addition, decarboxylation, and reductive allylation. The oxidative addition of 1 to [(dba)Pd(PPh₃)₂] (dba=dibenzylideneacetone) produces an allylpalladium cation and a carboxylate anion with a low activation barrier of +9.1 kcal mol^?1. The following rate‐determining decarboxylation proceeds via a solvent‐exposed α‐imino carboxylate anion rather than an O‐ligated allylpalladium carboxylate with an activation barrier of +22.7 kcal mol^?1. The 2‐azaallyl anion generated by this decarboxylation attacks the face of the allyl ligand opposite to the Pd center in an outer‐sphere process to produce major product 3 , with a lower activation barrier than that of the minor product 4 . A positive linear Hammett correlation [ρ=1.10 for the PPh₃ ligand] with the observed regioselectivity ( 3 versus 4 ) supports an outer‐sphere pathway for the allylation step. When Pd combined with the bis(diphenylphosphino)butane (dppb) ligand is employed as a catalyst, the decarboxylation still proceeds via the free carboxylate anion without direct assistance of the cationic Pd center. Consistent with experimental observations, electron‐withdrawing substituents on 2 were calculated to have lower activation barriers for decarboxylation and, thus, accelerate the overall reaction rates.     

1,1‐Organoboration of silylethynyltin compounds studied by multinuclear magnetic resonance spectroscopy: isomerization at the CC bonds and electron‐deficient Si?H?B bridges

1,1‐Organoboration, using triethyl‐, triallyl‐ and triphenyl‐borane (BEt₃, BAll₃, BPh₃), of dimethysilylethynyl(trimethyl)stannane, Me₃Sn? C?C? Si(H)Me₂ ( 1 ), affords alkenes bearing three different organometallic groups at the C?C bond. For BEt₃ and BPh₃, the first products are the alkenes 4 with boryl and stannyl groups in cis‐positions. These rearrange by consecutive 1,1‐deorganoboration and 1,1‐organoboration into the isomers 5 as the final products, where boryl and silyl groups are in cis‐positions linked by an electron‐deficient Si? H? B bridge. 1,1‐Ethylboration of bis(dimethylsilylethynyl)dimethylstannane, Me₂Sn[C?C? Si(H)Me₂]₂ ( 2 ), leads to the stannacyclopentadiene 6 along with non‐cyclic di(alkenyl)tin compounds 7 and 8 . 1,1‐Ethylboration of ethynyl(trimethylstannylethynyl)methylsilane, Me(H)Si(C?C? SnMe₃)C?C? H ( 3 ), leads selectively to a new silacyclopentadiene 13 as the final product. The reactions were monitored and the products were characterized by multinuclear magnetic resonance spectroscopy (¹H, ¹¹B, ¹³C, ²⁹Si and ¹¹⁹Sn NMR). Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis of 4‐silaspiro[3.4]octa‐1,5‐diene derivatives: hybrid spiro compounds

Trialkynyl(vinyl)silanes CH₂?CH? Si(C?C? R)₃ (R = Bu, Ph, p‐tolyl) were prepared and treated with 9‐borabicyclo[3.3.1]nonane (9‐BBN). Consecutive 1,2‐hydroboration and intramolecular 1,1‐carboboration reactions (each requires different reaction conditions) were studied. 1,2‐Hydroboration of the Si? vinyl group takes place at ambient temperature (23°C in tetrahydrofuran), followed by intramolecular 1,1‐vinylboration to give 1‐silacyclopent‐2‐ene derivatives, bearing still two alkynyl functions at the silicon atom. Further treatment with a second equivalent of 9‐BBN affords 1‐alkenyl‐1‐(alkynyl)‐1‐silacyclopent‐2‐ene derivatives. These undergo intramolecular 1,1‐vinylboration to give 4‐silaspiro[3.4]octa‐1,5‐dienes bearing the boryl groups at 2 and 6 positions. Protodeborylation of all new compounds (intermediates and final products) using acetic acid in slight excess afforded corresponding silanes including spirosilanes. All compounds were characterized using multinuclear NMR spectroscopy (¹H, ¹¹B, ¹³C, ²⁹Si) in solution state. Solid‐state structures for one of the trialkynyl(vinyl)silanes (R = p‐tolyl) and one of the 1‐silacyclopent‐2‐ene derivatives (R = Ph) were confirmed using X‐ray diffraction. Copyright © 2015 John Wiley & Sons, Ltd.     

Oxidative‐Insertion Reactivity Across a Geometrically Constrained Metal→Borane Interaction

While interest in cooperative reactivity of transition metals and Lewis acids is receiving significant attention, the scope of known reactions that directly exploit the polarized reverse‐dative σ‐bond of metal‐borane complexes (i.e., M → BR₃) remains limited. Described herein is that the platinum (boryl)iminomethane (BIM) complex [Pt(κ²‐N,B‐^Cy2BIM)(CNAr^Dipp2)] can effect the oxidative insertion of a range of unsaturated organic substrates, including azides, isocyantes, and nitriles, as well as CO₂ and elemental sulfur (S₈). In addition, alkyl migration processes available to the BIM framework allow for post‐insertion reaction sequences resulting in product release from the metal center.     

Formation of C(sp2)Boronate Esters by Borylative Cyclization of Alkynes Using BCl3

BCl₃ is an inexpensive electrophile which induces the borylative cyclization of a wide range of substituted alkynes to regioselectively form polycycles containing synthetically versatile C(sp²)? boronate esters. It proceeds rapidly, with good yields and is compatible with a range of functional groups and substitution patterns. Intermolecular 1,2‐carboboration of alkynes is also achieved using BCl₃ to generate trisubstituted vinyl boronate esters.     

Synthesis of Unsymmetrical Diboranes by Diborane Metathesis

Reactions of readily accessible magnesium‐centered pinacolatoboryl nucleophiles with [(Ph₂B)₂O] result in B?O bond activation of the diphenylborinic anhydride. Although [pinBBPh₂] is apparently generated when the nucleophilic boron unit is derived in situ from a magnesium diboranate, it cannot be isolated owing to its onward derivatization by a further {Bpin}^? equivalent. A reaction with a terminal magnesium boryl species similarly provides a boryloxide byproduct. In this case, however, the unsymmetrical B(sp²)?B(sp³) diborane may be intercepted as its DMAP adduct.     

Ion‐Pairing of Phosphonium Salts in Solution: C?H⋅⋅⋅Halogen and C?H⋅⋅⋅π Hydrogen Bonds

The ¹H NMR chemical shifts of the C(α)? H protons of arylmethyl triphenylphosphonium ions in CD₂Cl₂ solution strongly depend on the counteranions X^?. The values for the benzhydryl derivatives Ph₂CH? PPh₃⁺ X^?, for example, range from δ_H=8.25 (X^?=Cl^?) over 6.23 (X^?=BF₄^?) to 5.72 ppm (X^?=BPh₄^?). Similar, albeit weaker, counterion‐induced shifts are observed for the ortho‐protons of all aryl groups. Concentration‐dependent NMR studies show that the large shifts result from the deshielding of the protons by the anions, which decreases in the order Cl^? > Br^? ? BF₄^? > SbF₆^?. For the less bulky derivatives PhCH₂? PPh₃⁺ X^?, we also find C? H???Ph interactions between C(α)? H and a phenyl group of the BPh₄^? anion, which result in upfield NMR chemical shifts of the C(α)? H protons. These interactions could also be observed in crystals of (p‐CF₃‐C₆H₄)CH₂? PPh₃⁺ BPh₄^?. However, the dominant effects causing the counterion‐induced shifts in the NMR spectra are the C? H???X^? hydrogen bonds between the phosphonium ion and anions, in particular Cl^? or Br^?. This observation contradicts earlier interpretations which assigned these shifts predominantly to the ring current of the BPh₄^? anions. The concentration dependence of the ¹H NMR chemical shifts allowed us to determine the dissociation constants of the phosphonium salts in CD₂Cl₂ solution. The cation–anion interactions increase with the acidity of the C(α)? H protons and the basicity of the anion. The existence of C? H???X^? hydrogen bonds between the cations and anions is confirmed by quantum chemical calculations of the ion pair structures, as well as by X‐ray analyses of the crystals. The IR spectra of the Cl^? and Br^? salts in CD₂Cl₂ solution show strong red‐shifts of the C? H stretch bands. The C? H stretch bands of the tetrafluoroborate salt PhCH₂? PPh₃⁺ BF₄^? in CD₂Cl₂, however, show a blue‐shift compared to the corresponding BPh₄^? salt.     

Copper‐Catalyzed Regio‐ and Enantioselective Addition of Silicon Grignard Reagents to Alkenes Activated by Azaaryl Groups

A new application of silicon Grignard reagents in C(sp³)?Si bond formation is reported. With the aid of BF₃?OEt₂, these silicon nucleophiles add across alkenes activated by various azaaryl groups under copper catalysis. An enantioselective version employing benzoxazole‐activated alkenes as substrates and a CuI‐josiphos complex as catalyst has been developed, forming the C(sp3)?Si bond with good to high enantiomeric ratios (up to 97:3). The method expands the toolbox for “conjugate addition” type C(sp³)?Si bond formation.     

Magnesium-mediated sp3 C–H activation in cascade cyclization of 1-arylethynyl-2-alkyl-o-carboranes: efficient synthesis of carborane-fused cyclopentanes

This work reports an unprecedented cascade cyclization of 1-arylethynyl-2-alkyl-o-carboranes promoted by magnesium-mediated sp³ C–H activation. Treatment of 1-arylethynyl-2-alkyl-o-carboranes with MeMgBr gives a series of carborane-fused cyclopentanes in very good yields. Deuterium labelling and control experiments suggest that HMgBr, resulting in situ from the nucleophilic substitution of cage B–H bonds with Grignard reagent, initiates the reaction, in which magnesium-promoted intramolecular sp³ C–H activation serves as a key step. This work not only offers a new route for the synthesis of carborane-fused cyclopentanes, but also sheds some light on Mg-mediated C–H activation and functionalization.

An unprecedented cascade cyclization of 1-arylethynyl-2-alkyl-o-carboranes with Grignard reagent for synthesizing carborane-fused cyclopentanes has been disclosed, in which magnesium-mediated intramolecular sp³ C–H activation serves as a key step.     

Stereoselective Unsymmetrical 1,1-Diborylation of Alkynes with a Neutral sp2−sp3 Diboron Reagent

The incorporation of two distinct boryl groups at the same carbon center in organic molecules has attracted growing research interest due to its potential for facilitating controlled, precise synthesis through stepwise dual carbon-boron bond transformations. Here we report a method to access u nsymmetrical 1,1- d i b oryl a lkene (UDBA) stereoselectively via the reaction of readily available alkynes with a neutral sp²−sp³ diboron reagent (NHC) B H₂- B pin (NHC=N-heterocyclic carbene). Attributing to the chemically easily distinguishable nature of the sp² and sp³ boryl moieties, controllable stepwise derivatization of the resultant UDBAs is realized. This process leads to various multifunctionalized olefins and organoborons, such as acylboranes, which are difficult to prepare by other methods.     

Synthesis and Characterization of a Magnesium Boryl and a Beryllium‐Substituted Diazaborole

Reaction of a lithium boryl, [(THF)₂Li{B(DAB)}] (DAB=[(DipNCH)₂]^2?, Dip=2,6‐diisopropylphenyl), with a dinuclear magnesium(I) compound [{(^MesNacnac)Mg}₂] (^MesNacnac=[HC(MeCNMes)₂]^?, Mes=mesityl) unexpectedly afforded a rare example of a terminal magnesium boryl species, [(^MesNacnac)(THF)Mg{B(DAB)}]. Attempts to prepare the magnesium boryl via a salt metathesis reaction between the lithium boryl and a β‐diketiminato magnesium iodide compound, instead led to an intractable mixture of products. Similarly, reaction of the lithium boryl with a β‐diketiminato beryllium bromide precursor, [(^DepNacnac)BeBr] (Dep=2,6‐diethylphenyl) did not give a beryllium boryl, but instead afforded an unprecedented example of a beryllium substituted diazaborole heterocycle, [{(^DepNacnac)Be(4‐DAB^?H)}BBr]. For sake of comparison, the same group 2 halide precursor compounds were treated with a potassium gallyl analogue of the lithium boryl, viz. [(tmeda)K{:Ga(DAB)}] (tmeda=N,N,N’,N’‐tetramethylethylenediamine), but no reactions were observed.     

Towards a Molecular Understanding of Cation–Anion Interactions—Probing the Electronic Structure of Imidazolium Ionic Liquids by NMR Spectroscopy,X‐ray Photoelectron Spectroscopy and Theoretical Calculations

Ten [C₈C₁Im]⁺ (1‐methyl‐3‐octylimidazolium)‐based ionic liquids with anions Cl^?, Br^?, I^?, [NO₃]^?, [BF₄]^?, [TfO]^?, [PF₆]^?, [Tf₂N]^?, [Pf₂N]^?, and [FAP]^? (TfO=trifluoromethylsulfonate, Tf₂N=bis(trifluoromethylsulfonyl)imide, Pf₂N=bis(pentafluoroethylsulfonyl)imide, FAP=tris(pentafluoroethyl)trifluorophosphate) and two [C₈C₁C₁Im]⁺ (1,2‐dimethyl‐3‐octylimidazolium)‐based ionic liquids with anions Br^? and [Tf₂N]^? were investigated by using X‐ray photoelectron spectroscopy (XPS), NMR spectroscopy and theoretical calculations. While ¹H NMR spectroscopy is found to probe very specifically the strongest hydrogen‐bond interaction between the hydrogen attached to the C² position and the anion, a comparative XPS study provides first direct experimental evidence for cation–anion charge‐transfer phenomena in ionic liquids as a function of the ionic liquid’s anion. These charge‐transfer effects are found to be surprisingly similar for [C₈C₁Im]⁺ and [C₈C₁C₁Im]⁺ salts of the same anion, which in combination with theoretical calculations leads to the conclusion that hydrogen bonding and charge transfer occur independently from each other, but are both more pronounced for small and more strongly coordinating anions, and are greatly reduced in the case of large and weakly coordinating anions.     

Probing the reactivity of microhydrated α‐nucleophile in the anionic gas‐phase SN2 reaction

To probe the kinetic performance of microsolvated α‐nucleophile, the G2(+)_M calculations were carried out for the gas‐phase S_N2 reactions of monohydrated and dihydrated α‐oxy‐nucleophiles XO^?(H₂O)_{n = 1,2} (X = HO, CH₃O, F, Cl, Br), and α‐sulfur‐nucleophile, HSS^?(H₂O)_{n = 1,2}, toward CH₃Cl. We compared the reactivities of hydrated α‐nucleophiles to those of hydrated normal nucleophiles. Our calculations show that the α‐effect of monohydrated and dihydrated α‐oxy‐nucleophiles will become weaker than those of unhydrated ones if we apply a plot of activation barrier as a function of anion basicity. Whereas the enhanced reactivity of monohydrated and dihydrated ROO^? (R = H, Me) could be observed if compared them with the specific normal nucleophiles, RO^? (R = H, Me). This phenomena can not be seen in the comparisons of XO^?(H₂O)_{n = 1,2} (X = F, Cl, Br) with ClC₂H₄O^?(H₂O)_{n = 1,2}, a normal nucleophile with similar gas basicity to XO^?(H₂O)_{n = 1,2}. These results have been carefully analyzed by natural bond orbital theory and activation strain model. Meanwhile, the relationships between activation barriers with reaction energies and the ionization energies of α‐nucleophile are also discussed. © 2015 Wiley Periodicals, Inc.     

C(sp3)H Activation without a Directing Group: Regioselective Synthesis of N‐Ylide or N‐Heterocyclic Carbene Complexes Controlled by the Choice of Metal and Ligand

N‐Ylide complexes of Ir have been generated by C(sp³)?H activation of α‐pyridinium or α‐imidazolium esters in reactions with [Cp*IrCl₂]₂ and NaOAc. These reactions are rare examples of C(sp³)?H activation without a covalent directing group, which—even more unusually—occur α to a carbonyl group. For the reaction of the α‐imidazolium ester [ 3 H]Cl, the site selectivity of C?H activation could be controlled by the choice of metal and ligand: with [Cp*IrCl₂]₂ and NaOAc, C(sp³)?H activation gave the N‐ylide complex 4 ; in contrast, with Ag₂O followed by [Cp*IrCl₂]₂, C(sp²)?H activation gave the N‐heterocyclic carbene complex 5 . DFT calculations revealed that the N‐ylide complex 4 was the kinetic product of an ambiphilic C?H activation. Examination of the computed transition state for the reaction to give 4 indicated that unlike in related reactions, the acetate ligand appears to play the dominant role in C?H bond cleavage.