Quantum chemical study on enantioselective reduction of aromatic ketones catalyzed by chiral cyclic sulfur‐containing oxazaborolidines. Part 1. Structures and properties of catalysts

The ab initio molecular orbital method is employed to study the structures and properties of chiral cyclic sulfur‐containing oxazaborolidine, as a catalyst, and its borane adducts. All the structures are optimized completely by means of the Hartree–Fock method at 6‐31g* basis sets. The catalyst is a twisted chair structure and reacts with borane to form four plausible catalyst–borane adducts. Borane–sulfur adducts may be formed, but they barely react with aromatic ketone to form catalyst–borane–ketone adducts, because they are repulsed greatly by the atoms arising from the chair rear of the catalyst with a twisted chair structure. Borane–N adduct has the largest formation energy and is predicted to react easily with aromatic ketone to form catalyst–borane–ketone adducts. The formation of the catalyst–borane adducts causes the B_BH3 H_BH3 bond lengths of the BH₃ moiety to be increased and thus enhances the activity of the enantioselective catalytic reduction. The borane–N adduct is of great advantage to hydride transfer. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 78: 245–251, 2000     

Preparation of Stable Low‐Oxidation‐State Group 14 Element Amidohydrides and Hydride‐Mediated Ring‐Expansion Chemistry of N‐Heterocyclic Carbenes

Various low oxidation state (+2) group 14 element amidohydride adducts, IPr ? EH(BH₃)NHDipp (E=Si or Ge; IPr=[(HCNDipp)₂C:], Dipp=2,6‐iPr₂C₆H₃), were synthesized. Thermolysis of the reported adducts was investigated as a potential route to Si‐ and Ge‐based clusters; however, unexpected transmetallation chemistry occurred to yield the carbene–borane adduct, IPr ? BH₂NHDipp. When a solution of IPr ? BH₂NHDipp in toluene was heated to 100 °C, a rare C? N bond‐activation/ring‐expansion reaction involving the bound N‐heterocyclic carbene donor (IPr) transpired.     

Asymmetric synthesis of P-stereogenic o-hydroxyaryl-phosphine (borane) and phosphine-phosphinite ligands

The first asymmetric synthesis of P-stereogenic 2-hydroxyarylphosphine ligands is described, using borane complexation methodology. This synthesis is based on the highly stereoselective preparation of bromoarylphosphinite boranes, leading to the 2-hydroxyarylphosphine derivatives, by an intramolecular ortho Fries-like rearrangement mediated in basic conditions. The o-anisyl-2-hydroxynaphthylphenylphosphine borane has been decomplexed in EtOH, affording the P(III)-stereogenic hydroxyarylphosphine ligand with 84% yield. The interest of the hydroxyarylphosphine borane is also demonstrated by the preparation of a new class of phosphine-phosphinite ligands, by trapping the rearrangement products first with chlorodiphenylphosphine, Ph₂PCl, then with borane. The corresponding phosphine-phosphinites are obtained and purified as diborane complexes, with the decomplexation of these borane complexes being achieved by heating with dabco, to afford the free hybrid ligands with retention of the configuration at the P-atom (isolated yield up to 53%).     

Quantum-chemical study of adducts of germanium halides with nitrogen-containing donors

Structural and thermodynamic characteristics of adducts GeX₄ · nL (n = 1, 2; X = F, Cl, Br; L = NH₃, py, bipy, phen) have been calculated by the B3LYP density functional theory method. The enthalpies of sublimation of complexes trans-GeX₄ · 2py and the adduct GeCl₄ · bipy have been estimated for the first time. The rearrangement energies of the donor and acceptor fragments and the Ge-N bond energies for the 1:1 and 1:2 complexes have been calculated. While the rearrangement energy for germanium halides is lower by 19–63 kJ mol^?1 than that for silicon halides, the energy of the donor-acceptor bond in the former case is slightly lower. As a result, germanium adducts are slightly more stable than silicon adducts.     

A d10 Ni–(H2) Adduct as an Intermediate in HH Oxidative Addition across a NiB Bond

Bifunctional E? H activation offers a promising approach for the design of two‐electron‐reduction catalysts with late first‐row metals, such as Ni. To this end, we have been pursuing H₂ activation reactions at late‐metal boratranes and herein describe a diphosphine–borane‐supported Ni—(H₂) complex, [(^PhDPB^iPr)Ni(H₂)], which has been characterized in solution. ¹H NMR spectroscopy confirms the presence of an intact H₂ ligand. A range of data, including electronic‐structure calculations, suggests a d¹⁰ configuration for [(^PhDPB^iPr)Ni(H₂)] as most appropriate. Such a configuration is highly unusual among transition‐metal H₂ adducts. The nonclassical H₂ adduct is an intermediate in the complete activation of H₂ across the Ni? B interaction. Reaction‐coordinate analysis suggests synergistic activation of the H₂ ligand by both the Ni and B centers of the nickel boratrane subunit, thus highlighting an important role of the borane ligand both in stabilizing the d¹⁰ Ni—(H₂) interaction and in the H—H cleavage step.     

Zinc catalysed electrophilic C–H borylation of heteroarenes

Cationic zinc Lewis acids catalyse the C–H borylation of heteroarenes using pinacol borane (HBPin) or catechol borane (HBCat). An electrophile derived from [IDippZnEt][B(C₆F₅)₄] (IDipp = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) combined with N,N-dimethyl-p-toluidine (DMT) proved the most active in terms of C–H borylation scope and yield. Using this combination weakly activated heteroarenes, such as thiophene, were amenable to catalytic C–H borylation using HBCat. Competition reactions show these IDipp–zinc cations are highly oxophilic but less hydridophilic (relative to B(C₆F₅)₃), and that borylation proceeds via activation of the hydroborane (and not the heteroarene) by a zinc electrophile. Based on DFT calculations this activation is proposed to proceed by coordination of a hydroborane oxygen to the zinc centre to generate a boron electrophile that effects C–H borylation. Thus, Lewis acid binding to oxygen sites of hydroboranes represents an under-developed route to access reactive borenium-type electrophiles for C–H borylation.

Cationic zinc Lewis acids catalyse the C–H borylation of heteroarenes using pinacol borane (HBPin) or catechol borane (HBCat).     

Rh2[(R)-(+)-MTPA]4 as an NMR auxiliary for the enantiodifferentiation of chiral secondary and tertiary phosphine–borane complexes

The direct chiral recognition of secondary and tertiary phosphine–borane complexes is made possible by applying the dirhodium method (NMR in the presence of Rh₂[(R)-(+)-MTPA]₄, Rh¹). Due to the acid lability of the phosphine–borane complexes, it is advisable to use deuterated benzene as solvent rather than deuterated chloroform. The decomposition of the phosphine–borane complexes and the resulting Rh¹–phosphine adducts are also studied.     

Sequential C−H Borylation and N‐Demethylation of 1,1′‐Biphenylamines: Alternative Route to Polycyclic BN‐Heteroarenes

Described herein is an unprecedented access to BN‐polyaromatic compounds from 1,1′‐biphenylamines by sequential borane‐mediated C(sp²)?H borylation and intramolecular N‐demethylation. The conveniently in situ generated Piers’ borane from a borinic acid reacts with a series of N,N‐dimethyl‐1,1′‐biphenyl‐2‐amines in the presence of PhSiH₃ to afford six‐membered amine‐borane adducts bearing a C(sp²)?B bond at the C2′‐position. These species undergo an intramolecular N‐demethylation with a B(C₆F₅)₃ catalyst to provide BN‐isosteres of polyaromatics. According to computational studies, a stepwise ionic pathway is suggested. Photophysical characters of the resultant BN‐heteroarenes shown them to be distinctive from those of all‐carbon analogues.     

New Routes to a Series of σ‐Borane/Borate Complexes of Molybdenum and Ruthenium

A series of agostic σ‐borane/borate complexes have been synthesized and structurally characterized from simple borane adducts. A room‐temperature reaction of [Cp*Mo(CO)₃Me], 1 with Li[BH₃(EPh)] (Cp*=pentamethylcyclopentadienyl, E=S, Se, Te) yielded hydroborate complexes [Cp*Mo(CO)₂(μ‐H)BH₂EPh] in good yields. With 2‐mercapto‐benzothiazole, an N,S‐carbene‐anchored σ‐borate complex [Cp*Mo(CO)₂BH₃(1‐benzothiazol‐2‐ylidene)] ( 5 ) was isolated. Further, a transmetalation of the B‐agostic ruthenium complex [Cp*Ru(μ‐H)BHL₂] ( 6 , L=C₇H₄NS₂) with [Mn₂(CO)₁₀] affords a new B‐agostic complex, [Mn(CO)₃(μ‐H)BHL₂] ( 7 ) with the same structural motif in which the central metal is replaced by an isolobal and isoelectronic [Mn(CO)₃] unit. Natural‐bond‐orbital analyses of 5–7 indicate significant delocalization of the electron density from the filled σ_B?H orbital to the vacant metal orbital.     

SYNTHESIS AND CHARACTERIZATION OF THE FIRST BORANE ADDUCTS AND BORON CATIONS OF SOME N-ALKYL AND N-AMINOTRIPHENYLPHOSPHORANIMINES

Abstract

The first borane adducts of N-alkyl and N-aminotriphenylphosphoranimines, Ph₃P[dbnd]N—R, were prepared by two different general synthetic methods. The first method involved displacement of THF (tetrahydofuran) from THF-borane by the free imines, and the second employed the reaction of LiBH₄ with iminium bromides, Ph₃P[dbnd]N(R)HBr, in diethyl ether. Imine boranes, Ph₃P[dbnd]N(R)BH₃, were synthesized where R [dbnd] methyl, ethyl, n-propyl, isopropyl, isobutyl, t-butyl. dimethylamino, phenylamino, and methyl, phenylamino as the nitrogen attached groups. Symmetrical boron cations, (Ph₃P[dbnd]NR)₂, BH₂ ⁺, where R = methyl, ethyl, and n-propyl, were synthesized by displacement of iodide from in-situ generated iodoborane adducts, Ph₃P[dbnd]N(R)BH₂I, by the free imines. An attempt to form an unsymmetrical boron cation from (CH₃)₃ NBH₂I and Ph, P[dbnd]N(n-C₃H₇) resulted only in a mixture of the corresponding symmetrical boron cations. Physical, chemical and spectral properties of the borane adducts and boron cations, namely thermal and hydrolytic stabilities, infrared and NMR data are presented. Oxidative and reductive stabilities of the boron cations were studied. The borane adducts can be chlorinated with either HCI or Ph₃CCI. Relative base strengths of some imines were determined by following the exchange of BH₃ between borane adducts of (CH₃)₃ N or 4- (CH₃)C₅H₄ N and the imines via NMR.     

Zincocene and Dizincocene N‐Heterocyclic Carbene Complexes and Catalytic Hydrogenation of Imines and Ketones

The N‐heterocyclic carbene (NHC) adducts Zn(Cp^R)₂(NHC)] (Cp^R=C₅HMe₄, C₅H₄SiMe₃; NHC=ItBu, IDipp (Dipp=2,6‐diisopropylphenyl), IMes (Mes=mesityl), SIMes) were prepared and shown to be active catalysts for the hydrogenation of imines, whereas decamethylzincocene [ZnCp*₂] is highly active for the hydrogenation of ketones in the presence of noncoordinating NHCs. The abnormal carbene complex [Zn(OCHPh₂)₂(aItBu)]₂ was formed from spontaneous rearrangement of the ItBu ligand during incomplete hydrogenation of benzophenone. Two isolated Zn^I adducts [Zn₂Cp*₂(NHC)] (NHC=ItBu, SIMes) are presented and characterized as weak adducts on the basis of ¹³C NMR spectroscopic and X‐ray diffraction experiments. A mechanistic proposal for the reduction of [ZnCp*₂] with H₂ to give [Zn₂Cp*₂] is discussed.     

“Spontaneous” Ambient Temperature Dehydrocoupling of Aromatic Amine–Boranes

The dehydrocoupling/dehydrogenation behavior of primary arylamine–borane adducts ArNH₂ ? BH₃ ( 3 a – c ; Ar= a : Ph, b : p‐MeOC₆H₄, c : p‐CF₃C₆H₄) has been studied in detail both in solution at ambient temperature as well as in the solid state at ambient or elevated temperatures. The presence of a metal catalyst was found to be unnecessary for the release of H₂. From reactions of 3 a , b in concentrated solutions in THF at 22 °C over 24 h cyclotriborazanes (ArNH‐BH₂)₃ ( 7 a , b ) were isolated as THF adducts, 7 a , b? THF, or solvent‐free 7 a , which could not be obtained via heating of 3 a – c in the melt. The μ‐(anilino)diborane [H₂B(μ‐PhNH)(μ‐H)BH₂] ( 4 a ) was observed in the reaction of 3 a with BH₃?THF and was characterized in situ. The reaction of 3 a with PhNH₂ ( 2 a ) was found to provide a new, convenient method for the preparation of dianilinoborane (PhNH)₂BH ( 5 a ), which has potential generality. This observation, together with further studies of reactions of 4 a , 5 a , and 7 a , b , provided insight into the mechanism of the catalyst‐free ambient temperature dehydrocoupling of 3 a – c in solution. For example, the reaction of 4 a with 5 a yields 6 a and 7 a . It was found that borazines (ArN‐BH)₃ ( 6 a – c ) are not simply formed via dehydrogenation of cyclotriborazanes 7 a – c in solution. The transformation of 7 a to 6 a is slowly induced by 5 a and proceeds via regeneration of 3 a . The adducts 3 a – c also underwent rapid dehydrocoupling in the solid state at elevated temperatures and even very slowly at ambient temperature. From aniline–borane derivative 3 c , the linear iminoborane oligomer (p‐CF₃C₆H₄)N[BH‐NH(p‐CF₃C₆H₄)]₂ ( 11 ) was obtained. The single‐crystal X‐ray structures of 3 a – c , 5 a , 7 a , 7 b? THF, and 11 are discussed.     

Group 6 Transition‐Metal/Boron Frustrated Lewis Pair Templates Activate N2 and Allow its Facile Borylation and Silylation

The reaction of trans ‐[M(N₂)₂(dppe)₂] (M=Mo, 1_Mo , M=W, 1_W ) with B(C₆F₅)₃ ( 2 ) provides the adducts [(dppe)₂M=N=N‐B(C₆F₅)₃] ( 3 ) which can be regarded as M/B transition‐metal frustrated Lewis pair (TMFLP) templates activating dinitrogen. Easy borylation and silylation of the activated dinitrogen ligands in complexes 3 with a hydroborane and hydrosilane occur by splitting of the B−H and Si−H bonds between the N₂ moiety and the perfluoroaryl borane. This reactivity of 3 is reminiscent of conventional frustrated Lewis pair chemistry and constitutes an unprecedented approach for the functionalization of dinitrogen.     

Elucidating organ-specific metabolic toxicity chemistry from electrochemiluminescent enzyme/DNA arrays and bioreactor bead-LC-MS/MS

Human toxic responses are very often related to metabolism. Liver metabolism is traditionally studied, but other organs also convert chemicals and drugs to reactive metabolites leading to toxicity. When DNA damage is found, the effects are termed genotoxic. Here we describe a comprehensive new approach to evaluate chemical genotoxicity pathways from metabolites formed in situ by a broad spectrum of liver, lung, kidney and intestinal enzymes. DNA damage rates are measured with a microfluidic array featuring a 64-nanowell chip to facilitate fabrication of films of DNA, electrochemiluminescent (ECL) detection polymer [Ru(bpy)₂(PVP)₁₀]²⁺ {(PVP = poly(4-vinylpyridine))} and metabolic enzymes. First, multiple enzyme reactions are run on test compounds using the array, then ECL light related to the resulting DNA damage is measured. A companion method next facilitates reaction of target compounds with DNA/enzyme-coated magnetic beads in 96 well plates, after which DNA is hydrolyzed and nucleobase-metabolite adducts are detected by LC-MS/MS. The same organ enzymes are used as in the arrays. Outcomes revealed nucleobase adducts from DNA damage, enzymes responsible for reactive metabolites (e.g. cyt P450s), influence of bioconjugation, relative dynamics of enzymes suites from different organs, and pathways of possible genotoxic chemistry. Correlations between DNA damage rates from the cell-free array and organ-specific cell-based DNA damage were found. Results illustrate the power of the combined DNA/enzyme microarray/LC-MS/MS approach to efficiently explore a broad spectrum of organ-specific metabolic genotoxic pathways for drugs and environmental chemicals.     

Electrochemistry of α, α'-dibromoketones: Reduction of 2,4-dibromo-1,5-diphenyl-1,4-pentadien-3-one (α,α'-dibromo-dibenzylidene acetone) at the mercury electrode

2,4-Dibromo-1,5-diphenyl-1,4-pentadien-3-one (VIII (PhCH=CBrCOCBr=CHPh, α, ga'-dibromodibenzylidene acetone) is electroreduced in “aprotic” dimethylformamide at the mercury electrode; E_1/2 of the first step is ?0.97 V vs. SCE; two electrons/molecule of VIII were transferred (c.p.e.) and two Br^?/molecule of VIII were released. The product was identified as cis-1,5-diphenyl-1-penten-4-yn-3-one(PhCH=CHCOC=CPh), which is the rearrangement product of an unstable dimethylenecyclopropanone. In MeOH solutions, electroreduction of VIII follows a different path, the first two-electron step being substituted by a four-electron step (c.p.e.), which furnishes 3,4-diphenyl-cyclopent-2-enone, XIII. XIII seems to be a rearrangement product of a cyclic precursor. Subsequent two-step reduction of this intermediate in MeOH affords finally 1,5-diphenylpentan-3-one(α, α'-dibenzylacetone).     

Capturing HBCy2: Using N,O‐Chelated Complexes of Rhodium(I) and Iridium(I) for Chemoselective Hydroboration

1,3‐N,O‐chelated complexes of Rh^I and Ir^I cooperatively and reversibly stabilized the B?H bond of HBCy₂ to afford six‐membered metallaheterocycles (M=Rh ( 7 ) or Ir ( 8 )) having a δ‐[M]???H‐B agostic interaction. Treatment of these Shimoi‐type borane adducts 7 or 8 with both an aldehyde and an alkene resulted in chemoselective aldehyde hydroboration and reformation of the 1,3‐N,O‐chelated starting material. The observed chemoselectivity is inverted from that of free HBCy₂, which is selective for alkene hydroboration.     

Mixed-ligand complexes of paddlewheel dinuclear molybdenum as hydrodehalogenation catalysts for polyhaloalkanes

We developed a hydrodehalogenation reaction of polyhaloalkanes catalyzed by paddlewheel dimolybdenum complexes in combination with 1-methyl-3,6-bis(trimethylsilyl)-1,4-cyclohexadiene (MBTCD) as a non-toxic H-atom source as well as a salt-free reductant. A mixed-ligated dimolybdenum complex Mo₂(OAc)₂[CH(NAr)₂]₂ (3a, Ar = 4-MeOC₆H₄) having two acetates and two amidinates exhibited high catalytic activity in the presence of ⁿBu₄NCl, in which [ⁿBu₄N]₂[Mo₂{CH(NAr)₂}₂Cl₄] (9a), derived by treating 3a with ClSiMe₃ and ⁿBu₄NCl, was generated as a catalytically-active species in the hydrodehalogenation. All reaction processes, oxidation and reduction of the dimolybdenum complex, were clarified by control experiments, and the oxidized product, [ⁿBu₄N][Mo₂{CH(NAr)₂}₂Cl₄] (10a), was characterized by EPR and X-ray diffraction studies. Kinetic analysis of the hydrodehalogenation reaction as well as a deuterium-labelling experiment using MBTCD-d₈ suggested that the H-abstraction was the rate-determining step for the catalytic reaction.     

A novel preparation of chlorophospholenium chlorides and their application in the synthesis of phospholene boranes

A novel preparation of 1-chloro-3-methyl-3-phospholenium chlorides was developed by reacting 1-substituted-3-methyl-3-phospholene 1-oxides with oxalyl chloride. The obtained cyclic chlorophosphonium salts were reacted with LiBH₄ to afford the corresponding 1-substituted-3-methyl-3-phospholene boranes. The latter protocol involves a silane-free deoxygenation, and borane complex formation. In one instance, a 2-phospholene borane and the corresponding P-oxide were synthesized via rearrangement of the double bond in the cyclic chlorophosphonium salt. This double bond migration was investigated by quantum chemical calculations.     

Boron Lewis Acid‐Catalyzed Hydroboration of Alkenes with Pinacolborane: BArF3 Does What B(C6F5)3 Cannot Do!

The transition‐metal‐free hydroboration of various alkenes with pinacolborane (HBpin) initiated by tris[3,5‐bis(trifluoromethyl)phenyl]borane (BAr^F₃) is reported. The choice of the boron Lewis acid is crucial as the more prominent boron Lewis acid tris(pentafluorophenyl)borane (B(C₆F₅)₃) is reluctant to react. Unlike B(C₆F₅)₃, BAr^F₃ is found to engage in substituent redistribution with HBpin, resulting in the formation of Ar^FBpin and the electron‐deficient diboranes [H₂BAr^F]₂ and [(Ar^F)(H)B(μ‐H)₂BAr^F₂]. These in situ‐generated hydroboranes undergo regioselective hydroboration of styrene derivatives as well as aliphatic alkenes with cis diastereoselectivity. Another ligand metathesis of these adducts with HBpin subsequently affords the corresponding HBpin‐derived anti‐Markovnikov adducts. The reactive hydroboranes are regenerated in this step, thereby closing the catalytic cycle.     

An Intramolecular Silylene Borane Capable of Facile Activation of Small Molecules,Including Metal‐Free Dehydrogenation of Water

The first single‐component N‐heterocyclic silylene borane 1 (LSi‐R‐BMes₂; L=PhC(N^t Bu)₂; R=1,12‐xanthendiyl spacer; Mes=2,4,6‐Me₃C₆H₂), acting as a frustrated Lewis pair (FLP) in small‐molecule activation, can be synthesized in 65 % yields. Its HOMO is largely localized at the silicon(II) atom and the LUMO has mainly boron 2p character. In small‐molecule activation 1 allows access to the intramolecular silanone–borane 3 featuring a Si=O→B interaction through reaction with O₂, N₂O, or CO₂, and formation of silanethione borane 4 from reaction with S₈. The Si^II center in 1 undergoes immediate hydrogenation if exposed to H₂ at 1 atm pressure in benzene, affording the silane borane 5‐H₂ , L(H₂)Si‐R‐BMes₂. Remarkably, no H₂ activation occurs if the single silylene LSiPh and Mes₃B intermolecularly separated are exposed to dihydrogen. Unexpectedly, the pre‐organized Si–B separation in 1 enables a metal‐free dehydrogenation of H₂O to give the silanone–borane 3 as reactive intermediate.