Testing the veracity of claims of Lewis acid catalysis

Are reactions employing Lewis acids really catalysed by those Lewis acids, or by “hidden Brønsted acids”, i.e. Brønsted acids generated in situ by hydrolysis? Testing of a series of reactions using Sc(III), Fe(III), In(III) and Y(III) by addition of 2,6-di-t-butyl-4-methylpyridine reveal that all are likely to follow the latter pathway. A reaction claimed to be catalysed by CBr₄ through halogen bonding is also likely to be Brønsted acid catalysed.     

A theoretical comparison of Lewis acid vs bronsted acid catalysis for n-hexane --> propane + propene

Cracking of an all-trans n-alkane, via idealized Lewis acid and Bronsted acid catalysis, was examined using density functional theory. Optimized geometries and transitions states were determined for catalyst-reactant complexes, using AlCl3 and HCl.AlCl3 as the Lewis and Bronsted acids. For the Lewis acid cycle, hydride-transfer steps are seen to have large barriers in both forward and reverse directions, and an unstable physisorbed carbenium ion (lying 20 kcal mol(-1) above the chemisorbed intermediate) is the launching point for the beta-scission that leads to products. For the Bronsted acid cycle, proton-transfer steps have smaller barriers in both forward and reverse directions, and a semistable physisorbed alkanium ion is the launching point for the alkanium alpha-scission that leads to products. In the idealized Lewis cycle, formation of HCl units (and hence Bronsted acids) was found to be a common side reaction. A recent ionic-liquid catalysis study is mentioned as motivation, although our study is not a computational modeling study; we are more interested in the fundamental differences between Brosnted and Lewis mechanisms rather than merely mimicking a particular system. However, results of exploratory optimizations of various intermediates with Al2Cl7- as the catalyst are presented to provide the first step for future modeling studies on the ionic liquid system.     

取代硫酸、氢氟酸等液体酸催化剂的途径

高效固体酸催化剂无论对现有工业生产, 还是从环保考虑, 都是十分重要的。特别是对那些使用液体酸诸如H₂SO₄、HF 和A lCl₃ 等为催化剂的液相酸工艺。近年来考虑到均相和多相酸催化反应中起决定作用的酸位(中心) 之间的类似性, 根据近代均相酸催化理论, 通过对不同酸位(L 酸、B 酸、超强酸) 本质的分析, 对强酸催化剂提出了一个统一的酸结构模型。以此为依据, 可对一些强酸催化剂进行剪裁。     

Reactions of diazo esters with electron-deficient alkenes in the presence of Lewis acids

1,3-Dipolar cycloaddition reaction of diazo esters to electron-deficient dipolarophiles to yield the corresponding 1- or 2-pyrazolines was found to be significantly accelerated with Lewis acids (Yb(OTf)₃, Sc(OTf)₃, GaCl₃, EtAlCl₂). The use of GaCl₃ as the catalyst leads to the acceleration not only of the 1,3-dipolar cycloaddition reaction, but also subsequent insertion of the CHCO₂Me electrophilic fragment of methyl diazoacetate into the N-H bond of 2-pyrazolines formed. Such Lewis acids as SnCl₄, BF₃, TiCl₄, and In(OTf)₃ are not efficient in the described processes, since they rapidly decompose starting diazo compounds.     

Decarboxylation with Carbon Monoxide: The Direct Conversion of Carboxylic Acids into Potent Acid Triflate Electrophiles

We report a new strategy for the conversion of carboxylic acids into potent acid triflate electrophiles. The reaction involves oxidative carbonylation of carboxylic acids with I₂ in the presence of AgOTf, and is postulated to proceed via acyl hypoiodites that react with CO to form acid triflates. Coupling this chemistry with subsequent trapping with arenes offers a mild, room temperature approach to generate ketones directly from broadly available carboxylic acids without the use of corrosive and reactive Lewis or Bronsted acid additives, and instead from compounds that are readily available, stable, and functional group compatible.     

Evaluation of chiral bidentate ligand–metal complexes in asymmetric 1,3-dipolar cycloaddition reaction of nitrones with 3-alkenoyl-2-oxazolidinones

For evaluation of a chiral C₂-symmetric bis(oxazoline) ligand, its Lewis acid complexes-catalyzed asymmetric 1,3-dipolar cycloaddition reactions of nitrones with electron-deficient dipolarophiles, 3-(2-alkenoyl)-1,3-oxazolidin-2-ones, have been investigated and it was found that the cycloadditions using a Cu(II)-bis(oxazoline) complex under optimized reaction conditions induced extremely high enantioselectivity.     

`Thiobenzophenone S‐Methylide' (=(Diphenylmethylidenesulfonio)methanide), and C,C Multiple Bonds: Cycloadditions and Dipolarophilic Reactivities

Thiobenzophenone and diazomethane afford thiadiazoline 1 at −78°. By elimination of N₂ from 1 at −45° (t_1/2 ca. 1 h), (diphenylmethylidenesulfonio)methanide ( 2 ), which cannot be isolated but is interceptible by dipolarophiles, is set free. The nucleophilic 1,3‐dipole 2 undergoes cycloadditions with electrophilic C,C multiple bonds; the structures of 16 cycloadducts were elucidated. One‐step and two‐step cycloaddition pathways are discussed in the light of the steric course observed for (E)/(Z)‐isomeric ethylene derivatives. Competition experiments with pairs of dipolarophiles at −45° and HPLC analysis of the adducts provided relative rate constants of 26 dipolarophiles, involving 2 C≡C, 13 C=C, 9 C=S, and 2 N=N bonds. In accordance with Sustmann`s reactivity model of concerted cycloadditions, 2 shows the highest selectivity of all known 1,3‐dipoles, i.e., the largest spread of rate constants (k_rel=1 for methyl propiolate and 33×10⁶ for TCNE). As a consequence of low LU energies, thiones are very active dipolarophiles, and fluorene‐9‐thione (k_rel=79×10⁶) stands at the top.     

The Influence of Aluminum-Containing Lewis Acids on Polyisobutylene,Isobutylene-lsoprene Copolymers (Butyl Rubber), and Chlorinated Isobutylene-lsoprene Copolymer (Chlorobutyl)

The influence of aluminum-containing Lewis acids, e.g., AlCl₃, AlEtCl₂, AlEt₂Cl, AlEt₃, and AliBu₃, on polyisobutylene, isobutylene-isoprene copolymer (butyl rubber), and chlorinated butyl rubber has been investigated in nonpolar and polar solvents at various Lewis acid concentrations in the temperature range -10 to -78°C. Polyisobutylene does not degrade even under the most aggressive conditions employed (AlEtCl₂, -10°C). Butyl rubber degrades rapidly in the presence of AlEtCl₂ in the range -10 to -50°C. In contrast, no degradation occurs with the milder Lewis acid AlEt₂Cl; however, in conjunction with small amounts of a suitable Bronsted acid (i.e., HCl) immediate and extensive degradation takes place with AlEt₂Cl as well. Chlorobutyl rubber severely and very rapidly degrades in the presence of AlCl₃ and AlEtCl₂. With the less acidic AlEt₂Cl and AlEt₃, molecular weight breakdown can be prevented only when employing milder conditions, i.e., at low Lewis acid concentrations in nonpolar solvents at lowest temperatures. A comprehensive mechanism involving carbonium ions of these degradation processes is proposed.     

Investigation of Lewis Acid versus Lewis Base Catalysis in Asymmetric Cyanohydrin Synthesis

The asymmetric addition of trimethylsilyl cyanide to aldehydes can be catalysed by Lewis acids and/or Lewis bases, which activate the aldehyde and trimethylsilyl cyanide, respectively. It is not always apparent from the structure of the catalyst whether Lewis acid or Lewis base catalysis predominates. To investigate this in the context of using salen complexes of titanium, vanadium and aluminium as catalysts, a Hammett analysis of asymmetric cyanohydrin synthesis was undertaken. When Lewis acid catalysis is dominant, a significantly positive reaction constant is observed, whereas reactions dominated by Lewis base catalysis give much smaller reaction constants. [{Ti(salen)O}₂] was found to show the highest degree of Lewis acid catalysis, whereas two [VO(salen)X] (X=EtOSO₃ or NCS) complexes both displayed lower degrees of Lewis acid catalysis. In the case of reactions catalysed by [{Al(salen)}₂O] and triphenylphosphine oxide, a non‐linear Hammett plot was observed, which is indicative of a change in mechanism with increasing Lewis base catalysis as the carbonyl compound becomes more electron‐deficient. These results suggested that the aluminium complex/triphenylphosphine oxide catalyst system should also catalyse the asymmetric addition of trimethylsilyl cyanide to ketones and this was found to be the case.     

Reactivity sequences of dipolarophiles towards diazocarbonyl compounds - MO perturbation treatment

Whereas diazomethane cycloadditions are only accelerated by electron-attracting substituents in the olefinic or acetylenic dipolarophile, the cycloadditions of diazoacetic, diazomalonic and diazo(phenylsulfonyl)acetic ester show in accordance with the PMO treatment U-shaped activity functions when log k₂ is plotted versus the lowest IP of the dipolarophiles.     

The chemistry of fulminic acid revised

The availability of a new synthesis of fulminic acid by hydrolysis of trimcthylsilanecarbonitrile oxide allowed a reinvestigation of the chemistry of the title compound. Thus, cycloadditions to olefinic and acetylenic dipolarophiles are improved with respect to previous results and the oligomerisation is proved to occur via the reactive species hydroxyiminoacetonitrile oxide 7 and hydroxyiminomethyl-hydroxyiminoacetonitrile oxide 8. The Z-configuration, found for the oxime groups in these intermediates, is maintained in their derivatives, under kinetic controls.     

Selectivity in cycloadditions—-XII : The directive effect of enol ethers and thioenol ethers in cycloadditions of nitrile oxides

Cycloadditions of nitrile oxides to 2,3-dihydrofuran are highly regioselective whereas the regioselectivity of the cycloadditions to 2,3-dihydrothiophen is only moderate. The directing effect of oxygen and sulfur in these cycloadditions could be evaluated at 2.8 and 1.1 Kcal mol^-1 respectively. The related acyclic sulfur dipolarophiles, (E)-propenyl methyl and phenyl sulfides, similarly undergo cycloadditions with moderate regiochemistry.The different regioselectivities and reactivities of the dipolarophiles can be related to differences in energies and shapes of their highest occupied orbitals, which are also responsible for the diverging behaviour observed in the electrophilic reactions and 2 + 2 cycloadditions of enol and thioenol ethers.     

Synthesis of hantzsch 1,4‐dihydropyridines under solvent‐free condition using zn[(L)proline]2 as lewis acid catalyst

The present short communication describes a Lewis acid (Zn[(L)proline]₂) catalysed one pot synthesis of Hantzsch 1,4‐dihydropyridine (DHP) derivatives under solvent‐free condition by conventional heating and microwave irradiation. The Lewis acid catalyst Zn[(L)proline]₂ used in this reaction afford moderate to good yield. The catalyst is reusable upto five cycles without appreciable loss of its catalytic activity.     

Quantum-chemical study of the Lewis acid influence on the cycloaddition of benzonitrile oxide to acetonitrile, propyne and propene

Quantum chemical methods (MP2 and B3LYP) together with a topological analysis of the charge density have been used to study the BH₃- or BF₃-mediated reaction of benzonitrile oxide with acetonitrile, propyne and propene. In the reaction with propene or propyne, addition of Lewis acids has only little influence on the outcome of the reactions. The cycloaddition of nitrile oxides with nitriles, however, is generally promoted by strong Lewis acids. When the Lewis acid coordination takes place at the nitrile oxide the reactant is activated and the product binds weakly to the Lewis acid so that the reaction is expected to be catalytic. In the case of coordination to the nitrile the reaction is Lewis acid mediated. Here the reactant is not much influenced by addition of Lewis acid, but the transition state and the product are stabilised and consequently such processes require a stoichiometric amount of Lewis acid and form a stable Lewis acid-product complex.It has also been demonstrated that the different activation routes for these reactions involve different reaction mechanisms. Whereas the reaction of a Lewis acid coordinated nitrile oxide is of ‘inverse electron demand’, the Lewis acid coordinated nitrile reacts through a ‘normal electron demand’ cycloaddition.     

Solid state 13C NMR can distinguish between bronsted and Lewis acid adducts of amines

The solid ¹³C NMR spectra of solid complexes of phenethylamine with SnCl_4, Me₃SnCl, AlCl_3, and HCl are presented and discussed as a means of distinguishing between Bronsted and Lewis acid adducts of alkyl amines. Solution ¹³C NMR results are discussed in terms of species present in complex equilibria and their detection using the two NMR methods.     

trans-3,4-Disubstituted pyrrolidines by 1,3-dipolar cycloaddition: enantioselective approaches and their limitations

In the presence of a chiral Lewis acid as co-catalyst, the acid-catalysed 1,3-dipolar cycloaddition reaction yielding trans-3,4-disubstituted pyrrolidines from an azomethine ylide and achiral α,β-unsaturated dipolarophiles proceeded with low enantioselectivity. Therefore a number of α,β-unsaturated dipolarophiles linked to chiral auxiliaries were examined as substrates. Camphorsultam was the best auxiliary and gave good diastereoselectivity (dr=74:26). When combining chiral Lewis acids with a dipolarophile linked to a chiral auxiliary, the enantioselectivity could be slightly increased. As judged by ¹³C NMR, the small effect of the chiral Lewis acids on selectivity was probably due to breakdown of the initially formed complex with the dipolarophile caused by the dipole precursor.     

Solvolytic behaviour and the solubilities of various inorganic compounds, lewis acids and bases in fused monobromo acetic acid solvent system—II

Solubilities and the solvolytic behaviour of various inorganic compounds, Lewis acids and bases in fused monobromoacetic acid at 60 ± 0.5°C are discussed. Ionic compounds are fairly soluble, iodides and thiocyanates being comparatively more soluble than chlorides and bromides. Tetraalkyl ammonium halides are highly soluble in this solvent. Conductometric and spectroscopic studies of various Lewis acids and bases in fused monobromoacetic acid indicate their solvolytic behaviour and their subsequent ionization. The solvolyses products BBr₃·CH₂BrCOOH and SbCl₅·CH₂BrCOOH have been observed to be the strongest Bronsted acids. Auto-ionization of this solvent has been supported by acid/base titrations.     

Poly(vinyl chloride) stabilisation with organotin compounds: Part IV—Catalysis of the reverse reaction: Addition of HCl to double bonds

The addition of HCl to 2–4 hexadiene in chlorinated solvents leads to an equimolar mixture of isomers of chlorohexene of which the 2–3 isomer (chloro-2-hex-3-ene) is kinetically more favoured than the 4-2 (chloro-4-hex-2-ene). The reaction is catalysed by Lewis acids such as the organotin chlorides, in the order of their Lewis acidity, in the same way as the dehydrochlorination of the chlorohexenes and their isomerisation. The same carbocation intermediate is believed to be involved in these reactions and its formation can be catalysed by the Lewis acid. It may also be inhibited by organotin chlorides such as tributyltin chloride, which reacts with HCl to give dibutyltin dichloride and butane, and thus inhibits the formation of the catalyst charge transfer complex between HCl and the diene. Furthermore, because the disappearance of hexadiene, through oligomerisation, is shown to be catalysed less by organotin chlorides than by ZnCl₂, the yield of HCl addition in the presence of tin compounds is higher.     

Factors affecting the competitive reduction of 8,8-dimethylnaphthalene-1,4,5(8H)-trione in a Diels–Alder cycloaddition with hydroxysulfinyldienes

Competing reduction and cycloaddition products were formed in the reaction of 8,8-dimethylnaphthalene-1,4,5(8H)-trione with a hydroxysulfinyldiene. The ratio of reduction to cycloaddition products depended on the stereochemistry of the diene and on the solvent employed, being higher in ethanol than in benzene. The ratio was also affected by the addition of Lewis acids, decreasing in the order BF₃ = Al₂O₃ > MgCl₂ > ZnCl₂. The results help to explain and predict the occurrence of these competing processes in Diels–Alder cycloadditions involving quinonedienophiles.     

Inverse electron demand asymmetric cycloadditions of cyclic carbonyl ylides catalyzed by chiral Lewis acids—Scope and limitations of diazo and olefinic substrates

High enantioselectivities (94-96% ee) were obtained for the inverse electron-demand 1,3-dipolar cycloadditions between cyclohexyl vinyl ether and 2-benzopyrylium-4-olate generated via Rh₂(OAc)₄-catalyzed decomposition of o-methoxycarbonyl-α-diazoacetophenone. The reactions were effectively catalyzed by Eu(OTf)₃, Ho(OTf)₃, or Gd(OTf)₃ complexes (10 mol %) of chiral 2,6-bis[(4S,5S)-4,5-diphenyl-2-oxazolinyl]pyridine. The reactions with the other electron-rich dipolarophiles such as allyl alcohol, 2,3-dihydrofuran, and butyl-tert-butyldimethylsilylketene acetal showed moderate enanantioselectivities (60-73% ee). Good to high enantioselectivities (73-97% ee) were also obtained for the cycloadditions between 3-acyl-2-benzopyrylium-4-olates, generated from methyl 2-(2-diazo-1,3-dioxoalkyl)benzoates and butyl or cyclohexyl vinyl ethers, in the presence of binaphthyldiimine (BINIM)-Ni(II) complexes (10 mol %). Under similar conditions, the reaction between methyl 2-(2-diazo-1,3-dioxohexyl)benzoate and 2,3-dihydrofuran was highly endo-selective, and moderately enantioselective (70% ee). For the BINIM-Ni(II)-catalyzed reactions of cyclohexyl vinyl ether, the use of an epoxyindanone as the 3-acyl-2-benzopyrylium-4-olate precursor revealed that the chiral Lewis acid can function as a catalyst for asymmetric induction. The scope of the cyclic carbonyl ylides was extended to those generated from 1-diazo-2,5-pentanedione derivatives, which were reacted with butyl or TBS vinyl ether and catalyzed using the (4S,5S)-Pybox-4,5-Ph₂-Lu(OTf)₃ complex to give good levels of asymmetric inductions (75-84% ee).