Regioselective Hydration of Alkynes by Iron(III) Lewis/Brønsted Catalysis

The triflimide iron(III) salt [Fe(NTf(2) )(3) ] promotes the direct hydration of terminal and internal alkynes with very good Markovnikov regioselectivities and high yields. The enhanced carbophilic Lewis acidity of the Fe(III) cation mediated by the weakly-coordinating triflimide anion is crucial for the catalytic activity. The iron(III) metal salt can be recycled in the form of the OPPh(3) /[Fe(NTf(2) )(3) ] system with similar activity and selectivity. However, spectroscopic and kinetic studies show that [Fe(NTf(2) )(3) ] hydrolyzes under the reaction conditions and that catalytically less active Br?nsted species are formed, which points to a Lewis/Br?nsted co-catalysis. This triflimide-based catalytic system is regioselective for the hydration of internal aryl-alkynes and opens the door to a new synthetic route to alkyl ketophenones. As a proof of concept, the synthesis of two antipsychotics Haloperidol and Melperone, with general butyrophenone-like structure, is shown.     

Surfactant-type Brønsted acid catalyzed dehydrative nucleophilic substitutions of alcohols in water

A protocol for the dehydrative nucleophilic substitution of benzyl alcohols with a variety of carbon- and heteroatom-centered nucleophiles using dodecylbenzenesulfonic acid (DBSA) as a surfactant-type Br?nsted acid catalyst in water has been developed. The reaction system can be applied to the stereoselective C-glycosylation of 1-hydroxy sugars in water. [reaction: see text].     

Aminochlorination in water: first Brønsted acid-promoted synthesis of vicinal chloramines

A practical and scaleable route for the regio- and diastereoselective synthesis of vicinal chloramines from electron-deficient olefins and Chloramine-T promoted by Br?nsted acids in water has been realized for the first time. This novel protocol is efficient, mild, ecofriendly, and broadly applicable for the aminochlorination of various electron-deficient olefins including alpha,beta-unsaturated ketones, cinnamate, and cinnamide. Water represents as a privileged solvent for the aminochlorination reaction in our system.     

Probing the Brønsted Acidity of the External Surface of Faujasite-Type Zeolites

We outline two methodologies to selectively characterize the Brønsted acidity of the external surface of FAU-type zeolites by IR and NMR spectroscopy of adsorbed basic probe molecules. The challenge and goal are to develop reliable and quantitative IR and NMR methodologies to investigate the accessibility of acidic sites in the large pore FAU-type zeolite Y and its mesoporous derivatives often referred to as ultra-stable Y (USY). The accessibility of their Brønsted acid sites to probe molecules (n-alkylamines, n-alkylpyridines, n-alkylphosphine- and phenylphosphine-oxides) of different molecular sizes is quantitatively monitored either by IR or ³¹P NMR spectroscopy. It is now possible, for the first time to quantitatively discriminate between the Brønsted acidity located in the microporosity and on the external surface of large pore zeolites. For instance, the number of external acid sites on a Y (LZY-64) zeolite represents 2 % of its total acid sites while that of a USY (CBV760) represents 4 % while the latter has a much lower framework Si/Al ratio.     

Brønsted acid-promoted cyclizations of siloxyalkynes with arenes and alkenes

We have described the first Br?nsted acid-mediated cyclizations of siloxyalkynes with simple arenes and alkenes to afford substituted tetralone and cyclohexenone derivatives. The most notable aspect of the carbocyclizations involving siloxyalkynes is the ability to employ a range of substrates that are not restricted to those containing electron-rich arenes and alkenes. The key mechanistic feature of the reaction is the generation of a highly reactive ketenium ion upon protonation of siloxyalkyne. We believe that the low nucleophilicty of the counteranion is crucial for enabling the formation and effective interception of this highly reactive intermediate.     

Dual Brønsted acid/nucleophilic activation of carbonylimidazole derivatives

Carbonylimidazole derivatives have been found to be highly active acylation reagents for esterification and amidation in the presence of pyridinium salts. These reactions are thought to involve both Br?nsted acid and nucleophilic catalysis. This mode of activation has been applied to the synthesis of difficult to access oxazolidinones, as well as esters and amides. Finally, the use of pyridinium salts has been shown to accelerate the esterification of carboxylic acids with imidazole carbamates.     

Intramolecular cyclization of S-phenyl 3-arylpropynethioates by the action of Brønsted and Lewis acids

Russian Journal of Organic Chemistry -     

Brønsted basicities of diamines in the gas phase, acetonitrile, and tetrahydrofuran

A comprehensive basicity study of alpha,omega-alkanediamines and related bases has been carried out. Basicities in acetonitrile (AN, pK(a) values), tetrahydrofuran (THF, pK(alpha) values), and gas phase (GP, GB values), were measured for 16, 14, and 9 diamine bases and for several related monoamines. In addition the gas-phase basicities and equilibrium geometries were computed for 19 diamino bases and several related monoamines at the DFT B3LYP 6-311+G** level. The effects of the different factors (intrinsic basicity of the amino groups, formation of intramolecular hydrogen bonds, and molecular strain) determining the diamine basicities were estimated by using the method of isodesmic reactions. The results are discussed in terms of molecular structure and solvation effects. The GP basicity is determined by the molecular size and polarizability, the extent of alkylation, and the energy effect of intramolecular hydrogen bond formation in the protonated base. The basicity trends in the solvents differ very much from those in GP: 1) The solvents severely compress the basicity range of the bases studied (3.5 times for the 1,3-propanediamine family in AN, and 7 times in THF), and 2) while stepwise alkylation of the basicity center leads to a steady basicity increase in the gas phase, the picture is complex in the solvents. Significant differences are also evident between THF and AN. The high hydrogen bond acceptor strength of THF leads to this solvent favoring the bases with "naked" protonation centers. In particular, the basicity order of N-methylated 1,3-propanediamines is practically inverse to that in the gas phase. The picture in AN is intermediate between that of GP and THF.     

Rapid access to halohydrofurans via Brønsted acid-catalyzed hydroxylation/halocyclization of cyclopropyl methanols with water and electrophilic halides

A one-pot, two-step method to prepare 3-halohydrofurans efficiently by TfOH-catalyzed hydroxylation/halocyclization of cyclopropyl methanols with H(2)O and N-halosuccinimide (NXS, X=1, Br, Cl) or Selectfluor is described. The reactions proceed rapidly under mild and operationally straightforward conditions with a catalyst loading as low as 1 mol % and afford the 3-halohydrofuran products in moderate to excellent yields and, in most cases, with preferential cis diastereoselectivity. The method was shown to be applicable to cyclopropyl methanols containing electron-withdrawing, electron-donating, and sterically demanding functional groups and electrophilic halide sources. The mechanism is suggested to involve protonation of the alcohol substrate by the Br?nsted acid catalyst and ionization of the starting material. This results in ring-opening of the cyclopropane moiety and in situ formation of a homoallylic alcohol intermediate, which undergoes subsequent intramolecular halocyclization on treating with the electrophilic halide source to give the halohydrofuran. The observed cis product selectivity is thought to be determined by the reaction proceeding through an in situ generated unsaturated alcohol intermediate that contains a (Z)-alkene moiety under the kinetically controlled conditions.     

Brønsted Acid-Catalyzed General Petasis Allylation and Isoprenylation of Unactivated Ketones

Brønsted acid-catalyzed general Petasis allylation and isoprenylation of unactivated ketones were developed by using o-hydroxyaniline and the corresponding pinacolyl boronic esters. This robust methodology provided access to a broad variety of quaternary homoallylic amines and dienyl amines in high yields, proved to be applicable to a gram-scale synthesis, and allowed the synthesis of a potentially bioactive quaternary homoallylic aminodiol.     

Relationship between the Brønsted Coefficients of the Steps of a Heterogeneous Catalytic Reaction

Kinetics and Catalysis - The thermodynamics of the catalytic cycle under the influence of the reaction medium on the catalyst was considered. The change in the activation energy of the reaction...     

Identifying the Role of Brønsted and Lewis Acid Sites in the Diels-Alder Cycloaddition of 2,5-DMF and Ethylene

The role of Lewis and Brønsted acid sites in the Diels-Alder cycloaddition (DAC) of ethylene to 2,5-dimethylfuran (2,5-DMF) to p-xylene was investigated. Amorphous silica catalysts containing Al³⁺ (ASA), Ga³⁺ (ASG), and In³⁺ (ASI) were prepared via homogeneous deposition-precipitation. Silica modified with Zr⁴⁺ (ASZ) was prepared by impregnation. Their acidic properties were characterized by various IR and NMR spectroscopic techniques. Measurements using pyridine as a probe molecule highlighted the presence of mostly Lewis acid sites (LAS) in all materials. Using CO as a probe, in contrast, demonstrated the existence of Brønsted acid sites (BAS) in ASA and ASG, which were nearly absent in ASI and ASZ. Differences in basic strength can explain the contrast in results observed between the two probe molecules. The highest p-xylene yield (~20 %) in the DAC reaction, could be achieved with ASA and ASG. The lack of BAS in ASI and ASZ resulted in inferior performance in the DAC, with p-xylene yields below 5 %. These results indicate the importance of BAS for the DAC reaction. Several other heterogeneous and homogeneous catalysts were explored for the DAC reaction to show the generality of our conclusion that BAS play a critical role in obtaining p-xylene from 2,5-DMF and ethylene.     

Stereochemistry and mechanism of the Brønsted acid catalyzed intramolecular hydrofunctionalization of an unactivated cyclic alkene

Through employment of deuterium-labeled substrates, the triflic acid catalyzed intramolecular exo addition of the X-H(D) (X=N, O) bond of a sulfonamide, alcohol, or carboxylic acid across the C=C bond of a pendant cyclohexene moiety was found to occur, in each case, with exclusive formation (≥90%) of the anti-addition product without loss or scrambling of deuterium as determined by (1)H and (2)H NMR spectroscopy and mass spectrometry analysis. Kinetic analysis of the triflic-acid-catalyzed intramolecular hydroamination of N-(2-cyclohex-2'-enyl-2,2-diphenylethyl)-p-toluenesulfonamide (1a) established the second-order rate law: rate=k(2)[HOTf][1a] and the activation parameters ΔH(++)=(9.7±0.5) kcal mol(-1) and ΔS(++)=(-35±5) cal K(-1) mol(-1). An inverse α-secondary kinetic isotope effect of k(D)/k(H) =(1.15±0.03) was observed upon deuteration of the C2' position of 1a, consistent with partial C-N bond formation in the highest energy transition state of catalytic hydroamination. The results of these studies were consistent with a mechanism for the intramolecular hydroamination of 1a involving concerted, intermolecular proton transfer from an N-protonated sulfonamide to the alkenyl C3' position of 1a coupled with intramolecular anti addition of the pendant sulfonamide nitrogen atom to the alkenyl C2' position.     

Influence of the structure of polyfluorinated alcohols on Brønsted acidity/hydrogen-bond donor ability and consequences on the promoter effect

The influence of substituents on the properties of tri- and hexafluorinated alcohols derived from 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) was examined. Measurements of specific solvent-solute interactions revealed that H-bond donation (HBD) of fluorinated alcohols is sensitive to the steric hindrance of the OH group, whereas their Br?nsted acidity is dependent only on the number of fluorine atoms. For hexafluorinated alcohols (HFAs), their association with amines characterized by X-ray diffraction showed that the balance between HBD and acidity is influenced by their structure. Moreover, the ability of HFAs to donate H-bonds is exerted in synclinal (sc), synperiplanar (sp), and also antiperiplanar (ap) conformations along the C-O bond. Comparison of the effects of fluorinated alcohols as promoting solvents in three reactions is reported. The positive correlation between rate constants and H-bonding donation ability for sulfide oxidation and imino Diels-Alder reaction brings to light the role of this property, while acidity might have a minor influence. In the third reaction, epoxide opening by piperidine, none of these properties can clearly be put forward at this stage.     

Brønsted acid catalyzed enantioselective α-amidoalkylation in the synthesis of isoindoloisoquinolines

The Parham cyclization-intermolecular α-amidoalkylation sequence results in the facile enantioselective synthesis of 12b-substituted isoindoloisoquinolines (ee up to 95%) using BINOL-derived Br?nsted acids. α-Amidoalkylation of indole occurs through the formation of a chiral conjugate base/bicyclic quaternary N-acyliminium ion pair.     

Reactivity of Diphenylberyllium as a Brønsted Base and Its Synthetic Application

Diphenylberyllium [Be₃Ph₆] is shown here to react cleanly as a Brønsted base with a vast variety of protic compounds. Through the addition of the simple molecules tBuOH, HNPh₂ and HPPh₂, as well as the more complex 1,3-bis-(2,6-diisopropylphenyl)imidazolinium chloride, one or two phenyl groups in diphenylberyllium were protonated. As a result, the long-postulated structures of [Be₃(OtBu)₆] and [Be(μ-NPh₂)Ph]₂ have finally been verified and shown to be static in solution. Additionally [Be(μ-PPh₂)(HPPh₂)Ph]₂ was generated, which is only the second beryllium-phospanide to be prepared; the stark differences between its behaviour and that of the analogous amide were also examined. The first crystalline example of a beryllium Grignard reagent with a non-bulky aryl group has also been prepared; it is stabilised with an N-heterocyclic carbene.     

Trimethylsilylation of framework Brønsted acid sites in microporous zeolites and silico-aluminophosphates

Framework-bound alkoxy groups are well-studied intermediates in zeolite chemistry, but their low stability complicates their spectroscopic study in high-temperature reactions such as alkylation or dealkylation. Taking advantage of the much higher bond strength of Si-O versus C-O, we synthesized trimethylsilylated zeolites by reacting them with phenyltrimethylsilane in a catalytic flow reactor at 648 K. In favorable cases, the reaction accurately titrated the acid sites, and 29Si and 13C MAS NMR spectra of the derivatized catalysts measured at room temperature confirmed the proposed reaction.