Synthesis of 3,4-disubstituted piperidines by carbonyl ene and prins cyclizations: switching between kinetic and thermodynamic control with Brønsted and Lewis acid catalysts

A novel approach to cis and trans 3,4-disubstituted piperidines is described. Carbonyl ene cyclization of aldehydes 4a-e catalyzed by MeAlCl(2) in refluxing chloroform afforded the trans piperidines 7a-e with diastereomeric ratios of up to 93:7, while aldehyde 4f afforded solely the cis product 6f, which was resistant to isomerization to the trans isomer. It was demonstrated for 4a that the cyclization catalyzed by a variety of Lewis acids at low temperature proceeded under kinetic control to afford predominantly the cis piperidine 6a, and this isomerized to the thermodynamically more stable trans piperidine 7a on warming. In contrast, Prins cyclization of 4a-e catalyzed by concentrated hydrochloric acid in CH2Cl2 at low temperature afforded cis piperidines 6a-e with diastereomeric ratios of up to >98:2. The yield and diastereoselectivity of these cyclizations could be improved by using HCl-saturated CH2Cl2 to form the corresponding chloride, followed by elimination of HCl effected by ammonia. Aldehydes 4f and 4galso cyclized in good yield under the latter conditions. Mechanistic studies supported by DFT calculations (B3LYP/6-31G(d)) suggest that the cyclizations proceed via a mechanism with significant carbocationic character, with the cis carbocation being more stable than the trans carbocation. DFT calculations (B3LYP/6-31G(d)) of the transition state energies for concerted cyclization show that the cis piperidine is also the favored product from cyclization through a more concerted mechanism.     

Synergy between Brønsted acid sites and Lewis acid sites

Synergy between Br?nsted acid sites and Lewis acid sites in mesoporous Al-Zr-TUD-1 was demonstrated to exist in Br?nsted acid catalysed reactions, but not in Lewis acid catalysed reactions.     

Unprecedented synergistic effects between weak Lewis and Brønsted acids in Prins cyclization

Novel synergistic effects between Lewis and Br?nsted acids in Prins cyclization are reported. Non-reactive Lewis acids and non-reactive Br?nsted acids, which failed to perform Prins cyclization when used alone, have shown remarkable synergistic effects when used in combination to perform the reaction successfully.     

Brønsted acid-catalyzed intramolecular hydroamination of protected alkenylamines. Synthesis of pyrrolidines and piperidines

[reaction: see text]. The cyclization of aminoalkenes bearing an electron-withdrawing group on the nitrogen atom was catalyzed by triflic or sulfuric acid in toluene. Pyrrolidines and piperidines were formed in excellent yields. N-phenylanilides also underwent cyclization to form gamma-lactams.     

Complex containing a Lewis acid and Brønsted acid for the catalytic reactions of aza-Michael addition

The novel efficient complex catalyst containing a Lewis acid and a Brønsted acid have been prepared by the reaction of proline ion liquid and cuprous iodide. The catalyst was characterized by FT-IR techniques using pyridine as probe molecule. A fast, mild, and quantitative procedure for aza-Michael addition reactions between various amines and α,β-unsaturated carbonyl compounds and nitriles has been developed using the novel complex catalyst. The results showed that the novel catalyst owned high activities for the reactions with excellent yields within 1 min.     

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.     

Dynamical Equilibrium between Brønsted and Lewis Sites in Zeolites: Framework-Associated Octahedral Aluminum

While the structures of Brønsted acid sites (BAS) in zeolites are well understood, those of Lewis acid sites (LAS) remain an active area of investigation. Under hydrated conditions, the reversible formation of framework-associated octahedral aluminum has been observed in zeolites in the acidic form. However, the structure and formation mechanisms are currently unknown. In this work, combined experimental ²⁷Al NMR spectroscopy and computational data reveal for the first time the details of the zeolite framework-associated octahedral aluminium. The octahedral LAS site becomes kinetically allowed and thermodynamically stable under wet conditions in the presence of multiple nearby BAS sites. The critical condition for the existence of such octahedral LAS appears to be the availability of three protons: at lower proton concentration, either by increasing the Si/Al or by ion-exchange to non-acidic form, the tetrahedral BAS becomes thermodynamically more stable. This work resolves the question about the nature and reversibility of framework-associated octahedral aluminium in zeolites.     

Generation of a solid Brønsted acid site in a chiral framework

Protonation of chiral porous materials introduces a Br?nsted acid centre, the structure of which is unique to the heterogeneous phase requiring pore wall confinement for stable isolation.     

Synergistic role of Brønsted and Lewis acidity in alkali metal-exchanged heteropolyacid catalysts for esterification of acetic acid at room temperature

A series of Cs exchanged phosphotungstic acid (PTA) catalysts were synthesized by the ion exchanged method and were characterized by X-ray diffraction, FT-IR spectroscopy, pyridine adsorbed FT-IR spectroscopy, SEM, BF-TEM, ICP-OES and BET surface area analysis. For comparison purposes, K exchanged PTA, Cs and K exchanged phosphomolybdic acid (PMA) catalysts were also prepared. XRD diffractograms showed that the crystallites of the Keggin ion are maintained, while FT-IR spectra also revealed the characteristic bands of the Keggin ion at all metal loadings of all the catalysts. From pyridine adsorbed FT-IR spectroscopy, it was observed that the Brønsted and Lewis acidity were significantly maintained at lower metal loadings, whereas STEM analysis showed a uniform distribution of the elements which correlated well with the theoretical atomic values of the loaded metals for all the catalysts, which were verified by ICP results. The efficiency of various metal-exchanged heteropolyacid catalysts was assessed for the esterification reaction using various substrates, and the Cs exchanged phosphotungstic acid catalysts showed superior activity compared to the other catalysts. In particular, the Cs exchanged phosphotungstic acid with a 1 wt% loading showed the highest activity and was most tolerant to the presence of water that was produced in the reaction. The catalytic activity correlates well with the Brønsted and Lewis acidity, as well as Keggin ion density of the catalysts.     

Enantioselective bromocycloetherification by Lewis base/chiral Brønsted acid cooperative catalysis

A binary catalyst system for the enantioselective bromocycloetherification of 5-arylpentenols is described. The combination of an achiral Lewis base and a chiral Br?nsted acid affords good enantioselectivities for the cyclization of Z configured 5-arylpentenols to form bromomethyltetrahydrofurans. The constitutional site selectivity is highly dependent upon the aromatic substituent and the configuration of the double bond.     

Reversal of chemoselectivity in Diels-Alder reaction with alpha,beta-unsaturated aldehydes and ketones catalyzed by Brønsted acid or Lewis acid

[reaction: see text] High chemoselectivity was observed in the Diels-Alder reaction of alpha,beta-unsaturated aldehyde and alpha,beta-unsaturated ketone with cyclopentadiene. Using Tf2NH as catalyst, the reaction gave Diels-Alder adduct derived from alpha,beta-unsaturated ketone as a major product. On the other hand, bulky Lewis acid, B(C6F5)3, gave mainly the cycloadduct of alpha,beta-unsaturated aldehyde and cyclopentadiene.     

Chiral Brønsted acids in enantioselective carbonyl activations--activation modes and applications

Chiral phosphoric acids and derivatives have attracted considerable attention as a powerful tool in asymmetric catalysis. Various enantioselective reactions have been developed by using these efficient Br?nsted acid organocatalysts. Although initially the activation was restricted to reactive Br?nsted basic substrates, recent reports are demonstrating the versatility of phosphoric acid catalysts in the activation of carbonyl compounds in a stereochemically controlled fashion. This tutorial review gives an overview of enantioselective Br?nsted acid catalyzed transformations with the main focus on carbonyl activation. Different activation modes, key features of the catalysts and the applied substrates are presented and discussed with the goal to elucidate the origin of stereoselectivity in these Br?nsted acid catalyzed transformations.     

Efficient Synthesis of bis- and tris-Indolylalkanes Catalyzed by a Brønsted Acid–Surfactant Catalyst in Water

A simple and efficient synthesis of bis- and tris-indolylalkanes from carbonyls (aldehydes/ketones) and indoles with excellent yields in the presence of dodecylsulphonic acid (DSA) in water at room temperature is described. The catalyst is also applicable for the synthesis of 3,3-di(3-indolyl)oxindoles. The dodecylsulphonic acid acts as both Brønsted acid and surface-active agent in the reaction mixture.     

Novel solid acid with both Brønsted and Lewis acid sites for biodiesel synthesis

The solid acid with both Brønsted and Lewis acid sites has been synthesized from resorcinol-formaldehyde (RF) resin, hydroxyethylsulfonic acid and copper hydroxyethylsulfonate. The solid acid was applied to catalyze the transesterification of rapeseed oil. The results showed that the novel solid acid was very efficient for the biodiesel synthesis with the yield over 99% even for the rapeseed oil with high water content and both the free fatty acid and triglyceride could be efficiently transformed to the biodiesel products. The regular sphere structure, low cost, high acidity and catalytic activities gave the solid acid great potential for green chemical processes.     

Direct thioesterification from carboxylic acids and thiols catalyzed by a Brønsted acid

In the presence of a catalytic amount of trifluoromethanesulfonic acid, free carboxylic acids reacted with free thiols directly to afford the corresponding thioesters in high yields.