Nonaromatic amidine derivatives as acylation catalysts

[reaction: see text] Catalytic activity of nonaromatic bicyclic amidines and bicyclic isothioureas in acylation reactions was found to be remarkably dependent on the sizes of both rings. DBN and especially its thia-analogue (THTP) have been identified as highly active acylation catalysts.     

Mechanism of the Meerwein-Ponndorf-Verley-Oppenauer (MPVO) redox equilibrium on Sn- and Zr-beta zeolite catalysts

The mechanism of the Meerwein-Ponndorf-Verley (MPV) reduction of cyclohexanone with 2-butanol catalyzed by Sn-beta and Zr-beta zeolites has been theoretically investigated using density functional theory (DFT) and the cluster approach. An experimental catalytic study has shown that the active sites in the MPV reaction catalyzed by Sn-beta are the same partially hydrolyzed Sn-OH groups that were found to be active for the Baeyer-Villiger (BV) reaction. The computational study indicates that the mechanism of Sn-beta and Zr-beta catalysis is similar, and involves the following steps: adsorption of both the ketone and the alcohol on the Lewis acid center, deprotonation of the alcohol, carbon-to-carbon hydride transfer, proton transfer from the catalyst, and products exchange. As in the aluminum alkoxide catalyzed reaction, the hydride shift occurs through a six-membered transition state, and the role of the hydrolyzed and therefore more flexible M-OH bond is just to facilitate the initial deprotonation of the alcohol.     

Aminopyridines as acylation catalysts for tertiary alcohols

The acylation of unreactive alcohols with acid anhydrides is greatly facilitated by the addition of a catalytic (0.02–0.1 equivalent) amount of a 4-dialkylaminopyridine. The reaction is faster in nonpolar than in polar solvents and acetyl chloride is not as effective as acetic anhydride. Several pyridine, pyridazine, and quinoline derivatives have been examined as potential acylation catalysts. Of the systems examined, only a few of the 4-substituted pyridines were found to be acylation catalysts, the most effective being 4-pyrrolidinopyridine 4 and 1,1,3,3-tetramethyl-4-(4-pyridyl)guanidine 8. The reaction of t-butanol with an isocyanate is also accelerated by the presence of 4 but not as much as in the case of acylations. The cause of the pronounced effect of these pyridine species in catalyzing acylation reactions seems to be a combination of the increased donor ability of the 4-substituent and the stabilizing effect that this substituent has on an acyl pyridinium intermediate.     

Chiral N-heterocyclic carbenes as asymmetric acylation catalysts

Chiral N-heterocyclic carbenes are generated from C₂-symmetric 1,3-bis(1-arylethyl)imidazolium salts and potassium tert-butoxide. These C₂-symmetric imidazolidenyl carbenes catalyze enantioselective acylation of racemic secondary alcohols. The asymmetric acylation of 1-(1-naphthyl)ethanol was achieved in up to 68% ee of the acylated product, using (R,R)-1,3-bis[(1-naphthyl)ethyl]imidazolium tetrafluoroborate as a precursor of the chiral N-heterocyclic carbene and vinyl propionate as the acyl donor.     

Desymmetrization of glycerol derivatives with peptide-based acylation catalysts

[reaction: see text] Nucleophile-loaded peptides have been evaluated as catalysts for the desymmetrization of glycerol derivatives through an enantioselective acylation process. Enantiomeric excesses of up to 97% have been obtained for the monoacylated products. A range of other substrates have been examined that shed light on the mechanistic basis of the desymmetrizations.     

Highly active and reusable heterogeneous catalysts for acylation of anisole

In the present study, non-conventional solid acid catalysts such as NaY, metal ion exchanged zeolite NaY (Zn²⁺, Fe³⁺, Ce³⁺, La³⁺ and Nd³⁺), H-mordenite, H-β and HZSM-5 were used in order to overcome the disadvantages of conventional Friedel-Crafts catalysts for the acylation of anisole with acetic anhydride. Among the various zeolites studied, the HY zeolite shows an intermediate activity. Zeolite containing transition metal ions (Zn²⁺ and Fe³⁺) are less active and zeolite NaY is nearly inactive. The catalysts exhibit the activity in the order H-β>transition metal ions (Zn²⁺ and Fe³⁺)>HY>NaY zeolite. The highest catalytic activity of H-β could be due to its larger pore size. The type of acidity and the acid strength in zeolite Y were determined by FTIR and differential scanning calorimetric (DSC) studies on the pyridine adsorbed catalysts. The correlation of catalytic activity with acidity reveals that Brönsted acid sites in zeolite promote the acylation of anisole.     

Target-specific chemical acylation of lectins by ligand-tethered DMAP catalysts

Because sugar-binding proteins, so-called lectins, play important roles in many biological phenomena, the lectin-selective labeling should be useful for investigating biological processes involving lectins as well as providing molecular tools for analysis of saccharides and these derivatives. We describe herein a new strategy for lectin-selective labeling based on an acyl transfer reaction directed by ligand-tethered DMAP (4-dimethylaminopyridine). DMAP is an effective acyl transfer catalyst, which can activate an acyl ester for its transfer to a nucleophilic residue. To direct the acyl transfer reaction to a lectin of interest, we attached the DMAP to a saccharide ligand specific for the target lectin. It was clearly demonstrated by biochemical analyses that the target-selective labeling of Congerin II, an animal lectin having selective affinity for Lactose/LacNAc (N-acetyllactosamine), was achieved in the presence of Lac-tethered DMAPs and acyl donors containing probes such as fluorescent molecules or biotin. Conventional peptide mapping experiments using HPLC and tandem mass-mass analysis revealed that the acyl transfer reaction site-specifically occurred at Tyr 51 of Cong II. This strategy was successfully extended to other lectins by changing the ligand part of the ligand-tethered DMAP. We also demonstrated that this labeling method is applicable not only to purified lectin in test tubes, but also to crude mixtures such as E. coli lysates or homogenized animal tissue samples expressing Congerin.     

Efficient transesterification/acylation reactions mediated by N-heterocyclic carbene catalysts

Imidazol-2-ylidenes, a family of N-heterocyclic carbenes (NHC), are efficient catalysts in the transesterification involving numerous esters and alcohols. Low catalyst loadings of aryl- or alkyl-substituted NHC catalysts mediate the acylation of alcohols with enol acetates in short reaction times at room temperature. Commercially available and more difficult to cleave methyl esters react with primary alcohols in the presence of alkyl-substituted NHC to efficiently form the corresponding esters. While primary alcohols are selectively acylated over secondary alcohols with use of enol esters as acylating agents, methyl and ethyl esters can be employed as protective agents for secondary alcohols in the presence of the more active alkyl-substituted NHC catalysts. The NHC-catalyzed transesterification protocol was simplified by generating the imidazol-2-ylidene catalysts in situ.     

N-heterocyclic carbenes as versatile nucleophilic catalysts for transesterification/acylation reactions

[reaction: see text] Imidazol-2-ylidenes, a family of N-heterocyclic carbenes (NHC), are efficient catalysts in the transesterification between esters and alcohols. Low catalyst loadings of aryl- or alkyl-substituted NHC catalysts mediate the acylation of alcohols with vinyl acetate in convenient reaction times at room temperature. Commercially available and more difficult to cleave methyl esters react with numerous alcohols in the presence of alkyl-substituted NHC to form efficiently the corresponding esters in very short reaction times.     

Metal bis[trifluoromethyl)sulfonyl]amide complexes: highly efficient Friedel-Crafts acylation catalysts

A range of metal bis[(trifluoromethyl)sulfonyl]amide complexes, including many unreported ones, have been synthesised, most of which have been found to be excellent Friedel-Crafts acylation catalysts in the absence of solvent; these reactions have also been carried out in ionic liquids, which allow the catalysts to be recycled and reused.     

Friedel-crafts acylation of 2-methoxynaphthalene over h-beta catalysts: effect of Si/Al ratio

The acylation of 2-methoxynaphthalene with acetic anhydride was carried out over zeolite beta catalysts having various Si/Al ratios. It was found that the reaction performance is strongly dependent on the Si/Al ratio of the catalyst. The catalytic reaction features were elucidated in terms of the acidic properties of the catalysts. This revised version was published online in June 2006 with corrections to the Cover Date.     

First C-3 lithiation of DMAP: a new entry into chemical tuning of acylation catalysts

A TMSCH2Li-based reagent promoted the first C-3 lithiation of DMAP opening a direct access to functional diversity in acylation catalysts.     

Structure-enantioselectivity effects in 3,4-dihydropyrimido[2,1-b]benzothiazole-based isothioureas as enantioselective acylation catalysts

The catalytic activity and enantioselectivity in the kinetic resolution of (±)-1-naphthylethanol with a range of structurally related 3,4-dihydropyrimido[2,1-b]benzothiazole-based catalysts is examined. Of the isothiourea catalysts screened, (2S,3R)-2-phenyl-3-isopropyl substitution proved optimal, giving good levels of selectivity in the kinetic resolution of a number of secondary alcohols (S values up to >100 at ~50% conversion). Low catalyst loadings (0.10-0.25 mol%) of the optimal isothiourea can be used to generate enantiopure alcohols (>99% ee) in good yields.     

Vinylation and acylation of adamantane by vinyl acetate through the action of rhodium complexes

Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, p. 2897, December, 1991.     

Nucleophilic metal complexes as acylation catalysts: solvent-dependent "switch" mechanisms leading to the first catalyzed Staudinger reaction

[formula: see text] Catalytic acylation using complex transition metal salts MCo(CO)4 is demonstrated. Surprisingly, a solvent-dependent mechanistic "switch" results in a Lewis acid-based acylation mechanism in nonpolar media and a nucleophilic mechanism in polar organic media. These observations lead to the first example of a catalyzed Staudinger reaction to form beta-lactams.     

Influence of electronic and steric factors on 2,3-dihydroimidazo[1,2-a]pyridine-based enantioselective acylation catalysts

The catalytic activity and enantioselectivity of chiral 2,3-dihydroimidazo[1,2-a]pyridine (DHIP) derivatives was examined as a function of the steric environment of the nucleophilic nitrogen and the electronic properties of the pyridine ring. 2-Phenyl-6-trifluoromethyl-DHIP (CF₃-PIP) was confirmed to be the best catalyst in this series. In addition, three second-generation catalysts derived from the 1,2-dihydroimidazo[1,2-a]quinoline (DHIQ) core were tested and proved to be considerably more active than CF₃-PIP.     

Mechanism of homogeneously and heterogeneously catalysed Meerwein-Ponndorf-Verley-Oppenauer reactions for the racemisation of secondary alcohols

The mechanism of hydrogen transfer from alcohols to ketones, catalysed by lanthanide(III) isopropoxides or zeolite Beta has been studied. For the lanthanide catalysed reactions, (S)-1-phenyl-(1-(2)H(1))ethanol and acetophenone were used as case studies to determine the reaction pathway for the hydrogen transfer. Upon complete racemisation all deuterium was present at the 1-position, indicating that the reaction exclusively takes place via a carbon-to-carbon hydrogen transfer. Zeolite Beta with different Si/Al ratios was applied in the racemisation of (S)-1-phenylethanol. In this case the racemisation does not proceed via an oxidation/reduction pathway but via elimination of the hydroxy group and its re-addition. This mechanism, however, is not characteristic for all racemisation reactions with zeolite Beta. When 4-tert-butyl cyclohexanone is reduced with this catalyst, a classical MPV reaction takes place exclusively. This demonstrates that zeolite Beta has a substrate dependent reaction pathway.     

Chiral 1,2,4-triazoles: stereoselective acylation and chlorination

Acyl groups are transferred from diverse N- and O-acyl derivatives of chiral 3,5-bis-(1-hydroxyethyl)-[1,2,4]-triazole to amino acid esters enantioselectively, with 7% to 68% ee, depending on the temperature conditions and nature of the reagents. Thionyl chloride replaced the hydroxyl groups of (S)-1-[4-amino-5-((S)-1-hydroxy-ethyl)-[1,2,4]-triazol-3-yl]-ethanol 3 stereospecifically with inversion, as confirmed by X-ray analysis, which also revealed unusual crystal structures with asymmetric units comprising three molecules of 4-amino-3,5-bis(R-1-chloroethyl)-1,2,4-triazole 5 and four of 3,5-bis((R)-1-chloroethyl)-1H-1,2,4-triazole 6.