Acyl-transfer catalysts

NB. cat. denotes an enantiomerically highly enriched acyl transfer catalyst... 

Fig. 1 Chiral phosphines screened by Vedejs as asymmetric acyl transfer catalysts [42]...

Miller and co-workers have taken a totally different approach to design an efficient catalyst for enantioselective acylation. Their strategy relied on the use of a pep-tide-based backbone incorporating a 3-(l-imidazolyl)-(5)-alanine unit as the catalytic core. Upon treatment with an achiral acyl source these biomimetic enantioselective acyl transfer catalysts allow the formation of an acyl imidazolium ion in proximity to the chiral environment generated by the folding of the peptide [3, 159-174]. 

Vedejs and co-workers have explored the use of chiral phosphines as acyl transfer catalysts. The viability of this approach was proven when phosphine 1 was shown to catalyze the resolution of secondary alcohols with promising selectiv-ities (Scheme 2) [10,11]. 

A new class of chiral 4-A,A-dialkylaminopyridine acyl-transfer catalysts has been developed that are capable of exploiting both van der Waals (jt) and H-bonding interactions to allow remote chiral information to control stereochemically the kinetic resolutions of secondary alcohols with moderate to excellent selectivity (S = 6-30). Catalysts derived from (.S )- , -diarylprolinol (89 Ar = Ph, 2-naphthyl) in combination with isobutyric anhydride were found to possess high activity and selectivity across a broad range of substrates 89... 

Miller has developed various short peptides containing 3-(l-imidazolyl)-(S)-alanine as the catalytic core these biomimetic enantioselective acyl transfer catalysts allow the formation of an acyl imidazolium intermediate in a chiral environment formed by folding of the peptide [109-123]. The first catalyst of this type to be reported was tripeptide 27 in 1998 [109]. This peptide incorporates a C-terminal (R)-methylbenzylamide to encourage order-inducing stacking interactions in the acylimidazolium intermediate (Scheme 8.6). 

After that, the built-up Zinc-enzyme model (Fig. 6.2(b)) could effectively catalyze the hydrolysis of aryl phosphate. Another better hydrolyzing enzyme model is 4 nitrogen heterocyclic 12 silane cobalt complexes (Fig. 6.2(c)), which is one of the most effective acyl transferring catalysts. If the 4 nitrogen heterocyclic 12 silane cobalt complexes were covalently linked with -CD, the obtained enzyme model could increase 900-fold of the hydrolysis rate of PNPA (p-nitrophenol acetate). If the same group was conjugated onto the second hydroxyl group of f -CD, the obtained model could increase 2,900-3,700-fold of the hydrolysis rate of PNPA [21]. 

Enantioselective desymmetrisation of meso-diols mediated by nonenzy-matic acyl transfer catalysts 12CSR7803. 

Copeland GT, Miller SJ (2001) Selection of enantioselective acyl transfer catalysts fimn a pooled peptide library through a fluorescence-based activity assay an approach to kinetic resolution of secondary alcohols of broad structural scope. J Am Chem Soc 123 6496-6502... 

Using the DMAP scaffold as a model, numerous asymmetric acyl transfer catalysts have been developed, with... 

In the reciprocal experiment, the chiral alcohol methylmandelate, (13), is used as a CDA for the study of the enantiomeric purity of acids. Esterification is effected without racemisation with N, N-dicyclohexylcarbodiimide in the presence of the acyl transfer catalyst,... 

The remarkable efficiency of Shiina lactonization, which was mediated by acyl-transfer catalysts with MNBA, has been already demonstrated in a variety of successful total syntheses of natural products and biologically active compounds by other researchers (totaling over 370 citations to date). Furthermore, over 900 successful reactions using MNBA have been reported for the preparation of a variety of substrates including ester, amide, and lactone moieties. 

The reaction proceeds via the formation of a first chiral zwitterionic intermediate from pivaUc anhydride and the amidine-based catalyst A mixed anhydride is then generated in the presence of the racemic carboxylic acid and activated by the chiral acyl-transfer catalyst to form the second zwitterionic intermediate. The latter species selectively reacts with a nucleophilic alcohol to afford the desired enantioenriched carboxyUc ester (Scheme 41.10). 

Over the past few years, the design of enantioselective acyl transfer catalysts suitable for use with amines has become a major focus for the synthetic community. This endeavor has been particularly challenging due to the high nucleophilicity of most amines toward typical acylating agents, thus requiring a fine-tuning of the reactivity of the chiral selector to enable chiral induction. 

As further evidence, they isolated and characterized dioxolanone 48. In addition, they tested further pyridine-derived acyl-transfer catalysts 46 (Fig. 7.4) and detected that the ketone-derived catalysts are far more selective than the aldehyde-derived ones [55]. This was explained by an undirected background reaction from a nucleophilic attack of MeOH to the aldehyde catalyst. 

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