Asymmetric Acyl Transfer Research Articles

A New Saddle-Shaped Aza Analog of Tetraphenylene: Atroposelective Synthesis and Application as a Chiral Acylating Reagent

A New Saddle-Shaped Aza Analog of Tetraphenylene: Atroposelective Synthesis and Application as a Chiral Acylating Reagent

Chiral DMAP-N-oxides as Acyl Transfer Catalysts: Design, Synthesis, and Application in Asymmetric Steglich Rearrangement.

A DMAP-N-oxide, featuring an α-amino acid as the chiral source, was developed, synthesized and applied in asymmetric Steglich rearrangement. A series of O-acylated azlactones afforded C-acylated azlactones possessing a quaternary stereocenter in high yields (up to 97 % yield) and excellent enantioselectivities (up to 97 % ee). Compared to the widespread use of pyridine nitrogen, which serves as the nucleophilic site in the asymmetric acyl transfer reaction, we discovered that chiral DMAP-N-oxides, in which the oxygen now acts as the nucleophilic site, are efficient acyl transfer catalysts. Our finding might open a new door for the development of chiral DMAP-N-oxides for asymmetric acyl transfer reactions.

Chiral DMAP‐N‐oxides as Acyl Transfer Catalysts: Design, Synthesis, and Application in Asymmetric Steglich Rearrangement

AbstractA DMAP‐N‐oxide, featuring an α‐amino acid as the chiral source, was developed, synthesized and applied in asymmetric Steglich rearrangement. A series of O‐acylated azlactones afforded C‐acylated azlactones possessing a quaternary stereocenter in high yields (up to 97 % yield) and excellent enantioselectivities (up to 97 % ee). Compared to the widespread use of pyridine nitrogen, which serves as the nucleophilic site in the asymmetric acyl transfer reaction, we discovered that chiral DMAP‐N‐oxides, in which the oxygen now acts as the nucleophilic site, are efficient acyl transfer catalysts. Our finding might open a new door for the development of chiral DMAP‐N‐oxides for asymmetric acyl transfer reactions.

ChemInform Abstract: Stereocontrol of All‐Carbon Quaternary Centers Through Enantioselective Desymmetrization of meso Primary Diols by Organocatalyzed Acyl Transfer.

The symmetry breaking of meso primary diols bearing a tetrahydropyran ring was employed, using catalytic asymmetric acyl transfer, to control all-carbon quaternary stereocenters. The planar chiral Fu DMAP catalyst was used in this reaction to reach a high degree of enantioselectivity (up to 97:3 e.r.) through a synergic effect combining a desymmetrization step and a kinetic resolution. Moreover, a beneficial effect was exhibited by C6F6 solvent, yielding the first example of an organocatalyzed asymmetric acyl transfer. The desymmetrized monoesters were then used to obtain, after a straightforward ring opening sequence, complex polyketide building blocks bearing all-carbon quaternary stereocenters.

Stereocontrol of All‐Carbon Quaternary Centers through Enantioselective Desymmetrization of Meso Primary Diols by Organocatalyzed Acyl Transfer

AbstractThe symmetry breaking of meso primary diols bearing a tetrahydropyran ring was employed, using catalytic asymmetric acyl transfer, to control all‐carbon quaternary stereocenters. The planar chiral Fu DMAP catalyst was used in this reaction to reach a high degree of enantioselectivity (up to 97:3 e.r.) through a synergic effect combining a desymmetrization step and a kinetic resolution. Moreover, a beneficial effect was exhibited by C6F6 solvent, yielding the first example of an organocatalyzed asymmetric acyl transfer. The desymmetrized monoesters were then used to obtain, after a straightforward ring opening sequence, complex polyketide building blocks bearing all‐carbon quaternary stereocenters.

Stereocontrol of All‐Carbon Quaternary Centers through Enantioselective Desymmetrization of Meso Primary Diols by Organocatalyzed Acyl Transfer

The symmetry breaking of meso primary diols bearing a tetrahydropyran ring was employed, using catalytic asymmetric acyl transfer, to control all-carbon quaternary stereocenters. The planar chiral Fu DMAP catalyst was used in this reaction to reach a high degree of enantioselectivity (up to 97:3 e.r.) through a synergic effect combining a desymmetrization step and a kinetic resolution. Moreover, a beneficial effect was exhibited by C6F6 solvent, yielding the first example of an organocatalyzed asymmetric acyl transfer. The desymmetrized monoesters were then used to obtain, after a straightforward ring opening sequence, complex polyketide building blocks bearing all-carbon quaternary stereocenters.

ChemInform Abstract: Amine, Alcohol and Phosphine Catalysts for Acyl Transfer Reactions

AbstractReview: 239 refs.

Backbone Modification of β-Hairpin-Forming Tetrapeptides in Asymmetric Acyl Transfer Reactions

Synthetic oligopeptides as mimics of enzymes have been increasingly exploited as catalysts for asymmetric reactions, but highly effective oligopeptide catalysts with relatively low molecular weight are still in great demand. In this paper, we showed the conformational engineering of the β-hairpin-forming tetrapeptide 4 which was first reported by Miller's group as the catalyst for the asymmetric acyl transfer reaction of trans-2-(N-acetylamino)cyclohexan-1-ol (k(rel)=28). Through our backbone modification strategy, thioamide and sulfonamide as the isosteres of amide were introduced in the β-hairpin secondary structure. The thioxo peptides also adopt β-hairpin conformations as the oxopeptide supported by the combined use of NMR, IR, and X-ray techniques. Thioxo tetrapeptide 14 formed a more constrained β-hairpin conformation and therefore delivered much higher enantioselectivity (k(rel)=109) in the same reaction. Moreover, the examination of the conformational changes of tetrapeptide 8 upon the protonation of the N(π)-methylhistidine moiety provided evidence to explain the variation of its catalytic efficiency in the asymmetric acyl-transfer reaction.

ChemInform Abstract: Organocatalysis with Azahelicenes: The First Use of Helically Chiral Pyridine‐Based Catalysts in the Asymmetric Acyl Transfer Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Organocatalysis with azahelicenes: the first use of helically chiral pyridine-based catalysts in the asymmetric acyl transfer reaction

The successful utilisation of a helicene-based organocatalyst in acylative kinetic resolution of racemic secondary alcohol was described. Employing rac-1-phenylethanol, optically pure (–)-(M)-2-aza[6]helicene (5–20 mole %), isobutyric anhydride and N-ethyldiisopropylamine in chloroform at 22–40 °C, an asymmetric acyl transfer reaction took place overwhelming the uncatalysed background process. Moderate reactivity as well as selectivity factor (s = 9, 10) were observed. An effective control of the enantiodiscriminating step in acylative kinetic resolution by the helically chiral organocatalyst was proven for the first time.

Asymmetric Acyl Transfer Promoted by Readily Assembled Chiral 4‐N,N‐Dialkylaminopyridine Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Role of secondary structure in the asymmetric acylation reaction catalyzed by peptides based on chiral C alpha-tetrasubstituted alpha-amino acids.

In a recent series of papers, Miller and co-workers were able to show that His(pi-Me)-based, terminally protected peptides are potent catalysts of the asymmetric acyl transfer reaction, useful for the kinetic resolution of alcohols. In a structure-supporting solvent, one of the most active compounds, an Aib-containing tetrapeptide, is folded in a doubly intramolecularly H-bonded beta-hairpin motif incorporating a type-II' beta-turn conformation. In this work, we have expanded the study of the Miller tetrapeptide by examining a set of analogues and shorter sequences (dipeptide amides), characterized by chiral C(alpha)-tetrasubstituted alpha-amino acids of diverging bulkiness and optical configuration. Peptide synthesis in solution, conformational analysis by FT-IR absorption and (1)H NMR techniques, and screening of catalytic activity as well have been performed. Our results confirm the close relationship between the beta-hairpin 3D-structure and the catalytic activity of the peptides. A tetrapeptide analogue slightly more selective than the Miller compound has been found. However, the terminally protected, industrially more appealing, dipeptide amides are poorly effective.

Enantioselective synthesis of an aziridinomitosane and selective functionalizations of a key intermediate.

An enantioselective synthesis of mitosane core (-)-1 has been achieved. Key steps include a rapid assembly of a key eight-membered-ring intermediate employing ring-closing metathesis. Kinetic resolution of an advanced secondary alcohol was then accomplished by using a peptide-based asymmetric acyl transfer catalyst that was discovered from a parallel screen of catalyst candidates. Optically pure material was then converted to the mitosane core, which was the subject of additional studies on the selective modification to produce several substituted compounds containing a mitosane ring system.

A Biomimetic Approach to Asymmetric Acyl Transfer Catalysis

Small peptide catalysts containing modified histidine residues are reported that effect enantioselective acylation reactions. The catalysts described include octapeptide β-hairpins (e.g., 11) that exhibit high selectivities (up to krel = 51), tetrapeptide β-turns (e.g., 7) that afford moderate selectivities (up to krel = 28), and several simple derivatives of the modified histidine amino acid that do not exhibit appreciable enantioselectivity. Supporting structural studies (1H NMR and X-ray) are presented which lead to the proposal of a model in which catalyst rigidity and structural complexity contribute to higher degrees of enantioselection. A covalently rigidified octapeptide (20) is prepared through solid-phase Ru-catalyzed ring-closing metathesis; kinetic evaluation of this peptide reveals that substituents along the peptide backbone may be more important than covalent stabilization of a structural motif. Detailed kinetics studies on the most selective peptide catalysts are presented that suggest the...

Configurationally Stable Biaryl Analogues of 4-(Dimethylamino)pyridine: A Novel Class of Chiral Nucleophilic Catalysts

A short synthetic approach toward a novel class of chiral nucleophilic catalysts, the dissymmetry of which stems from restricted rotation about an Ar−Ar bond, has been developed. The key steps of the synthesis include preparation of a nucleophilic 1-methyl-2-pyrrolino[3,2-c]pyridine core 16 by ortho-lithiation and creation of the biaryl axes via Suzuki cross-coupling reactions. Comparative HPLC studies of racemization for configurationally labile biaryls 31, 38, and 43 containing 1-methyl-2-pyrrolino[3,2-c]pyridine, 4-(dimethylamino)pyridine, and 4-(1-pyrrolidino)pyridine cores, respectively, have demonstrated that a pyrrolidino substituent ortho to the biaryl axis is optimal for slowing Ar−Ar rotation. Biaryls containing all three cores have been shown to retain DMAP-like catalytic activity in the acylation of a hindered alcohol. Biaryls 55 and 56, which are configurationally stable at ambient temperature, have also been prepared via modification of configurationally labile derivatives. Compounds 55 and 56 in optically pure form should provide a useful starting point for studies on catalytic asymmetric acyl transfer using atropisomeric analogues of DMAP.

Asymmetric biochemical reduction, acylation and hydrolysis in the (diene)Fe(CO) 3 series: Experimental results and molecular modelling studies

Asymmetric reduction using bakers yeast and asymmetric acyl transfer using porcine pancreatic lipase may be used in the kinetic resolution and desymmetrization of acyclic (diene)Fe(CO) 3 complexes bearing CHO and CH 2OH substituents respectively. The results may be interpreted in terms of current active site models for these biotranformations.