Use Of Chiral Catalysts Research Articles

Chiral Biocatalytic Oxidations at 90 °C in Microemulsions Driven by Electrocatalytic Oxygen Reduction to Hydrogen Peroxide

AbstractChirality plays a significant role in the manufacture of pharmaceuticals and fine chemicals. The use of chemical catalysts to control stereoselectivity relies on the use of chiral catalysts with labor–intensive synthesis and purification. Natural enzymes offer inherent stereoselectivity, making them attractive catalysts for this purpose. We report here chiral biocatalytic oxidations in microemulsions driven by horseradish peroxidase coupled with a synthetic Cu2+‐polymer catalyst. This hybrid system features crosslinked layer–by–layer (LBL) films composed of polyions with Cu2+‐containing pyrene–labelled poly(2‐hydroxy‐3‐dipicolylamino) propyl methacrylate (Py−PGMADPA) to drive oxygen reduction to form hydrogen peroxide. Peroxide in turn activates horseradish peroxidase (HRP) crosslinked in LbL films on magnetic particle beads to biocatalytically oxidize styrene, ethylbenzene, and methyl phenylacetate to chiral products. R‐stereoisomers of these reactants were selectively formed with a high enantiomeric excess of ≥80 % at 90 °C. The enzyme films show high thermal stability at 90 °C in cetyltrimethylammonium bromide microemulsion. Reactions at 90 °C were essentially complete in 2 hr. This hybrid approach opens a door to new designs of biocatalytic syntheses using a separate electrocatalyst for enzyme activation.

Asymmetric [3+n]‐Cycloaddition Reactions of Donor‐Acceptor Cyclopropanes

Abstract[3+n]‐Cycloaddition reactions that employ donor‐acceptor cyclopropanes using either chiral catalysts and racemic cyclopropanes or achiral catalysts and chiral, non‐racemic, cyclopropanes have become useful transformations for the construction of carbocyclic and heterocyclic compounds, with both processes offering mechanistic and structural advantages in ring formation. Although the vast majority of asymmetric cycloaddition reactions of donor‐acceptor cyclopropanes have been performed with racemic cyclopropane compounds catalyzed by Lewis acids with chiral ligands, optically active cyclopropane compounds can serve the same role using Lewis acids without chiral ligands. This review covers the use of chiral catalysts with racemic donor‐acceptor cyclopropanes and the use of chiral non‐racemic donor‐acceptor cyclopropanes with achiral Lewis acid catalysts.

α-Branched amines by catalytic 1,1-addition of C-H bonds and aminating agents to terminal alkenes.

α-Branched amines are present in hundreds of pharmaceutical agents and clinical candidates and are important targets for synthesis. Here we show the convergent synthesis of α-branched amines from three readily accessible starting materials: aromatic C–H bond substrates, terminal alkenes, and aminating agents. This reaction proceeds by an intermolecular formation of C–C and C–N bonds at the sp3 carbon branch site through an uncommon 1,1-alkene addition pathway. The reaction is carried out under mild conditions and has high functional group compatibility. Ethylene and propylene feedstock chemicals are effective alkene inputs with ethylene in particular providing for the one step synthesis of α-methyl branched amines, a motif prevalent in drug structures. The reaction is scalable, and 1% loading of an air stable dimeric rhodium precatalyst is effective for several different types of products. The use of chiral catalysts also enables the asymmetric synthesis of α-branched amines.

ChemInform Abstract: New Potential of the Reductive Alkylation of Amines

AbstractReview: 156 refs.

ChemInform Abstract: Enantioselective Reactions of N‐Acyliminium Ions Using Chiral Organocatalysts

AbstractReview: 93 refs.

Enantioselective Reactions of N‐Acyliminium Ions Using Chiral Organocatalysts

N-acyliminium ions are reactive intermediates that can act as electron-deficient electrophiles toward weak or soft nucleophiles, thereby providing useful methods for both intermolecular- and intramolecular carbon-carbon and carbon-heteroatom bond formation. Nucleophilic additions to N-acyliminium ions constitute an important method for providing α-functionalized amino compounds and many other biologically active nitrogen-containing heterocycles. The development of efficient catalytic asymmetric reactions is a key objective in modern organic chemistry and is very important for the synthesis of natural products, pharmaceuticals, and agrochemicals. Various methods are available for this purpose and mostly rely on the use of chiral catalysts for enantioselective synthesis. This review deals with one aspect of such catalysis, which has emerged only in the past few years, and its applications in enantioselective reactions of N-acyliminium ions to provide various nitrogen-containing heterocycles.

Investigating the reaction mechanism and organocatalytic synthesis of α,α′-dihydroxy ketones

A biomimetic TK one-pot reaction using hydroxypyruvate and aldehydes to generate α,α'-dihydroxy ketones in water has recently been described. To investigate this tertiary-amine mediated reaction mechanism two approaches were used. Firstly, (13)C labelled lithium hydroxypyruvate was synthesised and used to establish where hydroxypyruvate is incorporated in the product. In separate experiments reaction intermediates were also successfully intercepted and structurally identified using ESI-MS with tandem mass spectrometry ESI-MS/MS. These studies indicated that two mechanisms appear to be operating, one involving the addition of the tertiary amine catalyst to hydroxypyruvate, the other an aldol-based mechanism. Since the first mechanism may enable facial stereodifferentiation in the addition of intermediates to the aldehyde, a preliminary study on the use of chiral catalysts was performed and the first asymmetric organocatalytic synthesis of α,α'-dihydroxy ketones in aqueous media achieved, in up to 50% ee, using a quinine ether catalyst.

Divergent outcomes of carbene transfer reactions from dirhodium- and copper-based catalysts separately or in combination.

Divergent outcomes of carbene transfer reactions from dirhodium- and copper-based catalysts separately or in combination.

Asymmetric Domino Reactions. Part B. Reactions Based on the Use of Chiral Catalysts and Biocatalysts

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.

Chiral Auxiliaries - Principles and Recent Applications

With modern methods for asymmetric catalysis breaking ground, the use of chiral auxiliaries seems to be old-fashioned and rather inefficient. However, for many transformations, chiral auxiliaries often represent the only selective method available. In addition, high levels of selectivity and reliability are often attractive characteristics of chiral auxiliaries and allow for the efficient and rapid synthesis of desired chiral compounds. In addition, even in cases with imperfect selectivity, the use of an attached chiral auxiliary allows the enrichment of diastereoselectivity, and hence enantioselectivity after removal of the auxiliary, by many standard separation techniques. This article gives an overview on the most important classes of chiral auxiliaries, discussing the mode of action and highlighting some recent applications. It does not deal with the use of chiral catalysts, chiral reagents or achiral auxiliaries.

Recent Advances in the Synthesis of Angucyclines

AbstractFor Abstract see ChemInform Abstract in Full Text.

Application of Chiral Cationic Catalysts to Several Classical Syntheses of Racemic Natural Products Transforms Them into Highly Enantioselective Pathways.

For Abstract see ChemInform Abstract in Full Text.

Recent Advances in the Synthesis of Angucyclines

The different strategies recently reported to construct the tetracyclic skeleton of angucyclines are presented: Diels-Alder and Friedel-Crafts reactions, nucleophilic additions, free radical annulations, rearrangements ofcyclobutenones and cobalt-mediated [2+2+2] cycloadditions. Among the asymmetric approaches, the most efficient corresponds to Diels-Alder reactions including the use of chiral catalysts, enantiopure vinyl cyclohexenes as dienes, synthesized from quinic acid or (S,S)-[(p-tolylsulfinyl)methyl]-p-quinol, and chiral dienophiles such as (S,S)-2-(p-tolylsulfinyl)-1,4-naphthoquinones.

Application of Chiral Cationic Catalysts to Several Classical Syntheses of Racemic Natural Products Transforms Them into Highly Enantioselective Pathways

This paper describes the application of chiral oxazaborolidinium cations of type 2 to various enantioselective Diels-Alder reactions that have served as early key steps for the syntheses of complex natural products. In the original syntheses these Diels-Alder reactions produced racemic adducts and led to racemic target molecules unless a separation of enantiomers by classical resolution was employed. By use of chiral catalysts of type 2, chiral products were obtained directly from Diels-Alder reactions of achiral components in excellent yield and enantioselectivity and with the mechanistically predicted absolute configuration. As a result, a number of classical syntheses could be converted to enantioselective versions, including (1) cortisone/cortisol (Merck/Sarett), (2) dendrobine (Kende), (3) vitamin B(12) (Eschenmoser), (4) myrocin C (Chu-Moyer/Danishefsky), (5) coriolin and hirsutene (Mehta), (6) dendrobatid 251F (Aube), (7) silphinene (Ito), and (8) nicandrenone core (Stoltz/Corey).

Atroposelective biaryl coupling with chiral catalysts: total synthesis of the antileishmanial naphthylisoquinoline alkaloids ancistrotanzanine B and ancistroealaine A.

[reaction: see text] The first total synthesis of the naphthylisoquinoline alkaloid ancistrotanzanine B and its atropo-diastereomer, ancistroealaine A, is described. The key step is the construction of the rotationally hindered and thus stereogenic biaryl axis by Suzuki coupling. While only weak internal asymmetric inductions by the stereogenic center in the dihydroisoquinoline part were observed, much better atropisomeric ratios in favor of ancistrotanzanine B were achieved by the use of chiral catalysts. Both alkaloids, in particular ancistrotanzanine B, show high antileishmanial activities.

New approach to biomimetic transamination using bifunctional [1,3]-proton transfer catalysis in thioxanthenyl dioxide imines.

A pyridoxamine equivalent, 9-aminothioxanthene 10,10-dioxide, has been designed that is capable of affording transamination in good to excellent yields of natural as well as artificial amino acids. Amidines and guanidines in catalytic amounts were capable of performing [1,3]-proton transfer in the imines under mild conditions, whereas various simple amines failed. The use of chiral catalysts resulted in modest asymmetric induction (ee < or = 45%). The electronic dependence in para-substituted phenyl glyoxylate imines, isotope effects, and computational studies support a stepwise, bifunctional mechanism for amidine and guanidine catalysts. Attempts toward an autocatalytic model system are described.

ASYMMETRIC CATALYSIS WINS

THE 2001 NOBEL PRIZE IN Chemistry will be shared by three scientists who devised techniques for catalytic asymmetric synthesis—the use of chiral catalysts to accelerate the production of single-enantiomer compounds for pharmaceutical use and a wide range of other applications. One-half of the approximately $950,000 prize will be split by Monsanto retiree William S. Knowles and chemistry professor Ryoji Noyori of Nagoya University, in Japan, for their work on catalytic asymmetric hydrogenation reactions. The other half goes to chemistry professor K. Barry Sharpless of Scripps Research Institute for research on catalytic asymmetric oxidations. According to the Royal Swedish Academy of Sciences, Stockholm, the discoveries made by the three men have had a very great impact on academic research and the development of new drugs and materials and are used in many industrial syntheses of drugs and other biologically active compounds. Sharpless and Noyori also shared—along with emeritus professor of chemistry ...

Applications of Intramolecular Cyclopropanations of Chiral Secondary Allylic Diazoacetates

The diastereomeric secondary allylic diazoacetates 6a,b and 8a,b, which were readily prepared from the common intermediate 4, were cyclized in the presence of the achiral catalyst Cu(TBS)2 to furnish mixtures of the adducts 9a,b/10a,b and 12a,b/13a,b, respectively; in these cyclizations, the diastereoselectivity of the reaction was substrate controlled. When 6a,b and 8a,b were cyclized in the presence of the chiral catalysts Rh2[(5S)-MEPY]4 or Rh2[(5R)-MEPY]4, the substrate-based selectivity could be reversed if the chirality of the substrate and catalyst were matched. The advantages associated with the use of chiral catalysts to effect the diastereoselective cyclization of chiral allylic diazoacetates were demonstrated by the synthesis of 25, which comprises the cyclopropane subunit found in the diterpene ingol B (14).

Chiral Pd organometallic complexes as catalysts in cyclopropanation reactions

Asymmetric cyclopropanation of styrene with diazoacetic esters is performed firstly using chiral amino acidato complexes of Pd(II) containing a C,N-cyclometallated group as an ancillary ligand as catalyst precursors. In general these catalytic systems provide good conversion to the corresponding cyclopropyl derivatives with a moderate trans selectivity, although the stereoselectivities obtained were low. With the use of chiral catalysts and chiral diazoacetic esters the diastereoselectivities were slightly improved.

Catalytic enantioselective synthesis of a key intermediate for the synthesis of prostanoids

A route has been demonstrated for the enantioselective synthesis of prostanoids from achiral starting materials by the use of chiral catalysts of the molecular robot class.