Kinetic Resolution Reaction Research Articles

ChemInform Abstract: Dynamic Kinetic Resolution in the Hydrolysis of an α-Bromo Ester.

Bromide can be employed to racemise an α-bromo ester more rapidly than the corresponding acid (carboxylate), and this rate difference has been employed as the basis of a dynamic kinetic resolution reaction.

Stereoselective formal synthesis of aspergillide A

The stereoselective formal synthesis of aspergillide A (1), a cytotoxic 14-membered macrolide, is disclosed. The key intermediate, a trisubstituted tetrahydropyran core is prepared by SmI 2 -induced intramolecular reductive cyclization as well as by using sequential α-aminooxylation, Horner-Wadsworth-Emmons olefination, and followed by Oxa-Michael cyclization. Other notable transformations in the synthesis include the use of Jacobsen's hydrolytic kinetic resolution, esterification, ring-closing metathesis (RCM), and cross-metathesis (CM) reactions.

ChemInform Abstract: A New Catalytic and Enantioselective Desymmetrization of Symmetrical Methylidene Cycloalkene Oxides.

Chiral copper complexes of C2-symmetrical phosphoroamidites were found to be highly effective catalysts for both kinetic resolution and novel desymmetrization reactions of new methylidene epoxycycloalkanes.

Self-association-free dimeric cinchona alkaloid organocatalysts: unprecedented catalytic activity, enantioselectivity and catalyst recyclability in dynamic kinetic resolution of racemic azlactones

Self-association-free, bifunctional, squaramide-based dimeric cinchona alkaloid organocatalysts show unprecedented catalytic activity, enantioselectivity and catalyst recyclability in the dynamic kinetic resolution (DKR) reaction of a broad range of racemic azlactones.

Asymmetric Ring Opening Reaction of Catalyst Immobilized on Silica Monolith with Bimodal Meso/Macroscopic Pore Structure

A route to synthesize porous materials with a bimodal macro/mesoscopic pore system has been investigated in this work. Large and molded meso/macroporous silica monoliths could be obtained by using monodispersed polymethylmethacrylate (PMMA) beads and Pluronic F-127/SBA-16 sol solutions. Phenolic ring-opening of epoxides was performed successfully by using chiral (salen)Co-BF3 complexes immobilized catalysts. Very high enantioselectivity up to 99% ee and conversion were obtained in phenolic kinetic resolution (PKR) reaction by immobilized catalysts.

The Current Chemical Utility of Marine and Terrestrial Filamentous Fungi in Side-Chain Chemistry

This review focuses on three aspects of the application of marine and terrestrial filamentous fungi to side-chain chemistry from 2000 to early 2006. The first section covers the generation of novel biologically active side-chain containing metabolites. This includes a range of antibiotic, cytotoxic and novel bioactive compounds. The second section discusses the use of these fungi both whole cell and lipases of fungal origin in the chemical modification of side-chains. Examples include reductive desymmetrization of pro-chiral ketones, dynamic kinetic resolution and unique reactions. The final section details the degradation of side-chains by fungi and includes lignin and steroid transformations for determination metabolism and the generation of new skeletal structure.

Oxidatively pure chiral (salen)Co(III)-X complexes in situ prepared by Lewis acid-promoted electron transfer from chiral (salen)Co(II) to oxygen: Their application in the hydrolytic kinetic resolution of terminal epoxides

The Lewis acid (MX 3)-promoted oxidation of chiral (salen)Co(II) complex afforded neither the mononuclear nor dinuclear heterobimetallic chiral (salen)Co complexes, such as [(salen)Co(III)-X]⋯MX 3 or [(salen)Co(III)-X] 2⋯MX 3, as reported in the literatures, but rather the Jacobsen's complexes, chiral (salen)Co(III)-X. The chiral (salen)Co(III)-X complexes in situ generated by the reaction of MX 3 and (salen)Co(II) in molar ratio of 1:3 were shown to have identical catalytic properties in the hydrolytic kinetic resolution (HKR) reactions of racemic epoxides, in terms of activity, enantioselectivity and stability, to those of the purified (salen)Co(III)-X complex. This result strongly indicates that metallic residues of Lewis acids (e.g., metal oxide residues) remained in the reaction mixture did not display any negative influence on the catalytic efficiencies. Thus, the present in situ method for catalyst activation can be applicable for large scale process for HKR reactions of racemic epoxides.

Towards a continuous dynamic kinetic resolution of 1-phenylethylamine using a membrane assisted, two vessel process

A continuous process with two separated reaction vessels provides a solution to the problems surrounding the combination of two catalysts in dynamic kinetic resolution reactions by retaining the biocatalyst in a lower temperature vessel with a microfiltration membrane and allowing the racemisation to occur efficiently in a higher temperature vessel.

A kinetic study of lipase‐catalyzed reversible kinetic resolution involving verification at miniplant‐scale

Lipase-catalyzed kinetic resolution of racemates is a popular method for synthesis of chiral synthons. Most of these resolutions are reversible equilibrium limited reactions. For the first time, an extensive kinetic model is proposed for kinetic resolution reactions, which takes into account the full reversibility of the reaction, substrate inhibition by an acyl donor and an acyl acceptor as well as alternative substrate inhibition by each enantiomer. For this purpose, the reversible enantioselective transesterification of (R/S)-1-methoxy-2-propanol with ethyl acetate catalyzed by Candida antarctica lipase B (CAL-B) is investigated. The detailed model presented here is valid for a wide range of substrate and product concentrations. Following model discrimination and the application of Haldane equations to reduce the degree of freedom in parameter estimation, the 11 free parameters are successfully identified. All parameters are fitted to the complete data set simultaneously. Six types of independent initial rate studies provide a solid data basis for the model. The effect of changes in substrate and product concentration on reaction kinetics is discussed. The developed model is used for simulations to study the behavior of reaction kinetics in a fixed bed reactor. The typical plot of enantiomeric excess versus conversion of substrate and product is evaluated at various initial substrate mixtures. The model is validated by comparison with experimental results obtained with a fixed bed reactor, which is part of a fully automated state-of-the-art miniplant.

Phosphoramidite Ligands in Iridium‐Catalyzed Allylic Substitution

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.

Phosphoramidite Ligands in Iridium‐Catalyzed Allylic Substitution

A new phosphoramidite ligand was used in the iridium-catalyzed allylic substitution reaction. This permitted high regio- and enantioselectivities on a wide variety of substrates and nucleophiles. Because of the stereospecificity of the reaction obtained by using branched substrates, a kinetic resolution reaction was attempted. The origin of the impressive efficiency of this ligand in terms of kinetics was explored in detail, as was the role of the substituent in the ortho-position of the amine moiety.

Enzyme‐Catalyzed Deracemization and Dynamic Kinetic Resolution Reactions

AbstractFor Abstract see ChemInform Abstract in Full Text.

A furan route to the asymmetric synthesis of trans-fused polyether building blocks

A novel route towards chiral trans-fused polyether lactones 7 and 12 has been developed starting with commercially available furfural. Sharpless kinetic resolution and ring-closing metathesis reactions served as key steps in the strategy.

Enantiopure β‐Hydroxy Morpholine Amides from Terminal Epoxides by Carbonylation at 1 atm.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantiopure beta-hydroxy morpholine amides from terminal epoxides by carbonylation at 1 atm.

As a consequence of the recently developed hydrolytic kinetic resolution (HKR) reaction,[1] a wide variety of terminal epoxides are now readily accessible in enantiopure form. The synthetic utility of this family of chiral building blocks is certainly well established, yet it is likely that new and valuable reactivity remains to be uncovered. In that context, we have sought to develop practical methodology to effect elaboration of these compounds to more highly functionalized chiral intermediates. In 1999, we reported the [Co2(CO)8]catalyzed carbonylation of enantiomerically enriched epoxides under 40 atm of CO, to afford b-hydroxy methyl esters in good yield [Eq. (1)].[2] However, the relatively high CO pressure precludes its widespread application in laboratory and industrial settings, and the scope of nucleophiles that could be employed to trap the acylcobalt intermediate was in fact quite limited.[3] As a result, we became interested in devising complementary methodology that would afford general access to broadly useful b-hydroxy carbonyl derivatives under mild conditions.

Catalytic electronic activation: indirect Sharpless asymmetric epoxidation of enals

The asymmetric epoxidation of allylic cyanohydrins using the Sharpless kinetic resolution (SKR) reaction was explored. The SKR methodology was extended to enals via in-situ conversion into the corresponding cyanohydrin. The prospect of achieving a dynamic Sharpless kinetic resolution was investigated and the enantioselectivity of the SKR of ( E)-2-hydroxy-3-methyl-4-phenyl-3-butenenitrile 1 studied. Reversible hydrocyanation of α-methyl cinnamaldehyde was developed and a one-pot hydrocyanation/epoxidation process achieved.

ChemInform Abstract: Practical Considerations in Kinetic Resolution Reactions

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.

Practical Considerations in Kinetic Resolution Reactions

This review provides a critical analysis of catalytic kinetic resolution reactions from a practical perspective, asking the question of when, if ever, is kinetic resolution the best option for the synthesis of an optically active target. A series of crucial conditions are identified, and it is postulated that if all of them are met, then indeed kinetic resolution can be highly practical. A variety of catalytic kinetic resolution processes are evaluated in the context of these criteria, with particular emphasis on catalyst availability, substrate scope, availability of the racemic substrate and of alternative methods for accessing enantiopure substrate or product, and key experimental considerations. It is found that several catalytic systems have been developed that offer almost unbeatable methods for the preparation of useful chiral building blocks.

Practical Considerations in Kinetic Resolution Reactions

Practical Considerations in Kinetic Resolution Reactions

Enzymatic Hydrolysis and Selective Racemisation Reactions of α-Chloro Esters

The kinetic resolution of α-chloro esters was effected with good selectivity using CLEC (Cross-Linked Enzyme Crystals) enzymes. The selective racemisation of α-chloro esters in the presence of α-chloro acids enabled a successful dynamic kinetic resolution reaction to be performed.