Kinetic Resolution Of Alcohols Research Articles

Preparation of chiral DMAP derivatives and investigation on their enantioselective catalytic activity in benzazetidine synthesis and kinetic resolutions of alcohols

4-dimethylaminopyridine (DMAP) is an extremely versatile catalyst active in a large series of chemical transformations because of its relevant basicity and nucleophilicity. In this paper, we present the synthesis of two chiral DMAP derivatives starting from 4-halopyridine and l-proline benzyl ester. The key steps of these preparations are a ZnII-coordinated dimer of proline ester and a variation of the Buchwald-Hartwig promoted by copper(I) salts. The preparation of these compounds was achieved with the use of inexpensive materials and facile procedures and does not require the use of any catalyst based on transition metals. In addition, these procedures open up the way for the preparation of a large variety of chiral DMAP organocatalysts. Their catalytic activity was tested in t-butoxycarbonyl transfer reactions, chosen as a benchmark because these transformations potentially profit from the presence of a nucleophilic catalyst. The kinetic resolution of alcohols and the enantioselective preparation of benzazetidines, in some experiments, was achieved with a noticeable enantiomeric ratio.

Lipase-Catalyzed Kinetic Resolution of Alcohols as Intermediates for the Synthesis of Heart Rate Reducing Agent Ivabradine

Ivabradine (Corlanor®), is a chiral benzocycloalkane currently employed and commercialized for the treatment of chronic stable angina pectoris and for the reduction in sinus tachycardia. The eutomer (S)-ivabradine is usually produced via chiral resolution of intermediates, by employing enantiopure auxiliary molecules or through preparative chiral HPLC separations. Recently, more sustainable biocatalytic approaches have been reported in literature for the preparation of the chiral amine precursor. In this work, we report on a novel biocatalyzed pathway, via a resolution study of a key alcohol intermediate used as a precursor of the chiral amine. After screening several enzymatic reaction conditions, employing different lipases and esterases both for the esterification and hydrolysis reactions, the best result was achieved with Pseudomonas cepacia Lipase and the final product was obtained in up to 96:4 enantiomeric ratio (e.r.) of an ivabradine alcohol precursor. This enantiomer was then efficiently converted into the desired amine in a facile three step synthetic sequence.

Kinetic Resolution of Alcohols by Using a Recyclable Isothiourea Catalyst

Kinetic Resolution of Alcohols by Using a Recyclable Isothiourea Catalyst

Cluster Preface: Silicon in Synthesis and Catalysis

Martin Oestreich is Professor of Organic Chemistry at the Technische Universität Berlin. His appointment was supported by the Einstein Foundation Berlin. He received his diploma degree with Paul Knochel (Marburg, 1996) and his doctoral degree with Dieter Hoppe (Münster, 1999). After a two-year postdoctoral stint with Larry E. Overman ­(Irvine, 1999–2001), he completed his habilitation with Reinhard ­Brückner (Freiburg, 2001–2005) and was appointed as Professor of Organic Chemistry at the Westfälische Wilhelms-Universität Münster (2006–2011). He also held visiting positions at Cardiff University in Wales (2005) and at The Australian National University in Canberra (2010). Martin Oestreich’s research focuses on silicon in synthesis and catalysis, the theme of the present SYNLETT Cluster. His early work centered on the use of silicon-stereogenic silicon reagents in asymmetric catalysis, and his laboratory continues to employ them as stereochemical probes in mechanistic investigations. His research group made fundamental contributions to catalytic carbon–silicon bond formation with nucleo­philic and, likewise, electrophilic silicon reagents, and Martin Oestreich is probably best known for his work in silylium-ion chemistry. Recent accomplishments of his laboratory include Friedel–Crafts-type C–H silylation, transfer hydrosilylation, and kinetic resolution of alcohols by enantioselective silylation.

Asymmetric Cycloetherification via the Kinetic Resolution of Alcohols Using Chiral Phosphoric Acid Catalysts

In this study, novel asymmetric cycloetherification via the kinetic resolution of secondary or tertiary alcohols using chiral phosphoric acid catalysts was developed, affording tetrahydropyrans (THPs) with two stereogenic centers. The cyclization of the recovered optically active alcohols afforded other stereoisomers of THPs. These protocols offer efficient synthetic routes to various optically active THP derivatives, which are important structures found in a range of biologically active agents.

Thermodynamic analysis of enzyme enantioselectivity: a statistical approach by means of new differential HybridMIF descriptors

The study of relationships between substrate structure and enzyme stereoselectivity was approached by means of a new molecular descriptor: the “differential Hybrid Molecular Interaction Field” (dH-MIF). The descriptor was conceived with the purpose of combining enthalpic and entropic information related to enzyme–enantiomer interactions. The dH-MIFs were developed based on experimental data previously published by the group of Karl Hult on the enantioselectivity of the W104A mutant of lipase B from Candida antarctica, which is endowed with an enlarged stereoselectivity pocket. Because of the increased conformational freedom of substrates, the entropic contribution to enantiodiscrimination is particularly relevant in kinetic resolution of alcohols catalyzed by this enzyme. By combining molecular dynamic simulations and GRID analysis the new dH-MIF descriptors proved to be able to extract both enthalpic and entropic information from models of the tetrahedral intermediates of enantiomers.

Kinetic Resolution of Alcohols by Chiral Brønsted Acid Catalyzed Acylation

Kinetic Resolution of Alcohols by Chiral Brønsted Acid Catalyzed Acylation

Enantioselective synthesis and absolute configuration of the sex pheromone of Hedypathes betulinus (Coleoptera: Cerambycidae)

The male-produced sex pheromone of Hedypathes betulinus was identified as a mixture of (E)-6,10-dimethyl-5,9-undecadien-2-one (geranylacetone) (1) and its respective alcohol (2) and acetate (3). Kinetic resolution of alcohol (2) promoted by CAL-B in organic media provided both, (R)-(−)-(E)-6,10-dimethyl-5,9-undecadien-2-yl acetate (3) and (S)-(+)-(E)-6,10-dimethyl-5,9-undecadien-2-ol (2) in high enantiomeric purity. Comparative GC analysis using a chiral column revealed the natural constituents as being (R)-(3) and a mixture of (R)- and (S)-(2) in a ratio of 82.3% and 17.6%, respectively.

Optically Active Chiral Ligands, Ferrocenyloxazolinylphosphines (FOXAPs): Development and Application to Catalytic Asymmetric Reactions

The development of optically active chiral ligands, ferrocenyloxazolinylphosphines (FOXAPs), and their application to catalytic asymmetric reactions are reviewed. FOXAPs have been prepared in high yields from the corresponding chiral oxazolinylferrocenes via diastereoselective lithiation followed by quenching with chlorodiphenylphosphine. They work quite effectively as chiral ligands for a variety of transition-metal-catalyzed asymmetric reactions such as hydrosilylation and transfer hydrogenation of ketones and imines, kinetic resolution of alcohols, carbon-carbon bond-forming reactions and ring-opening reactions.

Kinetic Resolution of Alcohols under Aerobic Conditions

Kinetic Resolution of Alcohols under Aerobic Conditions

Cationic oxorhenium chiral salen complexes for asymmetric hydrosilylation and kinetic resolution of alcohols

High valent transition metal oxo complexes are ubiquitous in catalytic oxidation and oxygen atom transfer reactions, while their application in catalytic reductions is only being realized in the past few years. Reaction of ReOCl 3(PPh 3) 2 with appropriate chiral salen ligands, followed by oxo abstraction with a silylium cation, afforded several cationic oxorhenium(V)-saldach complexes 1– 2, including a rare trinuclear rhenium cluster ( 2), all of which have been fully characterized. These complexes are effective catalysts for hydrosilylation of carbonyl compounds and silane alcoholysis, although the enantioselectivity for both reactions is rather low. An intermediate, featuring a partially reduced saldach ligand (a salen/salan hybrid), was identified in reaction of 1a with Et 3SiH. The reaction mechanism is discussed in light of results from a crossover experiment.

Oxidative Kinetic Resolution of Alcohols: O2 as a Terminal Oxidant

Oxidative Kinetic Resolution of Alcohols: O₂ as a Terminal Oxidant

光学活性フェロセニルオキサゾリニルホスフィン配位子（ＦＯＸＡＰ）の開発と触媒的不斉合成反応への応用

Recent development of optically active chiral ligands, ferrocenyloxazolinylphosphines (FOXAP), and their application to catalytic asymmetric reactions are reviewed. FOXAP have been prepared in high yields from the corresponding chiral oxazolinylferrocenes via diastereoselective lithiation followed by quenching with chlorodiphenylphosphine. They work as chiral ligands quite effectively for a variety of transition metal-catalyzed asymmetric reactions such as hydrosilylation and transfer hydrogenation of ketones and imines, kinetic resolution of alcohols, carbon-carbon bond forming reactions and ring-opening reactions.

Synthesis and Reactivity of New Chiral Bicyclic Phospholanes as Acyl‐Transfer Catalysts.

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Tetramisole-Based Organocatalyst for the Kinetic Resolution of Alcohols

Tetramisole-Based Organocatalyst for the Kinetic Resolution of Alcohols

Synthesis and Reactivity of New Chiral Bicyclic Phospholanes as Acyl-Transfer Catalysts

[structure: see text] Synthesis of chiral phosphines 1a, 14a, and 18a as nucleophilic catalysts for anhydride activation and kinetic resolution of alcohols is described. Radical cyclization of alkenylphosphines produced the phosphabicyclooctane (PBO) core of catalysts 1a and 14a, while 18a was made by quenching a metallocycle precursor with dichlorophenylphosphine. Catalysts 1a and 14a are less reactive, while 18a is comparable to the most reactive catalysts in the PBO family. The preferred ground-state geometries of phosphine-boranes were identified using computational methods, and were correlated with the catalytic reactivity of the corresponding free phosphines.

Dynamic Kinetic Resolution of Alcohols by a Racemization Catalyst and a Lipase

Dynamic Kinetic Resolution of Alcohols by a Racemization Catalyst and a Lipase

2,3‐Dihydroimidazo[1,2‐a]pyridines: A New Class of Enantioselective Acyl Transfer Catalysts and Their Use in Kinetic Resolution of Alcohols.

The long-known, but previously unexplored 2,3-dihydroimidazo[1,2-a]pyridine (DHIP) has been shown to be a competent acyl transfer catalyst. Its chiral 2-phenyl derivatives obtainable in two steps from commercially available starting materials have proved to be effective acylation catalysts, giving high levels of enantioselectivity (s = 20−85) in kinetic resolution of secondary benzylic alcohols. A transition state model explaining the observed selectivity has been proposed.

2,3-Dihydroimidazo[1,2-a]pyridines: a new class of enantioselective acyl transfer catalysts and their use in kinetic resolution of alcohols.

The long-known, but previously unexplored 2,3-dihydroimidazo[1,2-a]pyridine (DHIP) has been shown to be a competent acyl transfer catalyst. Its chiral 2-phenyl derivatives obtainable in two steps from commercially available starting materials have proved to be effective acylation catalysts, giving high levels of enantioselectivity (s = 20-85) in kinetic resolution of secondary benzylic alcohols. A transition state model explaining the observed selectivity has been proposed.

A comparison of monocyclic and bicyclic phospholanes as acyl-transfer catalysts.

The synthesis and evaluation of chiral phosphines 11, 15a, 19a, 24a, and 28a as nucleophilic catalysts for anhydride activation and kinetic resolution of alcohols is described. The relative reactivity follows the order 11a > 11b > 15a > 1 in the monocyclic series, and 24a > 19a > 28ain the bicyclic series, with an overall rate advantage of ca. 2 orders of magnitude for the bicyclic phospholanes over the monocyclic analogues. The increased reactivity of the bicyclic phospholanes for the acylation of alcohols is attributed to conformational effects and ground-state destabilization in a highly associative mechanism. Kinetic resolution data demonstrate promising enantioselectivities for 24a.