Applications In Stereoselective Synthesis Research Articles

Orthoesters: Multiple Role Players in Organic Synthesis

AbstractOrthoesters are characterized by three alkoxy groups attached to a single carbon atom. This functional group is used primarily as a masking group for carboxylic acids, due to its robust stability towards strong nucleophiles and bases. Besides this protection role, orthoesters have further utility as versatile precursors in organic synthesis. This review focuses on the latter role of orthoesters as well as their applications in stereoselective synthesis.

Chiral Thioureas-Preparation and Significance in Asymmetric Synthesis and Medicinal Chemistry.

For almost 20 years, thioureas have been experiencing a renaissance of interest with the emerged development of asymmetric organocatalysts. Due to their relatively high acidity and strong hydrogen bond donor capability, they differ significantly from ureas and offer, appropriately modified, great potential as organocatalysts, chelators, drug candidates, etc. The review focuses on the family of chiral thioureas, presenting an overview of the current state of knowledge on their synthesis and selected applications in stereoselective synthesis and drug development.

Characterization of a novel thermostable (S)-amine-transaminase from an Antarctic moderately-thermophilic bacterium Albidovulum sp. SLM16

Amine-transaminases (ATAs) are enzymes that catalyze the reversible transfer of an amino group between primary amines and carbonyl compounds. They have been widely studied in the last decades for their application in stereoselective synthesis of chiral amines, which are one of the most valuable building blocks in pharmaceuticals manufacturing. Their excellent enantioselectivity, use of low-cost substrates and no need for external cofactors has turned these enzymes into a promising alternative to the chemical synthesis of chiral amines. Nevertheless, its application at industrial scale remains limited mainly because most of the available ATAs are scarcely tolerant to harsh reaction conditions such as high temperatures and presence of organic solvents.In this work, a novel (S)-ATA was discovered in a thermophilic bacterium, Albidovulum sp. SLM16, isolated from a geothermal Antarctic environmental sample, more specifically from a shoreline fumarole in Deception Island. The transaminase-coding gene was identified in the genome of the microorganism, cloned and overexpressed in Escherichia coli for biochemical characterization. The activity of the recombinant ATA was optimal at 65 °C and pH 9.5. Molecular mass estimates suggest a 75 kDa homodimeric structure. The enzyme turned out to be highly thermostable, maintaining 80% of its specific activity after 5 days of incubation at 50 °C. These results indicate that ATA_SLM16 is an excellent candidate for potential applications in biocatalytic synthesis. To the best of our knowledge, this would be the first report of the characterization of a thermostable (S)-ATA discovered by means of in vivo screening of thermophilic microorganisms.

2-Azanorbornane--a versatile chiral aza-Diels-Alder cycloadduct: preparation, applications in stereoselective synthesis and biological activity.

The review presents the achievements in the field of preparation of chiral 2-azanorbornyl derivatives and their application in various stereoselective reactions as well as in biomimetic studies.

ChemInform Abstract: Advances in Asymmetric Hydrogenation and Hydride Reduction of Organophosphorus Compounds

AbstractReview: 106 refs.

ChemInform Abstract: Asymmetric Catalysis as a Method for the Synthesis of Chiral Organophosphorus Compounds

AbstractReview: [368 refs.

Advances in Asymmetric Hydrogenation and Hydride Reduction of Organophosphorus Compounds

This article describes the asymmetric synthesis of chiral organophosphorus compounds using methods of enantioselective hydride reduction and hydrogenation of corresponding unsaturated compounds. Many applications in stereoselective synthesis with reference to updated literature findings as well as the author's original research are discussed. The uses of chiral organophosphorus compounds in some asymmetric transformations leading to the formation of phosphorus analogues of important natural compounds were also presented.

Recent advances in asymmetric synthesis of Р-stereogenic phosphorus compounds.

This chapter points out significant advances in the asymmetric synthesis of P-chiral organophosphorus compounds with many applications in stereoselective synthesis and in asymmetric catalysis, making reference to updated literature findings as well as the author's original research. Asymmetric addition and cycloaddition reactions, oxidation, including metal catalyzed and non-metal biocatalytic methods are described, in addition to synthetic approaches via nucleophilic substitution of appropriately substituted precursors. Use of chiral organophosphorus compounds in some asymmetric transformations such as hydrogenation and alkyl/arylation reactions is also discussed.

Electron ionization-induced fragmentation of bridgehead-substituted norbornan-2-ones derived from fenchone

Camphor- and fenchone-based bridgehead-substituted norbornan-2-ones constitute an interesting class of chiral synthons with applications in stereoselective synthesis, due to the wide variety of stereocontrolled transformations which they can undergo. Despite their synthetic value, few mass spectral studies have been realized for these compounds due to the lack of general procedures for their preparation. In this paper we have carried out an electron ionization (EI) mass spectral study of a series of heteroatomically bridgehead-substituted 7,7-dimethylnorbornan-2-ones. Their cleavage mechanisms have been rationalized on the basis of the substituent shifts, as well as on the identification of relevant peaks through accurate mass measurements and collision-induced dissociation (CID) tandem mass-spectrometric experiments. The driving force for the main fragmentation pathways of C(1)-O- and C(1)-N-substituted 7,7-dimethylnorbornan-2-ones is the α-cleavage of the C(1)C(2) bond directed by the bridgehead substituent. Further rearrangements and fragmentations of the distonic ions initially formed lead to the major ions in the spectra of all the compounds. A comparison with the known behaviour of their isomeric 3,3-dimethylnorbornan-2-ones reveals that the key bridgehead heteroatom effect controlling the fragmentation pathways can be modulated by the position of the gem-dimethyl group. As a consequence, the corresponding fragmentation patterns of both isomeric series are very different. In contrast, the fragmentation patterns of 7,7-dimethyl-2-oxo-1-norbornanesulphonamides, whose main fragmentation pathway involves homolytic SN bond cleavage, are almost identical to those displayed by their 3,3-dimethylated isomers.

ChemInform Abstract: Synthesis of Enantioenriched Sulfoxides

AbstractReview: 326 refs.

Synthesis of enantioenriched sulfoxides

This review discusses strategies for the asymmetric synthesis of sulfoxides, compounds with many applications in stereoselective synthesis and in some cases with pharmaceutical application. The review describes asymmetric oxidation, including metal catalyzed and nonmetal and biological oxidation processes, in addition to synthetic approaches via nucleophilic substitution of appropriately substituted precursors. Kinetic resolution in oxidation of sulfoxides to the analogous sulfones is also discussed; in certain instances, access to enantioenriched sulfoxides can be achieved via a combination of asymmetric sulfide oxidation and complementary kinetic resolution in sulfoxide oxidation.

ChemInform Abstract: Preparation of Enantiomerically Enriched α‐Aminoorganostannanes and Their Applications in Stereoselective Synthesis

AbstractReview: 47 refs.

Preparation of enantiomerically enriched α‐aminoorganostannanes and their applications in stereoselective synthesis

This review deals with the preparation of chiral, nonracemic α-aminoorganostannanes and their applications in asymmetric synthesis. The pioneering works in this field date back almost 20 years ago and since then extensive research has been carried out to develop efficient and selective routes to highly enantioenriched α-aminoorganostannanes. The facile Sn/Li transmetalation of these compounds by n-BuLi has led to various applications in stereoselective synthesis. Selected examples using chiral α-aminoorganostannanes as starting materials will be reported.

Catalytic Enantioselective Radical Cyclization via Regiodivergent Epoxide Opening

A catalytic enantio- and diastereoselective radical cyclization using a regiodivergent epoxide opening (REO) for radical generation is described. It is demonstrated for the first time that the diastereoselectivity of cyclizations of acyclic radicals can be controlled catalytically. Building blocks for important applications in stereoselective synthesis are readily accessed.

Synthesis and stereoselective functionalization of silylated heterocycles as a new class of formyl anion equivalents

The fluoride ion-induced reactivity of a series of silyl heterocycles leads to the generation of nucleophilic species capable of interacting with electrophiles, thus disclosing new classes of formyl and acyl anion synthons. Moreover, when reacting stereodefined molecules, the stereoinformation of the reacting carbon-silicon bond is transferred to the newly formed carbon-carbon bond, suggesting possible applications in stereoselective synthesis. Thus, silyl dithiolanes, oxathiolanes, dioxolanes, thiazolidines and oxazolidines can be efficiently and stereoselectively functionalized under fluoride ion conditions in the presence of electrophiles. While direct access to silyl heterocycles is generally either prevented or troublesome, a novel protocol for their synthesis has also been developed, together with a simple general access route to several functionalized and stereodefined mercaptans, building blocks for the construction of silyl heterocycles.

Configurational stability and transfer of stereochemical information in the reactions of enantioenriched organolithium reagents.

The conversion of a prochiral methylene group into a stereogenic center by means of a lithiation/substitution sequence has emerged as a powerful synthetic transformation over the past 15 years. This reaction proceeds via a chiral organolithium intermediate, and the stereochemical fidelity of the overall reaction sequence is intimately dependent on the stereochemical behavior of the chiral organolithium as well as on the rate and stereochemical sense of the electrophilic substitution step. Chiral organolithium reagents were first reported by Letsinger, Curtin, and Applequist half a century ago. The lithiated intermediates in these early studies were not highly configurationally stable, and applications in stereoselective synthesis were not immediately forthcoming. The two decades that followed the 1980 report by Still and Sreekumar of a configurationally stable alpha-oxyorganolithium were marked by an increased interest in these reagents. As the synthetic applications of chiral organolithium reagents have grown, so have accompanying mechanistic studies of these intermediates which serve as the basis for this review.

Sulfimides (Sulfilimines): Applications in Stereoselective Synthesis

Aspects of the chemistry of sulfimides (sulfilimines) which are of importance in stereoselective synthesis are reviewed. The three principal sections cover bonding and configuration, preparation of enantiomerically enriched sulfimides from chiral and achiral starting materials and applications of chiral sulfimides in stereoselective synthesis, including stereospecific conversion to other chiral sulfur compounds, stereospecific electrocyclic reactions, diastereoselective and enantioselective reactions. Parallels are drawn with related reactions of other chiral sulfur compounds.