Advances In Asymmetric Synthesis Research Articles

Recent Advances in Asymmetric Synthesis of Chiral Cyclobutenes

AbstractCyclobutene scaffolds occur in natural products and bioactive compounds. Their unique structural features and intrinsic ring strain make cyclobutene a type of important building block in synthetic chemistry. In recent years, considerable efforts have been dedicated to the synthesis of chiral cyclobutenes. Enantioselective [2+2] cycloadditions and functionalization of cyclobutene derivatives have emerged as powerful and reliable protocols for achieving this goal, resulting in significant progress in this field. This review provides a comprehensive summary of the recent advancements in the asymmetric synthesis of chiral cyclobutenes, and the discussion is logically divided into four parts according to the reaction mode.

Recent advances in asymmetric synthesis of chiral amides and peptides: racemization-free coupling reagents.

Over past decades, chiral amides and peptides have emerged as powerful and versatile compounds due to their various biological activities and interesting molecular architectures. Although some chiral condensation reagents have been applied successfully for their synthesis, the introduction of racemization-free methods of amino acid activation have shown lots of advantages in terms of their low cost and low toxicity. In this review, advancements in amide and peptide synthesis using racemization-free coupling reagents over the last 10 years are summarized. Various racemization-free coupling reagents have been applied in the synthesis of enantioselective amides and peptides, including ynamides, allenones, HSi[OCH(CF3)2]3, Ta(OMe)5, Nb(OEt)5, Ta(OEt)5, TCFH-NMI, water-removable ynamides, DBAA, DATB, o-NosylOXY, TCBOXY, Boc-Oxyma, NDTP, 9-silafluorenyl dichlorides, the Mukaiyama reagent, EDC and T3P. The racemization-free reagents described in this review provide an alternative greener option for the asymmetric synthesis of chiral amides and peptides. We hope that this review will inspire further studies and developments in this field.

Recent Advances in Asymmetric Synthesis of Pyrrolidine-Based Organocatalysts and Their Application: A 15-Year Update

In 1971, chemists from Hoffmann-La Roche and Schering AG independently discovered a new asymmetric intramolecular aldol reaction catalyzed by the natural amino acid proline, a transformation now known as the Hajos-Parrish-Eder-Sauer-Wiechert reaction. These remarkable results remained forgotten until List and Barbas reported in 2000 that L-proline was also able to catalyze intermolecular aldol reactions with non-negligible enantioselectivities. In the same year, MacMillan reported on asymmetric Diels-Alder cycloadditions which were efficiently catalyzed by imidazolidinones deriving from natural amino acids. These two seminal reports marked the birth of modern asymmetric organocatalysis. A further important breakthrough in this field happened in 2005, when Jørgensen and Hayashi independently proposed the use of diarylprolinol silyl ethers for the asymmetric functionalization of aldehydes. During the last 20 years, asymmetric organocatalysis has emerged as a very powerful tool for the facile construction of complex molecular architectures. Along the way, a deeper knowledge of organocatalytic reaction mechanisms has been acquired, allowing for the fine-tuning of the structures of privileged catalysts or proposing completely new molecular entities that are able to efficiently catalyze these transformations. This review highlights the most recent advances in the asymmetric synthesis of organocatalysts deriving from or related to proline, starting from 2008.

Recent Advances in Asymmetric Synthesis of P-Chiral Phosphine Oxides

Recent Advances in Asymmetric Synthesis of P-Chiral Phosphine Oxides

Catalytic asymmetric synthesis of α-stereogenic carboxylic acids: recent advances.

Chiral carboxylic acids bearing an α-stereogenic center constitute the backbone of many natural products and therapeutic reagents as well as privileged chiral ligands and catalysts. Hence, it is not surprising that a large number of elegant catalytic asymmetric strategies have been developed toward the efficient synthesis of α-chiral carboxylic acids, such as α-hydroxy acids and α-amino acids. In this review, the recent advances in asymmetric synthesis of α-stereogenic free carboxylic acids via organocatalysis and transition metal catalysis are summarized (mainly from 2010 to 2020). The content is organized by the reaction type of the carboxyl source involved, including asymmetric functionalization of substituted carboxylic acids, cyclic anhydrides, α-keto acids, substituted α,β-unsaturated acids and so on. We hope that this review will motivate further interest in catalytic asymmetric synthesis of chiral α-substituted carboxylic acids.

Microreaction and membrane technologies for continuous single-enantiomer production: A review

ABSTRACT Microreaction and membrane technologies offer optimal conditions for controlling enantiomer synthesis and purification processes in continuous production, with numerous advantages over batch manufacturing. One of the many forces driving the development of such technologies for the production of single optical isomers is the need for enantiomerically pure pharmaceutical drugs because enantiomers may display opposite therapeutic effects or different treatment efficacies and side effects. Yet, despite advances in asymmetric synthesis and separation techniques, preparing enantiomerically pure compounds remains a challenging task. Here, we review the progress in microfluidics and membrane chiral separation over the last two decades. In addition to describing and critically assessing the state of the art in both disciplines, we provide an overview of their beneficial properties and characteristics for developing technologies toward producing enantiomerically pure compounds. Concomitantly, we evaluate efforts to integrate synthesis and membrane separation into a microfluidic platform and pinpoint the limiting factors that must be overcome before these platforms can be fully deployed in the industry.

Recent advances in asymmetric synthesis with CO2

Carbon dioxide (CO2) is an important and appealing C1 building block in chemical synthesis due to its nontoxicity, abundance, availability and sustainability. Tremendous progress has been achieved in the chemical transformation of CO2 into high value-added organic chemicals. However, the asymmetric synthesis with CO2 to form enantioenriched molecules, especially the catalytic process, has lagged far behind. The enantioselective incorporation of CO2 into organic compounds is highly desirable, as the corresponding chiral products, such as carboxylic acids and amino acids, are common structural units in a vast array of natural products and biologically active compounds. Herein, we discuss recent progress toward the enantioselective incorporation of CO2 into organic molecules, which mainly rely on three strategies: 1) kinetic resolution or desymmetrization of epoxides with CO2 to form chiral cyclic carbonates and polycarbonates; 2) nucleophilic attack of O- or N-nucleophiles to CO2 in tandem with asymmetric C–O bond formation to prepare chiral cyclic carbonates and carbamates; 3) direct enantioselective nucleophilic attack of organometallic reagents to CO2 with asymmetric C–C bond formation. Finally, challenges and future outlook in this area are also presented.

Recent advances in asymmetric synthesis of 2-substituted indoline derivatives

ABSTRACT Enantiomerically pure 2-substituted indolines are an important class of nitrogen heterocycles that occur frequently in many alkaloid natural products and biologically active compounds. Consequently, the synthesis of such skeletons is of great significance. The past years have witnessed a number of remarkable advances in the development of efficient strategies to construct this class of chiral compounds. This review summarizes the recent advances in asymmetric synthesis of 2-substituted indoline derivatives. Due to the limitation of the length, this review only summarizes those works published from January of 2012 to January of 2019. Meanwhile, methods towards synthesis of fused and spirocyclic indolines will not be discussed in this review.

Recent progress in asymmetric synthesis of aziridine derivatives (microreview)

This microreview describes recent advances in asymmetric synthesis of aziridine derivatives, which have been published over the last two years.

Chiral sulfoxides: advances in asymmetric synthesis and problems with the accurate determination of the stereochemical outcome.

Chiral sulfoxides are in extremely high demand in nearly every sector of the chemical industry concerned with the design and development of new synthetic reagents, drugs, and functional materials. The primary objective of this review is to update readers on the latest developments from the past five years (2011-2016) in the preparation of optically active sulfoxides. Methodologies covered include catalytic asymmetric sulfoxidation using either chemical, enzymatic, or hybrid biocatalytic means; kinetic resolution involving oxidation to sulfones, reduction to sulfides, modification of side chains, and imidation to sulfoximines; as well as various other methods including nucleophilic displacement at the sulfur atom for the desymmetrization of achiral sulfoxides, enantioselective recognition and separation based on either metal-organic frameworks (MOF's) or host-guest chemistry, and the Horner-Wadsworth-Emmons reaction. A second goal of this work concerns a critical discussion of the problem of the accurate determination of the stereochemical outcome of a reaction due to the self-disproportionation of enantiomers (SDE) phenomenon, particularly as it relates to chiral sulfoxides. The SDE is a little-appreciated phenomenon that can readily and spontaneously occur for scalemic samples when subjected to practically any physicochemical process. It has now been unequivocally demonstrated that ignorance in the SDE phenomenon inevitably leads to erroneous interpretation of the stereochemical outcome of catalytic enantioselective reactions, in particular, for the synthesis of chiral sulfoxides. It is hoped that this two-pronged approach to covering the chemistry of chiral sulfoxides will be appealing, engaging, and motivating for current research-active authors to respond to in their future publications in this exciting area of current research.

Recent advances in rhodium-catalyzed asymmetric synthesis of heterocycles.

Heterocycles are crucial structural motifs that are ubiquitously present in biologically active natural products and pharmaceutically important compounds. Over the past few decades, great attention has been paid to develop efficient methodologies for the construction of diverse enantioenriched heterocyclic frameworks. This review focuses on the recent impressive progress and advances in the asymmetric synthesis of heterocycles under rhodium catalysis.

ChemInform Abstract: Recent Advances in Asymmetric Synthesis of P — Stereogenic Phosphorus Compounds

AbstractReview: [201 refs.

Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols.

The chirality, or ‘handedness’, of a biologically active molecule can alter its physiological properties. For this reason, it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation1,2. Despite many recent advances in asymmetric synthesis, the development of general and practical strategies to obtain all possible stereoisomers of an organic compound bearing multiple contiguous stereocenters remains a significant challenge3. In this manuscript, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, these amino alcohol products were synthesized using the sequential copper hydride-catalyzed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino alcohol products, which contain up to three contiguous stereocenters. Catalyst control and stereospecificity were simultaneously leveraged to attain exceptional control of the product stereochemistry. Beyond the utility of this protocol, the strategy demonstrated here should inspire the development of methods providing complete sets of stereoisomers for other valuable synthetic targets.

Recent Advances in Asymmetric Synthesis of Optically Active Indole Derivatives from 3-Indolylmethanols

吲哚-3-基甲醇在酸作用下原位生成亲电性的类乙烯基亚胺（离子）中间体,然后在手性催化剂催化下被亲核试剂进攻生成具有潜在生物活性的光学活性3-取代吲哚衍生物.综述了吲哚-3-基甲醇不对称烷基化反应、不对称还原反应以及不对称重排反应合成光学活性3-取代吲哚衍生物的研究进展.

Recent Advances in Asymmetric Synthesis of Oxacephems

Recent Advances in Asymmetric Synthesis of Oxacephems

ChemInform Abstract: Recent Advances in Enzymatic and Chemical Deracemisation of Racemic Compounds

AbstractReview: 41 refs.

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.

Recent advances in enzymatic and chemical deracemisation of racemic compounds

Deracemisation of racemic compounds is still the most important strategy to produce optically pure compounds despite many recent advances in asymmetric synthesis. Especially deracemisation approaches that give rise to single enantiomers are preferred, which can be achieved either by invoking organocatalysts, metal complexes or enzymes - leading to dynamic kinetic resolution - or by applying other deracemisation techniques based on stereoinversion or enantioconvergence. In this tutorial review, we will provide an overview of new, recently developed approaches that lead to the important goal of creating organic compounds of single chirality.

Organocatalytic Asymmetric Synthesis Using Proline and Related Molecules. Part 1

Organocatalytic asymmetric synthesis has been extensively studied and several important procedures for preparing optically active organic compounds have been developed. Research in this area has progressed rapidly in the last ten years. This review addresses the most significant advances in asymmetric synthesis using proline and related chiral organocatalysts mainly focusing on aldol reactions from the viewpoint of synthetic interests. This includes (1) proline-catalyzed aldol reactions, (2) proline-related chiral catalysts, and (3) other types of amino acid catalysts.

Organocatalytic Asymmetric Synthesis Using Proline and Related Molecules. Part 2.

Organocatalytic asymmetric synthesis has been extensively studied and several important procedures for preparing optically active organic compounds have been developed. Research activities in this area have progressed rapidly in the last ten years. This review addresses the most significant advances in asymmetric synthesis using proline and related chiral organocatalysts, mainly from the viewpoint of synthetic applications. This includes (1) Mannich reactions, (2) Michael addition reactions, (3) α-oxidation, (4) α-amination, (5) α-sulfenylation / selenenylation, (6) α-halogenation, (7) cycloaddition reactions, and (8) miscellaneous reactions such as C-C bond formation, epoxidation / oxidation, and reduction.