Recent advances in chiral phosphine-silver(I) complex-catalyzed asymmetric reactions

Since the first report of silver(I)-catalyzed asymmetric aldol-type reaction of activated isocyanides with aldehydes using a chiral ferrocenylphosphine as a chiral phosphine ligand has been appeared in 1990, various chiral phosphine-silver(I) catalysts have been utilized in asymmetric transformations. This feature articles describes recent examples of chiral phosphine-silver(I) complex-catalyzed asymmetric reactions such as allylation, aldol reaction, Mannich-type reaction, hetero-Diels-Alder reaction, 1,3-dipolar cycloaddition and nitroso aldol reaction.     

Current applications of organocatalysts in asymmetric aldol reactions: An update

The aldol reaction is one of the most important carbon–carbon bond formations in synthetic organic chemistry. An enantioselective aldol reaction should provide an enantioenriched product. The organocatalytic asymmetric aldol reaction via an in situ generated enamine intermediate is one of the most powerful synthetic tools to achieve enantiomerically pure products. This approach is often used to obtain chiral β-hydroxycarbonyl compounds with excellent enantioselectivity. In this report, we update our previous review regarding the applications of organocatalysts in asymmetric aldol reactions leading to chiral β-hydroxycarbonyl compounds as versatile synthetic motifs frequently found in pharmaceutically desired intermediates and biologically active naturally occurring compounds.     

Direct Asymmetric Aldol Type Reaction with Ethyl Diazoacetate: Stereoselective Synthesis of α, β-Dihydroxy Esters

Enantioselective aldol condensation under catalytic condition remains a challenging task in modern organic synthesis, and numerous efforts have been directed to this area. In particular, the direct catalytic asymmetric aldol reaction is very attractive considering the requirement of atom efficiency. This has been studied only recently, and several very practical processes have been developed. We have recently initiated a study on the direct asymmetric aldol type reaction with ethyl diazoacetate as nucleophile. Moderate enantioselectivities (65% ～91% ee ) were achieved in the condensation of aldehydes with ethyl diazoacetate catalyzed by the chiral complex of BINOL derivatives-Zr (OBu- t )4. [1]     

Carbohydrate-based organocatalysts in direct asymmetric aqueous aldol reaction

Aldol reaction involving chiral amines as organocatalysts through enamine formation, like class-I aldolases, is one of the thriving areas of general interest and widely applicable asymmetric reactions. There are many natural and synthetic chiral templates known to work as efficient organocatalysts, but using carbohydrate templates for chiral induction in asymmetric aldol reactions is a relatively new area developed in the recent years. This review focuses on carbohydrates alone or their conjugates with previously known chiral moieties as organocatalysts for asymmetric aldol reactions.     

Diastereoselective Aldol Reaction with an Acetate Enolate: 2,6-Bis(2-isopropylphenyl)-3,5-dimethylphenol as an Extremely Effective Chiral Auxiliary

A C ₂ -symmetrical phenol was used as a chiral auxiliary in the asymmetric aldol reaction of chiral acetates with various aldehydes [Eq. (a)]. The reaction proceeds readily under mild conditions to provide aldol adducts with high enantioselectivity. LDA=lithium diisopropylamide.     

Amino oxazolines as a new class of organocatalyst for the direct intermolecular asymmetric aldol reaction between acetone and aromatic aldehydes

A series of chiral amino oxazolines were synthesized and screened as organocatalysts for asymmetric intermolecular aldol reactions between acetone and aromatic aldehydes. The reaction works well with a range of aromatic aldehydes showing good to high selectivity. The present new system of the organocatalyst was effective for the asymmetric aldol reaction for a wide range of aromatic aldehydes and isatin to carry out an asymmetric carbon–carbon bond forming reaction with a high enantioselectivity of up to 91%.     

A simple, short, and flexible synthesis of viridiofungin derivatives

Described herein is a simple, flexible, and efficient synthesis of the skeleton of the viridiofungins, a family of microbial secondary metabolites. The synthesis utilizes an asymmetric aldol reaction of a chiral oxazolidinone, a diastereoselective alkylation of a chiral 1,3-dioxolan-2-one, and a geometrically selective alkene cross-metathesis reaction as the key C-C bond-forming steps.     

Current progress in the asymmetric aldol addition reaction

Control of stereochemistry during aldol addition reactions has attracted considerable interest over the years as the aldol reaction is one of the most fundamental tools for the construction of new carbon-carbon bonds. Several strategies have been implemented whereby eventually any single possible stereoisomeric aldol product can be accessed by choosing the appropriate procedure. With earlier methods, stoichiometric quantities of chiral reagents were required for efficient asymmetric induction, with the auxiliary most often attached covalently to the substrate carbonyl. Lewis acid catalyzed addition reactions of silyl enolates to aldehydes (Mukaiyama reaction) later opened the way for catalytic asymmetric induction. In the last few years, both chiral metal complexes and small chiral organic molecules have been found to catalyse the direct aldol addition of unmodified ketones to aldehydes with relatively high chemical and stereochemical efficiency. These techniques along with the more recent developments in the area are discussed in this tutorial review.     

Development of Asymmetric Reactions Catalyzed by Chiral Organotin‐Alkoxide Reagents

Asymmetric catalysis under almost‐neutral reaction conditions is key for the efficient synthesis of optically active polar molecules. We have developed catalytic enantioselective reactions of acyclic or cyclic alkenyl esters by using an (S)‐BINOL‐derived chiral tin‐dibromide reagent that possesses a bulky aryl group at the 3 or 3′ position as the chiral pre‐catalyst in the presence of a sodium alkoxide and an alcohol, in which a chiral tin alkoxide bromide is generated in situ and recycled with the assistance of an alcohol. In this Personal Account, we describe three types of asymmetric transformation that proceed through a chiral tin enolate: 1) The asymmetric aldol reaction of alkenyl esters or unsaturated lactones with aldehydes or isatins; 2) the asymmetric three‐component Mannich‐type reaction of alkenyl esters and related cycloaddition reactions; and 3) the asymmetric N‐nitroso aldol reaction of unsaturated lactones with nitrosoarenes.     

The state of the art in asymmetric induction: the aldol reaction as a case study

This review highlights the achievements in asymmetric induction in the context of the aldol reaction during the years 2003–2007. While chiral auxiliary-mediated methods are the best understood and developed, catalytic methods based on chiral metal–ligand complexes and more recently organocatalysts promise to improve the efficacy and economics of asymmetric induction. This review provides a brief summary of work prior to 2003 on chiral auxiliaries, metal catalysts and organocatalysts, and then delineates the state of the art in each process. It appears that no one method of achieving asymmetric induction in the aldol reaction is universally superior.     

Direct asymmetric aldol reaction of aryl ketones with aryl aldehydes catalyzed by chiral BINOL-derived zincate catalyst

Direct asymmetric aldol reaction of aryl ketones with aryl aldehydes catalyzed by chiral metal complex is reported for the first time herein. Two novel semicrown chiral ligands 1a and 1b were synthesized from (S)- and (R)-BINOL, respectively, and then employed to catalyze the direct asymmetric aldol addition of aryl ketones to aryl aldehydes. Introduced with 2.0 equiv of diethylzinc, 1b had higher enantioselectivity than 1a. Up to 97% yield and up to 80% enantioselectivity were achieved.     

Asymmetric aldol reaction via memory of chirality

Asymmetric aldol reactions of α-amino acid derivatives via memory of chirality were developed. Chiral oxazolidones with contiguous tetra- and trisubstituted chiral centers were obtained in 78-94% ee by the asymmetric aldol reaction followed by intramolecular acylation.     

Study of the lanthanide-catalyzed, aqueous, asymmetric Mukaiyama aldol reaction

The development of efficient methods for the asymmetric Mukaiyama aldol reaction in aqueous solution has received great attention. We have developed a new series of chiral lanthanide-containing complexes that produce Mukaiyama aldol products with outstanding enantioselectivities. In this paper, we describe an optimized ligand synthesis, trends in stereoselectivity that result from changing lanthanide ions, and an exploration of substrate scope that includes aromatic and aliphatic aldehydes and silyl enol ethers derived from aromatic and aliphatic ketones.     

Synthesis of [6]helicene-based sulfonic acid,sulfonamide, and disulfonimides

The synthesis of helically chiral [6]helicene-based sulfonic acid and sulfonamide from enantiomerically pure 1-acetylthio-5,6,9,10-tetrahydro[6]helicene is reported. The first helically chiral disulfonimides were developed as a synthetic application of [6]helicene-based sulfonamide. This new class of organocatalysts was tested in an asymmetric Mukaiyama aldol reaction to obtain up to quantitative yields and enantioselectivities up to 24%.     

手性噁唑硼烷酮催化不对称ALDOL反应进展

本文论述了手性口恶唑硼烷酮在催化不对称 aldol反应中的应用 ,讨论了反应机理。     

Synthesis of chiral organocatalysts derived from aziridines: application in asymmetric aldol reaction

We report the synthesis of a new series of highly efficient chiral organocatalysts derived via the regio- and stereoselective ring opening of chiral aziridines with azide anions. The catalysts have proved to be very efficient for a direct asymmetric aldol reaction, both with cyclic as well as acyclic ketones in brine with 2 mol % of catalyst loading, and afforded the products in excellent yields (up to 99%) and enantioselectivities (up to >99%). The chiral aldol adduct obtained has further been converted to a chiral azetidine ring via a convenient pathway.     

Catalytic enantioselective alkylative aldol reaction: efficient multicomponent assembly of dialkylzincs, allenic esters, and ketones toward highly functionalized delta-lactones with tetrasubstituted chiral centers

A general catalytic asymmetric alkylative aldol reaction is described as a new entry to the catalytic asymmetric multicomponent reaction (CAMCR). Highly functionalized delta-lactones were produced in the presence of a catalytic amount of the Cu(OAc)2-DIFLUORPHOS complex through three-component assembly of dialkylzincs, allenic esters, and unactivated ketones. This CAMCR constructs two C-C bonds and one tetrasubstituted chiral center simultaneously. Conjugate addition of alkylcopper species to an allenic ester produced highly active copper enolate in situ, and the successive asymmetric aldol addition to ketones followed by lactonization afforded the desired products. The addition of MS4A and Lewis base (Ph2S=O, DMSO, or HMPA) is important for obtaining a high yield, with suppression of the undesired alpha-addition pathway. Control/crossover experiments suggest that the addition of a Lewis base facilitated the retro-aldol reaction of the alpha-adducts (proofreading effect). The ketone and copper enolate generated through the retro-aldol reaction were converted to the desired lactone through the gamma-aldol pathway, which was trapped by irreversible lactone formation.     

Storable, powdered chiral zirconium complex for asymmetric aldol and hetero Diels-Alder reactions

A storable, powdered chiral zirconium catalyst for asymmetric aldol and hetero Diels-Alder reactions has been developed. The catalyst has the same activity as that prepared in situ even after being stored for 3 months. Moreover, this chiral Zr catalyst worked efficiently not only for asymmetric aldol reactions but also for asymmetric hetero Diels-Alder reactions affording the corresponding addition products with high enantioselectivities.     

Small organic molecule catalyzed enantioselective direct aldol reaction in water

Protonated pyrrolidine based small organic molecules have been designed and evaluated for the asymmetric direct aldol reaction in water. The designed organocatalysts are multifunctional in nature and exploit the combined effect of hydrogen bonding and hydrophobic interactions for enantioselective catalysis in water. As a result a unique direct asymmetric aldol reaction in water catalyzed by a small organic molecule having an amide linkage has been developed. The developed catalyst affords chiral β-hydroxyketones in good yields (93%) and enantioselectivities (upto 62%) in water.     

Remote asymmetric induction with vinylketene silyl n,o-acetal

A highly regio- and diastereoselective TiCl4-mediated vinylogous Mukaiyama aldol reaction using the chiral vinylketene silyl N,O-acetal has been developed. The present vinylogous Mukaiyama aldol reaction provides a unique and effective means of controlling remote asymmetric induction. The methyl group at the alpha-position is important in achieving a high level of stereoselectivity. From a synthetic point of view, this methodology can provide a one-step construction of delta-hydroxy-alpha,gamma-dimethyl-alpha,beta-unsaturated carbonyl unit that is seen in many natural polyketide products.