Highly chemo- and enantioselective vinylogous aldol/cyclization cascade reaction to construct chiral 5,6-dihydropyran-2-ones

An organocatalytic chemo- and enantioselective vinylogous aldol/cyclization cascade reaction between β,γ-unsaturated amides and β,γ-unsaturated α-keto esters was developed. With 5?mol% of chiral tertiary amine-thiourea catalyst C3, highly functionalized 5,6-dihydropyran-2-ones with a quaternary stereocenter were constructed in a straightforward manner with high yields (up to 99%) and excellent enantioselectivities (up to 98% ee).     

Recent advances towards catalytic asymmetric Conia-ene-type reactions

Conia-ene reactions,as a type of ene reactions,have not become a remarkable focus until the beginning of21~(st) century,when Lewis acids served as powerful catalysts and found an increasingly broad utilization in this field.Consequently,the catalytic Conia-ene reactions have gained great significance in synthetic chemistry due to their high efficiency and atom economy on the construction of valuable cyclic molecules.During the past two decades,the rapid development of transition-metal catalysis and organocatalysis has imposed a profound impact on the exploration of asymmetric Conia-ene reactions.As a result,several strategies have been developed and applied successfully.Organized on the basis of the catalytic system,this review comprehensively presents a summary of recent progress achieved in this emerging domain,aimed at highlighting the reactions' features,practicalities,and the mechanistic rationale is presented where possible.     

Rationally designed organocatalyst for direct asymmetric aldol reaction in the presence of water

A rationally designed organocatalyst for direct asymmetric aldol reaction in the presence of water has been developed. High yield (up to 99%), diastereoselectivity (up to 99:1) and enantioselectivity (up to 97%) were obtained under optimal conditions.     

Solvent-free asymmetric vinylogous aldol reaction of Chan's diene with aromatic aldehydes catalyzed by hydrogen bonding

Chan's diene proved to react with aromatic aldehydes under organocatalytic conditions in presence of a chiral naphthyl-TADDOL derivative to give vinylogous aldols (up to 65% ee) with complete γ-selectivity. A further process of hetero-Diels-Alder cycloaddition, leading to chiral pyran-4-one derivatives (up to 60% ee), was favoured by electron-withdrawing substituents on the aromatic ring.     

Highly efficient prolinamide-based organocatalysts for the direct asymmetric aldol reaction in brine

Four prolinamide-based organocatalysts were readily synthesized and applied to the direct asymmetric aldol reactions of ketones and aromatic aldehydes in brine. When 2,4-dinitrophenol (DNP) was used as an acidic additive, 1 mol % low loading of 2b afforded aldol products with excellent diastereoselectivity of up to 98/2 dr and high enantioselectivity of up to 97% ee.     

2-Chlorotetrafluoroethanesulfinamide induced asymmetric vinylogous Mannich reaction

The generality of (S)-2-chlorotetrafluoroethanesulfinamide (CTFSA) induced asymmetric vinylogous Mannich (AVM) addition reaction has been investigated. The reaction of aldimines derived from (S)-CTFSA with 2-(tert-butyldimethylsilyloxy) furan (TBSOF) took place regioselectively at the γ-site at room temperature in DMSO under air atmosphere to give the desired addition products in syn-configuration with high diastereoselectivities (up to 98:2 dr). However, anti-configuration product as major isomer was obtained in the presence of tetra-butyl ammonium fluoride (TBAF) at −78 °C. Facile removal of the auxiliary group without epimerization demonstrated their synthetic potential for piperidone derivatives.     

Rationally designed 4-phenoxy substituted prolinamide phenols organocatalyst for the direct aldol reaction in water

A rationally designed 4-phenoxy substituted prolinamide phenols as an efficient hydrophobic organocatalyst for direct asymmetric aldol reaction in water has been developed. High yield (up to 99%), diastereoselectivity (up to 99:1), and enantioselectivity (up to 97%) were obtained under optimal condition. The influence of substituent groups on the reactivity of catalysts was studied in detail.     

Dipeptide-catalyzed direct asymmetric aldol reactions in the presence of water

The l-proline-based dipeptide has been discovered and developed as an efficient catalyst for the direct asymmetric aldol reactions of unmodified ketones with various aldehydes including aromatic, aliphatic, heteroaromatic, and unsaturated aldehydes in the presence of water at 0 °C. The resulted methodology and optimal conditions led to the corresponding aldol products with high yields (up to 94%) and good enantioselectivities (up to 97% ee).     

Metal/linked-BINOL complexes: Applications in direct catalytic asymmetric Mannich-type reactions

Development of metal/linked-BINOL complexes and their applications in direct catalytic asymmetric Mannich-type reactions of hydroxyketones are reviewed. A Et₂Zn/linked-BINOL complex was effective for diastereo- and enantioselective synthesis of β-amino alcohols. By choosing the proper protective groups on the imine nitrogen, either anti- or syn-β-amino alcohol was obtained in excellent enantioselectivity (up to >99.5% ee) using the same zinc catalysis. Y{N(SiMe₃)₂}₃/linked-BINOL complex was effective for various hydroxyketones, affording syn-β-amino alcohols with high enantioselectivity (up to 98% ee). To broaden the nucleophile scope to carboxylic acid derivatives, N-acylpyrrole was utilized as an ester equivalent donor. In(O-iPr)₃/linked-BINOL complex was effective for generating an In-enolate from N-acylpyrrole in situ, giving Mannich adducts with high enantioselectivity (up to 98% ee).     

Recent development of vinylogous Mukaiyama aldol reactions

The vinylogous Mukaiyama aldol reaction (VMAR) is a powerful tool of polyketide synthesis, which constructs a large size structure by simultaneous introduction of the stereogenic center(s) and the α,β-unsaturated carbonyl group. A variety of stereocontrolled VMARs have been developed and applied to natural product synthesis. This review is focused on recent development of the vinylogous Mukaiyama aldol reaction using s-trans silyl dienolates.     

Chiral Phebox-rhodium complexes as catalysts for asymmetric direct aldol reaction

Chiral bis(oxazolinyl)phenyl-rhodium complexes act as catalysts in the combination of AgOTf for direct aldol reaction of ketones and aromatic aldehydes to give the corresponding β-hydroxyketones in high anti-selectivity and a good to high enantioselectivity up to 91% ee.     

Recent advances in the asymmetric catalytic synthesis of chiral 3-hydroxy and 3-aminooxindoles and derivatives: Medicinally relevant compounds

Several oxindole derivatives, of natural or synthetic origin, have been identified as medicinally appealing compounds, with a plethora of bioactivities reported. Chiral 3-hydroxy and 3-aminooxindole scaffolds have captured the attention of several research groups, due to their importance in drug discovery. In this review, we systematically address the wide variety of asymmetric catalytic methodologies employed in the preparation of these relevant chiral scaffolds, present in many biologically active compounds and/or natural products. Special focus will be given to the nature of the catalyst used.     

Enantioselective vinylogous aldol reaction of Chan’s diene catalyzed by hydrogen-bonding

Hydrogen-bonding activation of aromatic aldehydes by a TADDOL-derivative promotes the vinylogous aldol reaction of Chan’s diene in moderate efficiency and enantioselectivity. Electron-poor aromatic aldehydes show an enhanced reactivity and a competing asymmetric hetero-Diels-Alder reaction takes place in comparable (or higher) yields and enantiomeric excesses.     

Recent progress in copper catalyzed asymmetric Henry reaction

Henry reaction is one of the most classical reactions to construct synthetically useful product nitro alcohol, which as a privileged skeleton is widely distributed in various pharmaceuticals. This review summarizes the recent progress of copper-catalyzed asymmetric Henry reaction from 2011 to 2016. The significant progress that has been made in this area will be highlighted and some of challenges that the author believes may be hindering further progress will be revealed.     

Organocatalytic asymmetric aldol reactions mediated by a cysteine-derived prolinamide

In this Letter, a cysteine-derived prolinamide is described to act as a robust and effective organocatalyst for enantioselective aldol reactions.     

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.     

Enantiopure azetidine-2-carboxamides as organocatalysts for direct asymmetric aldol reactions in aqueous and organic media

A family of enantiopure azetidine-2-caboxamides was asymmetrically synthesized, and was examined as organocatalyst in direct aldol reactions. A well chosen chiral azetidine-2-caboxamide was found to smoothly catalyze the direct aldol reaction of various benzaldehydes with acetone in brine, and β-hydroxy ketones were produced with enantiomeric excess up to 96%. The reaction of benzaldehydes with cyclic ketones also led to the formation of anti-products in diastereomeric ratio up to 99:1 and enantiomeric excess up to 99%.     

New N-terminal prolyl-dipeptide derivatives as organocatalysts for direct asymmetric aldol reaction

A series of new N-terminal prolyl-dipeptide derivatives have been synthesized and evaluated as organocatalysts for the direct asymmetric aldol reaction of acetone with electron-deficient aromatic aldehydes. At room temperature, the presence of 10 mol % of catalysts 2 and 5 efficiently catalyzes the direct asymmetric aldol reaction to give the aldol adducts with modest to excellent enantiomeric excesses (ee) values, which are up to 96%.     

模拟醛缩酶催化不对称直接Aldol反应新进展

对天然醛缩酶的作用机理进行了一般性阐述，在此基础上详细回顾了近几年对 两类醛缩酶的模拟催化不对称直接Aldol反应，并对其发展前景作了展望。     

Asymmetric, catalytic, vinylogous aldol reactions using pyrrole-based dienoxy silanes. Enantioselective synthesis of α,β-unsaturated γ-butyrolactam synthons

A practical, catalytic and enantioselective vinylogous Mukaiyama aldol reaction between 2-silyloxypyrrole donors and aromatic or heteroaromatic aldehyde acceptors is described. Using an enantiopure bisphosphoramide catalyst in conjunction with SiCl₄, a variety of α,β-unsaturated-δ-hydroxylated γ-butyrolactam compounds were synthesized in high yields and with good to excellent levels of site-, diastereo- and enantioselectivity.