Piperidine promoted aldol reaction of alkynyl aldehydes and ethyl diazoacetate

Complex diazo compounds containing propargyl alcohol functional group were prepared by an efficient aldol reaction of alkynyl aldehydes and ethyl diazoacetate in good yields. Piperidine was utilized as a base to catalyze this transformation. The aldol reaction showed broad substrate scopes and good functional group compatibility.     

Carbene‐Catalyzed Enantioselective Aldol Reaction: Post‐Aldol Stereochemistry Control and Formation of Quaternary Stereogenic Centers

The dominated approaches for asymmetric aldol reactions have primarily focused on the aldol carbon–carbon bond‐forming events. Here we postulate and develop a new catalytic strategy that seeks to modulate the reaction thermodynamics and control the product enantioselectivities via post‐aldol processes. Specifically, an NHC catalyst is used to activate a masked enolate substrate (vinyl carbonate) to promote the aldol reaction in a non‐enantioselective manner. This reversible aldol event is subsequently followed by an enantioselective acylative kinetic resolution that is mediated by the same (chiral) NHC catalyst without introducing any additional substance. This post‐aldol process takes care of the enantioselectivity issues and drives the otherwise reversible aldol reaction toward a complete conversion. The acylated aldol products bearing quaternary/tetrasubstituted carbon stereogenic centers are formed in good yields and high optical purities.     

Trichlorosilyl triflate for enantioselective direct-type aldol reaction with chiral phosphine oxide

Trichlorosilyl triflate, in the presence of a chiral Lewis base catalyst, provides an effective method for the enantioselective direct-type aldol reaction of aldehydes and ketones. A chiral Lewis base induces both the production and activation of trichlorosilyl enol ether, yielding an aldol product in good yield and with high diastereo- and enantioselectivities.     

Direct asymmetric aldol-Tishchenko reaction of aliphatic ketones catalyzed by syn-aminoalcohol-Yb(III) complexes

The asymmetric direct aldol condensation of aldehydes with ethyl- and propylketones is catalyzed by syn-alpha-aminoalcohol-Yb(OTf)3 complexes, yielding the anti-1,3-diol monoesters with high diastereocontrol and good enantioselectivity. Three adjacent stereogenic centers are created in a simultaneous aldol condensation and Evans-Tishchenko reduction in an acyclic system.     

Stereoselective aldol additions of achiral ethyl ketone-derived trichlorosilyl enolates

Methods for the preparation of geometrically defined enoxy(trichlorosilanes) derived from ethyl ketone enolates have been developed. The addition of enoxy(trichlorosilanes) (trichlorosilyl enolates) to aldehydes proceeds with good yields in the presence of catalytic amounts of chiral phosphoramides. The reaction of Z-trichlorosilyl enolates to aryl aldehydes affords aldol products with good to excellent diastereo- and enantioselectivities. Phosphoramide-catalyzed aldol additions lacked substrate generality providing modest selectivities with unsaturated and aliphatic aldehydes. In all cases, the phosphoramide-catalyzed aldol addition of E-trichlorosilyl enolates to aldehydes provided good yields with moderate to good stereoselectivities.     

Organocatalytic asymmetric syn-selective direct aldol reactions in water

A practical and convenient organocatalytic strategy is developed to provide a direct route to syn-selective aldol products in the presence of water. The siloxy serine organocatalyst mediates the direct aldol reaction of TBSO-protected hydroxyacetone with a variety of aldehydes to provide the aldol products in good yields and enantioselectivities up to 92%.     

Chiral ytterbium complex-catalyzed direct asymmetric aldol-Tishchenko reaction: synthesis of anti-1,3-diols

The asymmetric aldol-Tishchenko reaction of aromatic aldehydes with aliphatic and aromatic ketones has been developed as an efficient strategy for the synthesis of anti-1,3-diols in good yield with high diastereocontrol and good levels of enantioselectivity. This domino-type reaction is catalyzed by a chiral ytterbium complex that promotes both the aldol reaction through enolization of the carbonyl compound and the Evans-Tishchenko reduction of the aldol intermediate. The stereochemistry of the resulting diols is also investigated and finally proved by using CD techniques.     

Réaction pseudo-multicomposants entre le glutaconate de diméthyle et des aldéhydes aromatiques induite par le bromure de phénylzinc : accès domino à des dihydropyranones 2,3,5-trisubstituées

Phenylzinc bromide enables a pseudo three-component reaction of methyl glutaconate and aromatic aldehydes. Unsaturated trisubstituted δ-valerolactones (dihydropyranones) are obtained in fair to good yields by an aldol/aldol/elimination/lactonization domino process that allows the formation of four new bonds in a single step. A putative reaction mechanism is proposed.     

Aldol reactions of a cyclobutanone enolate

Addition of an aldehyde and zinc chloride to a cyclobutanone enolate, prepared by the reaction of an α-chlorocyclobutanone with dimethylcopperlithium, gave an aldol adduct in good yield.     

Sequential hydroformylation/aldol reactions: versatile and controllable access to functionalised carbocycles from unsaturated carbonyl compounds

Three different modes of hydroformylation/aldol reaction sequences involving either acid-catalysed aldol reactions, Mukaiyama aldol addition of pre-formed enolsilanes or aldol addition of in situ generated boron enolates can be applied to unsaturated ketones and ketoesters to afford the corresponding carbocyclic aldol adducts in good yields proceeding through the intermediate activated ketoaldehydes. In selected cases, complimentary, synthetically useful diastereoselectivities were observed in the products.     

L‐Proline‐Catalyzed Asymmetric Direct Aldol Reaction of Heteroaromatic Aldehydes and Acetone: Improvement of Catalytic Efficiency in Ionic Liquid bmim [BF4]

l‐proline in bmim [BF₄] ionic liquid has been successfully used as an efficient and reusable catalyst for the direct asymmetric aldol reaction of acetone with different heteroaromatic aldehydes to afford higher selectivity of the aldol products with good enantioselectivity.     

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%.     

Novel chiral gallium Lewis acid catalysts with semi-crown ligands for aqueous asymmetric Mukaiyama aldol reactions

Asymmetric Mukaiyama aldol reactions in aqueous media (water-ethanol = 9:1) were catalyzed by chiral gallium catalysts with semi-crown ligands to give aldol products with good yields, syn-diastereoselectivities and enantioselectivities.     

Role of Adamantane Amide Based on L-Proline Double-H Potential Organocatalyst in Aldol Reaction with Product Separated via Host-guest Interaction

Chiral organocatalysts of 4-adamantane amide based on L-proline with double hydrogen potential were synthesized and used in asymmetric aldol reactions. The reactions were evaluated in toluene under -20℃. A series of aldol products was obtained from moderate to good yields(up to 98%) with excellent diastereoselectivities(up to >99:1) and enantioselectivities(up to >99%). The aldol products in the system were separated by α-cyclodextrin via host-guest interaction and determined by chiral HPLC. The catalyst could be reused up to five times. The 4-substitution position played an important role in diastereoselectivity and enantioselectivity.     

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).     

Diastereoselective aldol additions of chiral beta-hydroxy ethyl ketone enolates catalyzed by Lewis bases

The trichlorosilyl enolates derived from chiral ethyl ketones bearing a beta-hydroxyl group and an alpha-stereogenic center were employed in the phosphoramide-catalyzed aldol reaction. The addition of Z-enolates to achiral aldehydes produced aldol products in good yields and high syn relative diastereoselectivities. The internal diastereoselectivity is controlled by the catalyst configuration, allowing for selective formation of either syn diastereomer. [reaction: see text]     

Sodium phenoxide-phosphine oxides as extremely active Lewis base catalysts for the Mukaiyama aldol reaction with ketones

A highly efficient Mukaiyama aldol reaction between ketones and trimethylsilyl enolates catalyzed by sodium phenoxide-phosphine oxides as simple homogeneous Lewis base catalysts (0.5-10 mol %) was developed, which minimized competing retro-aldol reaction. For a variety of aromatic ketones and aldimines, aldol and Mannich-type products with an alpha-quaternary carbon center were obtained in good to excellent yields. Up to 100 mmol scale of benzophenone and trimethylsilyl enolate with 0.5 mol % of catalyst was established in 97% yield (34.8 g).     

Review of the aldol reaction

Aldol condensation is an important synthetic method widely used in organic synthesis. Development of catalytic methods that avoids the production of stoichiometric by-products while maintaining high levels of control available from stoichiometric processes provides an atom-economical alternative for these important transformations. Indeed, numerous catalysts for the aldol reaction have been reported in recent years, including enzymes, catalytic antibodies, organometals, organocatalysts, and small molecules. The direct aldol reaction is the most important reaction employed by synthetic chemists and is common in nature. Recently, various Lewis acids have been examined as catalysts for aldol reactions, but aldol condensation in a micellar medium has not been studied in detail so far. Because of stronger environmental concerns, organic reactions in green media, especially in water, have attracted more attention. It is believed that micelles act as nano reactors to enhance the reaction rates and give very good to excellent yields of end products.     

Surface-Mediated Solid Phase Reaction. IX. A Convenient Procedure for Aldol Reaction of Ketene Silyl Acetals with Aldehydes on the Solid Surface of Alumina

The aldol reaction of ketene silyl acetals with aldehydes proceeds efficiently on the solid surface of alumina impregnated with anhydrous zinc chloride under sonication providing aldol products in high yields and with good stereoselectivity.     

Zn(pybox)-complex-catalyzed asymmetric aqueous Mukaiyama-aldol reactions

Catalytic asymmetric aldol reactions in aqueous media have been developed using chiral zinc complex. The aldol products have been obtained in high yields, high diastereocontrol, and good level of enantioselectivity. Various aromatic and alpha,beta-unsaturated aldehydes and silyl enol ethers derived from ketones can be employed in this reaction to provide the aldol adducts in good to high yield. The elaborated catalytic system has been found as selective for aliphatic aldehydes as well.