The first example of a catalytic asymmetric aldol-Tishchenko reaction of aldehydes and aliphatic ketones

A number of combinations of Lewis acids and chiral ligands has been screened for the enantioselective direct tandem aldol condensation--Evans-Tishchenko reduction of aldehydes and ketones. Chiral ytterbium complexes were found to catalyze the condensation of aromatic aldehydes with 3-pentanone (and other ketones) giving rise to the anti-1,3-diol monoesters in good yield, and with high diastereocontrol and moderate levels of enantioselectivity. Three adjacent stereogenic centers are created in one reaction sequence in acyclic systems.     

Asymmetric aldol-Tishchenko reaction catalyzed by Yb-complexes with basic amino acid-derived ligands

Simple amino acid-derived esters have been identified as promising chiral sources for the ytterbium-catalyzed aldol-Tishchenko reaction of aromatic aldehydes with aliphatic ketones. The 1,3-anti-diols with three stereogenic centers were isolated in excellent yields, complete anti-diastereocontrol and enantioselectivities of up to 50% ee.     

Highly stereoselective direct aldol reactions catalyzed by (S)-NOBIN-l-prolinamide

(S)-NOBIN-l-prolinamide was employed as organocatalyst in the direct aldol reactions of different ketones and aromatic aldehydes using dioxane as solvent and in the presence of water as additive. Acetone led to the aldol products in up to 93% ee, while cyclic ketones furnished the anti-aldols in moderate to high yield, excellent diastereoselectivity (up to >99/<1 anti/syn ratio) and high ee (up to 95%).     

Solvent-free Mukaiyama and Mukaiyama-Michael vinylogous reactions of a dioxinone-derived silyl enol ether promoted by Lewis bases

The vinylogous aldol-type addition of a dienolsilyl ether, derived from 2,2,6-trimethyl-4H-1,3-dioxin-4-one, showed to occur with complete γ-selectivity by enolate activation promoted by neutral Lewis bases under solvent-free conditions. Moderate to high yields were obtained with aromatic, hetero-aromatic, and aliphatic aldehydes, as well as activated ketones. Under the same conditions and in the absence of catalyst, the first Mukaiyama-Michael addition of the masked acetoacetate ester to α,β-unsaturated aldehydes took place in satisfactory way.     

Catalytic stereoselective Mannich reaction under solvent-free conditions

Silicon tetrachloride catalyzed one-pot three-component Mannich reaction of cyclic ketones, aromatic aldehydes, and aromatic amine under solvent-free conditions affords the corresponding β-amino ketones with excellent yield and good to excellent anti-selectivity.     

Nucleophilic difluoromethylenation of aldehydes and ketones using diethyl difluoro(trimethylsilyl)methylphosphonate

A new nucleophilic difluoromethylenation of aldehydes and ketones using diethyl difluoro(trimethylsilyl)methylphosphonate (1) has been achieved. The reactive carbanion species were generated under mild reaction conditions with a catalytic amount of initiator. This methodology was compatible with non-enolizable and in some cases with enolizable aldehydes and ketones and provided a straightforward access to phosphates of syn and anti 2,2-difluoro-1,3-diols.     

Highly efficient and solvent-free direct aldol reaction catalyzed by glucosamine-derived prolinamide

The catalytic activity of novel sugar-based prolinamides in the aldol reaction between ketones and aryl aldehydes has been examined. The prolinamide 1c was found to be an efficient organocatalyst for the asymmetric aldol reaction under solvent-free conditions. A variety of ketones and aldehydes were used as substrates and the corresponding aldol products were obtained in excellent chemical yields with high levels of anti diastereoselectivity (up to 99:1) and enantioselectivity (up to >99%).     

Aluminum enolates via retroaldol reaction: catalytic tandem aldol-transfer—Tischtschenko reaction of aldehydes with aldol adducts of ketones to ketones

Bidentate aluminum chelates derived from biphenol, binaphthol and catechol were found to be efficient catalysts for aldol-transfer reactions of ketone to ketone aldol adducts with aliphatic or aromatic aldehydes giving rise to the formation of aldol adducts of ketones to the aldehydes. In the presence of an excess of an aliphatic aldehyde, a catalytic tandem aldol-transfer—Tischtschenko reaction is observed. The tandem reaction produces monoesters of 1,3-diols with high anti selectivity and with modest to good chemical yield. 1,2-Unsaturated aldehydes are less reactive in the aldol-transfer reaction and require 2-4 times higher load of the catalyst to be used than aliphatic and aromatic aldehydes. Poor diastereoselectivity was observed in the formation of α-substituted aldols and 2-substituted monoesters of anti-1,3-diols indicating that the aldol-transfer reaction is not diastereoselective with the catalysts studied. The utility of the highly 1,3-anti selective formation of diolmonoesters was found to be limited by acyl migration.     

Highly enantioselective aldol reactions using a tropos dibenz[c,e]azepine organocatalyst

The four-step synthesis of a chiral primary tertiary diamine salt, possessing a tropos dibenz[c,e]azepine ring is described. It is shown that 3.5-5 mol % of this salt is capable of promoting highly enantioselective crossed-aldol reactions between cyclohexanone and a series of aromatic aldehydes. In all cases, the aldol reactions proceed with high diastereoselectivity for the anti-aldol product. The outcome of crossed-aldol reactions involving other cyclic ketones and acyclic ketones are also described. All examples involving cyclic ketones result in selectivity for the anti-aldol products, whereas acyclic ketones were found to favour the syn-aldol products. A discussion on the role of the chiral primary tertiary diamine salt in the catalysis of the aldol reactions is also presented.     

HClO4-SiO2 catalyzed stereoselective synthesis of β-amino ketones via a direct Mannich-type reaction

The HClO₄-SiO₂ catalyzed three-component, one-pot Mannich reaction of ketones, aromatic aldehydes and aromatic amines is carried out in ethanol to afford the corresponding β-amino ketones in good yields and high stereoselectivities in favor of the anti-isomer. Three new compounds are reported.     

A new type of amino amide organocatalyzed enantioselective crossed aldol reaction of ketones with aromatic aldehydes

A new type of amino amide organocatalysts was designed and synthesized from commercially available amino acids in easy steps. Their catalytic activities were examined in enantioselective crossed aldol reaction of various acyclic and cyclic ketones with aromatic aldehydes to afford the corresponding chiral anti-aldol adducts with good to excellent chemical yields, diastereoselectivities and enantioselectivities (up to 99%, up to syn:anti?=?1:99, up to 97% ee).     

Highly enantioselective vinylogous addition of 2-trimethylsilyloxyfuran to aldehydes promoted by the SiCl4/chiral Lewis base system

This paper reports the regio-, diastereo- and highly enantioselective vinylogous aldol reaction of 2-trimethylsilyloxyfuran (TMSOF) promoted by the SiCl₄/Lewis base catalytic system. Several electron-pair donors proved to be effective as SiCl₄ activators versus the TMSOF γ-selective addition to aldehydes giving rise to different diastereoisomeric ratios, while Denmark’s chiral bis-phosphoramide (R,R)-7 gave the highest enantioselectivity for both the anti- and syn-diastereoisomers. Furthermore, by using ambident electrophiles such as α,β-unsaturated aldehydes, the SiCl₄/Lewis base-promoted process leads exclusively to the 1,2-addition products.     

Stereoselective aldol additions of titanium enolates of N-acetyl-4-isopropyl-thiazolidinethione

The addition of chlorotitanium enolates of N-acetyl isopropyl thiazolidine-2-thione to aldehydes was investigated. The stereoselectivity of the aldol products was controlled by the number of equivalents of base added. The syn aldol product was obtained preferentially when 2 equiv of Lewis acid and 1 equiv of base were employed. The anti aldol product was obtained preferentially when 1 equiv of Lewis acid and 2 equiv of base were employed for unsaturated aldehydes. Unexpected results were found with hindered aldehydes when 2 equiv of base were employed.     

Stereocontrolled addition of boron enolates to trans α,β-aziridine aldehydes. A new route to anti-1,2-amino alcohols

A study of the addition of boron enolates of methyl ketones to trans α,β-aziridine aldehydes is reported. The reaction proceeds with excellent anti stereoselectivity furnishing functionalized products, capable of other controlled transformations, some of which are described.     

Direct asymmetric aldol reactions in brine using novel sulfonamide catalyst

Direct asymmetric aldol reactions of aldehydes with ketones in the presence of a catalytic amount of sulfonamide 4 and trifluoroacetic acid afforded the corresponding anti-aldol products in moderate to excellent yields with 85-93% ee.     

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.     

Enantioselective anti-Mannich reaction catalyzed by modularly designed organocatalysts

A highly stereoselective method for achieving the anti-Mannich reaction of aldehydes and ketones with ethyl (4-methoxyphenylimino)acetate was realized using the modularly designed organocatalysts (MDOs) self-assembled from cinchona alkaloid derivatives and (R)-pyrrolidien-3-carboxylic acid in the reaction media. The desired anti-Mannich products were obtained in good to excellent yields (up to 93%), excellent diastereoselectivities (up to 99:1 dr), and good to high enantioselectivities (up to 99% ee).     

ZrOCl2·8H2O: an efficient Lewis acid catalyst for the one-pot multicomponent synthesis of β-acetamido ketones

Aromatic aldehydes were reacted in one-pot with enolisable ketones, acetonitrile and acetyl chloride at ambient temperature in the presence of ZrOCl₂·8H₂O to furnish the corresponding β-acetamido ketones in very good to excellent yields. X-ray crystallographic analysis of one anti-β-acetamido ketone exhibited a two-dimensional supramolecular framework by a combination of N-H?O, C-H?O and C-H?π (arene) hydrogen bonds.     

1-Methylimidazole 3-N-oxide as a new promoter for the Morita-Baylis-Hillman reaction

The Morita-Baylis-Hillman reaction of aldehydes with α,β-unsaturated ketones can be affected by the Lewis bases. We have found that 1-methylimidazole 3-N-oxide promoted the Morita-Baylis-Hillman reaction of various activated aldehyde compounds in non-solvent system. This is a mild reaction condition and requires no special equipment to give the Morita-Baylis-Hillman adducts.     

Highly stereoselective anti-aldol reactions catalyzed by simple chiral diamines and their unique application in configuration switch of aldol products

Chiral derivatives of trans-1,2-diaminocyclohexane with different N,N-dialkyl groups in well-defined orientations have been synthesized, and applied as catalysts for the asymmetric aldol reaction between a variety of aldehydes and ketones. Enantiomeric catalyst 1j catalyzed the reaction in ethanol and provided excellent diastereoselectivity and enantioselectivity. Significantly, simple replacement of organic solvents with water switched the products of the aldol reactions from anti to syn configuration. Such catalytic reactions led to the products with anti to syn diastereoselectivity up to 99:1 in ethanol, while in water gave the products with syn to anti diastereoselectivity up to 99:1.