Substrate-controlled stereoselectivity in the Yamamoto aldol reaction

The Yamamoto aldol reaction is a vinylogous aldol reaction that relies on bulky aluminium-based Lewis acids. These activate both the aldehyde as well as become part of the enolate moiety. The report discloses the first detailed study on the substrate-controlled Yamamoto aldol reaction in which 2,3-syn and 2,3-anti disubstituted aldehydes serve as the stereodirecting elements. The "size" of the substituent in the β-position strongly determines the facial selectivity of enolate addition to the aldehyde. Large substituents favour formation of 1,3-syn diols while slim alkynyl groups preferentially lead to 1,3-anti products.     

Dipole interaction-controlled stereoselectivity in aldol reaction of alpha-CF3 enolate with fluoral

The stereoselectivity of a reaction is generally determined by minimizing steric repulsion. However, the aldol reaction of alpha-CF(3)-ketone (Z)-enolate with fluoral anomalously gave an anti-aldol through a sterically demanding transition state, because of the strong dipole interaction of the two CF(3) groups. We have thus disclosed a paradigm shift from steric to electronic control of reaction stereoselectivity. [reaction: see text]     

Glucosamine-based primary amines as organocatalysts for the asymmetric aldol reaction

Glucosamine derivatives have been synthesized starting from commercially available N-acetyl-D-glucosamine/glucosamine hydrochloride and have been employed successfully as efficient organocatalysts for the direct asymmetric aldol reaction between cyclohexanone and aryl aldehydes having diversified substituents. Furthermore, the anomeric effect of various groups present at the anomeric position on the catalytic activity of these organocatalysts was also studied.     

The pH of the reaction controls the stereoselectivity of organocatalyzed direct aldol reactions in water

The direct aldol reaction of 4-nitrobenzaldehyde and cyclohexanone, catalyzed by a protonated prolinamide catalyst in water, proceeds with the formation of aldol product that has high diastereoselectivity and enantioselectivity in an optimal pH range of 4–5.     

Theoretical studies on the mechanism and stereoselectivity of Rh(Phebox)-catalyzed asymmetric reductive aldol reaction

Density functional theory calculations (B3LYP) have been carried out to understand the mechanism and stereochemistry of an asymmetric reductive aldol reaction of benzaldehyde and tert-butyl acrylate with hydrosilanes catalyzed by Rh(Phebox-ip)(OAc)(2)(OH(2)). According to the calculations, the reaction proceeds via five steps: (1) oxidative addition of hydrosilane, (2) hydride migration to carbon-carbon double bond of tert-butyl acrylate, which determines the chirality at C2, (3) tautomerization from rhodium bound C-enolate to rhodium bound O-enolate, (4) intramolecular aldol reaction, which determines the chirality at C3 and consequently the anti/syn-selectivity, and (5) reductive elimination to release aldol product. The hydride migration is the rate-determining step with a calculated activation energy of 23.3 kcal mol(-1). In good agreement with experimental results, the formation of anti-aldolates is found to be the most favorable pathway. The observed Si-facial selectivity in both hydride migration and aldol reaction are well-rationalized by analyzing crucial transition structures. The Re-facial attack transition state is disfavored because of steric hindrance between the isopropyl group of the catalyst and the tert-butyl acrylate.     

Direct asymmetric aldol reaction catalyzed by nanocrystalline magnesium oxide

Nanomaterials with their three-dimensional structure and defined size and shape are considered to be suitable candidates for proper alignment with prochiral substrates for unidirectional introduction of reacting species to induce an asymmetric centre. The reusable and suitably aligned nanocrystalline magnesium oxide catalyzed direct asymmetric aldol reaction afforded the chiral β-hydroxy carbonyl compounds in good yields and moderate ee's.     

Direct asymmetric aldol reaction of hydroxyacetone promoted by chiral tertiary amines

The tertiary amine-catalyzed direct asymmetric aldol reaction of hydroxyacetone with a variety of aromatic aldehydes is developed. Using 5-10 mol % of quinidine as catalyst, the direct aldol condensation products were obtained in reasonable yields and with asymmetric induction (up to 47% ee). The present approach is extended to asymmetric organocatalytic strategies for the preparation of 1,2-diols.     

Highly enantioselective direct aldol reaction catalyzed by cinchona derived primary amines

Highly enantioselective aldol reactions of aldehydes with cyclic ketones catalyzed by a primary amine derived from cinchonine are reported. Aromatic aldehydes reacted with various cyclic ketones cleanly to afford the anti-aldol adducts in up to 99% yield, with good diastereoselectivities (up to 9 : 1) and excellent enantioselectivities (up to 99% ee).     

Metal exchange reaction between magnesium octaphenyltetraazaporphyrinate and d-metals salts in dimethylformamide

Reaction of metal exchange between magnesium octaphenyltetraazaporphyrinate with copper and cobalt chlorides in dimethylformamide has been studied by spectrophotometry. Parameters of the reactions kinetics have been determined, and their mechanism has been suggested.     

A DFT study of the origins of the stereoselectivity in the aldol reaction of bicyclic amino ketones in the presence of water

Experimental diastereoselectivities of the direct solvent-less (neat) aldol reactions of tropinone (8-methyl-8-azabicyclo[3.2.1]octan-3-one) and granatanone (pseudopelletierine, 9-methyl-9-azabicyclo[3.3.1]nonan-3-one) in the presence of catalytic amounts of water are most accurately reproduced by thermodynamic distributions of isomeric products calculated in the gas phase at the B3LYP/6-31g(d) level of theory. Less than 30% systematic errors, on average, exist in the predicted anti/syn-diastereomeric ratio (dr) for the solvent-less reaction of tropinone with several aromatic aldehydes. The CPCM-B3LYP/6-31g(d) method reproduces the anti/syn-diastereomeric ratio of the aqueous aldol reaction of tropinone with several aromatic aldehydes with reasonable deviation (0-88%), excellent (0-10)% agreement was found for the reactions of tropinone and granatanone with benzaldehyde. Qualitatively satisfactory agreement was also found for dr values in different solvents (DMF, THF, and Et₃N). The density functional theory (DFT) results support the notion of the thermodynamic control of the reaction.     

Synthesis of indoles from pyridinium salts 5. Secondary amines in the reaction of 3-nitropyridinium salts with acetone

The use of secondary amines in the reaction of 3-nitropyridinium salts with acetone makes it possible to isolate stable intermediates in the formation of indoles — (o-N,N-dialkylaminobenzyl)ketones — and to observe new reaction pathways — the formation of bisindolylpropanes and p-nitroanilines.See [1] for Communication 4.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1213–1221, September, 1988.     

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.     

Direct aldol reaction of trifluoroacetaldehyde ethyl hemiacetal with ketones by use of the combination of amines and acids

Trifluoroacetaldehyde ethyl hemiacetal reacts with unmodified ketones in the presence of 30-50 each mol % of amines and acids at ambient temperature, affording the corresponding β-hydroxy-β-trifluoromethylated ketones in good yields with good to excellent diastereoselectivities.     

Very high stereoselectivity in organocatalyzed desymmetrizing aldol reactions of 3-substituted cyclobutanones

N-Phenylsulfonyl (S)-proline catalyzes the direct aldol reaction of 3-substituted cyclobutanones and aryl aldehydes in good yield and with excellent diastereoselectivity and enantioselectivity. This desymmetrization process provides highly functionalized cyclobutanones with control over three contiguous stereogenic centers.     

Asymmetric aldol reaction using a very simple primary amine catalyst: divergent stereoselectivity by using 2,6-difluorophenyl moiety

Asymmetric aldol reactions of aliphatic ketones or aldehydes with aromatic aldehydes or isatins were catalyzed by a very simple and flexible N-(2,6-difluorophenyl)-l-valinamide. Interestingly, stereochemical course of the reaction of hydroxyacetones or α-branched aliphatic aldehydes as aldol donors was different from that of cycloalkanones.     

Effects of magnesium salts on photoinduced electron transfer reaction between ammonia, 2,5-dimethylhexa-2,4-diene, and 9-cyanophenanthrene

Mechanistic studies and product analyses were performed on the single electron transfer (SET) promoted photoamination reaction between 2,5-dimethylhexa-2,4-diene (1) and 9-cyanophenanthrene in order to gain a comprehensive understanding of the effects of additive metal salts. The product selectivity of this process was found to be dramatically increased by the addition of Mg²⁺ salts. An investigation involving the analyses of fluorescence and time-resolved absorption spectroscopic properties reveals that Mg²⁺ enhances the rate of the initial SET step and stabilizes the resulting radical ion pair in this photoreaction.