Enantioselective organocatalytic aldol reaction of unactivated ketones with isatins

Enantioselective organocatalytic direct aldol reaction of unactivated ketones with various isatin derivatives was developed using cinchonine based urea ligand employing a noncovalent catalysis mechanism. Using this protocol we can access functionalized 3-alkyl-3-hydroxyindolin-2-ones in high yields with good to excellent enantioselectivities.     

Highly enantioselective aldol reactions catalyzed by reusable upper rim-functionalized calix[4]arene-based l-proline organocatalyst in aqueous conditions

A series of upper rim-functionalized calix[4]arene-based l-Proline derivatives have been synthesized and employed for the enantioselective aldol reactions between cyclic ketones and aromatic aldehydes in the presence of water. Good to excellent yields (up to 96%), enantioselectivities (up to 99% ee), as well as diastereoselectivities (up to 99:1 dr) were obtained under the optimal reaction conditions. Detailed experiments clearly showed that the hydrophobic calixarene platform not only contributed to the good reactivities and enantioselectivities, but also exhibited size-selective catalysis function. Moreover, the organocatalyst can be readily recovered and reused for several runs without significant loss in its enantioselectivity.     

An unexpected inversion of enantioselectivity in the proline catalyzed intramolecular Baylis-Hillman reaction

A highly enantioselective proline catalyzed intramolecular Baylis-Hillman reaction of hept-2-enedial is reported. Addition of imidazole to the mixture results in an unusual inversion of enantioselectivity.     

Asymmetric aldol reaction of isatins with acetone in the presence of terpene amino alcohols

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Zinc-mediated synthesis of 3-alkynyl-3-hydroxyindolin-2-ones by addition of iodoalkynes to isatins

An efficient and economical method was developed for synthesis of 3 alkynyl-3-hydroxyindolin-2-ones by addition of iodoalkynes to isatins using zinc dust.     

tert-Butyl esters of tripeptides based on Pro-Phe as organocatalysts for the asymmetric aldol reaction in aqueous or organic medium

The enantioselective aldol reaction between ketones and aldehydes constitutes one the most common reaction models for the evaluation of novel organocatalysts. The last few years, it has been shown that the organocatalytic aldol reaction can be performed in water. A family of tripeptides consisting of proline, phenylalanine, and tert-butyl esters of amino acids was successfully employed in this asymmetric transformation. The products of the reaction between various ketones and aldehydes were obtained in high yields (up to 99%) with excellent diastereo- (up to 97:3 dr) and enantioselectivities (up to 99% ee). The C-terminal amino acid determines the ability of the tripeptide (Pro-Phe-AA-O^tBu) to act efficiently in aqueous or organic medium.     

A new class of chiral pyrrolidine for asymmetric Michael addition reactions. New mechanism via simple 4+2 type attack of the enamine on the trans-nitrostyrene

A new chiral organocatalyst is described in this paper. A new mechanism for the overall Michael condensation of ketones with nitroolefins using our catalyst is suggested based on molecular modelling studies.     

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.     

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.     

Development of an N-sulfinyl prolinamide for the asymmetric aldol reaction

A new class of organocatalysts is reported that incorporates an N-sulfinyl amide in place of the carboxylic acid of proline to serve as a hydrogen bond donor, chiral directing group, and solubilizing element. The successful application of this type of catalyst to the asymmetric aldol reaction of acetone and aryl aldehydes, for which proline performs poorly, is also described.     

Density functional study of the l-proline-catalyzed α-aminoxylation of aldehydes reaction: The reaction mechanism and selectivity

The reaction mechanism of the l-proline-catalyzed α-aminoxylation reaction between aldehyde and nitrosobenzene has been investigated using density functional theory (DFT) calculation. Our calculation results reveal following conclusions [1]. The first step that corresponds to the formation of C–O bond, is the stereocontrolling and rate-determining step [2]. Among four reaction channels, the syn-attack reaction channel is more favorable than that of the anti one, and the TS-ss channel dominates among the four channels for this reaction in the step of C–O bond formation [3]. The intermolecular hydrogen bond between the acidic hydrogen of l-proline and the N atom of the nitrosobenzene in an early stage of the process catalyzes very effectively the C–O bond formation by a large stabilization of the negative charge that is developing at the O atom along the electrophilic attack [4]. The effect of solvent decreases the activation energy, and also, the calculated energy barriers are decrease with the enhancement of dielectric constants for C–O bond formation step. These results are in good agreement with experiment, and allow us to explain the origin of the catalysis and stereoselectivity for l-proline-catalyzed α-aminoxylation of aldehyde reaction. The addition of H₂O to substituted imine proline, intermolecular proton-transfer steps, and the l-proline elimination process were also studied in this paper.     

Water opportunities: catalyst and solvent in Mukaiyama aldol addition of Rawal’s diene to carbonyl derivatives

Addition reactions between Rawal’s diene and different carbonyl compounds are rapidly and efficiently promoted by water. No catalyst or any other additive, water as an eco-friendly medium, clean reaction conditions, a simple work-up, and short reaction times are the salient features in this procedure. The protocol is general, proceeding well with moderate to good yields for various aldehydes and activated ketones. Based on the experimental ¹H NMR results, a Mukaiyama aldol mechanism was proposed as the reaction pathway, affording open chain products.     

An enantioselective Michael addition of malonate to nitroalkenes catalyzed by low loading demethylquinine salts in water

An enantioselective Michael addition of malonate to nitroalkenes is efficiently catalyzed by low loading demethylquinine salts in water; the yield range from 49% to 93% and the ee up to 90%.     

An organocatalytic route to the synthesis of lactone moiety of compactin and mevinolin

An efficient synthesis of lactone moiety of compactin has been achieved. The stereogenic centers were generated by means of iterative proline-catalyzed sequential α-aminoxylation and Horner-Wadsworth-Emmons (HWE) olefination of aldehydes.     

Direct enantioselective aldol reactions catalyzed by calix[4]arene-based l-proline derivatives in the water

Two novel p-tert-butylcalix[4]arene-based chiral organocatalysts derived from l-proline have been developed to catalyze direct aldol reactions between cyclohexanone and aromatic aldehydes in water. Under the optimal conditions, high yields (up to 95%), enantioselectivities (up to 90%), and moderate diastereoselectivities (up to 65:35) were obtained. Considering the catalytic inefficiency of sole proline for the aldol reaction in water, these results clearly display the enormous effect of the hydrophobic part of calix[4]arene of compound A.     

Mechanistic study of asymmetric Michael addition of malonates to enones catalyzed by a primary amino acid lithium salt

A mechanistic study was carried out for the asymmetric Michael addition reaction of malonates to enones catalyzed by a primary amino acid lithium salt to elucidate the origin of the asymmetric induction. A primary β-amino acid salt catalyst, O-TBDPS β-homoserine lithium salt, exhibited much higher enantioselectivity than that achieved with the corresponding catalysts derived from α- and γ-amino acids for this reaction. Detailed studies of the transition states with DFT calculations revealed that the lithium cation and carboxylate group of the β-amino acid salt catalyst have important roles in achieving high enantioselectivity in the Michael addition reaction of malonates to enones.     

Controlling the oxidative addition of aryl halides to Au(I)

By means of density functional theory calculations, we computationally analyze the physical factors governing the oxidative addition of aryl halides to gold(I) complexes. Using the activation strain model of chemical reactivity, it is found that the strain energy associated with the bending of the gold(I) complex plays a key role in controlling the activation barrier of the process. A systematic study on how the reaction barrier depends on the nature of the aryl halide, ligand, and counteranion allows us to identify the best combination of gold(I) complex and aryl halide to achieve a feasible (i.e., low barrier) oxidative addition to gold(I), a process considered as kinetically sluggish so far. © 2014 Wiley Periodicals, Inc.     

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.     

Direct addition of supercritical alcohols, acetone or acetonitrile to the alkenes without catalysts

The reactions of the alkenes with supercritical organic compounds under non-catalytic conditions were investigated. The H and CR₂OH, CH₂COCH₃ or CH₂CN of supercritical alcohols (CHR₂OH), acetone (CH₃COCH₃) or acetonitrile (CH₃CN) added to the CC bonds of alkenes form C-C bonds between the α-carbons of the supercritical organic compounds and the sp² carbons of the alkenes.