An air-stable chiral Hf-based catalyst for asymmetric Mannich-type reactions

A new class of isolable, air-stable, storable, and Hf-based catalyst has been developed. In the presence of 10 mol % of the powdered Hf catalyst, the asymmetric Mannich-type reactions of imines with silicon enolates derived from esters proceeded smoothly to afford the corresponding Mannich-type adducts in high yields with high enantioselectivities. Hafnium single crystals for X-ray analysis were obtained, and the crystals also showed high performance in the asymmetric Mannich-type reactions.     

Storable, powdered chiral zirconium complex for asymmetric aldol and hetero Diels-Alder reactions

A storable, powdered chiral zirconium catalyst for asymmetric aldol and hetero Diels-Alder reactions has been developed. The catalyst has the same activity as that prepared in situ even after being stored for 3 months. Moreover, this chiral Zr catalyst worked efficiently not only for asymmetric aldol reactions but also for asymmetric hetero Diels-Alder reactions affording the corresponding addition products with high enantioselectivities.     

Catalytic asymmetric aza Diels-Alder reactions of hydrazones using a chiral zirconium catalyst

Catalytic asymmetric aza Diels-Alder reactions of acylhydrazones with Danishefsky’s dienes have been developed. A chiral zirconium complex derived from zirconium propoxide and 3,3′,6,6′-I₄BINOL was found to be effective in this reaction, and the desired optically active 2,3-dihydro-4-pyridone derivatives were obtained with high enantioselectivities. Asymmetric formal synthesis of a natural product, coniine, was conducted using this catalytic asymmetric reaction as a key step.     

Remarkably stable chiral zirconium complexes for asymmetric Mannich-type reactions

Isolable, air-stable, storable, and highly selective chiral zirconium catalysts for asymmetric Mannich-type reactions have been developed. The reactions of imines with silicon enolates proceeded smoothly using 1-10 mol % of the powdered zirconium catalyst to afford the corresponding adducts in high yields with high stereoselectivities. The catalyst could be recovered and reused without significant loss of activity. On the other hand, zirconium single crystals for X-ray analysis were obtained, and the crystals also showed high performance in the asymmetric Mannich-type reactions. Although NMR analyses of these zirconium catalysts showed different structures in dichloromethane, the formation of the same key intermediate from the different catalysts was indicated.     

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.     

Phthalimido-prolinamide: a new chiral catalyst for solvent free enantioselective aldol reactions

A new prolinamide derivative phthalimido-prolinamide 1 was developed for organocatalytic enantioselective direct aldol reactions of various aldehydes with ketones. The catalytic protocol is effective with 15 mol % of catalyst under solvent free and additive free reaction conditions. By employing a catalytic amount of water, the efficiency of the reaction increased further and the desired products β-hydroxy carbonyl compounds were obtained in high yields and stereoselectivities.     

Catalytic, asymmetric trans-selective hetero Diels-Alder reactions using a chiral zirconium complex

[reaction: see text] The first catalytic, asymmetric 2,3-trans-selective hetero Diels-Alder reaction has been developed. The reactions of aldehydes with Danishefsky's dienes proceeded smoothly to afford the pyranone derivatives in high yields with high trans-selectivities and enantioselectivities in the presence of a chiral zirconium complex, which was prepared from zirconium tert-butoxide and (R)-3,3'-diiodobinaphthol or its derivatives, primary alcohol, and a small amount of water. This reaction was applied to the concise synthesis of (+)-prelactone C.     

Theoretical elucidation on the regio-, diastereo-, and enantio-selectivities of chiral primary-tertiary diamine catalyst for asymmetric direct aldol reactions of aliphatic ketones

The asymmetric direct aldol reactions of aliphatic ketones (acetone, butanone, and cyclohexanone) with 4-nitrobenzaldehyde catalyzed by a chiral primary-tertiary diamine catalyst (trans-N,N-dimethyl diaminocyclohexane) have been investigated by performing density functional theory calculations to rationalize the experimentally observed stereoselectivities. Focused on the crucial C-C bond-forming steps, we located several low-lying transition states and predicted their relative stabilities. The calculated results demonstrate that the catalytic direct aldol reactions of acetone favors the (S)-enantiomer and that butanone prefers the branched syn-selective product, while cyclohexanone yields predominantly the opposite anti-selective product. The theoretical results are in good agreement with the experimental findings and provide a reasonable explanation for the high enantioselectivity and diastereoselectivity, as well as regioselectivity, of the aldol reactions under consideration.     

Air-stable,storable, and highly selective chiral Lewis acid catalyst

An air-stable, storable, and highly selective chiral Lewis acid catalyst for asymmetric Mannich-type reactions has been developed. The catalyst can be stored for more than three months in air at room temperature without loss of activity. Moreover, it has also been demonstrated that the catalyst can be recovered and reused. [structure: see text]     

Oxazolidinones as chiral auxiliaries in asymmetric aldol reactions applied to total synthesis

Asymmetric aldol reactions of oxazolidinones as chiral auxiliaries have been achieved and attracted significant consideration as one of the most powerful synthetic tools for the carbon–carbon bond-forming reactions. The methodology has been highly successful in the stereoselective construction of a number of natural products, antibiotics, and other medicinally important compounds. The present review is focused on the utility and versatility of oxazolidinones (Evans chiral auxiliaries) in the asymmetric aldol condensations for the total synthesis of natural products and complex targets.     

Noncovalently supported heterogeneous chiral amine catalysts for asymmetric direct aldol and Michael addition reactions

A new strategy for the immobilization of asymmetric organocatalysts by combining polystyrene (PS)/sulfonic acids and chiral amines in situ through acid-base interactions is presented. The PS/sulfonic acids play a dual role as catalyst anchors and modulators for activity and stereoselectivity. Different types of polymeric sulfonic acids were examined and 1% divinylbenzene (DVB) cross-linked PS/sulfonic acid 1 e with a medium loading of sulfonic acid moieties was found to be the optimal support. Furthermore, the noncovalency of this system allows combinatorial screening of optimal catalysts for the targeted reactions. In this regard, highly efficient and enantioselective heterogeneous catalysts were identified for the asymmetric direct aldol and Michael addition reactions. The catalysts could be easily recovered by filtration and reused for six cycles with similar stereoselectivity but slightly decreased activity. Significantly, the deactivated catalysts could be regenerated following an acidic washing/amine recharging procedure.     

New glyco-oxazolidin-2-ones as chiral auxiliaries in boron-mediated asymmetric aldol reactions

Two new chiral glyco-oxazolidin-2-one auxiliaries based on d-glucose are described. Some N-acyl derivatives were synthesized and used in dialkylboron-mediated asymmetric aldol reactions. All reactions delivered as the major diastereomer those predicted by the Zimmerman–Traxler model and were separated by column chromatography and mostly isolated in moderate to good yields.     

An efficient synthesis of chiral phosphinyl oxide pyrrolidines and their application to asymmetric direct aldol reactions

Chiral pyrrolidine-based phosphinyl oxides were synthesized and their performance as organocatalysts for asymmetric direct aldol reactions was evaluated. High enantioselectivities and diastereoselectivies were achieved for a range of cyclic ketones and aromatic aldehydes.     

The application of a structurally simple,recyclable, and large-scale l-prolinamide catalyst for asymmetric aldol reactions

A highly efficient, bifunctional prolinamide catalyst, which consists of chiral proline and trans-cyclohexanediamine moieties, was prepared and evaluated in the direct asymmetric aldol reactions of various ketones and aldehydes. The catalyst displayed impressive catalytic activity toward heterocyclic ketones containing oxygen, sulfur, or nitrogen, which have not been sufficiently explored. The substrate scope also covered cyclic and acyclic ketones. With heterocyclic ketones or cyclohexanone, the aldol reactions gave products in high yields and with respectable enantioselectivities (87–99% ee) and diastereoselectivities (up to >99:1 anti/syn). The catalyst could be recycled and reused up to seven times resulting in good yields and with good selectivities. This catalyst is also efficient in large-scale reactions with the enantioselectivities remaining at the same level as in the experimental scale reactions.     

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.     

手性胺催化不对称水相aldol反应研究进展

Aldol反应作为最重要的碳碳键形成反应之一,在有机合成中有着重要作用,本文综述了手性伯胺,仲胺催化剂催化的水相aldol反应的最新研究进展。     

(S,S)-(+)-pseudoephedrine as chiral auxiliary in asymmetric acetate aldol reactions

The asymmetric acetate-type aldol reaction using (S,S)-(+)-pseudoephedrine has been studied in detail. Experimental variables like the nature of the metal counterion of the enolate, the presence of additives and the structure of the aldehyde have been examined in order to reach to the highest possible yields and diastereoselectivities.     

Synthesis and evaluation of a new non-cross-linked polystyrene supported hydantoin chiral auxiliary for asymmetric aldol reactions

A new non-cross-linked polystyrene supported chiral hydantoin was prepared and it was shown to be a particularly effective chiral auxiliary for asymmetric aldol reactions, affording high yields and excellent diastereoselectivity. Furthermore, the recovery and recycling of the polymer-supported chiral auxiliary have been successfully achieved without an appreciable reduction in the yield or diastereoselectivity.