Catalytic asymmetric aldol reactions in aqueous media

Nature has perfected the stereospecific aldol reaction by using aldolase enzymes. While virtually all the biochemical aldol reactions use unmodified donor and acceptor carbonyls and take place under catalytic control in an aqueous environment, the chemical domain of the aldol addition has mostly relied on prior transformation of carbonyl substrates, and the whole process traditionally is carried out in anhydrous solvents. The area of aqua-asymmetric aldol reactions has received much attention recently in light of the perception both of its green chemistry advantages and its analogy to eon-perfected enzyme catalysis. Both chiral metal complexes and small chiral organic molecules have been recently reported to catalyze aldol reactions with relatively high chemical and stereochemical efficiency. This tutorial review describes recent developments in this area.     

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。     

Catalytic asymmetric mannich-type reactions activated by ZnF2 chiral diamine in aqueous media

Catalytic asymmetric Mannich-type reactions of an alpha-hydrazono ester with silicon enolates in aqueous media have been developed by using ZnF2 and chiral diamines as catalysts. In these reactions, both Zn2+ and a fluoride anion were necessary to achieve high yields and enantioselectivities, suggesting a double activation mechanism, in which Zn2+ activates the alpha-hydrazono ester and the fluoride anion simultaneously activates the silicon enolate. When chiral diamine ligands bearing methoxy-substituted aromatic rings were employed, the reactions in aqueous THF were markedly accelerated. Furthermore, the use of these diamines facilitated the asymmetric Mannich-type reactions in water without any organic cosolvents. It is noteworthy that either syn or anti adducts were stereospecifically obtained from (E)- or (Z)-silicon enolates, respectively. Interestingly, these reactions proceeded smoothly only in the presence of water. On the basis of several experimental results, it can be concluded that the reaction mechanism is likely to be a fluoride-catalyzed one, in which the ZnF2 chiral diamine complex is regenerated from the Me3SiF formed during the reaction.     

Catalytic asymmetric carbon-carbon bond-forming reactions in aqueous media

Use of water as a reaction solvent or co-solvent has received much attention in synthetic organic chemistry. Recently, successful examples of catalytic asymmetric carbon-carbon bond formation in aqueous media have been developed. Most of these examples show characteristic features that are realized only in the presence of water. The role of water in these reactions is also discussed here.     

Direct asymmetric aldol reaction in aqueous media using polymer-supported peptide

PEG-PS resin-supported tripeptide/zinc chloride catalyst system has been developed for use in the direct asymmetric aldol reaction of acetone with aldehydes in aqueous media. The peptide catalyst could be separated from the reaction mixture by filtration, and was reusable at least five times without significant change in its activity and selectivity.     

Catalytic asymmetric Nazarov reactions promoted by chiral Lewis acid complexes

Divinyl ketones bearing alpha-ester or alpha-amide groups undergo Nazarov cyclizations to give cylopentenones using copper-bisoxazoline Lewis acid complexes with moderate to good ees. [reaction: see text]     

Catalytic asymmetric Michael reactions using a chiral rhodium complex

Catalytic asymmetric Michael reaction of β-keto esters and methyl vinyl ketone was achieved using a chiral diamine-based Rh complex to give the Michael adducts in up to 75% e.e.     

Catalytic asymmetric Pauson-Khand-type reactions of enynes with formaldehyde in aqueous media

The first example of an aqueous, asymmetric, and CO gas-free Pauson-Khand-type reaction is described. Using formaldehyde as a commercially available substitute for carbon monoxide, combined use of a hydrophilic phosphine (TPPTS) and a hydrophobic, chiral phosphine (tolBINAP) enable the reaction to proceed smoothly in aqueous media, even in the absence of carbon monoxide, and stereoselectively.     

Direct organocatalytic aldol reactions in buffered aqueous media

Organocatalytic cross-aldol reactions catalyzed by cyclic secondary amines in aqueous media provide a direct route to a variety of aldols including carbohydrate derivatives and may warrant consideration as a prebiotic route to sugars.     

手性金属催化剂在不对称环丙烷化反应中的应用进展

手性金属催化剂在不对称环丙烷化反应中的应用一直是不对称合成领域的一个热点。对三十多年来的这一领域的手性金属催化剂的发展作了详细的归纳和评述。     

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.     

Enantiopure azetidine-2-carboxamides as organocatalysts for direct asymmetric aldol reactions in aqueous and organic media

A family of enantiopure azetidine-2-caboxamides was asymmetrically synthesized, and was examined as organocatalyst in direct aldol reactions. A well chosen chiral azetidine-2-caboxamide was found to smoothly catalyze the direct aldol reaction of various benzaldehydes with acetone in brine, and β-hydroxy ketones were produced with enantiomeric excess up to 96%. The reaction of benzaldehydes with cyclic ketones also led to the formation of anti-products in diastereomeric ratio up to 99:1 and enantiomeric excess up to 99%.     

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.     

Nucleophilic substitution reactions in tetranitrodibenzo-18-crown-6

The nature of the reaction of a reagent with tetranitrodibenzo-18-crown-6 was found to depend on its basicity. This behavior was interpreted in the framework of the theory of hard and soft acids and bases.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 605–608, May, 1992.     

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.     

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.     

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.     

The catalytic asymmetric Mannich-type reactions in aqueous media

The catalytic, diastereo- and enantioselective Mannich-type reaction of a hydrazono ester with silyl enol ethers in aqueous media has been successfully achieved with ZnF(2), a chiral diamine ligand, and trifluoromethanesulfonic acid.     

A new organocatalyst derived from abietic acid and 4-hydroxy-l-proline for direct asymmetric aldol reactions in aqueous media

Enantioselective direct aldol reactions were carried out in aqueous media with a new organocatalyst that was derived from 4-hydroxy-l-proline and abietic acid via a simple and convenient synthetic protocol with a high overall yield (75%). The new organocatalyst was used for aldol reactions between substituted aromatic aldehydes and various ketones in the presence of several acid additives in aqueous media. The corresponding aldol products were obtained in high isolated yields (up to 99%) and with high anti-diastereoselectivities (up to 94%) and enantioselectivities (>99.9%). The catalyst loading can be efficiently reduced to only 1 mol %. The aldol reactions were found to be extremely fast which is very unusual in organocatalyzed reactions in water.     

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.