Enantioselective alkynylation of ketones with trimethoxysilylalkynes using lithium binaphtholate as a catalyst

Chiral lithium 3,3′-diphenylbinaphtholate successfully catalyzed the alkynylation of ketone with trimethoxysilylalkyne, affording chiral tertiary propargylic alcohols in high chemical yields and high enantioselectivities. The present reaction could be extended to the alkynylation of acetylpyridine, which afforded a biologically active pyridyl propargylic alcohol in good enantioselectivity.     

A bimetallic aluminium(salen) complex for asymmetric cyanohydrin synthesis

In the presence of a phosphine oxide cocatalyst, a bimetallic aluminium(salen) complex was found to catalyse the asymmetric addition of trimethylsilyl cyanide to aldehydes. Under optimised conditions, enantioselectivities of 53-96% were obtained using 2 mol % of the catalyst. An analysis of the reaction kinetics showed that the reactions exhibited first-order kinetics, with the rate of reaction being independent of the aldehyde concentration.     

Synthetic and mechanistic studies on asymmetric cyanohydrin synthesis using a titanium(salen) bimetallic catalyst

A bimetallic titanium(salen) complex 1 was found to catalyse the asymmetric addition of ethyl cyanoformate to aldehydes. Best results were obtained using 5 mol% of the catalyst at −40 °C and under these conditions, both aromatic and aliphatic aldehydes were converted into cyanohydrin carbonates with up to 99% enantiomeric excess. The same catalyst could also be used to catalyse the asymmetric addition of potassium cyanide to aldehydes in the presence of propionic anhydride, leading to cyanohydrin esters. Mechanistic studies showed that the enantiomeric excess of the product increased during the early stages of this reaction. However, by adding a ‘sacrificial aldehyde’ this effect could be eliminated. The structure of the catalyst in solution was investigated using variable concentration, variable temperature and variable solvent NMR studies. These experiments showed that the catalyst exists as a mixture of monometallic 4 and bimetallic 1 species, a result which is consistent with previous mechanistic studies on the asymmetric addition of trimethylsilyl cyanide to aldehydes and ketones catalysed by the same catalyst. A mechanistic rationale for all of these observations is reported.     

Identification of a highly effective asymmetric phase-transfer catalyst derived from α-methylnaphthylamine

A library of quaternary ammonium salts has been generated via reaction of simple chiral amines with a series of conformationally dynamic biphenyl units. Screening of this library against the alkylation of a glycine imine has led to the identification of a highly effective asymmetric phase-transfer catalyst derived from α-methylnaphthylamine.     

Mechanistic comparison of aluminium based catalysts for asymmetric cyanohydrin synthesis

A kinetic analysis of the asymmetric addition of trimethylsilyl cyanide to benzaldehyde using three aluminium based catalysts has been carried out. All three catalysts displayed rate equations, which were first order in trimethylsilyl cyanide concentration and zero order in benzaldehyde concentration. The results are consistent with a common mechanism for effective asymmetric catalysis of cyanohydrin synthesis, involving combined activation of the aldehyde by a Lewis acid and activation of the trimethylsilyl cyanide by a Lewis base. The mechanistic analysis was also applied to a magnesium-based catalyst system to demonstrate its general applicability.     

Binolam-AlCl: a two-centre catalyst for the synthesis of enantioenriched cyanohydrin O-phosphates

The enantioselective synthesis of cyanohydrin O‐phosphates by using in situ generated bifunctional catalysts (R)‐ or (S)‐3,3′‐bis(diethylaminomethyl)‐1,1′‐binaphthol–aluminium chloride (binolam–AlCl) is reported. The reaction, which can be described as an overall cyano‐O‐phosphorylation of aldehydes, has a wide scope and applicability. Evidence is also provided, including ab initio and DFT calculations, in support of supported by the Lewis acid/Brønsted base (LABB) dual role of the catalyst in inducing first the key enantioselective hydrocyanation, which is then followed by O‐phosphorylation. A brief screening of the synthetic usefulness of the resulting cyanohydrin O‐phosphates unveiles some interesting applications. Among them, chemoselective hydrolysis, reduction and palladium‐catalysed nucleophilic allyl substitution, thereby leading to enantiomerically enriched α‐O‐phosphorylated α‐hydroxy esters, β‐amino alcohols and γ‐cyanoallyl alcohols, respectively. Naturally occurring (?)‐tembamide and (?)‐aegeline are synthesised accordingly.     

Chiral salen-aluminum complex as a catalyst for enantioselective alpha-addition of isocyanides to aldehydes: asymmetric synthesis of 2-(1-hydroxyalkyl)-5-aminooxazoles

In the presence of a catalytic amount of (salen)Al(III)Cl complex (4e), reaction between alpha-isocyanoacetamides (1) and aldehydes (2) afforded the corresponding 5-aminooxazoles (3) in good yields and enantioselectivity.     

C2-symmetric proline-derived tetraamine as highly effective catalyst for direct asymmetric Michael addition of ketones to chalcones

A C(2)-symmetric tetraamine catalyst was developed for the asymmetric Michael addition of ketones to chalcones. The corresponding adducts 1,5-dicarbonyl compounds were obtained in good chemical yields with high levels of diastereo- and enantioselectivities (up to >99 : 1 dr and 93% ee) under mild conditions. By studying the ESI-MS of the intermediates, a proposed mechanism was disclosed.     

Chiral copper-Schiff base catalyst for asymmetric henry reaction

Five copper-Schiff base complexes were synthesized conveniently from copper(II) acetate monohydrate, salicylaldehydes, and amino alcohols. The complexes were shown to be effective as catalysts in the asymmetric Henry reaction affording nitro alkanols in up to 98% yield with moderate and good enantiomeric excess (up to ee 38.6%). Published in Russian in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 12, pp. 1754–1755. The text was submitted by the authors in English.     

Eu(III) dithiocarbamate complex and N-p-tolylsulfonylphenylalanine as a novel chiral catalyst for the asymmetric synthesis of cyanohydrins

The use of a new chiral lanthanide complex derived from a europium dithiocarbamate complex and a N-tosylated amino acid for the asymmetric synthesis of cyanohydrins is described. In some cases, high enantioselectivities were observed.     

Chiral bisformamides as effective organocatalysts for the asymmetric one-pot, three-component strecker reaction

C2-symmetric chiral bisformamides have been shown to catalyze the asymmetric one-pot, three-component Strecker reaction, which produced the alpha-amino nitriles in excellent yields (up to 99%) with good enantioselectivities (up to 86% ee). Optically pure products could be obtained after a single recrystallization. A possible transition state (TS 1) has been proposed to explain the origin of asymmetric inductivity and reactivity according to the geometry of catalyst 2a optimized at the B3LYP/6-31G(d) level and the absolute configuration of product 4a.     

Chiral amine-polyoxometalate hybrids as highly efficient and recoverable asymmetric enamine catalysts

Chiral amine and polyoxometalate (POM) acids were combined to give highly efficient, stereoselective, and recoverable enamine-based catalysts. Less than 1 mol % of chiral amine loading was sufficient for good catalytic activity, and the catalyst could be recovered and reused 6 times with unchanged enantioselectivity and slightly decreased activity.     

Nanosized magnesium oxide as a highly effective heterogeneous base catalyst for the rapid synthesis of pyranopyrazoles via a tandem four-component reaction

A four-component reaction of hydrazine hydrate or phenyl hydrazine, ethyl 3-alkyl-3-oxo propanoate, aldehydes and malononitrile has been achieved in the presence of nanosized magnesium oxide as a highly effective heterogeneous base catalyst to produce of 6-amino-3-alkyl-4-aryl-5-cyano-1,4-dihydropyrano[2,3-c]pyrazole derivatives in excellent yields and in a short experimental time. This method is simple and rapid for focusing a pyrano ring with a pyrazole ring.     

Protonated N'-benzyl-N'-prolyl proline hydrazide as highly enantioselective catalyst for direct asymmetric aldol reaction

Protonated N'-benzyl-N'-l-prolyl-l-proline hydrazide has been developed as a highly enantioselective catalyst for the asymmetric direct aldol reaction of aromatic aldehydes with ketones.     

A metallocene-pyrrolidinopyridine nucleophilic catalyst for asymmetric synthesis

[reaction: see text] A highly active chiral 4-aminopyridine nucleophilic catalyst, available in three steps from (S,S)-hexane-2,5-diol, was applied to the asymmetric Steglich rearrangement of O-aceylated azlactones (1 mol % loading, up to 76% ee).     

N,N-Diarylammonium pyrosulfate as a highly effective reverse micelle-type catalyst for hydrolysis of esters

Reverse micelle-type N,N-diarylammonium pyrosulfate (3-5 mol %) efficiently catalyzes the hydrolysis of esters (up to 100 mmol scale) under organic solvent-free conditions. The present method is successfully applied to the hydrolysis of various esters without the decomposition of the base-sensitive moieties and without any loss of optical purity for α-heterosubstituted carboxylic acids.     

Novel pyrrolidine-thiohydantoins/thioxotetrahydropyrimidinones as highly effective catalysts for the asymmetric Michael addition

The synthesis of novel organocatalysts consisting of a pyrrolidine moiety and a thiohydantoin or a thioxotetrahydropyrimidinone ring is described. The compound combining the pyrrolidine with the thioxotetrahydropyrimidinone was found to be a highly effective catalyst for the Michael reaction. Low catalyst loadings (1-2.5%) can be employed leading to quantitative yields and excellent stereoselectivities in the reaction between cyclic ketones and nitroolefins.     

Phase selectively soluble dendrimer-bound osmium complex: a highly effective and easily recyclable catalyst for olefin dihydroxylation

A new switched biphasic catalysis system for highly effective olefin dihydroxylation has been described, in which the dendritic osmium catalyst preferred to dissolve in the non-polar organic layer and could be easily separated from the polar diol products through phase separation induced by addition of water at the end of the reaction.     

Application of MerCO as a chiral catalyst in asymmetric synthesis: asymmetric borane reduction of ketones

The borane reduction of aryl methyl ketones catalyzed by MerCO [(1R,2S,3R)-3-mercaptocamphan-2-ol] produced 1-aryl ethyl alcohols in 92% e.e. at 50°C in toluene. Significant temperature and solvent effects were observed in this reaction.