Highly enantioselective conjugate addition of thiols using mild scandium triflate catalysis

A Sc complex of (4S,5S)-diphenyl PYBOX 1 was found to serve as a catalyst for the asymmetric conjugate addition reactions between various thiols and 3-crotonoyl-2-oxazolidinone, affording the corresponding adducts in good yields and high enantioselectivies (up to 92% ee). A new improved method for making (4S,5S)-diphenyl PYBOX is presented.     

Catalytic synthesis of 1,4-dihydropyridine derivatives using scandium(III) triflate

Scandium(III) triflate smoothly catalyzed the reaction of imines with ethyl propiolate (2.5 equiv) to produce the corresponding N-substituted 1,4-dihydropyridines in good yields in toluene or BTF under reflux conditions. It also catalyzed the reaction of aniline and ethyl propiolate (3.2 equiv) to give another 1,4-dihydropyridine bearing three ester groups in moderate yield under the same conditions.     

Trapping an elusive intermediate in manganese-oxo cubane chemistry

A new member of the Mn-oxo cubane core complex family [Mn2III,2IV4O4L6] (1), where L = (p-MeOPh)2PO2-, has been synthesized and characterized. Compound 1 possesses structurally inequivalent MnIII and MnIV with clear valence electron localization in the crystal phase, quite unlike the structurally equivalent sites, tetrahedral core symmetry, and delocalized valence of its analogue where L = Ph2PO2-. Compound 1 exhibits appreciable positive shifts (0.1-0.3 V) of both the oxidation and reduction electrochemical potentials, attributable to the remote electron donating p-MeO groups. Reduction of 1 by methanol yields a novel core complex [MnIII4O2(OMe)2(MeOH)[(p-MeOPh)2PO2]6] (2). Each MnIII of 2 is tetragonally distorted due to the Jahn-Teller effect with elongated Mn-O bonds that are directed at the two micro3-MeO bridges and neither of the two micro3-oxos. These electronically driven distortions provide a structural rationale for the greater basicity of the former sites and explain why 2 of the 4 corner oxos are preferentially reduced to water molecules.     

Stereoselective catalytic tishchenko reduction of β-hydroxyketones using scandium triflate

A number of aliphatic and aromatic β-hydroxyketones were reduced to 1,3-diol monoesters by aldehydes in the presence of a catalytic amount of scandium triflate. Chiral substrates were reduced with high 1,3-anti diastereoselectivity.     

Transnitrosation of nitrosothiols: characterization of an elusive intermediate

We report an investigation of the reaction between (S)-nitroso-l-cysteine ethyl ester and l-cysteine ethyl ester as a model of physiologically relevant transnitrosation processes. Our theoretical and experimental evidence clearly supports the existence of a nitroxyl disulfide intermediate in solution.     

Secondary benzylation using benzyl alcohols catalyzed by lanthanoid, scandium, and hafnium triflate

The combination of a secondary benzyl alcohol and a metal triflate (e.g., La, Yb, Sc, and Hf triflate) in nitromethane was a highly effective secondary-benzylation system. Secondary benzylation of carbon (aromatic compounds, olefins, an enol acetate), nitrogen (amide derivatives), and oxygen (alcohols) nucleophiles was carried out with a secondary benzyl alcohol and 0.01-1 mol % of a metal triflate in the presence of water. Secondary benzyl alcohols and nucleophiles bearing acid-sensitive functional groups (e.g., tert-butyldimethylsilyloxy and acetoxy groups and methyl and benzyl esters) could be used for alkylation. Hf(OTf)4 was the most active catalyst for this alkylation, and trifluoromethanesulfonic acid (triflic acid, TfOH) was also a good catalyst. The catalytic activity of metal triflates and TfOH increased in the order La(OTf)3 < Yb(OTf)3 < TfOH < Sc(OTf)3 < Hf(OTf)4. A mechanistic study was also performed. The reaction of 1-phenylethanol (4a) in the presence of Sc(OTf)3 in nitromethane gave an equilibrium mixture of 4a and bis(1-phenylethyl) ether (54). Addition of a carbon nucleophile to the equilibrium mixture gave alkylated product in high yield.     

Aluminium triflate: an efficient recyclable Lewis acid catalyst for the aminolysis of epoxides

Epoxides are powerful starting materials for a range of useful materials and can be converted into, amongst others, amino alcohols. In this work, a range of epoxides was ring-opened using various alkyl- and arylamines under the action of aluminium triflate as a catalyst. This catalyst was found to be highly active, producing the desired amino alcohol products in high yields with low catalyst loadings. Additionally, it was shown that the aluminium triflate catalyst is recyclable by simple extraction into water and may be re-used several times.     

Stereoselective acylation of 20-(S)-camptothecin with amino acid derivatives using scandium triflate/DMAP

Facile esterification of the hindered 3° alcohol 20-(S)-camptothecin with Boc protected chiral amino acids or derivatives under mild conditions has been achieved in high yield using the combination of Sc(OTf)₃ and DMAP. The isomeric purity of the product was maintained under these conditions.     

Convenient removal of N-tert-butyl from amides with scandium triflate

Scandium triflate has been used as a convenient and efficient catalyst for removal of N-tert-butyl from amide groups. A variety of N-tert-butyl aryl and alkyl amides under these conditions gave the corresponding primary amide in high yields. With the use of microwave heating the deprotection reaction could be completed within 1 h.     

Enantioselective Michael additions on α,β-unsaturated N-acylated oxazolidin-2-ones using mild scandium triflate catalysis

The asymmetric conjugate addition of thiophenol to (E)-3-crotonoyloxazolidin-2-one catalysed by the scandium(III) triflate complex of Ph-PYBOX gave the corresponding adduct in 66% ee. Lanthanoid triflates gave lower enantioselectivities (?28% ee).     

Palladium-catalysed dimerization of vinylarenes using indium triflate as an effective co-catalyst

A palladium-indium triflate catalyst was found to be much more active for the dimerization of vinylarenes compared with generally used cationic palladium(II) catalysts.     

Lewis Acid catalyzed dipolar cycloadditions of an activated imidate

An evaluation of simple Lewis acids revealed that N-malonylimidates undergo catalyzed [3+2] cycloaddition reactions with aldehydes, imines, and activated olefins to form oxazolines, imidazolines, and pyrrolines, respectively. Reactions proceed optimally at ambient temperature with the addition of 5 mol % of MgCl(2) in CH(3)CN. Experiments aimed at elucidation of the reactive intermediate undergoing cycloaddition suggest that the Lewis acid promotes a 1,2-prototropic shift to give a metal-coordinated azomethine ylide, rather than ionization and proton transfer to give a nitrile ylide.     

Stereoselective synthesis of tetrahydropyran-4-ones from dioxinones catalyzed by scandium(III) triflate

[reaction: see text] A scandium triflate catalyzed, diastereoselective cyclization between aldehydes and beta-hydroxy dioxinones has been discovered. This process capitalizes on the untapped nucleophilicity of the embedded enol ether within the dioxinone core. The bicyclic compounds from the resulting cyclization can be isolated, or alternatively, alkoxide nucleophiles can be directly added. This in situ addition fragments the dioxinone rings and delivers the 3-carboxy-substituted tetrahydropyran-4-ones in good yields with high levels of diastereoselectivity.     

Selective particle trapping using an oscillating microbubble

The ability to isolate and sort analytes within complex microfluidic volumes is essential to the success of lab-on-a-chip (LOC) devices. In this study, acoustically-excited oscillating bubbles are used to selectively trap particles, with the selectivity being a function of both particle size and density. The operating principle is based on the interplay between the strong microstreaming-induced drag force and the attractive secondary Bjerknes force. Depending upon the size of the bubble, and thus its resonant frequency, it is possible to cause one force to dominate over the other, resulting in either particle attraction or repulsion. A theoretical analysis reveals the extent of the contribution of each force for a given particle size; in close agreement with experimental findings. Density-based trapping is also demonstrated, highlighting that denser particles experience a larger secondary Bjerknes force resulting in their attraction. This study showcases the excellent applicability and versatility of using oscillating bubbles as a trapping and sorting mechanism within LOC devices.     

Ring-opening reactions of MCPs with sulfonamides promoted by metal triflate Lewis acids

The reaction of aromatic MCPs with sulfonamides catalyzed by Lewis acids affords the corresponding ring-opened homoallylic sulfonamides in good yields and the reaction of aliphatic MCPs with sulfonamides gives the corresponding pyrrolidine derivatives under the same conditions. Through deuterium-labeling experiments, we found that the reaction process is involved with the rearrangement of a cyclopropylcarbinyl cation and a nonclassic carbonium ion.     

Highly efficient one-pot synthesis of primary amides catalyzed by scandium(III) triflate under controlled MW

The present Letter highlights a versatile synthetic protocol for the one-pot synthesis of primary amides employing scandium(III) triflate as a catalyst in water under controlled MW. This methodology offers excellent yields in shorter reaction times with enhanced selectivity.     

Chemoselective thioacetalization and transthioacetalization of carbonyl compounds catalyzed by immobilized scandium(III) triflate in ionic liquids

Immobilized scandium triflate [Sc(OTf)₃] in ionic liquids has been found to be an extremely efficient and recyclable catalyst for the thioacetalization and transthioacetalization of both aromatic and aliphatic aldehydes. Significant rate acceleration and chemoselectivity was achieved by employing this catalytic system.     

Separation and determination of scandium using N-benzoylphenylhydroxylamine

Scandium may be determined using N-benzoylphenylhydroxylamine, which precipitates a complex containing scandium and reagent in the ratio 1:3. This precipitate may be utilised for the gravimetric determination of scandium by conversion to SC₂O₃ at 600°. It is possible to separate scandium from zirconium, titanium and the rare earth elements by extraction.