Organocatalytic asymmetric direct vinylogous aldol reactions of γ-crotonolactone with aromatic aldehydes

The direct aldol reaction of γ-crotonolactone and various aromatic aldehydes is catalyzed by bifunctional aminothiourea and aminosquaramide organocatalysts to provide diastereomerically and enantiomerically enriched 5-substituted 2(5H) furanones (γ-butenolides). The reaction is a simple alternative to the classical vinylogous aldol reaction of silyloxy furans.     

An efficient asymmetric aldol reaction of Chan's diene promoted by chiral Ti(IV)–BINOL complex

1,3-Bis-(trimethylsilyloxy)-1-methoxy-buta-1,3-diene (Chan's diene) can be conveniently used in asymmetric aldol reaction with aromatic, heteroaromatic, α,β-unsaturated and aliphatic aldehydes in the presence of catalytic amounts (2–8% mol) of chiral Ti(IV)/(R)-BINOL complex.     

Catalytic enantioselective allylation of aldehydes using β-amido functionalized allylstannanes with chiral In(OTf)3/i-Pr-pybox complexes

The enantioselective allylation of aldehydes using a variety of β-amido functionalized allyltributylstannanes proceeded smoothly with good to high yields and enantioselectivities in the presence of 10 mol % of a chiral catalytic complex prepared from In(OTf)₃ and 2,6-bis[(S)-4-isopropyloxazolin-2-yl]pyridine {(S)-i-Pr-pybox}, providing the corresponding chiral γ-hydroxy amides.     

Catalytic asymmetric direct aldol reaction of α-alkyl azlactones and aliphatic aldehydes

An unprecedented highly diastereoselective and enantioselective aldol reaction of α-alkyl azlactones and aliphatic aldehydes was achieved with cinchona alkaloid catalysts. To our knowledge, this reaction provides the first useful catalytic asymmetric access toward β-hydroxy-α-amino acids bearing alkyl substituents, which are structural motifs embedded in many natural products.     

Direct asymmetric aldol reaction of acetone with α-ketoesters catalyzed by primary-tertiary diamine organocatalysts

Novel primary-tertiary diamine organocatalysts derived from l-serine were utilized to promote enantioselective aldol reaction of acetone with α-ketoesters. The desired products were obtained in high yields and with good to excellent enantioselectivities (up to 95% ee).     

Brønsted acids as additives for the direct asymmetric aldol reaction catalyzed by l-prolinethioamides. direct evidence for enamine-iminium catalysis

The use of protonated l-prolinethioamide instead of the free base derivative 1 as the organocatalyst for the direct aldol addition has a profound and appreciable effect on both the yield and the stereochemical course of the reaction. 4-Nitrobenzaldehyde (2) reacts with acetone in the presence of the protonated catalyst 1.TFA, affording aldol product 3 with a yield up to 99% and an ee up to 98%. The catalyst loading can be lowered to 2.5 mol %. More than 20 different acids were investigated as an additive, and its role as cocatalyst has been discussed. Furthermore, reactions of l-prolinethioamide salts with acetone have been monitored using ESI-MS and 1H NMR techniques, giving insight into the mechanism of the direct aldol reaction. The presumed formation of the iminium salt 10 has been unambiguously confirmed.     

Asymmetric aza-Friedel–Crafts reaction of indoles induced by O-pivaloylated d-galactosylamine as the chiral auxiliary

The diastereoselective formation of β-N-glycosidically linked 3-indolyl methanamine derivatives 5 has been achieved with high yield via an aza-Friedel–Crafts reaction. The reaction was performed by using O-pivaloylated galactosylamine 1 as a chiral template and SnCl₄ combining TBAI as catalyst in DCM at ?50 °C.     

Selfcondensation of 2-methylpropanal with homochiral BINOL catalysts as a model asymmetric aldol–Tishchenko reaction

Binaphtholate catalysts were used to investigate the stereochemistry of 2-methylpropanal selfcondensation. Several steps of this condensation were found to be affected weakly or moderately by homochiral catalysts, but with opposite enantioselectivities.     

Diastereoselectivity in theLewis acid mediated aldol reaction of chiral α, β-epoxyaldehydes with a ketene silyl acetal

Summary The Lewis acid mediated aldol reaction of chiral , -cis andtrans epoxyaldehydes1 and2 withtert-butyl ketene silyl acetal proceeds mainly withanti diastereofacial preference. The best results were obtained forcis epoxyaldehyde1 in the presence of catalytic amounts of BiCl₃·1.5 eq. ZnI₂ (anti:syn 13:1), whereas the poorest stereoselectivity was observed when an excess of LiClO₄ was used (anti:syn 1:1). The more stable epoxyaldehyde conformers were determined and the diastereofacial preference was found to be in agreement with a nucleophilic attack on the energetically more favoured conformers.

---

Diastereoselektivität derLewis-Säure-katalysierten Aldolreaction zwischen chiralen , -Epoxyaldehyden und einem Ketensilylacetal

Zusammenfassung DieLewis-Säure-katalysierte Aldolreaktion der chiralen , -cis- und -trans-Epoxyaldehyde1 und2 mittert-Butylketensilylacetal verläuft stereoselektivanti. Die besten Ergebnisse wurden für dencis-Epoxyaldehyd1 in Gegenwart katalytischer Mengen BiCl3·1.5 eq. Znl₂ erhalten (anti:syn 13:1). Die geringste Stereoselektivität trat auf, wenn LiClO₄ im Überschuß eingesetzt wurde (anti:syn 1:1). Das beobachtete Verhalten steht mit einem nucleophilen Angriff am energetisch günstigeren Konformeren im Einklang.

     

Highly diastereoselective vinylogous Mukaiyama aldol reaction of α-keto phosphonates with 2-(trimethylsilyloxy)furan catalyzed by Cu(OTf)2

The diastereospecific formation of δ-hydroxyalkylbutenolide phosphonate has been achieved via a vinylogous Mukaiyama aldol reaction. The reaction was performed using α-ketophosphonate 1 and 2-(trimethylsilyloxy)furan 2 mediated by Cu(OTf)(2) and 2,2,2-trifluoroethanol as additive in CH(2)Cl(2). The reaction proceeds rapidly and affords the corresponding 5-(hydroxy(aryl)methyl) furan-2(5H)-one phosphonates 3 in high yields with good to excellent diastereoselectivities (d.r. up to >99?:?1). 5-(Hydroxy(alkyl)methyl)furan-2(5H)-one phosphonates could also be obtained with good diastereoselectivities.     

The direct catalytic asymmetric aldol reaction of α-substituted nitroacetates with aqueous formaldehyde under base-free neutral phase-transfer conditions

Enantioselective direct aldol reaction of α-substituted nitroacetates with aqueous formaldehyde for the synthesis of α-alkyl serines has been achieved under base-free neutral phase-transfer conditions with a bifunctional chiral phase-transfer catalyst.     

Catalytic asymmetric Mannich reaction of glycine Schiff bases with α-amido sulfones as precursors of aliphatic imines

A general and practical Cu(I)-Fesulphos-catalyzed Mannich reaction of glycinate Schiff bases with aliphatic imines generated in situ from α-amido sulfones is described. Imines with linear and branched alkyl chains, including substrates bearing functional groups, can be efficiently applied. The resulting syn-configured orthogonally protected β-alkyl-α,β-diamino acid derivatives are produced with excellent levels of diastereo- (typically syn/anti >90?:?<10) and enantioselectivity (generally ≥90% ee).