Primary amine catalyzed aldol reaction of isatins and acetaldehyde

Several cinchona alkaloid-derived chiral primary amines were applied as the catalyst for the cross aldol reaction of isatins with acetaldehyde. With the quinine-derived amine catalyst 3, the desired aldol products were obtained in high yields and good enantioselectivities (up to 93% ee) under the optimized conditions. Although other enolizable aldehydes and ketones may also be applied in this reaction, the ee values obtained are usually low. A mechanism was proposed to account for the formation of the major enantiomer in this reaction.     

Glucose-containing imidazolium salt-catalyzed cross-aldol reaction of isatins and unactivated ketones

Research on Chemical Intermediates - Ketone–ketone cross-aldol reaction of isatins and unactivated ketones was catalyzed by glucose-containing imidazolium salt...     

Enantioselective organocatalytic aldol reaction of unactivated ketones with isatins

Enantioselective organocatalytic direct aldol reaction of unactivated ketones with various isatin derivatives was developed using cinchonine based urea ligand employing a noncovalent catalysis mechanism. Using this protocol we can access functionalized 3-alkyl-3-hydroxyindolin-2-ones in high yields with good to excellent enantioselectivities.     

An efficient and environmentally friendly DABCO catalyzed Henry reaction of isatins

An efficient and general method has been described for the synthesis of 3-hydroxy-3-(nitromethyl)indolin-2-one by the reaction of isatins with nitromethane/nitroethane in the presence of DABCO. The reaction is catalytic, very rapid, yields are very high and avoids the use of solvents for reaction. The protocol is applicable for substituted isatins as well as substituted nitroalkanes.     

Base-catalyzed reaction between isatins and N-Boc-3-pyrrolin-2-one

The base-catalyzed reaction between isatins and N-Boc-3-pyrrolin-2-one yields Morita–Baylis–Hillman (MBH) adducts instead of the expected aldol products in good to high yields (up to 97%). Various organic and inorganic bases are efficient catalysts for this reaction. Our study excluded the Morita–Baylis–Hillman mechanism for the formation of the MBH-type products. The MBH products are most likely formed as a result of the subsequent isomerization of the original aldol products between isatins and N-Boc-3-pyrrolin-2-one.     

Nickel(II)-catalyzed addition reaction of arylboronic acids to isatins

A Ni-catalyzed addition of arylboronic acids to isatins was first developed. The reaction, driven by Ni(acac)₂ and dppp as the phosphine ligand, gave 3-aryl-3-hydroxy-2-oxindoles in up to 97% yield. Scopes of benzyl-protected isatins and arylboronic acids were examined. Substituted phenylboronic acids along with fused-ring and heterocyclic boronic acids reacted with isatins smoothly. Preliminary asymmetric catalysis was investigated as well, showing moderate enantioselectivity. The mechanism was also described.     

Unnatural tripeptide as highly enantioselective organocatalyst for asymmetric aldol reaction of isatins

The development of unnatural tripeptides as highly enantioselective organocatalysts for the asymmetric aldol reaction of isatins was achieved. H-Pro-Gly-d-Ala-OH with the d-alanine residue as the C-terminal amino acid residue expressed the best enantioselectivity. The H-Pro-Gly-d-Ala-OH-catalyzed reaction of isatins gave various aldol adducts with up to 93% yield and up to 97% ee. Investigation of the transition state via DFT calculation revealed that high optical purity was realized by the d-alanine controlled steric environment.     

Cascade reaction of isatins with heterocyclic ketene aminals: synthesis of imidazopyrroloquinoline derivatives

A concise and efficient route for the synthesis of highly substituted imidazopyrroloquinoline derivatives by simply refluxing a reaction mixture of different types of isatins and heterocyclic ketene aminals (HKAs) by acetic acid was developed. This method is suitable for combinatorial and parallel syntheses in drug discovery; consequently, a library of highly substituted imidazopyrroloquinoline derivatives was rapidly constructed using the present protocol.     

A novel stereoselective carbon-chain extension reaction at the C-6 position of 1,6-anhydropyranose

6-Bromo-1,6-anhydro-d-mannose triacetate reacted with a variety of carbon nucleophiles such as allylsilane, silylacetylenes, propargylsilane, and aromatic compounds in the presence of silver triflate to give the corresponding chain extended products at C-6 in high exo-selectivities. The product obtained from the reaction with propargylsilane was efficiently transformed into a naturally occurring heptopyranose derivative found in bacterial lipopolysaccharide.     

Highly effective and enantioselective Phospho-Aldol reaction of diphenyl phosphite with N-alkylated isatins catalyzed by quinine

Cinchona alkaloids were first successfully reported to promote enantioselective Phospho-Aldol reaction of diphenyl phosphite to a variety of N-alkylated isatin derivatives in good to excellent yields (up to 99%) and moderate to good enantioselectivities (up to 73% ee) almost in no time.     

A novel wall reaction of OH

A moderately fast second-order reaction between OH and atomic hydrogen, which occurred on the halocarbon-coated or acid-washed walls of a standard discharge-flow apparatus, has been investigated using epr spectroscopy. The reaction that occurred in a halocarbon-coated flowtube was found to be unusual in that it produced a reactive product, namely, atomic oxygen.     

Asymmetric aldol reaction of isatins with acetone in the presence of terpene amino alcohols

1. Download : Download high-res image (104KB)
2. Download : Download full-size image

     

Catalytic asymmetric synthesis of 3-hydroxyl-2-oxindoles via enantioselective Morita-Baylis-Hillman reaction of isatins

The enantioselective Morita-Baylis-Hillman reaction of acrylates to isatins was investigated for the first time, employing bifunctional phosphinothiourea organocatalysts based on chiral cyclohexane scaffold. The 3-hydroxyl-2-oxindole derivatives were obtained in excellent yields with moderate enantioselectivity (up to 69% ee) in the presence of 10 mol % catalyst 1b.     

An efficient synthesis of spiroacridinone derivatives from the facile reaction of isatins,dimedone, and 5-aminoindazole (6-aminoindazole or 5-aminoindole)

We have developed a simple and facil protocol for the synthesis of tetrahydrospiro(indoline-3,11′-pyrazolo[4,3-a]acridine)-2,10′(7′H)-dione, tetrahydrospiro(indoline-3, 11′-pyrazolo[3,4-a]acridine)-2,10′(7′H)-dione, and tetrahydrospiro (indoline-3,11′-pyrrolo[3,2-a]acridine)-2,10′(7′H)-dione via PTSA·H₂O-induced cyclization reaction from isatins, dimedone, and 5-aminoindazole (6-aminoindazole or 5-aminoindole) in mixed solvent (EtOH and CH₃CN). In this research, 5-aminoindazole, 6-aminoindazole, and 5-aminoindole were effectively used to react with isatins and dimedone to give spiroacridinone derivatives. The advantages of this method are mild conditions, convenient manipulation, high yields, and a wide range of substrates.     

Mass-spectrometric investigation of isatins

It is shown that in the mass spectra of N-alkylisatins with a normal C₁-C₁₀ chain the intensity of the [M-CO]⁺- and [M-(2CO)]⁺. peaks characteristic for isatin and N-methylisatin decreases as the alkyl radical is lengthened, whereas the intensity of the peak formed as a result of successive loss by the molecular ion of a CO group and a portion of the radical as a result of cleavage of the bond at the α-carbon atom increases. Fragments due to α,β,γ... cleavages, both without migration and with migration of the hydrogen atoms, appear in the spectra of N-alkylisatins commencing with chains containing more than two C atoms.     

A novel bicyclic ketal fragmentation reaction

Bicyclic ketals of the 6,8-dioxabicyclo[3.2.1]octane series are specifically cleaved to give δ, ε-unsaturated ketones by treatment of the ketal with acetyl iodide.     

A novel palladium-catalyzed intramolecular redox reaction

[reaction: see text] A new type of palladium-catalyzed redox reaction is described, forming enones from 2-(2-bromobenzyl)-ketones with an overall loss of HBr. The scope and limitations of the reaction are demonstrated by a series of cyclic and acyclic substrates. The mechanism most probably involves the formation of an intramolecular arylpalladium enolate and is related to the oxidation of silyl enol ethers with palladium acetate.     

Spirooxindoles: reaction of 2,6-diaminopyrimidin-4(3H)-one and isatins

A simple and efficient cyclocondensation reaction of 2,6-diaminopyrimidin-4(3H)-one and isatins for the synthesis of spiro[pyrimido[4,5-b]quinoline-5,5′-pyrrolo[2,3-d]pyrimidine] and spiro[indoline-pyrido[2,3-d:6,5-d′]dipyrimidine] derivatives is reported.