Stereoselective synthesis of isoindolinones and tert-butyl sulfoxides

A reaction of Grignard reagents with an optically pure N-sulfinylimine derived from methyl 2-formylbenzoate yields enantioenriched isoindolinones and tert-butyl sulfoxides. The products are formed by the addition of the nucleophile to N-sulfinylimine followed by cyclization to form N-tert-butylsulfinylisoindolinone, which readily undergoes substitution with a second equivalent of Grignard reagent. The reaction can be carried out in dichloromethane at room temperature or at elevated temperatures without any loss of stereoselectivity. The use of nucleophiles other than Grignard reagents has also been investigated.     

Synthesis of oxindoles via Cu-mediated reactions between N-phenylacrylamides and ethyl 2-bromo-2-methylpropionate

A novel way of synthesizing alkylated oxindoles via Cu-mediated atom transfer radical addition reaction between N-phenylacrylamides and ethyl 2-bromo-2-methylpropionate has been described. It was found that the use of N,N,N′,N′-1,1,2,2,-tetramethylethylenediamine as ligand was important for achieving good yields. Additionally, the use of DMSO as solvent and running the reaction at 130?°C were also crucial. In some cases, the product can be further brominated when the reaction temperature was raised to 150?°C.     

Reactivity of spiroanthraceneoxazolidines with cyclopropanes: An approach to the oxindole alkaloid scaffold

The reaction of N-methylspiro[anthracene-oxazolidine] with spiro[cyclopropane-3,3′-indolin]-2-ones in the presence of MgI₂ formed the corresponding spiro[pyrrolidine-3,3′-indolin]-2-ones in 42–65% yields. The use of N-benzylspiro[anthracene-oxazolidine] in this reaction led to the formation of a mixture of the corresponding N-methyl- and N-benzylpyrrolidines.     

Cu-nanoparticles: a chemoselective catalyst for the aza-Michael reactions of N-alkyl- and N-arylpiperazines with acrylonitrile

A novel method for effecting the aza-Michael reactions of N-alkyl- and N-arylpiperazines with acrylonitrile using Cu-nanoparticles is described. The method features the use of 10 mol % Cu (14-17 nm) nanoparticles under mild reaction conditions to afford the addition products in good to excellent yields. The Cu-nanoparticles selectively catalysed the aza-Michael reaction of N-alkyl- and N-arylpiperazines in the presence of aromatic amino or aliphatic hydroxy groups.     

Convenient preparation of dichloromethyl alkyl ethers

Dichloromethyl alkyl ethers have been synthesized from alkyl formates (C1–C4) and oxalyl chloride in the presence of catalytic amount of N-methylformanilide. N,N-Dimethylformamide is not suitable for the reaction. The method has the advantages of simple experimental procedure, which is applicable to large scale synthesis, without use of harmful reagents.     

First application of chiral ionic liquids in asymmetric Baylis-Hillman reaction

The first example of the use of chiral ionic liquids as reaction media in the asymmetric Baylis-Hillman reaction was described using N-alkyl-N-methylephedrinium salts. Good yields and significant enantiomeric excesses were obtained.     

An efficient and greener protocol towards synthesis of unsymmetrical N,N′-biphenyl urea

A simple and efficient route for the synthesis of Unsymmetrical N,N′-diphenyl urea have been developed in aqueous medium under base and catalyst free condition from corresponding substituted isocyanate and amines. The remarkable key feature of the reaction includes the use of water as an inexpensive and environmentally benign reaction medium, absence of base and any additional catalyst, and easy isolation of the product.     

Enantioselective synthesis of homocarbocyclic-2′-oxo-3′-azanucleosides

The enantioselective synthesis of homocarbocyclic-2′oxo-3′-azanucleosides has been performed by cycloaddition reaction of the N-glycosyl nitrones with allyl nucleobases. The use of nitrones originated from two different carbohydrates, the N-ribosyl nitrone and the N-mannosyl nitrone, proceeded in a stereocontrolled and predictable manner with a good degree of enantioselectivity, so allowing an easy entry to both enantiomers.     

Palladium catalyzed aroylation of NH-sulfoximines with aryl halides using chloroform as the CO precursor

A palladium-catalyzed aroylation of NH-sulfoximines for the efficient synthesis of N-aroyl sulfoximines from aryl halides and chloroform has been developed. The mild reaction conditions (temperature, catalyst loading) and the use of a CO surrogate render this transformation a useful method for the synthesis of N-aroyl sulfoximines from available feedstock.     

[4+1] Cycloaddition of N-acylimine derivatives with isocyanides: efficient synthesis of 5-aminooxazoles and 5-aminothiazoles

[4+1] Cycloaddition reaction between isocyanides and N-acylimine derivatives generated from N-acyl N,O-acetals acting as isocyanophiles has been developed. These reactions proceeded smoothly and cleanly to afford the corresponding 5-aminooxazoles in high yields. This reaction was extended to the syntheses of 5-aminothiazoles by using N-thioacyl N,O-acetals. A wide range of N-acyl N,O-acetals, N-thioacyl N,O-acetals, and isocyanides were found to be applicable to this reaction.     

N-Bromosuccinimide mediated synthesis of triazatruxenes from indoles

A new synthetic method for triazatruxenes from indoles is developed using N-bromosuccinimide (NBS) as a user-friendly reagent. Major reaction parameters including the amount of NBS, substrate concentration, temperature, addition rate and addition method are investigated. Additional experiments are also conducted in order to gain access toward the reaction mechanism. Compared to the use of Br₂ in the conventional method, this reaction requires less reaction time, provides better yields, and displays excellent reproducibility. The reaction can be conveniently performed at 10 g scale and it is also applicable to several substituted indoles, benzoindole, and N-alkyl indoles.     

Selective reduction of nitroarenes to N-arylhydroxylamines by use of Zn in a CO2–H2O system, promoted by ultrasound

The promoting effect of ultrasound on the selective reduction of nitroarenes to N-arylhydroxylamines by use of Zn in an environmentally benign CO₂–H₂O system has been demonstrated. The yield of N-phenylhydroxylamine reaches 95 % when the reaction is carried out with a Zn-to-nitrobenzene molar ratio of 2.2 under ultrasound (40 kHz) at 25 °C and normal pressure of CO₂ for 60 min. Application of ultrasound to the reaction has the advantages of higher yield of N-arylhydroxylamines, shorter reaction time, and consumption of less Zn.     

N,N,N,N-Tetramethyl-1,3-propanediamine as the catalyst of choice for the Baylis-Hillman reaction of cycloalkenone: rate acceleration by stabilizing the zwitterionic intermediate via the ion-dipole interaction

N,N,N^′,N^′-Tetramethyl-1,3-propanediamine (TMPDA) can be used as an efficient catalyst for the Baylis-Hillman reaction of cycloalkenones. The increased reaction rate was thought be derived from the stabilizing effect of the zwitterionic intermediate via the ion-dipole interaction.     

Synthesis of fluorinated imines and carbodiimides from azides via aza-Wittig reaction

The Staudinger reaction of fluoroalkylazides were studied. A series of N-fluoroalkylimines were synthesized via aza-Wittig reaction of N-fluoroalkyliminophosphoranes. The N,N′-difluoroalkylated carbodiimide was also synthesized via the reaction of N-fluoroalkyliminophosphoranes with carbon dioxide or carbon disulfide.     

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.     

Novel C2-symmetric chiral O,N,N,O-tetradentate 2,2-bipyridyldiolpropane ligands: synthesis and application in asymmetric diethylzinc addition to aldehydes

First synthesis of C₂-symmetric chiral O,N,N,O-tetradentate 2,2-bipyridyldiolpropane ligands is described. The Mukaiyama–Michael reaction was applied as an important reaction for the synthesis of 2,2-bipyridylpropane 9. Among the ligands synthesized, ligand 11 exhibits excellent chiral induction (up to 97% ee) in diethylzinc addition to various aldehydes. The use of additional Lewis acid such as Ti(OⁱPr)₄ in diethylzinc addition reaction is not required for the present catalytic system.     

Sialylation reactions with N,N-dibenzylthiosialoside donor

A new sialyl donor, N,N-dibenzyl-protected p-toluenethiosialoside, was synthesized and its sialylation reaction was investigated. This reaction proceeded in a preactivation manner and preferred to provide β-anomeric coupling products. The β-selectivity was rationalized based on the assumption that N,N-dibenzylamino group could serve as an oriented group to activate the hydroxyl group of acceptor from β-face.     

Studies toward a synthesis of C3-epimauritine D: construction of the macrocycle

We successfully synthesized a 14-membered cyclic enamide of C3-epimauritine D from the cis-2,3-pyrrolidinediol derivative. Treatment of the pyrrolidinediol with nitrobenzonitrile in an S_NAr reaction efficiently installed the desired aryl-alkyl ether linkage on the N-heterocyclic system. Macrocyclization was successfully achieved by the use of TFFH as the peptide coupling reagent in the presence of HOAt.     

Novel preparation of N-arylmethyl-N-arylmethyleneamine N-oxides from benzylic bromides with zinc and isobutyl nitrite

Treatment of benzylic bromides with Zn and LiCl, followed by the reaction with i-butyl nitrite gave N-arylmethyl-N-arylmethyleneamine N-oxides in moderate yields. The present reaction is a novel and simple method for the preparation of nitrones from benzylic bromides, although the yields are moderate.     

Experimental and computational study of intermolecular migration of N,N-dimethylcarbamoyl group from N(7) to N(1) on a 7-azaindoline derivative

N,N-Dimethylcarbamoylation of the anilinic nitrogen atom N(1) on the spiro 7-azaindoline consists of two steps. The first step is N,N-dimethylcarbamoylation of the pyridyl nitrogen atom N(7), leading to the formation of an isolable intermediate. The second step is intermolecular migration of the N,N-dimethylcarbamoyl group from the pyridyl nitrogen atom N(7) to the anilinic nitrogen atom N(1). We accomplished optimization of the reaction conditions based on the revealed reaction mechanism and a large scale synthesis of compound 3 in quantitative yield.