A new and efficient synthesis of 2-azatryptophans

This paper describes a new and simple synthesis of 2-azatryptophans in five steps from 2-ethylaniline. This methodology allows to obtain either the amino acid or the amino ester, according to the treatment and the reaction time, and its scaling up for multigram synthesis.     

A highly efficient solid-phase synthesis of 1,3-substituted xanthines

A first solid-phase route to 1,3-substituted xanthines has been developed using PS-MB-CHO resin. Cyclocondensation of the polymer-bound aminoimidazole with isocyanates followed by alkylation provided 1,3-substituted xanthines in high yields. Libraries of 12 xanthines and 4 thioxanthines were prepared.     

A facile and efficient synthesis of enyne-reaction precursors by multicomponent reactions

Using improved reaction protocols for three-component coupling reactions of aldehydes, dienophiles, and amides (AAD-reaction) or anhydrides (ANAD-reaction) or orthoesters (ALAD-reaction), a variety of functionalized hexahydroisoindolo derivatives were synthesized and fully characterized. Condensation of ubiquitous available aldehydes with unsaturated amides or anhydrides or orthoesters and subsequent Diels-Alder reactions with electron deficient dienophiles furnishes endo-selective enyne-reaction precursors in good to excellent yield.     

An efficient solid-phase synthesis of 2-alkyl-4,6-diaminopyrimidines and 2,4,6-triaminopyrimidines

An efficient and simple approach for the solid-phase synthesis of 2,4,6-triaminopyrimidines and 2-alkyl-4,6-diaminopyrimidines is described. Primary amines were immobilized on 2-(4-formyl-3-methoxyphenoxy)ethyl polystyrene resin via reductive amination. Attachment of two different 4,6-dichloropyrimidines led to the corresponding 4-chloro-6-aminopyrimidine intermediates. Aromatic nucleophilic substitution with various aliphatic amines or the corresponding lithium amides afforded the desired aminopyrimidines in high yield and excellent purity after acidic cleavage from the resin. The products were characterized by LC-MS, ¹H and ¹³C NMR spectroscopy. Deuterium exchange experiments revealed that the investigated aminopyrimidines have a general tendency toward C-5 protonation.     

An efficient and chemoselective synthesis of N-substituted 2-aminopyridines via a microwave-assisted multicomponent reaction

A facile and selective synthesis of N-substituted 2-aminopyridines is accomplished via microwave-assisted multi-component reactions controlled by the basicity of amine and the nature of solvent. In addition, a possible mechanism accounting for the reaction was proposed.     

A new and efficient one-pot procedure for the synthesis of 2-styrylquinolines

A one-pot combination of a modified Friedländer annulation and a Knoevenagel condensation provides 2-styrylquinolines in good to excellent yields. A variety of substrates are reacted in one-pot in the presence of 1-methylimidazolium trifluoroacetate ([Hmim]TFA).     

Novel and efficient synthesis of iminocoumarins via copper-catalyzed multicomponent reaction

A variety of substituted iminocoumarins are prepared in good to excellent yields via a copper-catalyzed multicomponenet reaction of sulfonyl azides, terminal alkynes, and salicylaldehydes or o-hydroxylacetophenones. The method is general, mild, versatile, and efficient. A plausible mechanism for the domino process is proposed.     

A new and efficient one-pot synthesis of indoles

The synthesis of indoles is accomplished in high yields from phenylhydrazines and pyruvic acid using microwave irradiation.     

A new and highly efficient synthesis of hydroxyporphyrins

A new synthesis of hydroxyporphyrins is reported. The method involves nucleophilic displacement of a nitro group using the sodium salt of E-benzaldoxime and is a general process allowing the synthesis of both β-hydroxyporphyrins and meso-hydroxyporphyrins. Activation of the porphyrin system towards nucleophilic attack is achieved by complexation of the macrocycle with the relatively electronegative nickel(II) or copper(II) ions. Thus, treatment of either the copper(II) or the nickel(II) chelates of 2-nitro-5, 10,15,20-tetraphenylporphyrin with the sodium salt of E-benzaldoxime gave the corresponding 2-hydroxyporphyrin in high yield. Similar treatment of the copper(II) or the nickel(II) chelates of 5-nitro-2, 3,7,8,12,13,17,18-octaethylporphyrin gave the corresponding 5-hydroxyporphyrin, again in high yield. These reactions show that metallo-nitroporphyrins display similar electrophilic properties to much simpler nitro-arene systems. The nickel(II) 5-hydroxyporphyrin 10 was cleanly demetallated on treatment with concentrated sulfuric acid to give the corresponding free-base oxophlorin thereby greatly increasing the general utility of the hydroxylation methodology. Conversion of (5-methoxy-15-nitro-2,3,7,8,12,13,17,18-octaethylporphyrinato) nickel(II) 16 into (5-acetoxy-15-methoxy-2,3,7,8,12,13,17,18-octaethyl-porphyrinato) nickel(II) 18 established that the reaction mechanism involves regiospecific replacement (i.e., ipso-substitution) of the nitro group by the oxygen nucleophile.     

A new safety-catch protecting group and linker for solid-phase synthesis

The use of two derivatives of 2-methoxy-4-methylsulfinylbenzyl alcohol is demonstrated as a safety-catch protecting group and linker for solid-phase peptide synthesis. The protecting group and linker are stable to TFA and are readily removed under reductive acidolytic conditions.     

New efficient route for solid-phase synthesis of benzimidazole derivatives

A simple and efficient method for the solid-phase synthesis of benzimidazole libraries is described. Monoalkylation of various o-phenylenediamines on resin-bound bromoacetamide proceeded smoothly to give the monoalkyl resin-bound o-phenylenediamines in high yields. Subsequent cyclization of the diamines with various aldehydes afforded solid-supported benzimidazoles. Cleavage from the resin gave benzimidazoles in good yields. The present method enabled the introduction of the diversity on the benzene ring of imidazoles. Azabenzimidazoles, such as 4-azabenzimidazoles, 5-azabenzimidazoles, and purines, were also synthesized in good yields with high purities by the same procedure.     

A new diastereoselective multicomponent, one-pot strategy for the synthesis of 3-substituted isoindolinones via efficient C-C bond formation

A new three-component reaction among o-phthalaldehyde, N-alkyl/aryl substituted urea, and an aromatic aldehyde has been developed at ambient condition, and a class of isoindolinones with novel C-3 substitution were conveniently synthesized. The general diastereomeric excess as high as over 99% of the products indicated the excellent stereoselectivity posed in this multicomponent reaction.     

An efficient protocol for the solid-phase synthesis of malondiamides

A novel and straightforward solid-phase synthesis of malondiamides containing a free nitrogen has been developed. These intermediates, which can be directly obtained in good yield and purity, can be further derivatised. This approach can be used for the synthesis of large split-and-mix-libraries.     

An efficient multicomponent stereoselective synthesis of 1,2,4-trisubstituted 1,3-thiazetidines

The first one-pot three-component coupling reaction of O,O-diethyl hydrogen phosphorodithioate, aldehydes, and aldimines affording 1,2,4-trisubstituted 1,3-thiazetidines is reported. The product is obtained in moderate to high yields (45-94%) and has excellent diastereoselectivity (90-96%) in favour of the cis isomer. Shorter reaction times, ambient temperature, operational simplicity, and high yields are the salient features of the present procedure.     

A simple and efficient synthesis of new cyclic ureas

A facile access to a wide range of original saturated N-heterocyclic ureas is described using, as a key step, a Michael-type reaction involving isocyanates or amines on a piperidine framework possessing an α,β-unsaturated ester functionality.     

A new efficient and versatile synthesis of alkyl prosphorylcholines

A short and general synthetic method is described for the preparation of new phosphorylcholines.     

A cesium fluoride promoted efficient and rapid multicomponent synthesis of functionalized 2-amino-3-cyano-4H-pyran and spirooxindole derivatives

A rapid, one-pot and highly efficient protocol for the synthesis of pharmaceutically interesting functionalized 2-amino-3-cyano-4H-pyran and spirooxindole derivatives has been developed using commercially available Cs F as a catalyst in the reaction of malononitrile and aryl aldehydes or isatins with 1,3-cyclohexanediones. The major advantages of this methodology are excellent yield at ambient temperature, very short reaction time(5–10 min), and use of an inexpensive catalyst.     

PPA-SiO_2 catalyzed efficient synthesis of polyhydroquinoline derivatives through Hantzsch multicomponent condensation under solvent-free conditions

Silica gel-supported polyphosphoric acid（PPA-SiO₂） was found to be an efficient catalyst for the one-pot four-component Hantzsch condensation reaction of aryl aldehydes,dimedone,ethyl acetoacetate and ammonium acetate to afford the corresponding polyhydroquinoline derivatives in high yields.The main advantages of the present approach are short reaction times,clean reaction profiles,simple experimental and workup procedures.     

A multicomponent synthesis of cyclopropanes

A multicomponent synthesis of cyclopropanes is described. The title compounds were obtained in high yields from commercially available materials.     

A facile and efficient procedure for the synthesis of new benzimidazole-2-thione derivatives

A series of benzimidazole-2-thione derivatives was synthesized using a reaction between the macrocyclic aminal 16H,13H-5:12,7:14-dimethanedibenzo[d,i]-[1,3,6,8] tetraazecine (DMDBTA, 5) and various nucleophiles in the presence of carbon disulfide. A full chemical characterization using IR, 1H-, 13C-NMR and GC-MS analyses of the new compounds is provided. These compounds were separated from the reaction mixture by column chromatography (CC) in highly pure form in 15%-51.4% yield.