Letters in Organic Chemistry - Volume 6, Issue 3, 2009

In this work we aimed at finding a concise method for the design of the new pharmacologically active compound 6, which is a precursor to obtaining non-protein amino acid 7 considered as GABA analogue, furthermore it can be used to construct enantiopure, conformationally restricted peptides. For this purpose the Schmidt reaction was applied.

The cyclization of 2,3-dimethoxy-1,3-butadiene with oxalyl chloride provides a new method for the synthesis of 4,5-dimethoxy-o-benzoquinone.

Sodium hydride (NaH) in hexamethylphosphoric triamide (HMPA) has been introduced as an economical and efficient reagent towards the creation of 1,2- or 5,6-enopyranosides from the corresponding halogenated or tosylated pyranosides. NaH/HMPA has several advantages compared to NaH/DMF: elimination products are produced in high yields even from sterically-hindered halides as well as tosylates.

Two novel double axial chiral guanidines were designed according to the concept of double axial chirality. The practical synthetic procedures from (S)-1,1'-binaphthol have been developed. The title compounds were fully characterized by NMR, MS, IR and elemental analysis or HRMS. The two chiral guanidines can be interesting catalysts for asymmetric catalysis and preliminary asymmetric catalytic activity was investigated in Henry reaction and conjugate addition.

Cyclization of in situ generated 5-aminoimidazoles with various malondialdehydes or 1,3-diketones gave substituted imidazo[1,5-a]pyrimidines. However, cyclization of 2-aminopyrroles and 5-amino-1-methylimidazoles resulted in condensations on a carbon atom of the heterocyclic ring instead of nitrogen generating 1H-pyrrolo[2,3- b]pyridines (i.e. 7-azaindoles) and 3-methyl-3H-imidazo[4,5-b]pyridines, respectively. In these cases the addition of pyrrolidine to the reaction mixture after the initial condensation between the amino group and one of the carbonyl groups of the malondialdehydes or 1,3-diketones significantly increased the yields of 1H-pyrrolo[2,3-b]pyridines and 3-methyl- 3H-imidazo[4,5-b]pyridines.

A new series of 2-aryl-1,2,3,4-tetrahydroquinolines has been synthesized in good yields through a BiCl3- catalyzed three-component Povarov reaction (imino Diels-Alder cycloaddition) between anilines, benzaldehydes and Nvinylpyrrolidin- 2-one in MeCN. The same series has been prepared without solvent using microwave radiation, which resulted in better yields, a considerable decrease in reaction times and simplified workup.

N-substituted 1,4-dihydropyridines bearing a carboxyl group at the 4-position were synthesized in solvent-free conditions with Cu2+ as the catalyst, imine and β-ketoester as starting materials. The possible mechanism which consists of addition-rearrangement process was proposed and examined by the reaction of isolated product of first addition to β- ketoester.

7-amino-2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-triones were synthesized via the three-component condensation of luminol, dimedone, and aromatic aldehydes in EtOH at 80 °C for 9-15 min catalyzed by solid silica sulfuric acid (SSA) and the luminescence of products was studied in details.

Allylsilane addition to the dihydro-2H-1,4-oxazinones, 1, proceeded in moderate to good yields with transdiastereoselectivity. The yield of addition reactions of 5-phenyl-5,6-dihydro-2H-1,4-oxazin-2-one with allylsilanes is improved over the corresponding additions of Grignard reagents to 1 and illustrates a simple path to protected β,β- disubstituted α-amino acids.

A series of lanthanoid (Ln3+) based Lewis acid catalysts were investigated as alternatives to other metal based catalysts for the formation of Michler's hydride, 4,4'-methylenebis(N,N-dimethylaniline) (1). The lanthanoid based Lewis acid catalysts were superior to previously published catalysts resulting in formation of 4,4'-methylenebis(N,Ndimethylaniline) (1) and N,N-dimethyl-4-(4-(methylamino)benzyl)aniline (2). If paraformaldehyde was added to the reaction only 4,4'-methylenebis(N,N-dimethylaniline) (1) was formed.

A simple and efficient synthesis of N-acylsulfonamides has been accomplished by the reaction of sulfonamides with anhydrides under solvent-free conditions in the presence of HClO4-SiO2 or NaHSO4-SiO2.

Treatment of 1-acetylanthracene (1-AcAN) and 9-acetylanthracene (9-AcAN) with PPA at 80-120 °C leads to the nearly complete conversion of these isomers into 2-acetylanthracene (2-AcAN), an illustration of the Agranat-Gore rearrangement of polycyclic aromatic ketones (PAKs). Ab initio MP2/6-31(d) calculations predict the following order of stabilities: for σ-complexes: 9-AcAN>1-AcAN>2-AcAN; for ketones: 2-AcAN>1-AcAN>9-AcAN; for O-protonated ketones: 2-AcAN>1-AcAN>9-AcAN. Thus, 9-AcAN is the kinetically controlled product, whereas 2-AcAN is the thermodynamically controlled product. No reverse rearrangements of 2-AcAN to either 9-AcAN or 1-AcAN and of 1-AcAN to 9-AcAN were observed. The results strengthen the pattern of reversibility in Friedel-Crafts acylations of PAHs.

A number of alkynols have been prepared by Sonogoshira coupling of propargyl alcohol to disubstituted aromatic halides. Chelation controlled addition of organometallic nucleophiles to these alkynols was then affected followed by the addition of sulfur dioxide. This methodology was used to prepare a number of oxathiolene oxides which have been screened as NQO1 (quinone oxidoreductase) inducers.

With DL-valinol, 3-amino-1-propanol and o-aminothiophenol, aroyl(bi/tri)cyclic lactones 1 and 2 were cyclized to isoindole- 4-6, 8, 9, pyrimidinone- 10 or thiazepine- 7 condensed heterocycles. The ketal lactone 3 furnished the benzthiazoloisoindole 9 and mixtures of epimeric hydroxyphthalazinoquinazolinones 11 and 12. The structures were established by means of 1H and 13C NMR spectroscopy and in some cases by X-ray crystallography.

In this report, the recognition points of tryptophan by 2-hydroxypropyl-alpha-cyclodextrin (HPαCD) are presented. This cyclodextrin exhibited greater thermodynamic chiral selectivity towards DL-tryptophan than the hydroxypropylated beta form. FTIR spectroscopy was used to tentatively evidence this chiral discrimination in solid state HPαCDTrp complexes. An inclusion complex was only detected for the HPαCD-DTrp sample, while HPαCD-LTrp immediately decomposed after crystallization, which left a mechanical mixture of tryptophan and cyclodextrin.

Amino alcohol functionalized new chiral ionic liquids have been synthesized from (+)-α-pinene, an easily available natural product. The effectiveness of these CILs as phase transfer catalysts (PTC) in enantioselective C-C bond formation has been demonstrated through the addition of diethylzinc to representative aldehydes, and the corresponding chiral alcohols with good yields and enantiomeric excess have been obtained.