Letters in Organic Chemistry - Volume 11, Issue 5, 2014

A novel, efficient and one-pot method for preparation of 1, 8-dioxo-octahydroxanthene derivatives is reported using Nafion-H as an effective heterogeneous catalyst under thermal and solvent-free conditions. This method has the advantages of high yields, a cleaner reaction, simple methodology, easy work-up and greener conditions. The catalyst is easily prepared, stable, reusable and efficient under the reaction conditions.

Aqueous tetra-n-butyl ammonium hydroxide solution (TBAOH) has been used as a green reaction medium and efficient catalyst for the O-alkylation of alcohols and phenols as well as S-alkylation of thiols under a novel, mild and convenient procedure. Herein, TBAOH has been used as a strong base, medium of reaction and phase transfer reagent.

An efficient stereoselective total synthesis of (+)-Cephalosporolide D from commercially available and inexpensive starting material, (±)-propylene epoxide, is described. The key steps involved in this synthesis are α- aminoxylation catalyzed by L-proline, followed by in situ reduction using NaBH4 and Yamaguchi macrolactonization.

The cycloaddition reactions between dinitronaphthalenes and (E)-1-trimethylsilyloxy-1,3-butadiene produce nitrophenanthrenol derivatives as principal products. The primary adducts suffer the irreversible lost of nitrous acid and, consequently, the aromatization. In these reactions it is frequent to observe the presence of naphthalenyl-1H-pyrrole derivatives as a result of a hetero Diels-Alder process, which is competitive with the normal way. The global electrophilic character of the dienophile is responsible of these results. Other dienes (or dienophiles/electrophiles) with electron donor substitution in C-1 show a different behavior in which the hetero Diels-Alder products prevail. In the series explored only the substrate 1-cyano-4-nitronaphthalene produces the naphthalenyl-1H-pyrrole derivative as principal product, probably as a consequence of its charge distribution. A combination between stereoelectronic effects in the electrophile and the type of substitution joint to the nucleophilicity of the diene is responsible of the results and regioselectivity observed in these polar cycloaddition reactions. In all the cases studied the regioselectivity expected by theoretical calculations corresponds with the ones obtained experimentally.

One-pot preparation of a variety of pharmacologically pertinent xanthone heterocycles has efficiently been achieved from their respective phenol compounds and salicylic acid/ thiosalicylic acid in the presence of the catalytic amount of heteropoly acid. Most of the reactions showed high regioselectivity and produced xanthones/ thioxanthones in good yields under microwave irradiation.

In the course of catalytic and solvent-free reactions, urea and ortho-phenylene diamine enter into a reaction and produce a highly important heterocyclic compound. Apart from the importance of the synthesized heterocyclic compound, it should be known which one of the reactants (urea or ortho-phenylene diamine) attacks as the nucleophile, and which one of them reacts as the electrophile. To clear off this subject considering urea molecule attacking the carbon centre of the benzene as the nucleophile, it will be then possible to develop several useful reactions based on the substitution process. Moreover, the results of such study could substitute the expensive isotopic labelling studies by employing the theoretical work. These calculations were performed at B3LYP/6-311++G(2d,2p) level.

A clean and efficient procedure is described for the synthesis of 7-(4-hydroxy-2-oxo-2H-1-benzopyran-3-yl)- 6H,7H-[1]benzopyrano[4,3-b][1]benzopyran-6-ones and 2-(2,3,4,9-tetrahydro-3,3-dimethyl-1-oxo-1H-xanthen-9-yl)-3- hydroxy-5,5-dimethyl-2-cyclohexen-1-ones from a quasi-Knoevenagel-Michael reaction sequence of salicylaldehydes with compounds having active methylene groups [4-hydroxycoumarin (4-hydroxy-2H-1-benzopyran-2-one) and dimedone (5,5-dimethyl-1,3-cyclohexanedione)] in a ratio of 1:2, in the presence of a catalytic amount of 60% Zr(HSO4)4/SiO2 as an efficient heterogeneous catalyst at 60 °C and under solvent-free conditions.

((S)-1-(1,3,5-trimethyl)benzylpyrrolidin-2-yl)diphenylmethanol (1d) was found to be an effective chiral ligand in the asymmetric transfer reaction of phenyl to aldehydes to give the corresponding adducts in excellent enantioselectivity (up to 98% ee) with very high yields (up to 99%).

Nanosilica chloride was prepared with modification of the surface by applying ultrasonic irradiation and has been employed as an efficient, heterogeneous and effective catalyst in the preparation of 3,4- dihydropyrimidinones (DHPMs) under solvent-free conditions. Simple workup procedure, short reaction time, and good to excellent yield of the product, are other advantages of this catalyst.

The synthesis of the disodium salt of fenidronate by the reaction of benzoic acid with phosphorus trichloride and phosphorous acid in methanesulfonic acid was investigated and optimized. It was enough to use 3.2 equivalents of phosphorus trichloride and there was no need to apply phosphorous acid. Both the one-step and two-step versions led to similar results giving the product in ca. 45% yield and in high purity. It was also possible to start directly from benzoyl chloride or ethyl benzoate. The work-up included in all cases hydrolysis and pH adjustment followed by purification. The fenidronic acid standard that was necessary for the analysis of our samples was prepared by another approach, by the addition of dimethyl phosphite to the carbonyl group of the α-oxophosphonate, followed by hydrolysis of the tetramethyl ester so formed.

α-Fluoro-β-trifluoromethyl-α,β-unsaturated esters were synthesized via the reaction of diethyl (1-fluoro-1- carbethoxymethyl) phosphonate with a variety of aromatic/heterocyclic trifluoromethyl ketones and trifluoroacetaldehyde ethyl hemiacetal by the Horner-Wadsworth-Emmons (HWE) coupling. The effect of base, solvent, as well as reactant ratio has been investigated. The present method is highly stereoselective, attractive and convenient for the synthesis of the target compounds due to the availability of the reagents, simplicity of the approach and good yields of the products.

A series of new fluorinated thieno[2,3-d]pyrimidine derivatives containing hydrazone substructure was synthesized by a five-step procedure, including trifluoroacetylation, cyclization, chlorination, substitution by hydrazine, and condensation reaction. The structures of these newly synthesized compounds were confirmed by IR, NMR, EI-MS, elemental analysis and single-crystal X-ray diffraction. The preliminary bioassay result showed that some title compounds exhibited relatively good fungicidal activity against Fusarium oxysporium f.sp.vasinfectum at the concentration of 50 μg·mL-1, especially the inhibition rate of compound 6b reached above 90%.

A simple and facile approach to highly functionalized imidazole derivatives in moderate to good yields has been developed. This method involves copper catalyzed aerobic [3+2] cycloaddition of amidines with nitroolefins in absence of ligand. Based on observation of the intermediates, possible reaction mechanism different from the same reported approach was proposed.