Structure and catalytic activity of organopalladium(II) complexes based on 4,5-dihydro-1H-imidazol-5-one derivatives

The paper describes preparation of a chiral bidentate ligand - 2-(2-bromophenyl)-4,5-dihydro-1H-imidazol-5-one, and a tridentate ligand - 2-bromo-1,3-bis(4,5-dihydro-1H-imidazol-5-on-2-yl)benzene, whose oxidative addition reaction with Pd(0) giving neutral organopalladium(II) complexes has been studied. The structure of these complexes was studied by means of NMR spectroscopy and X-ray diffraction. After transformation of the neutral organopalladium(II) complexes into the corresponding ionic species the latter were studied as enantioselctive catalysts for asymmetric Friedel-Crafts alkylation and Michael addition.     

The synthesis of 3,5-dimethylpyrazol-1-yl-vl-v-triazolo[4,5-d]pyridazines and substituted 3,5-dimethylpyrazol-1 -ylimidazo[4,5-d]pyridazines

The synthesis of 4-(3,5-dimethylpyrazol-1-yl)-v-triazolo[4,5-d]pyridazine, 4-(3,5-dimethylpyrazol-1-yl)imid-azo[4,5-d]pyridazine and several S-substituted derivatives of 4-(3,5-dimethylpyrazol-1-yl)imidazo[4,5-d]pyrid-azine-2-thiol is reported. These syntheses were carried out to provide a variety of interesting compounds for biological screening.     

Synthesis and properties of 1,2-dihydropyridazino[4,5-b]indole II

The possibility of the synthesis of substituted 1,2-dihydropyridazino[4,5-b]indoles by the reaction of 1-methyl-2-carbomethoxy-3-(α-halobenzyl)indole or 1-methyl-2-carbomethoxy-3-(α-acetoxybenzyl)indole with hydrazines was demonstrated. The oxidation, reduction, and acylation reactions of the resulting 1,2-dihydropyridazino[4,5-b]indoles were studied.     

Regio- and stereospecific synthesis of dl-4,5-dibromo-4,5-dideoxy-3,6-O-methyl-chiro-inositol

The regio- and stereospecific synthesis of dl-4,5-dibromo-4,5-dideoxy-3,6-O-methyl-chiro-inositol is reported. Bromination of p-benzoquinone followed by reduction of the carbonyl groups with NaBH₄ gave the corresponding trans-dibromodiol compound, which was reacted with sodium methoxide to produce dimethoxy conduritol-B. Regiospecific bromination of the alkene moiety furnished the desired chiro-inositol derivative.     

Synthesis of 4,5-Dihydroisoxazoles Bearing Phosphonate Moiety

Abstract

Introduction of phosphoryl group usually leads to the improvement of biological activity of the parent molecule. A facile synthetic route was introduced based on an intramolecular silylnitronate-olefin cyclo-addition (ISOC) reaction. Thus, 3-(β-diethoxyphosphoryl)-ethyl-5-methoxycarbonyl - 4,5 -dihydroisoxazole (1), 3-(α-diethoxyphosphoryl- α -substituted methyl) - 5 - methoxycarbonyl - 4,5 - dihydroisoxazole (2) and 3 - methyl - 4 -alkyl(aryl) - 5 - bisphosphoryl - 4,5 - dihydroisoxazole (3) were prepared from diethyl methylphosphonate, diethylphosphite and methylene bisphosphonate respectively after treatment with BuLi or LDA and appropriate nitroalkene followed by ClSiMe₃. Condensation of but - 3 - en - 1 - yl phosphonate with nitroalkene, followed by ClSiMe₃, led to the stereoselective synthesis of fused carboisoxazole derivatives (4). In the case of aryl substituted α- nitroalkene, the reaction undergoes stereoselectively due to the formation of transition state of the least steric hindrance during the Michael addition step, which gave rise to the exclusive formation of erythro isomers. With alkyl substituted α- nitroalkenes, the diastereoselectivity was not obvious as the result of minor steric difference of the related groups. It seems necessary to point out that the stereochemistry involved in the ISOC reaction is quite different from an intramolecular nitrile-oxide olefin cycloaddition (INOC) process presumably due to the formation of transition states with diverse steric environments. Since 4,5-dihydroisoxazole derivatives are synthetic equivalent of β- hydroxy ketones, 1,3 - diketones, γ- aminoalcohols, α β- unsaturated ketones, the present contribution should expand the field of applications of 4,5 -dihydroisoxazole derivatives in the natural products synthesis by building block strategy.     

Synthesis of 3,5-Disubstituted-4,5-dihydroindeno[1,2-c] [1,2]diazepin-6(1H)-ones

3,5-Disubstituted 4,5-dihydroindeno[1,2-c][1,2]diazepin-6 (1H)-ones ( 3a–g ) were obtained in 29–72% yields by condensing 2-(substituted-2-acylethyl)-1,3-indandiones ( 1a–n ) with hydrazine. The NH group of the indenodiazepinones 3a–g is quite unreactive. Two methods based on the Michael reaction were used for preparing the acylethylindandiones 1a–n : one from 1,3-indandione and chalcone-type compounds and the other from 2-benzylidene-1,3-indandione and acetophenones. The latter method was found more practical and of more general application.     

An efficient synthesis of optically active (2R,3R)-2-methyl-3-[(1R)-1-methylprop-2-enyl]cyclopentanone, a useful chiral building block for synthesis of vitamin D and steroids

An efficient synthesis of optically active (2R,3R)-2-methyl-3-[(1R)-1-methylprop-2-enyl]cyclopentanone, a useful chiral building block for synthesis of vitamin D and steroids, has been developed starting from readily accessible optically active secondary propargyl phosphate (R)-2, where the asymmetric Michael addition of a chiral allenyltitanium to alkylidenemalonate 3 is a key reaction.     

Asymmetric total synthesis of (20S)-Camptothecin using a chiral auxiliary strategy

An asymmetric eight-step total synthesis of (20S)-camptothecin, starting from the known compound tert-butyl (2-chloroquinolin-3-yl)methylcarbamate, is described. A Heck reaction followed by an intramolecular Michael addition to form the C-ring provides the first key step in this synthesis. The construction of the 20(S) chiral center relies on a chiral auxiliary-mediated Michael addition using (2R,5R)-2-tert-butyl-5-ethyl-1,3-dioxolan-4-one as the auxiliary.     

Imidazolium-based chiral ionic liquids: synthesis and application

Synthesis of chiral ionic liquids containing an imidazole nucleus and chiral centers on N-substituents is reported. [(2S,3S)-2,3-Dihydroxybutane-1,4-bis(3-butylimidazolium)]-[bis(trifluoromethanesulfonyl)amide]₂ and [(4S,5S)-2-phenyl-1,3-dioxolane-4,5-bis(1-methylimidazolium)]-[bis(trifluoromethanesulfonyl)amide]₂ induced enantioselectivity in the Michael addition of malonic esters to chalcones.     

Synthesis of substituted thiazolo[4,5-b]pyridines and other annulated heterocycles via SN2→Thorpe-Ziegler→Thorpe-Guareschi domino reactions

A new combinatorial method for the preparation of substituted thiazolo[4,5-b]pyridines, which utilizes cyanoacetamide, heterocumulenes (isothiocyanates, carbon bisulfide), and ethyl-4-chloroacetoacetate in a new S_N2→Thorpe-Ziegler→Thorpe-Guareschi domino reactions has been developed. The obtained thiazolo[4,5-b]pyridines were then used together with aldehydes and malononitrile in another Knoevenagel reaction→Michael reaction→hetero-Thorpe-Ziegler domino reaction for the synthesis of substituted 4,6-dihydro-5H-pyrano[2,3-d]thiazolo[4,5-b]pyridines.     

Alkylation of 1-hydroxy-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 5,7-dioxide

Alkylation of 1-hydroxy-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 5,7-dioxide 1 and its silver salt 10 with different alkylating agents (diazomethane, diazoacetone, bromoacetone, α-bromoacetophenone, methyl iodide, methyl vinyl ketone) was studied. Alkylation of compound 1 with diazo compounds and salt 10 with halocompounds results predominantly in O-alkylation products, 1-alkoxy-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 5,7-dioxides. The Michael reaction of compound 1 with methyl vinyl ketone involves the triazole nitrogen atom to give 1-(3-oxobutyl)-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 3,4,6-trioxide. The structures of the compounds synthesized were established by ¹H, ¹³C, ¹⁴N NMR spectroscopy and mass spectrometry.     

Novel and practical asymmetric synthesis of β2,3-amino esters using asymmetric Michael addition of chiral amine

A practical method for the synthesis of chiral β^2,3-amino esters having various substituents was developed, which is characterized by an asymmetric Michael addition reaction of a chiral lithium amide with trisubstituted (E)-α,β-unsaturated esters. We found that a highly face-selective protonation occurred by the quick addition of water to the enolate intermediate derived from the Michael addition reaction to afford N-protected β^2,3-amino esters in moderate to excellent yields. This finding was made possible by the facile preparation of geometrically pure trisubstituted (E)-α,β-unsaturated esters, which was established recently by our group. The subsequent deprotection of the amino group in the Michael adduct by using N-iodosuccinimide (NIS) efficiently provided β^2,3-amino esters having various substituents.     

Synthesis of functionalized chiral ammonium,imidazolium, and pyridinium-based ionic liquids derived from (−)-ephedrine using solvent-free microwave activation. Applications for the asymmetric Michael addition

An efficient procedure for the synthesis of functionalized chiral ammonium, imidazolium, and pyridinium-based ionic liquids derived from (1R, 2S)-ephedrine using solvent-free microwave activation has been described. Good yields were obtained in very short reaction time. These chiral ionic liquids were used as chiral reaction media for the asymmetric Michael addition, giving good yields and moderate enantioselectivities.     

Conversion of γ-bicyclic lactams to 4,5-dihydro-2H-pyridazin-3-ones

Bicyclic lactams are uniquely suited as precursors for the synthesis of chiral substituted 4,5-dihydro-2H-pyridazinones. This paper describes the development of a method for the direct conversion of unsubstituted and 4-substituted γ-bicyclic lactams to 4,5-dihydro-2H-pyridazin-3-ones and 2-phenyl-4,5-dihydro-2H-pyridazin-3-ones.     

Solution-phase parallel synthesis of new 2H-pyrimido-[4,5-e][1,2,4]triazin-3-ylidenecyanamides

A practical synthesis of 2H-pyrimido[4,5-e][1,2,4]triazin-3-ylidenecyanamides has been developed. The key step is the coupling reaction of an aryldiazonium salt with 1-cyano-3-(2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-ylamino)-2-methylisothiourea followed by intramolecular cyclization. A library of 2H-pyrimido[4,5-e][1,2,4]triazin-3-ylidenecyanamides was prepared in two steps from 6-aminouracils using this method.     

Chirality and conformational changes in 4,5-diaryltriphenylenes

Line-shape analysis of temperature dependent NMR spectra of several substituted 4,5-diphenyl-triphenylenes has been performed to determine the free energy of activation for rotation (ΔG_rot^*) of the phenyl groups. The rotational barrier (ΔG_rot^*) depends on the presence and position of substituents on the phenyl groups; it is the largest in compounds with ortho-substituents. The independent determined free energy of activation of racemization (ΔG_rac^*) is about equal to ΔG_rot^* in 4-phenyl-5-(3,5-dimethylphenyl)triphenylene, but in 4,5-bis-(3,5- dimethylphenyl) triphenylene ΔG_rac^* is much larger than ΔG_rot^*. It is concluded that the racemization does not occur via a process in which the phenyl groups remain parallel but via a molecular movement in which the phenyl groups turn around each other like cog wheels.     

Chiral sulfamide-catalyzed asymmetric Michael addition of protected 3-hydroxypropanal to β-nitrostyrenes

Organocatalytic asymmetric Michael addition of 3-(OTBS)-propanal to β-nitrostyrenes catalyzed by chiral sulfamides was investigated. Good d.r. (up to 80:20) and excellent enantioselectivities (up to >99% ee) were achieved. Both the N-[(1R,2R)-2-aminocyclohexyl]-N’-(phenylmethyl)sulfamide 7b and the novel chiral N-[(1R,2R)-2-aminocyclohexyl]-N’-[3,5-bis(trifluoromethyl)phenyl]sulfamide 7a were identified as efficient primary amine organocatalysts.     

Reactions of 4,5-diaminopyrazoles with chalcones and acetylarenes

Reaction of 3-methyl-1-(4-nitrophenyl)-4,5-diaminopyrazole with chalcones and acetylarenes gave 1H-2,3-dihydropyrazolo[4,5-b]-1,5-diazepines. The structure of one of these was confirmed by x-ray analysis. 3,5-Diphenyl- and 3-oxo-4,5-diaminopyrazoles did not take part in this reaction.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 506–510, April, 1992.     

O-(α-Phenylethyl)hydroxylamine as a ‘chiral ammonia equivalent’: synthesis and resolution of 5-oxopyrrolidine- and 6-oxopiperidine-3-carboxylic acids

An approach to the synthesis and resolution of five- and six-membered lactams (i.e., 5-oxopyrrolidine- and 6-oxopiperidine-3-carboxylic acids) is described. The method relies on the one-pot Michael reaction—cyclization of itaconic acid or diethyl homoitaconate and enantiopure O-(α-phenylethyl)hydroxylamine as a ‘chiral ammonia equivalent’. It is shown that this chiral auxiliary can be used for the separation of diastereomeric lactam products and then easily removed by catalytic hydrogenolysis.     

The first preparation of (1S,5R)-(−)- and (1R,5S)-(+)-7-phenyl-3-borabicyclo[3.3.1]non-6-enes and their application for synthesis of chiral cyclohexene derivatives

(1S,5R)-(−)- and (1R,5S)-(+)-7-phenyl-3-borabicyclo[3.3.1]non-6-enes of 97-98% de that differed only by the location of the double bond were prepared by the resolution of diastereomeric intramolecular chelates with l- and d-prolinol. Deboronation of chiral bicyclic boranes obtained was used for synthesis of optically active 3,5-dimethyl- and 3,5-dihydroxymethyl-1-phenylcyclohexenes.