Silicon-carbon unsaturated compounds. 73. Photolysis of cis- and trans-1,2-dimethyl-1,2-diphenyl-1,2-disilacyclohexane in the presence of tert-butyl alcohol and acetone

Irradiation of cis-1,2-dimethyl-1,2-diphenyl-1,2-disilacyclohexane (1a) in the presence of tert-butyl alcohol in hexane with a low-pressure mercury lamp bearing a Vycor filter proceeded with high stereospecificity to give cis-2,3-benzo-1-tert-butoxy-1,4-dimethyl-4-phenyl-1,4-disilacyclooct-2-ene (2a), in 33% isolated yield, together with a 15% yield of 1-[(tert-butoxy)methylphenylsilyl]-4-(methylphenylsilyl)butane (3). The photolysis of trans-1,2-dimethyl-1,2-diphenyl-1,2-disilacyclohexane (1b) with tert-butyl alcohol under the same conditions gave stereospecifically trans-2,3-benzo-1-tert-butoxy-1,4-dimethyl-4-phenyl-1,4-disilacyclooct-2-ene (2b) in 41% isolated yield, along with a 12% yield of 3. Similar photolysis of 1a and 1b with tert-butyl alcohol-d₁ produced 2a and 2b, respectively, in addition to 1-[(tert-butoxy)(monodeuteriomethyl)(phenyl)silyl]-4-(methylphenylsilyl)butane. When 1a and 1b were photolyzed with acetone in a hexane solution, cis- and trans-2,3-benzo-1-isopropoxy-1,4-dimethyl-4-phenyl-1,4-disilacyclooct-2-ene (4a and 4b) were obtained in 25% and 23% isolated yield. In both photolyses, 1-(hydroxymethylphenylsilyl)-4-(methylphenylsilyl)butane (5) was also isolated in 4% and 5% yield, respectively. The photolysis of 1a with acetone-d₆ under the same conditions gave 4a-d₆ and 5-d₁ in 18% and 4% yields.     

Synthesis of new tetracyclic 7-oxo-pyrido[3,2,1-de]acridine derivatives

A series of (±)3-hydroxyl- and 2,3-dihydroxy-2,3-dihydro-7-oxopyrido[3,2,1-de]acridines were synthesized for antitumor evaluation. These agents can be considered as analogues of glyfoline or (±)1,2-dihydroxyacronycine derivatives. The key intermediates, 3,7-dioxopyrido[3,2,1-de]acridines (15a,b or 24a,b), for constructing the target compounds were synthesized either from 3-(N,N-diphenylamino)propionic acid (14a,b) by treating with Eaton’s reagent (P₂O₅/MsOH) (Method 1) or from (9-oxo-9H-acridin-10-yl)propionic acid (23a-c) via ring cyclization under the same reaction conditions (Method 2). Compounds 15a,b and 24a,b were converted into (±)3-hydroxy derivatives (25a-d), which were then further transformed into pyrido[3,2,1-de]acridin-7-one (28a-d) by treating with methanesulfonic anhydride in pyridine via dehydration. 1,2-Dihydroxylation of 28a-d afforded (±)cis-2,3-dihydroxy-7-oxopyrido[3,2,1-de]acridine (29a-d). Derivatives of (±)3-hydroxy (25a,b) and (±)cis-2,3-dihydroxy (29a-d) were further converted into their O-acetyl congeners 26a,b and 30a-d, respectively. We also synthesized 2,3-cyclic carbonate (31, 32, and 33) from 29a-c. The anti-proliferative study revealed that these agents exhibited low cytotoxicity in inhibiting human lymphoblastic leukemia CCRF-CEM cell growth in culture.     

Stereochemical substituent effects: investigation of the cyano, amide and carboxylate group

Three pairs of diastereomeric piperidines, cis- and trans-2-methylpiperidine-3-carboxylate (6a and 6b), cis- and trans-2-methylpiperidine-3-carboxylamide (9a and 9b) and cis- and trans-2-methyl-3-cyanopiperidine (11a and 11b), were synthesised for the purpose of investigating the effect of the axial versus equatorial carboxylate, carboxamide and cyano group on piperidine base strength. The pK_a values of the six compounds were determined to be 11.0 (6a), 10.4 (6b), 9.5 (9a), 9.3 (9b), 7.8 (11a) and 8.0 (11b). This shows that the strong electron-withdrawing effect of the cyano group and the effect of the amide group are relatively independent of spacial orientation. The carboxylate, on the other hand is considerably less electron-withdrawing when axial.     

Synthesis and structure of highly substituted pyrazole ligands and their complexes with platinum(II) and palladium(II) metal ions

Reaction of 3-methoxycarbonyl-2-methyl- or 3-dimethoxyphosphoryl-2-methyl-substituted 4-oxo-4H-chromones 1 with N-methylhydrazine resulted in the formation of isomeric, highly substituted pyrazoles 4 (major products) and 5 (minor products). Intramolecular transesterification of 4 and 5 under basic conditions led, respectively, to tricyclic derivatives 7 and 8. The structures of pyrazoles 4a (dimethyl 2-methyl-4-oxo-4H-chromen-3-yl-phosphonate) and 4b (methyl 4-oxo-2-methyl-4H-chromene-3-carboxylate) were confirmed by X-ray crystallography. Pyrazoles 4a and 4b were used as ligands (L) in the formation of ML₂Cl₂ complexes with platinum(II) or palladium(II) metal ions (M). Potassium tetrachloroplatinate(II), used as the metal ion reagent, gave both trans-[Pt(4a)₂Cl₂] and cis-[Pt(4a)₂Cl₂], complexes with ligand 4a, and only cis-[Pt(4b)₂Cl₂] isomer with ligand 4b. Palladium complexes were obtained by the reaction of bis(benzonitrile)dichloropalladium(II) with the test ligands. trans-[Pd(4a)₂Cl₂] and trans-[Pd(4b)₂Cl₂] were the exclusive products of these reactions. The structures of all the complexes were confirmed by IR, ¹H NMR and FAB MS spectral analysis, elemental analysis and Kurnakov tests.     

Novel rhenium oxocomplexes of indazole-3-carboxylic acid – Synthesis,X-ray studies,spectroscopic characterization and DFT calculations

Three novel rhenium oxocomplexes incorporating indazole-3-carboxylate ligand: cis-[ReOCl₂(Ind-3-COO)(PPh₃)]·OPPh₃ (1a), cis-[ReOCl₂(Ind-3-COO)(PPh₃)] (1b) and cis-[ReOBr₂(Ind-3-COO)(PPh₃)]·OPPh₃ (2) have been synthesized and characterised spectroscopically and structurally (by single-crystal X-ray diffraction). The 1a and 2 are isostructural in solid state. The electronic spectrum of 1a was investigated at the TDDFT level employing B3LYP functional in combination with LANL2DZ. Additional information about binding in the complex 1a was obtained by NBO analysis.     

Pyrrolide-imine benzyl complexes of zirconium and hafnium: synthesis, structures, and efficient ethylene polymerization catalysis

A series of pyrrolyl-imines HL^1-6 was prepared by the condensation of pyrrole-2-carboxyaldehyde with different amines. The reaction of 2 equiv of pyrrolyl-imine with tetrabenzyl complexes of hafnium and zirconium M(CH₂Ph)₄ (M=Hf or Zr) gave dibenzyl complexes (L^3-6)₂M(CH₂Ph)₂, which were characterized by NMR spectroscopy and crystal structure analysis. NMR spectra of the complexes with secondary alkyl substituents at the imine nitrogen (isopropyl: 3a, 4-tert-butylcyclohexyl: 4a and 4b) suggest that rapid racemization between Δ and Λ configurations occurs in solution on the NMR time scale. The complexes with pyrrolide-imine ligands with a tertiary alkyl group such as tert-butyl (5a and 5b) or 1-adamantyl (6a and 6b) at the imine nitrogen possess cis-configured benzyl groups. Hafnium complexes 5a and 6a react with B(C₆F₅)₃ in bromobenzene-d₅ to give the corresponding cationic benzyl complexes, which exhibit high activity for ethylene polymerization (5a: 2242 kg-polymer/ mol-Hf h bar, 6a: 2096 kg-polymer/ mol-Hf h bar). Zirconium complexes 5b and 6b display a remarkably high ethylene polymerization activity when activated with methylaluminoxane (5b: 17,952 kg-polymer/mol-Zr h bar, 6b: 22,944 kg-polymer/mol-Zr h bar).     

C11H12 Hydrocarbons—II : Preparation of tricyclo[5.4.0.0]undeca-3,8,10-triene a norbornenone route from cycloheptatriene

A stereoselective 6-step synthesis of the C₁₁H₁₂ hydrocarbon cis,anti,cis-tricyclo[5.4.0.0^2,5]undeca-3,8,10-triene (2a) is described. The dichloro compound 3c was prepared by the selective reduction of 3a with chromous perchlorate-ethylenediamine complex, a general reagent for this type of transformation. Irradiation of 3c produced 6a and 7a in ∼ 7:1 ratio. Reduction of the mixture with sodium produced ketal mixture 6b and 7b. The ketals were hydrolyzed to ketones 6c and 7c and the ketones decarbonylated to 2a and an isomeric hydrocarbon tentatively assigned as homobasketene 2b′. Hydrocarbon 2a was readily obtained pure by a silver nitrate extraction procedure and 2b′ by preparative VPC. It was shown that pure 6c gives only 2a and therefore, 7c is the source of 2b′. The stereochemical assignments, based on both spectral and chemical evidence, are discussed.     

Synthesis of new bicyclic lactam peptidomimetics by ring-closing metathesis reactions

An efficient and versatile synthetic method for the preparation of new fused bicyclic lactams 3a and 3b is described. The spirane cyclopentane nucleus was easily installed by diallylation of the pyroglutamate derivative 18 followed by ring-closing metathesis (RCM). A more practical and stereoselective method for the allylation of the α-methoxy carbamate 21, involving the use of InCl₃ as a Lewis acid, was developed. In the crucial coupling reaction of the diastereomeric mixture of cis- and trans-pirrolidine derivatives 5a and 5b with N-Cbz vinyl phenylalanine only the cis isomer was found to react. An RCM reaction on the dipeptides 25a and 25b followed by catalytic hydrogenation, gave the final epimeric bicyclic lactams 3a and 3b. The same synthetic sequence on the model compound 7, lacking the spiro cyclopentane nucleus, is also reported.     

A new class of azobenzene chelators for Mg and Ca in buffer at physiological pH

A new class of azobenzene-based chelators, trans-3a and trans-3b (3a and 3b), were designed and synthesized in two steps. Both 3a and 3b were readily dissolved in a buffer solution at physiological pH. The values of the dissociation constant of 3a and 3b for Mg²⁺ and Ca²⁺ were determined by the Hills plot; K_d^Mg=1.12 mM and K_d^Ca=660 μM for 3a and K_d^Mg=158 μM and K_d^Ca=200 μM for 3b, respectively. On irradiation at 489 nm light, 3a isomerized to give cis-form, which underwent cis-to-trans thermal isomerization in darkness at room temperature. The change in the absorption spectrum of the irradiated solution of 3a in the presence of Mg²⁺, showing the cis-to-trans thermal isomerization, indicates that the affinity of cis-3a for Mg²⁺ is lower than that of 3a.     

Synthesis of procyanidins by stepwise- and self-condensation using 3,4-cis-4-acetoxy-3-O-acetyl-4-dehydro-5,7,3′,4′-tetra-O-benzyl-(+)-catechin and (−)-epicatechin as a key building monomer

3,4-cis-4-Acetoxy-3-O-acetyl-4-dehydro-5,7,3′,4′-tetra-O-benzyl-(+)-catechin (1a) or (−)-epicatechin (1b) reacted high regio- and stereo-selectively with 1.5 equiv of the 5,7,3′,4′-tetra-O-benzyloxyflavan-3-ol (4a or 4b) in the presence of 1 equiv of TMSOTf to give the corresponding procyanidins. On the other hand, the self-condensation of 1a in the presence of a catalytic amount of B(C₆F₅)₃ afforded wide-range procyanidins from dimer to 15-mer like a biomass.     

Synthesis and molecular structures of dinuclear complexes with 1,2-dihydro-1,2-diphenyl-naphtho[1,8-c,d]1,2-diphosphole as a bridging ligand

A bisphosphine in which a PhP-PPh bond bridges 1,8-positions of naphthalene, 1,2-dihydro-1,2-diphenyl-naphtho[1,8-cd]-1,2-diphosphole (1), was used as a bridging ligand for the preparation of dinuclear group 6 metal complexes. Free trans-1, a more stable isomer having two phenyl groups on phosphorus centers mutually trans with respect to a naphthalene plane, was allowed to react with two equivalents of M(CO)₅(thf) (M = W, Mo, Cr) at room temperature to give dinuclear complexes (OC)₅M(μ-trans-1)M(CO)₅ (M = W (2a), Mo (2b), Cr (2c)). The preparation of the corresponding dinuclear complexes bridged by the cis isomer of 1 was also carried out starting from the free trans-1 in the following way. Mono-nuclear complexes M(trans-1)(CO)₅ (M = W (3a), Mo (3b), Cr (3c)) which had been prepared by a reaction of trans-1 with one equivalent of the corresponding M(CO)₅(thf) (M = W, Mo, Cr) complex, were heated in toluene, wherein a part of the trans-3a-c was converted to their respective cis isomer M(cis-1)(CO)₅. Each cis trans mixture of the mono-nuclear complexes 3a-c was treated with the corresponding M(CO)₅(thf) to give a cis trans mixture of the respective dinuclear complexes 2a-c. The cis isomer of the ditungsten complex 2a was isolated, and its molecular structure was confirmed by X-ray analysis, showing a shorter W?W distance of 5.1661(3) Å than that of 5.8317(2) Å in trans-2a.     

The investigation of stereogenic properties of cyclotriphosphazene derivatives with two different chiral centres

Hexachlorocyclotriphosphazene N₃P₃Cl₆ and gem-disubstituted cyclotriphosphazene derivatives N₃P₃Cl₄X₂ (X = Ph, PhS, PhNH) were reacted with N-methyl-1,3-propanediamine and 3-amino-1-propanol to give compounds (9a-12a, 9b-12b) which exist as cis and trans geometric isomers and are two different racemic isomers, respectively to describe the stereogenic properties of a series of chiral cyclotriphosphazene compounds with two different centres of chirality. The geometric isomers were separated by column chromatography on silica gel and analysed by elemental analysis, mass spectrometry, and ³¹P and ¹H NMR spectroscopies, and also the geometric forms (cis or trans) of 9b, 10a, 11a, 11b and 12a have been determined by the X-ray crystallography. The enantiomers of all racemic compounds have been analysed by the changes in ³¹P NMR spectra on addition of a Chiral Solvating Agent (CSA), (R)-(+)-2,2,2-trifluoro-1-(9′-anthryl)ethanol. On the other hand, the racemic forms of chiral cyclotriphosphazene derivatives have been confirmed by contribution of chiral HPLC methods which have been developed for this study.     

Using ligand exchange reactions to control the coordination environment of Pt(II) acetylide complexes: applications to conjugated metallacyclynes

Ligand exchange of cis-bis(diphenylphosphino)ethylene (dppee) with trans-(Ph₃P)₂Pt(CCR)₂ easily generates the cis-complexes (dppee)Pt(CCR)₂ in 64-95% yield. This transformation is used to convert pyridine-containing macrocycle 7 to its cis-analogue 8 and the macrocyclic bipyridine analogue 10 to the unique macrocyclic ligand 11. X-ray structural characterization of trans-complexes 5a and 5b and cis-complexes 6a and 6b are reported, as is the structure of the strained macrocycle 8.     

Stereoselective synthesis of (−)-diospongins A and B and their stereoisomers at C-5

Antiosteoporotic diarylheptanoids (−)-diospongins A (1) and B (2) were synthesized stereoselectively. The key steps in the synthesis include a stereospecific Pd^II-catalyzed cyclization of chiral 1,5,7-trihydroxy-2-heptenes, 6a and 6b, to form cis and trans tetrahydropyran rings and a regioselective Wacker oxidation of β-(tetrahydro-2H-pyran-2-yl)styrenes, 5a and 5b. Their C-5 epimers 3 and 4 were also synthesized.     

Phosphorus–nitrogen compounds: Part 19. Syntheses,structural and electrochemical investigations,biological activities,and DNA interactions of new spirocyclic monoferrocenylcyclotriphosphazenes

The reactions of hexachlorocyclotriphosphazatriene, N₃P₃Cl₆, with N-alkyl-N-ferrocenylmethylethylene diamines, FcCH₂NH(CH₂)₂NHR₁ [R₁ = Me (1) and Et (2)], and sodium [3-(N-ferrocenylmethylamino)-1-propanoxide] (3) produce spirocyclic monoferrocenyl tetrachlorophosphazenes (1a–3a). The tetrapyrrolidinophosphazenes (1b–3b) are prepared from the reactions of corresponding phosphazenes (1a–3a) with excess pyrrolidine. The reaction of 1a with excess morpholine affords geminal-morpholino phosphazene (1c), whilst the reactions of 2a and 3a give diethylaminotrimorpholino (2c) and fully substituted morpholino products (3c), respectively. The structural investigations of the compounds are examined by Fourier transform IR, MS, ¹H, ¹³C, ³¹P NMR, DEPT, HETCOR, and HMBC techniques. The crystal structures of 3b and 3c are determined using X-ray crystallography. Cyclic voltammetric and chronoamperometric data show that compounds 1a–3a, 1b–3b, and 1c–3c exhibit electrochemically reversible one-electron oxidation of Fc redox centers which are hardly affected by the substituents on the phosphazene ring. The compounds 1b, 2b, 3b, and 3c are screened for antibacterial activities against Gram-positive and Gram-negative bacteria and for antifungal activities against yeast strains. In addition, the antituberculosis activities (in vitro) of these compounds are evaluated against INH-susceptible reference strain M. tuberculosis H37Rv, and six multi-drug resistant clinical M. tuberculosis isolates. Compound 2b is found to be the most active against the susceptible the reference strain. In addition, 1b, 2b, and 3c are active against all the multidrug-resistant clinical isolates at the highest concentrations. Gel electrophoresis data indicate that the compounds promote the formation of strand breaks in plasmid DNA. Almost all the concentrations lost of supercoiled DNA suggests that the compound 3b is very efficient plasmid-modifier. The compounds inhibit BamHI cleavage of pUC18 DNA while restricting HindIII.     

Steric promotion in the cycloplatination of primary amines

The reactions of primary amines (S)-(−)-α-methylbenzylamine (1a) and (R)-(+)-1-(1-naphthyl)ethylamine (1b) with cis-[PtCl₂(dmso)₂] in the presence of Na(CH₃CO₂) carried out in refluxing toluene–methanol mixtures produced cyclometallated compounds [PtCl{NH₂CH(CH₃)C₆H₄}{SOMe₂}] (2a) and [PtCl{NH₂CH(CH₃)C₁₀H₆}{SOMe₂}] (2b) in moderate and quantitative yields, respectively. Compound 2b was also obtained at room temperature, in the absence of Na(CH₃CO₂). The reactions of 2a and 2b with phosphines were studied. The obtained compounds were fully characterized and the factors that facilitate cycloplatination of primary amines are discussed.     

An efficient approach to the synthesis of tri-substituted iminothiazolidenes and their effects on the human neuroblastoma cell line

Starting from cis-oriented epoxytriflate pentoses 1 and 4, an expeditious route to the chiral thioazolidene derivatives 2a-3a and 5a-6a in good yields is described. A minor amount of structural isomers 2b-3b and 5b-6b has also been observed. The newly formed compounds show activity against the human neuroblastoma cell line SK-N-LO.     

Effect of ortho-substituents on the stereochemistry of 2-(o-substituted phenyl)-1H-imidazoline-palladium complexes

Palladium complexes composed of [Pd(Ln)₂Cl₂] (n = 1, 2, 3, 4, 6), [L5a]₂[PdCl₄] and [Pd(L5b)₂], where L1 = 4,5-dihydro-2-phenyl-1H-imidazole (=2-phenyl-1H-imidazoline), L2 = 2-(o-fluorophenyl)-1H-imidazoline, L3 = 2-(o-methylphenyl)-1H-imidazoline, L4 = 2-(o-tert-butylphenyl)-1H-imidazoline, L5a = 2-(o-hydroxyphenyl)-1H-imidazolinium, L5b = 2-(1H-imidazolin-2-yl)phenolate, and L6 = 2-(o-methylphenyl)-1H-imidazole, were synthesized. Molecular structures of the isolated palladium complexes were characterized by single crystal X-ray diffraction analysis. The effect of ortho-substituents on the phenyl ring on trans-chlorine geometry was noted for complexes [Pd(L1)₂Cl₂] 1a and 1b, [Pd(L2)₂Cl₂] 2 and [Pd(L6)₂Cl₂] 6, whereas cis-chlorine geometry was observed for [Pd(L3)₂Cl₂] 3 and [Pd(L4)₂Cl₂] 4. PdCl₂ reacts with 2-(o-hydroxyphenyl)-1H-imidazoline in DMF to give [L5a]⁺ and [L5b]^- so that [L5a]₂[PdCl₄] 5a and [Pd(L5b)₂] 5b were obtained. In complex 5b, as an N,O-bidentate ligand, two ligands L5b coordinated with the central Pd(II) ion in the trans-form. The coordination of PdCl₂ with 2-(o-hydroxyphenyl)-1H-imidazolines in solution was investigated by NMR spectroscopy.     

Synthesis and evaluation of new chiral diols based on the dicyclopentadiene skeleton

The resolution by Lipase PS of rac-5 (from reduction of ketone 6, obtained from dicyclopentadiene with a new environment-friendly synthesis) gives (2S)-5, which was further reduced to the endo(2R)-1a alcohol. The endo(2S)-1b alcohol was obtained from camphor with a multistep synthesis. Pinacol couplings of 3a,b, carried out with Mg/Hg or Corey's general procedure respectively, afforded with high diastereoselectivity the C₂ symmetry diols (2R,2′R)-2a and (2S,2′S)-2b, with endo oriented OH functions. The enantiogenic power of the endo alcohol (2R)-1a and (2S)-1b and of the diols (2R,2′R)-2a and (2S,2′S)-2b was tested towards the LiAlH₄ reduction of acetophenone. The C₂ symmetry appears to play a fundamental role.     

Synthesis and reactivity of new functionalized Pd(II) cyclometallated complexes with boronic esters

Treatment of the functionalized Schiff base ligands with boronic esters 1a, 1b, 1c and 1d with palladium (II) acetate in toluene gave the polynuclear cyclometallated complexes 2a, 2b, 2c and 2d, respectively, as air-stable solids, with the ligand as a terdentate [C,N,O] moiety after deprotonation of the -OH group. Reaction of 1j with palladium (II) acetate in toluene gave the dinuclear cyclometallated complex 5j. Reaction of the cyclometallated complexes with triphenylphosphine gave the mononuclear species 3a, 3b, 3c, 3d and 6j with cleavage of the polynuclear structure. Treatment of 2c with the diphosphine Ph₂PC₅H₄FeC₅H₄PPh₂ (dppf) in 1:2 molar ratio gave the dinuclear cyclometallated complex 4c as an air-stable solid.Deprotection of the boronic ester can be easily achieved; thus, by stirring the cyclometallated complex 3a in a mixture of acetone/water, 3e is obtained in good yield. Reaction of the tetrameric complex 2a with cis-1,2-cyclopentanediol in chloroform gave complex 2c after a transesterification reaction. Under similar conditions complexes 3a and 3d behaved similarly: with cis-1,2-cyclopentanediol, pinacol or diethanolamine complexes 3c, 3b, 3g and 3f, were obtained. The pinacol derivatives 3b and 3g experiment the Petasis reaction with glyoxylic acid and morpholine in dichloromethane to give complexes 3h, and 3i, respectively.