Diastereoselective synthesis of 1-alkyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3′-(1′,2′,3′,4′-tetrahydroquinolines)

Knoevenagel products formed by the condensation of N-monoalkyl barbituric acids with o-tert-amino benzaldehydes undergo tert-amino effect reactions (T-reactions) yielding 1-alkyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3′-(1′,2′,3′,4′-tetrahydroquinoline) derivatives as a mixture of (S^∗,S^∗)- and (S^∗,R^∗)-diastereomers. Mostly, the major diastereomer has the S^∗,S^∗-configuration. According to X-ray diffraction data in the solid form and NOE data in solution, diastereoselectivity of the T-reactions can be associated with the structure of the Knoevenagel products whose conformation is fixed by the strong intramolecular C-H?π interaction.     

Synthesis of cyclic bis(3′-5′)diguanylic acid (c-di-GMP) analogs

This paper reports the synthesis of cyclic bis(3′-5′)diguanylic acid (c-di-GMP) analogs, including the monophosphorothioic acid of c-di-GMP (c-GpGps), cyclic bis(3′-5′)guanylic/adenylic acid (c-GpAp), and cyclic bis(3′-5′)guanylic/inosinic acid (c-GpIp). These compounds are expected to be important, both in elucidating the mechanism of bioactive c-di-GMP and in designing and creating new bioactive c-di-GMP-related artificial derivatives.     

Stereoselective synthesis of (1′S,3R,4R)-4-acetoxy-3-(2′-fluoro-1′-trimethylsilyloxyethyl)-2-azetidinone

A stereoselective synthesis of (1′S,3R,4R)-4-acetoxy-3-(2′-fluoro-1′-trimethylsilyloxyethyl)-2-azetidinone as a new fluorine-containing intermediate towards β-lactams, is described. The synthetic key step relies upon the dynamic kinetic resolution (DKR) of ethyl 2-benzamidomethyl-4-fluoro-3-oxo-butanoate via asymmetric transfer hydrogenation catalyzed by [Ru(η⁶-arene)(S,S)-R₂NSO₂DPEN].     

Novel four-component route to the synthesis of spiro[indoline-3,4′-pyridine]-3′-carboxylate derivatives

An effective route to spiro[indoline-3,4′-pyridine]-3′-carboxylate derivatives is described. This involves reaction of isatin, 1-phenyl-2-(1,1,1-triphenyl-λ⁵-phosphanylidene)-1-ethanone, and benzylamine derivatives or aliphatic amines in the presence of alkyl acetoacetate (1,3-dicarbonyl compounds) in dry methanol under reflux conditions. The reactive 1:1 enaminone, which is obtained from the addition of the amine to 1,3-dicarbonyl compound, adds to the α,β-unsaturated ketone, which is formed from the reaction of isatin and 1-phenyl-2-(1,1,1-triphenyl-λ⁵-phosphanylidene)-1-ethanone, to produce the alkyl 1′-benzyl-2′-methyl-2-oxo-6′-phenyl-1′H-spiro[indoline-3,4′-pyridine]-3′-carboxylate derivatives in excellent yields.     

Highly diastereoselective chemoenzymatic synthesis of (2′R)- and (2′S)-2′-deoxy[2′-H]guanosines

In an effort to develop an efficient synthetic method of highly diastereoselective (2′R)- and (2′S)-2′-deoxy[2′-²H]guanosines, chemoenzymatic conversion was investigated. The synthesis of (2′R > 98% de)-2′-deoxy[2′-²H]guanosine was achieved by biological transdeoxyribosylation using (2′R > 98% de)-2′-deoxy[2′-²H]uridine, 2,6-diaminopurine, and Enterobacter aerogenes AJ-11125, followed by treatment with adenosine deaminase. (2′S > 98% de)-2′-Deoxy[2′-²H]guanosine was synthesized from (2′S > 98% de)-2′-deoxy[2′-²H]uridine and 2,6-diaminopurine using thymidine phosphorylase and purine nucleoside phosphorylase instead of E. aerogenes AJ-11125.     

A regioselective three-component reaction for synthesis of novel 1′H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione derivatives

A ring opening and regioselective three-component reaction of isatoic anhydride, isatins, and aromatic or aliphatic primary amines in the presence of catalytic amount of KAl(SO₄)₂·12H₂O (alum) to yield a novel series of 1′H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione is described.     

Proton NMR study on two structures of 3′-O-(acetylimino)3′-de(phosphinico)-thymidylyl-(3,5′)-deoxythymidine in aqueous solution

The solution structure of one of dithymidine monophosphate (TpT) analogues, containing an (N-acetyl)imino backbone linkage (NCOCH₃) of 3′-O-(acetylimino)3′-de(phosphinico)-thymidylyl-(3,5′)-deoxythymidine (T_NT), has been determined by proton NMR. Two structures, designated as major and minor forms, in a ratio of about 3:2 coexist when the solution temperature is <25°C. Both forms adopt anti conformation with respect to the glycosidic bond, S-type deoxyribofuranose pucker, and have no base stacking. The backbone torsion angles ε′, φ_ON, φ_NC, and γ′ are trans, gauche⁺, gauche⁺, and gauche⁺ for the major form; and gauche⁻, gauche⁻, gauche⁻, and gauche⁺ for the minor form. Only major form is found at >25°C.     

Synthesis of dihydropyrazolo[3′,4′:3,4]pyrrolo[1,2-a]indoles and spiro-[3H-indole-3,3′-[Δ-1,2,4]-triazolin]-2-ones via intra and intermolecular 1,3-dipolar cycloadditions

A new class of dihydropyrazolo[3′,4′:3,4]pyrrolo[1,2-a]indoles and spiro[3H-indole-3,3′-[Δ²-1,2,4]-triazoline]-2-ones were synthesised via intra and intermolecular 1,3-dipolar cycloaddition reactions in good yields.     

Application and details of photoinduced oxidative cyclization of 5-(4′,9′-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-triones and related compounds

As novel methodology for synthesizing the furan ring, a photoinduced oxidative cyclization of 5-(4′,9′-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-triones (7a-c) and related compounds 9a-c was accomplished to give 5,10-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1,3H)-dionylium tetrafluoroborates (8a-c⁺·BF₄⁻) and related compounds 2a-c⁺·BF₄⁻, respectively. In the photoinduced oxidative cyclization, the molecular oxygen in air is used as oxidant and the reaction proceeds under mild conditions to give desired products without byproducts, and thus, it is interesting from the viewpoint of the green chemistry. On the reactions of the mono-substituted derivatives 7d,e and 9e,f, the selectivity of the photoinduced cyclizations were reversed as compared with those of the DDQ-promoted oxidative cyclizations. By the NMR monitoring of the reactions of 7a and deuterated compound 7a-D₂ under degassed conditions, the details of the reaction pathway were clarified and rationalized on the basis of the MO calculation by the 6-31G^∗ basis set of the MP2 levels as well.     

Efficient synthesis of the cyclopentanone fragrances (Z)-3-(2-oxopropyl)-2-(pent-2-en-1-yl)cyclopentanone and Magnolione

This paper describes the selective syntheses of two cis-isomer-enriched cyclopentanone fragrances: (Z)-3-(2-oxopropyl)-2-(pent-2-en-1-yl)cyclopentanone (four steps, 62% overall yield, 67% cis) and Magnolione^® (five steps, 60% overall yield, 55% cis). In addition, the asymmetric synthesis of (3aR,7aS)-5-methyl-2,3,3a,4,7,7a-hexahydro-1H-inden-1-one as well as (3a′R,7a′S)-5′-methyl-2′,3′,3a′,4′,7′,7a′-hexahydrospiro[[1,3]dioxolane-2,1′-indene] has been realized by an efficient kinetic resolution, which enables the selective synthesis of the 2S,3R-isomer-enriched 3 and 4.     

Synthesis of (3′R,5′S)-3′-hydroxycotinine using 1,3-dipolar cycloaddition of a nitrone

To synthesize (3′R,5′S)-3′-hydroxycotinine [(+)-1], the main metabolite of nicotine (2), cycloaddition of C-(3-pyridyl)nitrones 3a, 3c, and 15 with (2R)- and (2S)-N-(acryloyl)bornane-10,2-sultam [(2R)- and (2S)-8] was examined. Among them, l-gulose-derived nitrone 15 underwent stereoselective cycloaddition with (2S)-8 to afford cycloadduct 16, which was elaborated to (+)-1.     

Synthesis and optical properties of a poly(2′,5′-dioctyloxy-4,4′,4″- terphenylenevinylene) with high content of (Z) vinylene units

Poly(2′,5′-dioctyloxy-4,4′,4″-terphenylenevinylene) with (E) configuration of the vinylene double bonds was prepared by Suzuki-Miyaura polymerization of (E)-4,4′-dibromostilbene and 2,5-dioctyloxy-1,4-benzenediboronic acid. Attempts to extend this simple procedure to the synthesis of the polymer with (Z) configuration, starting from (Z)-4,4′-dibromostilbene, were unsuccessful. However, the use of (Z)-4,4′-diiodostilbene and a careful choice of Pd catalyst and experimental conditions, lead to a material with a >95/<5 (Z)/(E) ratio of vinylene units. The investigation of optical properties of both the (E) and (Z) polymers evidenced that (Z) linkages act as defects which reduce the effective conjugation length in the polymer backbone.     

New active ruthenium(II) complexes based N3,N3′-bis(diphenylphosphino)-2,2′-bipyridine-3,3′-diamine and P,P′-diphenylphosphinous acid-P,P′-[2,2′-bipyridine]-3,3′-diyl ester ligands for transfer hydrogenation of aromatic ketones by propan-2-ol

The dimeric starting material [Ru(η⁶-p-cymene)(μ-Cl)Cl]₂ reacts with N3,N3′-bis(diphenylphosphino)-2,2′-bipyridine-3,3′-diamine, 1 and P,P′-diphenylphosphinous acid-P,P′-[2,2′-bipyridine]-3,3′-diyl ester, 2 ligands to afford bridged dinuclear complexes [C₁₀H₆N₂{NHPPh₂-Ru(η⁶-p-cymene)Cl₂}₂], 3 and [C₁₀H₆N₂{OPPh₂-Ru(η⁶-p-cymene)Cl₂}₂], 4 in quantitative yields. These bis(aminophosphine) and bis(phosphinite) based Ru(II) complexes serve as active catalyst precursors for the transfer hydrogenation of acetophenone derivatives in 2-propanol and especially 4 acts as a good catalyst, giving the corresponding alcohols in 99% yield in 20 min (TOF ? 280 h⁻¹).     

Synthesis of a new bidentate ferrocenyl N-heterocyclic carbene ligand precursor and the palladium (II) complex trans-[PdCl2(CfcC)], where (CfcC) = 1,1′-di-tert-butyl-3,3′-(1,1′-dimethyleneferrocenyl)-diimidazol-2-ylidene

A new ferrocenyl-N-heterocyclic carbene ligand precursor 1,1′-bis[(1-tert-butylimidazolium)-3-methyl]ferrocene dichloride has been synthesised and structurally characterised. The imidazolium salt was readily deprotonated in situ with KN(SiMe₃)₂ and reacted with [PdCl₂ (cod)] to afford the structurally characterised palladium (II) complex trans-[PdCl₂(C^∧fc^∧C)], where (cod) = 1,5-cyclooctadiene and (C^∧fc^∧C) = 1,1′-di-tert-butyl-3,3′-(1,1′-dimethyleneferrocenyl)-diimidazol-2-ylidene.     

Interaction of 2-(2′,6′-dialkylphenylazo)-4-methylphenols with iridium. C-H activation and migration of alkyl group

Reaction of 2-(2′,6′-diethylphenylazo)-4-methylphenol (L²) with [Ir(PPh₃)₃Cl] afforded two organoiridium complexes 3 and 4 via C-H bond activation of an ethyl group in the arylazo fragment of the L² ligand. In both the complexes the azo ligand binds to iridium as a dianionic tridentate C,N,O-donor. Two triphenylphosphines and a hydride (in the case of complex 3) or chloride (in the case of complex 4) are also coordinated to the metal center. A similar reaction of [Ir(PPh₃)₃Cl] with 2-(2′,6′-diisopropylphenylazo)-4-methylphenol (L³) yielded another organoiridium complex 5, where migration of one iso-propyl group from its original location (say, the 2′ position) to the corresponding third position (say, the 4′ position) took place through C-C bond activation. In this complex the modified azo ligand binds to iridium as a dianionic tridentate C,N,O-donor. Two triphenylphosphines and a hydride are also coordinated to the metal center. The structures of complexes 3 and 4 have been optimized through DFT calculations. The structure of complex 5 has been determined by X-ray crystallography. All the complexes show characteristic ¹H NMR signals and intense transitions in the visible region. Cyclic voltammetry on all the complexes shows an oxidation within 0.66-1.10 V vs SCE, followed by a second oxidation within 1.15-1.33 V vs SCE and a reduction within −0.96 to −1.07 V vs SCE.     

A simple synthesis of the pentacyclic lamellarin skeleton from 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1-methyl(benzyl)-3,4-dihydroisoquinolines

The basic structural framework of lamellarin alkaloids, 8,9-dihydro-6H-chromeno[4′,3′:4,5]pyrrolo[2,1-a]isoquinoline derivatives, has been obtained in good yields via Grob synthesis between 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1-methyl-3,4-dihydroisoquinolines in refluxing isobutanol. In the case of 1-benzyl-3,4-dihydroisoquinolines, a dynamic NMR effect was observed in the ¹H and ¹⁹F NMR spectra of the products as a result of restricted rotation about the single bond linking the benzene ring and the heterocyclic system. When the reaction was carried out with 3-nitro-2-(trichloromethyl)-2H-chromenes in toluene at room temperature, only Michael adducts, as a mixture of two diastereomers, were isolated.     

Synthesis and characterization of novel poly(2-methoxy-(5-(6′-dimethylphosphonate)-hexyloxy)-1,4-phenylenevinylene-ran-2-methoxy-5-(2′-ethylhexyloxy)-1,4-phenylenevinylene)s (MEH-PO-PPVs) and their tunable emission colors

Poly(2-methoxy-(5-(6′-dimethylphosphonate)-hexyloxy)-1,4-phenylenevinylene-ran-2-methoxy-5-(2′-ethylhexyloxy)-1,4-phenylenevinylene) (MEH-PO-PPV) was synthesized via Heck coupling reaction of MPOHOB-2Br (1) (1-methoxy-(4-(6-dimethylphosphonate)-hexyloxy)-2,5-dibromobenzene), MEHOB-2Br (2) (1-methoxy-4-(6-bromohexyloxy)-2,5-dibromobenzene), and MEHOB-DV (4) (1-methoxy-4-(2′-ethylhexyloxy)-2,5-divinylbenzene) by varying the molar ratios of monomers. The monomers and their intermediates were characterized by ¹H NMR, FT-IR, and melting point and elemental analyzer, and subsequent polymers by FT-IR, ¹H NMR, GPC, DSC, TGA, and solubility test. The optical (UV-vis, PL) and electrical properties (CV) of polymers were also evaluated. MEH-PO-PPV, containing phosphine oxide groups, exhibited better solubility, lower HOMO and LUMO levels, and larger band gaps. In addition, the PL emission gradually shifted to shorter wavelength, providing 570 (MEH-10PO-PPV), 519 (MEH-30PO-PPV), and of 465 nm (MEH-50PO-PPV) as the PO content increased, compared with 598 nm (MEH-PPV).     

Synergistic liquid-liquid extractive spectrophotometric determination of gold(III) using 1-(2′,4′-dinitro aminophenyl)-4,4,6-trimethyl-1,4-dihydropyrimidine-2-thiol

Synergistic liquid-liquid extractive spectrophotometric determination of gold(III) using 1-(2′,4′-dinitro aminophenyl)-4,4,6-trimethyl-1,4-dihydro pyrimidine-2-thiol [2′,4′-dinitro APTPT] has been described. Equal volumes (5 cm³) of the 2′,4′-dinitro APTPT (0.02 mol L⁻¹) in the presence of pyridine (0.5 mol L⁻¹) form an orange-red coloured ternary complex with gold(III) of molar ratio 1:1:1 at pH 1.8-2.4 with 5 min of shaking. The absorbance of coloured organic layer in 1,2-dichloroethane is measured spectrophotometrically at 445 nm against reagent blank. A pronounced synergism has been observed by the binary mixture of 2′,4′-dinitro APTPT and pyridine, which shows that the enhancement in the absorbance is observed in the presence of pyridine by the adduct formation in the organic phase. Beer's law was obeyed in the concentration range 2.5-20.0 μg mL⁻¹, with molar absorptivity and Sandell's sensitivity values of 8.7 × 10³ dm³ mol⁻¹ cm⁻¹ and 0.023 μg cm⁻² respectively. A repetition of the method was checked by finding relative standard deviation (R.S.D.) (n = 10) which was 0.17%. The composition of the gold(III)-2′,4′-dinitro APTPT-pyridine adduct was established by slope analysis, molar ratio and Job's method. The ternary complex was stable for more than 48 h. The influence of various factors such as pH, 2′,4′-dinitro APTPT concentration, solvent and pyridine on the degree of complexation has been established. A number of foreign ions tested for their interferences and use of suitable masking agents wherever necessary are tabulated, which show that selectivity of the method has been enhanced. The method is successfully employed for the determination of gold(III) in binary, synthetic mixtures and ayurvedic samples. The reliability of the method is assured by inter-comparison of experimental values, using an atomic absorption spectrometer.     

Enantioselective total synthesis of (2R,3R,6R)-N-methyl-6-(deca-1′,3′,5′-trienyl)-3-methoxy-2-methylpiperidine, an insecticidal alkaloid

An insecticidal piperidine alkaloid, (2R,3R,6R)-N-methyl-6-(deca-1′,3′,5′-trienyl)-3-methoxy-2-methylpiperidine, was efficiently synthesized in a stereoselective manner starting from d-alanine. Chiral center at C-6 was controlled by hydrogenation of imine and side chain was introduced by Julia olefination. The absolute configuration of natural product was determined to be 2R, 3R, 6R.     

Reaction of 1-substituted 3-aminoquinoline-2,4-diones with isothiocyanates. An easy pathway to generate novel 2-thioxo-1′H-spiro[imidazoline-5,3′-indole]-2,2′-diones

3-Butyl-3-amino-1H,3H-quinoline-2,4-diones react with isothiocyanates to give novel 3a-butyl-9b-hydroxy-2-thioxo-1,2,3,3a,5,9b-hexahydro-imidazo[4,5-c]quinolin-2-ones in high yields. These compounds rearrange in boiling acetic acid or concd hydrochloric acid to give (E)- and/or (Z)-4-butylidene-2-thioxo-1′H-spiro[imidazoline-5,3′-indole]-2,2′-diones. All compounds were characterized by their ¹H, ¹³C, IR and MS spectra, and some of them also by ¹⁵N NMR. The structure of one compound was investigated by single-crystal X-ray diffraction.