Synthesis, stereochemical and conformational properties of trans-2,3-dihydro-2-methyl-3-(1,2,4-triazolyl)-4H-1-benzopyran-4-one oxime ethers

A convenient synthesis and structural characterization of (Z)- and (E)-trans-2,3-dihydro-2-methyl-3-(1,2,4-triazolyl)-4H-1-benzopyran-4-one oxime ethers has been achieved. By analysis of vicinal interproton coupling constants, it is believed that trans-2,3-dihydro-2-methyl-3-(1,2,4-triazolyl)-4H-1-benzopyran-4-ones which exist predominantly in the diequatorial half-chair or sofa conformation was found to exist predominantly in the diaxial orientation upon conversion to the corresponding oxime ether derivatives.     

Synthesis of alkyl 4-alkyl-2-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylates as peptidomimetic building blocks

A general synthesis of new alkyl 4-alkyl-2-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate peptidomimetic building blocks from the corresponding alkyl 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylates through carbanion oxidation is described.     

Selective syntheses of benzoxazoles and N-(2-hydroxyaryl)pyrrolidin-2-ones from the corresponding cyclopropyl amides with PPh3/CX4

Benzoxazoles 2 can be smoothly synthesized by treatment of starting materials of N-(2-hydroxyaryl) cyclopropyl amides 1 with PPh₃/CCl₄ in acetonitrile in good yields. When PPh₃/CBr₄/MS 4 Å was used in the reaction system, the corresponding ring-expanding products 3 were obtained in moderate to good yields in acetonitrile at 80 °C. Using DCE as a solvent in this reaction, the corresponding 2-(3-chloropropyl)benzoxazoles 5 were obtained as major products.     

Facile stereoselective synthesis of cis- and trans-3-alkoxyazetidin-2-ones

A highly stereoselective synthesis of cis- and trans-3-alkoxy-3-phenyl/benzylthioazetidin-2-ones is described. The reaction of α-chlorosulfide-β-lactams with various alcohols catalyzed by a Lewis acid such as ZnCl₂ in the presence of molecular sieves (3-4 Å) leads to cis-3-alkoxy-3-phenyl/benzylthio-β-lactams whereas treatment of potassium 2-alkoxy-2-phenylthioethanoate with appropriate Schiff's base using POCl₃ in the presence of triethylamine leads to the formation of trans-3-alkoxy-3-phenylthioazetidin-2-ones as major products.     

Synthesis and reactivity of trans-2-aryl-3-chloroazetidines

Several trans-2-aryl-3-chloroazetidines were synthesized in a stereoselective way by reduction of the corresponding β-lactams, which were formed by a Staudinger reaction using different benzaldimines and chloroketene. The resulting chloroazetidines proved to be excellent building blocks for the synthesis of different 3-substituted azetidines through nucleophilic substitution of the chlorine by different carbon, nitrogen, sulfur and oxygen nucleophiles in good to high yields. Since these substitution reactions took place with retention of stereochemistry, the intermediacy of bicyclic azonio[1.1.0]bicyclobutanes is proposed.     

Stereoselective synthesis of CF3-substituted trans- and cis-enediynes via carbocupration or hydrostannation reactions of CF3-containing diyne

CF₃-containing diyne, readily prepared from (Z)-2,3,3,3-tetrafluoro-1-iodoprop-1-ene in two steps, was smoothly subjected to carbocupration reaction with various organocuprates, followed by treatment of the resultant carbocupration adducts with iodine, the corresponding vinyl iodides being formed in good yields in a cis-addition manner. Thus obtained iodide could be successfully converted into CF₃-substituted trans-enediynes in high yields. Also, hydrostannation reaction of the diyne proceeded well in a trans-addition manner to give the corresponding vinylstannane in high yield. The vinylstannane was also found to be effectively convertible to CF₃-substituted cis-enediynes in high yields.     

New stereoselective syntheses of cis- and trans-2-methyl-4-arylpiperidines

A stereoselective approach has been developed for the synthesis of cis- and trans-2-methyl-4-arylpiperidines from a common intermediate. The Ni-catalyzed hydrogenolysis of N-Boc-2-methyl-4-aryl-4-piperidinols, obtained by addition of organometallic reagents on N-Boc-2-methyl-4-piperidone, afforded the trans derivatives with up to 95% selectivity whereas the corresponding cis isomers were obtained in the presence of palladium catalysts.     

Efficient desulfurization of 2-thiopyrimidine nucleosides to the corresponding 4-pyrimidinone analogues using trans-2-(phenylsulfonyl)-3-phenyloxaziridine

A brief treatment of 2-thiopyrimidine nucleosides (s²U^∗) with trans-2-phenylsulfonyl-3-phenyloxaziridine (PSO) results in efficient substrate desulfurization leading to the corresponding 4-pyrimidinone analogues (H²U^∗). The key transformation proceeds through oxidation of the 2-thiocarbonyl group to a sulfur oxyacid derivative and subsequent elimination of sulfur dioxide. 4-Pyrimidinone 1-β-d-riboside (H²U) has been transformed into the respective phosphoramidite, a ready-to-use monomer for the introduction of a modified nucleoside into an oligonucleotide chain. Moreover, the effective desulfurization of the 2-thiouridine nucleotide could be achieved directly at the oligonucleotide level, by treatment of the TdA(s²U)dGdC oligonucleotide with PSO, as verified by MALDI-TOF mass spectrometry.     

Stereodivergent reduction of enelactams embedded in hexahydroindoles. Synthesis of trans-3-substituted-cis-3a-methyloctahydroindoles

A stereodivergent synthesis of cis- and trans-octahydroindole derivatives from the ethylene acetal of methyl 1-benzyl-3a-methyl-2,5-dioxo-2,3,3a,5,6-hexahydro-1H-3-indoleacetate is reported. Under ionic reduction conditions the enamide group was reduced to afford a trans-ring fused product, while a hydrogenation process led to the formation of a cis-ring fused lactam, which was transformed into a building block for daphniphyllum alkaloid synthesis after an epimerization at C-3.     

Cyclic oligomers in the cationic polymerization of cis- and trans-2,3-dimethylthiirane

Under the influence of triethyloxonium tetrafluoroborate in methylene chloride, cis- and trans-2,3-dimethylthiirane are transformed to their corresponding polymers almost instantaneously (at temperatures between 0 and 20 °) but within a few hours these polymers completely degrade to form a mixture of low molecular weight substances. The cis-monomer leads to a mixture of cyclic tetramer, cis-butene and two geometric isomers of 3,4,6,7-tetramethyl-1,2,5-trithiepane. By ¹H-NMR it was shown that these two isomers are the trans-cis-trans and the trans-trans-trans forms. The trans-monomer leads to a mixture of trans-butene and 3,4,6,7-tetramethyl-1,2,5-trithiepane which is present as a mixture of the cis-cis-cis and the cis-trans-cis isomers. In both cases, the butene and the trithiepanes were formed in equimolar quantities. The formation of these oligomers is explained by assuming that polymerization occurs via an SN2 propagation reaction between the three-membered cyclic sulphonium ion (the active species) and monomer, followed by a degradation reaction occurring via a back-biting mechanism.     

A mild and efficient aza-Diels-Alder reaction of N-benzhydryl imines with trans-1-methoxy-2-methyl-3-trimethylsiloxybuta-1,3-diene catalyzed by Yb(OTf)3

The aza-Diels-Alder reaction of trans-1-methoxy-2-methyl-3-trimethylsiloxybuta-1,3-diene with N-benzhydryl imines in the presence of Yb(OTf)₃ in toluene at room temperature gave the corresponding 2,5-disubstituted 2,3-dihydro-4-pyridones in high yields. This reaction can also be carried out with diene, aldehydes, and amine in a three-component one-pot reaction manner in moderate to high yields under solvent-free conditions. The relationship between Lewis acids and activity, solvents and catalyst loading were studied. Some investigation towards the reaction mechanism was discussed.     

The Thorpe-Ziegler-type reaction of 3-cyanopyridine-2(1H)-thiones with Biginelli 6-bromomethyl-3,4-dihydropyrimidin-2(1H)-ones: cascade assembling of tetra- and pentacyclic heterocyclic scaffolds

3-Cyanopyridine-2(1H)-thiones have been shown to react with Biginelli-type ethyl 4-aryl-6-(bromomethyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates upon heating in DMF giving rise to ethyl 4-aryl-6-{[(3-cyanopyridin-2-yl)thio]methyl}-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates. The latter upon treatment with an excess of NaH or t-BuOK in boiling DMF undergo a tandem Thorpe-Ziegler-type heterocyclization to give pyrido[3″,2″:4′,5′]thieno[2′,3′:5,6]pyrido[4,3-d]pyrimidine derivatives in good yields. Selected compounds were tested for antibacterial and antifungal activity.     

6-Chloro-2(2H)-pyranone: a new 2(2H)-pyranone synthon

6-Chloro-2(2H)-pyranone, which can be prepared in high yield from commercially available trans-glutaconic acid, undergoes facile Pd/Cu-catalyzed reaction with various 1-alkynes to give rise to the corresponding 6-(1-alkynyl)-2(2H)-pyranones in moderate to good yields. These last hitherto unknown compounds have been used as direct precursors to 6-alkyl- and 6-[(Z)-1-alkenyl]-2(2H)-pyranones.     

Synthesis of polyhydroxylated 2H-azirines and 2-halo-2H-azirines from 3-azido-2,3-dideoxyhexopyranoses by alkoxyl radical fragmentation

The reaction of 3-azido-2,3-dideoxypyranose and 3-azido-2,3-dideoxy-2-halohexopyranose compounds with (diacetoxyiodo)benzene and iodine generated 2-azido-1,2-dideoxy-1-iodoalditols and 2-azido-1,2-dideoxy-1-halo-1-iodoalditols, respectively. These beta-iodo azides could be transformed by chemoselective dehydroiodination into 2-azido-1,2-dideoxy-4- O-formyl-pent-1-enitols and (Z, E)-2-azido-1,2-dideoxy-1-halo-4- O-formyl-pent-1-enitols in good yields. Thermolysis and photochemical studies of these vinyl azides and 1-halovinyl azides for the synthesis of polyhydroxylated 3-alkyl-2 H-azirines and the hitherto unknown 2-halo-3-alkyl-2 H-azirines have also been accomplished.     

A convenient synthesis of 3-alkyl-2,3-dihydro-2,4-dioxo-6-phenyl-, 3-alkyl-2,3-dihydro-4-oxo-6-phenyl-2-thioxo-, and 3-alkyl-2-arylimino-2,3-dihydro-4-oxo-6-phenyl-4H-1,3-thiazines

The reactions of 1-alkylamino-1-alkylthio-3-phenylpropene-3-thiones 3 with thiophosgene and phosgene in toluene, followed by treatment of the reaction mixture with triethylamine gave 3-alkyl-2,3-dihydro-4-oxo-6-phenyl-2-thioxo- 4 , 3-alkyl-2,3-dihydro-2,4-dioxo-6-phenyl-4H-1,3-thiazines 5 , respectively in good to excellent yields. Similarly treatment of compounds 3 with N-arylimidoyl dichloride in benzene at room temperature gave 3-alkyl-2-arylimino-2,3-dihydro-4-oxo-6-phenyl-4H-1,3-thiazines 6 in excellent yields. The reactions of compounds 3 with oxalyl chloride in toluene gave also 5 in good yields.     

Regio- and stereoselective reduction of trans-4-phenylbut-3-en-2-one using carrot,celeriac, and beetroot enzyme systems in an organic solvent

(S)-trans-4-Phenylbut-3-en-2-ol has been obtained in excellent yields and with high enantiomeric excess in the reduction of trans-4-phenylbut-3-en-2-one using the comminuted roots of carrot (Daucus carota L.), celeriac (Apium graveolens L. var. rapaceum), and beetroot (Beta vulgaris L. subsp. Vulgaris) in isooctane. This is the first Letter of this bioreduction with plant tissue in an organic solvent.     

Rearrangements of N-alkyl-/aryl-nitrones derived from 4-oxo-4H-1-benzopyran-3-carboxaldehyde--a solvent-dependent process

C-(4-Oxo-4H-1-benzopyran-3-yl)-N-alkyl-/aryl-nitrones derived from 4-oxo-4H-1-benzopyran-3-carboxaldehyde, rearrange to 2-alkyl-/aryl-amino-3-formylchromone and/or 3-(alkyl-/aryl-aminomethylene)chroman-2,4-dione depending upon the reaction medium. 3-(Alkylaminomethylene)chroman-2,4-dione has been utilized in the synthesis of 1-benzopyrano[3,4-d]isoxazole-4-one.     

The conformation and vibrational spectra of trans-1,4-dicyanocyclohexane

The IR spectra of trans-1,4-dicyanocyclohexane as a melt, as a solute in various solvents, as KI and polyethylene pellets and as amorphous and annealed crystalline solids at 90 K have been recorded in the region 4000-50 cm^?1. Additional spectra at high pressures (1–50 kbar) have been recorded and the dichroic ratios of oriented polycrystalline films are obtained above 200 cm^?1. Raman spectra of the compound as a melt, as an amorphous and crystalline solid at 90 K and dissolved in acetone, chloroform and benzene have also been recorded.The compound exists as an equilibrium mixture of ee and aa conformers in solution, in the melt and in the amorphous solid at 90 K, but as one conformer only, apparently the ee form, in the crystalline state. Unlike the corresponding dihalocyclohexanes, trans-1,4-dicyanocyclohexane cannot be converted to an “aa crystal” either by exposure to high pressure or by annealing to a metastable crystal.The fundamental frequencies of both conformers have been interpreted in terms of C_2h molecular symmetry and the assignments supported with a force constant calculation by the overlay technique transferring force constants from various related molecules.     

Enzymatic resolution of trans-2-hydroxycyclohexanecarbonitrile in supercritical carbon dioxide

A novel, highly enantioselective (E ? 100) and environmentally benign method is presented for the kinetic resolution of trans-2-hydroxycyclohexanecarbonitrile in supercritical carbon dioxide. Using Candida antarctica Lipase B as a biocatalyst and vinyl acetate as an acyl donor, enantiomerically pure (1S,2R)-acetoxycyclohexanecarbonitrile and (1R,2S)-hydroxycyclohexanecarbonitrile were obtained in quantitative yields and excellent ee (98%) values.     

Synthesis and characterization of aliphatic unsaturated polyesters from trans-4-octene-1,8-dioic and trans-3-hexene-1,6-dioic acids

The influence of the double bond on the thermodynamic parameters, T_m, ΔH_m and ΔS_m of some unsaturated aliphatic polyesters has been found to depend on the number of —CH₂— groups separating the double bond from the ester linkage. Thus, T_m's of the polyesters derived from trans-4-octene-1,8-dioic acid (OD) are lower than those for the corresponding saturated polyesters; no such effect has been observed by comparing T_m's of polyesters derived from trans-3-hexene-1,6-dioic acid (HD) and adipic acid respectively. X-ray investigation has shown, for polyesters of the OD series, the presence of the two polymorphic forms.