New synthesis of cis-3,4-diaryl-1-tosylpyrrolidines

Unsymmetrically substituted cis-3,4-diarylpyrrolidines are synthesized in nearly 25% overall yields starting from 4-aryl-1,2,5,6-tetrahydropyridines by iterative reactions using the combination of m-chloroperoxybenzoic acid (MCPBA) and boron trifluoride etherate (BF₃·OEt₂) followed by Grignard addition, elimination and hydrogenation sequence.     

Concise synthesis of multiply substituted stereodefined cis,cis-2,4-diene-1,6-dials, cis,cis-2,4-diene-1,6-diols and further applications

Reactions of 1,4-dilithio-1,3-dienes with DMF afforded multiply substituted stereodefined cis,cis-2,4-diene-1,6-dials in high yields. Treatment of these 1,6-dials with LiAlH₄ or RLi resulted in the formation of their corresponding 1,6-diols. These bifunctional compounds, cis,cis-2,4-diene-1,6-dials and -1,6-diols are otherwise not readily available. Further reaction of these 1,6-diols with an aldehyde catalyzed by strong acids led to the formation of oxacycles of novel structures.     

Efficient one-pot trans-dihydroxylation of 2H-pyrans using dimethyldioxirane (DMD): synthesis of trans-3,4-dihydroxy-3,4-dihydro-O-methyloctandreolones, orixalone D, and trans-3,4-dihydroxy-3,4-dihydromollugin natural products

An efficient one-pot formation of trans-diols on 2H-pyranyl rings was achieved by dimethyldioxirane in wet acetone. This new methodology was applied to the synthesis of natural products containing trans-diol on the pyranyl rings such as trans-3,4-dihydroxy-3,4-dihydro-O-methyloctandreolones, orixalone D, and trans-3,4-dihydroxy-3,4-dihydromollugin.     

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.     

The first asymmetric synthesis of all four isomers of cis- and trans-3,4-dihydroxy-3,4-dihydromollugin

Asymmetric synthesis of all the four stereoisomers of cis-3,4-dihydroxy-3,4-dihydromollugins 4 and 6 and trans-3,4-dihydroxy-3,4-dihydromollugins 5 and 7 was achieved. The O-methoxymethyl mollugin derivatives were dihydroxylated to (−)- and (+)-cis-3,4-dihydroxy-3,4-dihydromollugin derivatives using both AD-mix-α and AD-mix-β. Deprotection of the MOM-ethers of cis-dihydroxy compounds resulted in the targeted stereoisomers (−)-(3R,4R)-cis-3,4-dihydroxy-3,4-dihydromollugin 4, (−)-(3R,4S)-trans-3,4-dihydroxy-3,4-dihydromollugin 5, (+)-(3S,4S)-cis-3,4-dihydroxy-3,4-dihydromollugin 6 and (+)-(3S,4R)-trans-3,4-dihydroxy-3,4-dihydromollugin 7. These routes were paved with difficulties, for example, incompatibility of the substrates with AD-mixes, the unexpected formation of trans-dihydroxy compounds and failures in deprotection protocols.     

Synthesis characterization and X-ray crystal structures of cis-1,4-diaminocyclohexane-platinum(II) nucleobase adducts

Platinum complexes of the type [Pt(cis-1,4-DACH)(L)₂]X, where cis-1,4-DACH = cis-1,4-diaminocyclohexane; L = adenine (ade) (1), hypoxanthine (hyp) (2), 9-methylguanine (9-megua) (3), cytosine (cyt) (4), or 1-methylcytosine (1-mecyt) (5); and X = SO₄ or Cl₂ groups, were synthesized and characterized by elemental analysis and by ¹H, ¹³C, and ¹⁹⁵Pt nuclear magnetic resonance spectroscopy. The crystals of [Pt(cis-1,4-DACH)(9-megua)₂]SO₄[9-megua-H]₂SO₄ (3) and [Pt(cis-1,4-DACH)(1-mecyt)₂]Cl₂ · 6H₂O (5) were also subjected to single-crystal X-ray diffraction. The base/PtN4 coordination plane dihedral angles were 74.55° and 85.61° in complex 3 and 78.12° and 81.80° in complex 5. The platinum had distorted square planar geometry in both complexes; the two adjacent corners were occupied by the two nitrogen atoms of cis-1,4-DACH, and the other two corners were occupied by the two N7 atoms of 9-megua in complex 3 and the two N3 atoms of 1-mecyt in complex 5. The cis-1,4-DACH, which has a unique twist-boat configuration, formed a seven-member chelating ring with platinum, which led to considerable strain during bidentate cis-1,4-DACH binding. Cations of both complexes 3 and 5 adopted C₂ molecular symmetry. These adducts were the models for the intrastand cross-links that were relevant to the binding of the Pt(II) antitumor drugs to DNA.     

Efficient synthesis of cis-2,6-di-(2-quinolylpiperidine)

An efficient synthesis of cis-2,6-di-(2-quinolylpiperidine) has been developed. The key steps involve Wittig reaction of N-Cbz-protected cis-piperidine-2,6-dicarboxaldehyde (3) with 2-(triphenylphosphinyl-methyl)quinoline bromide (4) and sequential removal of the N-Cbz group and double bond reduction. This synthetic procedure provides an efficient preparation for this useful norlobelane analogue.     

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.     

Anodic formation of 3,6-diaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and 2(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles

3,6-Disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles together with the unknown systems 2-(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles were obtained by anodic oxidation, under aprotic conditions, of aryl aldehyde N-(5-aryl-1,3,4-thiadiazol-2-yl) hydrazones. Mechanistic proposals are given.     

A rapid and practical entry into cis-1,4-aminocyclohexanols

A selective and practical approach for the formation of cis-1,4-aminocyclohexanol was developed. The key transformation involves a one-pot imine formation/ Lewis acid-directed imine reduction and results in a highly selective attack of the reducing agent. This simple and practical method is easily amenable to large-scale synthesis.     

Solvent effect in cis-1,4 polymerization of 1,3-butadiene by a catalyst based on neodymium

In this work a laboratory polymerization scale process was studied for the production of polybutadiene with high content of cis-1,4 repeating units. A Ziegler-Natta catalytic system based on neodymium versatate (catalyst), diisobutylaluminium hydride (cocatalyst) and tert-butyl chloride (chlorinating agent) was used. The influence of solvent nature (pure grade) and possible contaminants (electron donors) in a recovered solvent from a butadiene-styrene anionic polymerization industrial plant on the stereoselectivity and catalytic activity, molecular weight and molecular weight distribution of the resultant polybutadienes was studied. The polymers were characterized by infrared spectroscopy and size exclusion chromatography. Polybutadienes with cis-1,4 units content in the range of 99-98% were produced. The polymers weight-average molecular weight, , varied from 2.23 × 10⁵ to 4.47 × 10⁵ and the molecular weight distribution, MWD, from 3.1 to 5.1.     

Concise synthesis of trans- and cis-3,4-disubstituted piperidines based on regio- and stereoselective allylation of cyclopentenyl esters

3,4-Disubstituted piperidines were synthesized through anti S_N2′ allylation of 4-substituted 2-cyclopentenyl esters with reagents based on RMgX and CuX, thus allowing equal access to both trans- and cis-isomers. As an application, the paroxetine intermediate was synthesized efficiently. During the investigation, the MeOCH₂CO₂ group was found to show high reactivity in the pivotal anti S_N2′ type reaction using the reagent derived from (i-PrO)Me₂SiCH₂MgCl and CuCN.     

Regioselective synthesis of 2-unsubstituted 1-aryl-4- and 1-aryl-5-acylimidazoles

An efficient and simple method for the synthesis of 2-unsubstituted 1-aryl-4- and 1-aryl-5-acylimidazoles has been developed. It consists in the condensation of α-diketone monooximes with aromatic amines and formaldehyde on the presence of boron trifluoride etherate, leading to the formation of stable boron trifluoride complexes of N-oxides. Further reduction of these complexes led to the corresponding imidazoles. This method permits broad variations of substituents in the aryl part of these compounds.     

Synthesis of trans/cis 4-substituted 3-furyl-2-phenethyltetrahydroisoquinolin-1-ones: conformation of the trans-4-(pyrrolidinylcarbonyl) derivative

The title compounds were synthesized starting from homophthalic anhydride and an imine. The amides obtained showed unexpected values for ³J_3,4 that cannot be used to deduce their configuration and conformation. This problem was resolved for one representative compound (the 4-(pyrrolidinylcarbonyl) derivative) by means of detailed NMR studies, X-ray diffraction and theoretical calculations. The compound has the trans configuration. In the solid state, its conformation is with dipseudoaxial (aa) oriented substituents at positions 3 and 4. In different solvents and in the gas-phase, the majority of the data reveal that the observed value of ³J_3,4 results from an equilibrium of the ee and aa conformers.     

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.     

Synthesis of melampolides and cis,cis-germacranolides as natural herbicide models

The comparative study between the theoretical molecular properties of the starting materials and the yields in the transformation of melampolides to cis,cis-germacranolides using SeO₂/t-BuOOH (TBHP) as oxidant allows to establish a feasible relationship with their values of dipolar moment. Conditions for this transformation are optimized and some mechanistic considerations are made based in this finding. Cluster analysis of the phytotoxic activity of the melampolides and cis,cis-germacranolides obtained shows that the activity is greatly influenced by the spatial shape of the backbone, prevailing upon other factors such as the presence of reactive functional groups.     

New synthesis of 3-arylpyrrolines

We present an easy and straightforward synthesis of 3-arylpyrrolines 4a-g by repeated treatment of 4-aryl-1,2,5,6-tetrahydropyridines 2a-g with m-chloroperoxybenzoic acid (MCPBA) and boron trifluoride etherate (BF₃-OEt₂). The transformation proceeds via epoxidation, ring contraction, Baeyer-Villiger oxidation and elimination reaction and affords 3-arylpyrrolines 4a-g with 61-70% yield. This facile strategy was also used to synthesize racemic baclofen (6).     

Synthesis of cis-3,4-dibromopyrrolidine and its crystal and molecular structure

Synthesis and structural studies of 3,4-dibromopyrrolidine hydrochloride are reported. The conformation of the dibromopyrrolidine ring is a slightly deformed envelope with ΔC_s(3–4) = 4.03°. The Br atoms have cis conformation. Short Cl?H—N hydrogen bonds link the 3,4-dibromopyrrolidine cations and Cl^? anions along the a-axis.     

Optically active 4-amino-4-aryl-5,5,5-trifluoropentan-2-ones: Versatile reagents for synthesis of chiral 4-trifluoromethyl-3,4-dihydroazin-2-ones

A cyclocondensation of disubstituted (thio)ureas and isocyanates derived from enantiomerically enriched 4-amino-4-aryl-5,5,5-trifluoropentan-2-ones affords a novel synthetic access to chiral 4-trifluoromethyl-substituted 3,4-dihydropyrimidin-2(1H)-(thi)ones and 3,4-dihydro-1,3-oxazin-2-ones, respectively.     

Theoretical study of 2,5-diphenyl-1,4-distyrylbenzene (A model compound of PPV): A comparison of the electronic structure and photophysical properties of cis- and trans-isomers

2,5-Diphenyl-1,4-distyrylbenzene (DPDSB), a model compound of PPV, have been synthesized with two isomers: cis- and trans-DPDSB in our lab. We have found three distinguishing features of photophysical properties between these two isomers. To explain these three special spectral behaviors, the quantum-chemical computations were performed to investigate the ground-state and excited-state molecular geometries, electronic structure, absorption and emission properties, potential–energy curve of the ground-state and excited-state, and so on. According to our calculated results, the nature causing above distinguishing photophysical properties is larger configuration displacement of cis-DPDSB than trans-DPDSB from the ground-state to the excited-state, especially for the changes in torsion angle along vinyl double bonds in cis-DPDSB.