Letters in Organic Chemistry - Volume 6, Issue 1, 2009

The ylides Ph3E-C6H6N2O3 (7, E = P (a), As (b), Sb (c)) have been prepared through the reaction of Ph3E and 5- bromo-1,3-dimethyl-2,4,6(1H,3H,5H)-pyrimidinetrione (5-bromo-1,3-dimethylbarbituric acid) 6 in the presence of triethylamine. Their characterisation was performed by nuclear magnetic resonance (NMR), mass spectrometry (MS) and elemental analysis.

(1S,1'R,5'R,7'R)-1-Hydroxy-exo-brevicomin has been synthesized in a highly efficient manner using Dglucono- δ-lactone as a chiral precursor. The synthesis involves the Grignard cross coupling, Wacker oxidation and intramolecular acetalization as the key steps.

An efficient and green procedure for the synthesis of raloxifene has been developed by using Suzuki couplings, Friedel-Crafts acylation, and copper catalyzed coupling reactions in an ionic liquid.

The course of Kabachnik-Fields reaction in the synthesis of 3-substituted quinoline-based α-aminophosphonates under microwave irradiation has been investigated. Some unexpected monoester hydrogen phosphonate derivatives, obtained along with diethyl phosphonates by reaction of quinoline-3-carboxaldehyde and aniline as well as 3- aminoquinoline and benzaldehyde, respectively, with diethyl phosphite, have been analyzed and discussed.

This manuscript describes the first example of silver ion complex of a dendritic tetranitrile ligand catalyzed one-pot three component Mannich reaction and 1,5-benzodiazepine synthesis. The catalyst can be separated from the products by a change in the solvent. The catalyst is reusable.

(R)-3-Aminotetradecanoic acid (iturinic acid) has been synthesized starting from dodecanoyl chloride. This new synthetic approach involved the enantioselective reduction of an ynone to the corresponding propargylic alcohol and then into a protected propargylic amine. The iturinic acid was obtained by the transformation of a (phenylseleno)acetylene intermediate into a carboxylic group followed by N-deprotection.

This paper especially deals with the problem associated with the reaction of α-bromocarboxyl compound and 5- membered ω-lactam ring. Specific heterogeneous copper catalyst was used to achieve the C-N nucleophilic coupling. Synthetic pathway of ethyl-6-(2,5-dioxopyrrolidin-1-yl)-2-(2-oxopyrrolidin-1-yl)hexanoate as the key intermediate of new potential transdermal enhancers is described. All generated compounds were characterized by NMR and IR spectroscopy.

Six of new N'-tert-butyl-N'-substitutedbenzoyl-N-(2,4-dimethyl-2,3-dihydrobenzofuran)-7-carbohydrazide derivatives and five of new N'-tert-butyl-N'-substitutedbenzoyl-N-(5-methylchroman)-8-carbohydrazide derivatives were designed and synthesized from m-cresol. The synthesis highlighted that some kinds of reactions were ameliorated in methodology. An important feature is that 1-(3-allyl-2-hydroxy-4-methylphenyl)ethanone can easily be transformed into 1-(2,3-dihydro-2,4-dimethylbenzofuran-7-yl)ethanone just with concentrated sulfuric acid as catalyst. In addition, we found that 1-(5-methyl-2H-chromen-8-yl)ethanone could not be reduced to 1-(5-methylchroman-8-yl)ethanone directly by hydrogen with Pd/C as catalyst. It is an effective method for protecting 1-(5-methyl-2H-chromen-8-yl)ethanone with ethylene glycol to obtain 5-methyl-8-(2-methyl-1,3-dioxolan-2-yl)-2H-chromene and then reducing by hydrogen with Pd/C as catalyst to produce 1-(5-methylchroman-8-yl)ethanone in one step. Furthermore, SOCl2 can convert 2,3-dihydro-2,4- dimethylbenzofuran-7-carboxylic acid to 2,3-dihydro-2,4-dimethylbenzofuran-7-carbonyl chloride, but it is inefficient for transforming 5-methylchroman-8-carboxylic acid to the corresponding acyl chloride. Hence, different heterocycles on the benzene ring of benzoheterocyle moiety have influence on the reaction property of the corresponding acid.

A series of nine inclusion complexes have been prepared in the solid state between three different 2- chloroethylnitrososulfamides (CENS) and three different cyclodextrins (β-cyclodextrin, methyl-β-cyclodextrin and (2- hydroxylpropyl)-β-cyclodextrin). The formation of inclusion complexes with a 1/1 stoichiometry has been confirmed. NMR studies showed that the CENS moiety is encapsulated in CDs cavities in a tilted equatorial orientation. Since biological evaluation showed that the cyclodextrins have only a slight effect on the activity of the drugs toward two cancer cell lines, the possibility exists that the complexes may find pharmaceutical use by improving the drugs' in vivo bioavailability and stability.

The photochemical behaviors of benzonorbornene derivatives were investigated in the solid state as well as in the solution. In acetonitrile solution, benzonorbornene derivatives underwent the Norrish type II reaction affording a ratio of 1:1 of cyclization and cleavage products, whereas in the solid state, the sole cyclization product was obtained. The stereochemistry of the photoproducts was identified by the X-ray crystallography. Enantiomeric excesses of up to 97% can be achieved through the use of the solid-state ionic chiral auxiliary method of asymmetric synthesis.

Organocatalytic asymmetric additions of unmodified aldehydes to β-nitrostyrenes are important carbon-carbon bond formation reactions and have become very attractive recently, because they are metal-free and environmentally benign. This work employed a series of L-proline-based diphenyl dipeptidols to catalyze this reaction. The results showed that these dipeptidols were effective organocatalysts with the yield up to 99%. 3a was optimal with the highest enantioselectivity up to 75% and dr (syn/anti) up to 94/6. In addition, the mechanism of this asymmetric reaction is also discussed.

The scope and the limitations of 3-chloro-2-pyridinyl lithium condensation to aldehydes were envisioned depending on metallation conditions or condensation time and temperatures. The procedure was applied to various aromatic, aliphatic or functionalized aldehydes to afford a new and efficient access to 2-(polyhydroxyalkyl)pyridines.

Several potential methods for the preparation of 1,2-bis(pyrazol-1-yl)benzene, a prospective ligand for transitional metals, starting from 1,2-dihalobenzenes and pyrazole have been studied. Cross-couplings of 1,2-dichloro-, - dibromo- and -diiodobenzenes with pyrazole using palladium and copper catalysts were unsatisfactory because of dehalogenation side reactions or a lack of reactivity. On the other hand, nucleophilic aromatic substitution of fluorine in 1,2- difluorobenzene under the action of sodium pyrazolide gave a good yield of the desired product.

Using various substrates and ligands, we show that electron-deficient, bidentate phosphines are the ligands of choice for palladium-catalyzed arylation of electron-rich olefins. This is in contrast to the reaction of electron-deficient olefins, which benefit from electron-rich monodentate phosphines. A tentative explanation is offered based on DFT calculations.

The synthesis of two natural products - Taxifolione and Taxifolial D - isolated from the marine alga Caulerpa taxifolia invading the Mediterranean Sea was performed. Coupling reactions allowed for a rapid synthesis. The surprising Z configuration of Taxifolial D was confirmed after synthesis and comparison of each synthetic stereoisomer.

New sulfonated Cy3 and Cy5 phosphoramidites and solid supports were synthesized. These building blocks were used in the synthesis of terminally or internally labeled oligodeoxynucleotides. Mild deprotection schemes were applied to the sulfocyanine-labeled oligonucleotides.

An alternative heterogeneously palladium catalysed procedure for the synthesis of functional stilbenes and bibenzyls is reported. Starting from aryl bromides and using simple commercially available Pd/C catalyst at a low catalytic rate (1 mol%), stilbenes are obtained with 30-100% GC-yields and bibenzyls are produced in a one-pot fashion with 27-100% GC-yields. The procedure showed, however, some limitations when applied to strongly deactivated aryl bromides that could be in some extent overcome by using corresponding iodo derivatives.

Hitherto unreported [1,2,3]-triazolyl coumarin and quinolone derivatives in good to excellent yields have been expediently synthesized from 6- and 7-azidocoumarin and 6-azidoquinolone by copper (I) catalyzed 1,3-dipolar cycloaddition. Azidocoumarins and azidoquinolones were in turn prepared efficiently from the corresponding amines. Fluorescence studies of the newly synthesized [1,2,3]- triazolyl coumarin and quinolone derivatives are also described.

An efficient synthesis of the selective H4 receptor agonist 4-methylhistamine is described. This approach can be used to prepare, without purification steps and in high yield, significant quantities of the product, useful as pharmacological tool to investigate the physiological roles of the histamine H4 receptor.

A new solid-phase synthesis of pyrrolizidine nucleus related to hyacinthacine core using L-proline as the starting material is reported. The final step is a new approach with a cyclization-cleave strategy, which releases the product from the resin in good yields under Baylis-Hillman conditions.