Letters in Organic Chemistry - Volume 4, Issue 6, 2007

An efficient protocol based on the combination of microwave dielectric heating and PASP synthesis using the Wittig reaction was developed and applied to the preparation of α,β-unsaturated methyl esters, key intermediates of new sigma ligands. The stereochemistry of the products was also investigated showing a high E:Z isomeric ratio.

The chiral (S)-3-alkyl-3-(pyrrol-1-yl)prop-1-enes 1a-c were hydroformylated at 20°C and high pressure (100 atm) giving the branched aldehydes 2-methyl-3-(pyrrol-1-yl)alkanales (2+2') with a good regio-selectivity and a high diastereomeric excess (2/2' up to 90:10). The absolute configuration of the diastereomers was assigned via NMR measurements, 2S,3S being the predominant one.

The palladium-catalyzed reaction of 5-(4-hydroxyphenyl)-1,2,4-oxadiazoles with ethyl α-O-Δ2-glucopyranoside afforded ethyl 4-O-[4-(1,2,4-oxadiazol-5-yl)phenyl]-2,3-dideoxy-α-D-erythro-hex-2-enopyranosides. Bishydroxylation of the latter compounds gave the corresponding ethyl 4-O-[4-(1,2,4-oxadiazol-5-yl)phenyl]-α-Dmannopyranosides.

Indium complexes of chiral pyridine bis(diphenyloxazoline)-type ligands have been investigated as catalysts for the asymmetric allylation of aldehydes and ketones. Promoted by these chiral catalysts, allyltributylstannane reacted with aldehydes and ketones to afford the corresponding optically active homoallylic alcohols smoothly.

Diphenoxymethane (1a and 1b) and biphenol derivatives (1c and 1d) bearing urea groups were prepared to be used in anion recognition. Diphenoxymethane derivative (1a) selectively bound chloride anion (Cl-) in 1:1 complexes. However, biphenol derivatives (1c and 1d) did not show a clear selectivity in anion recognition. The association constants of the complexes were determined by 1H-NMR titrations in CDCl3.

The acid-catalyzed rearrangement of morphine (1), codeine (3), 3-deoxynormorphine (14) and Ncyclopropylmethyl- 3-deoxynormorphine (11) was investigated with methanesulfonic acid. The yield in the rearrangement reaction was significantly improved using milder reaction conditions, compared to the earlier reported methods. As an evidence for the mechanism of the acid-catalyzed rearrangement of morphinans, the diene intermediate 13 was isolated. A new method, using boron trifluoride etherate was elaborated for the rearrangement of morphinandienes.

Nine dimeric bile acid-amino acid conjugates as the mimic of cycle peptide and they have been synthesized in good yield and their structures were well confirmed by 1H NMR, 13C NMR and mass spectra. The ESI-MSn technique was used to probe the conformation of these molecules. The preliminary bioactivity tests showed that some of the title compounds could inhibit the growth of human breast cancer cell MCF-7. The antitumor activity probably derived from the unique sandwich-type amphiphilic conformation.

A facile regio and stereoselective methoxy-bromination of alkenes using LiBr and (diacetoxyiodo)benzene as oxidant is reported.

A series of new chiral 2-(6,8-dichloro-4-methyl-1,1,3-trioxo-3,4-dihydro-1H-1λ6-benzo[1,2,4]thiadiazin-2-yl) carboxylic acids 7a-g containing the chiral amino acid residue were synthesized by adopting the chemical transformations, which have not affected the chirality of the amino acid residue. No significant racemization of the chiral centre was observed during the synthesis of enantiomeric benzothiadiazine 1,1-dioxide derivatives from the corresponding D and L amino acids. Structures of all the newly synthesized compounds were determined by analytical and spectral data.

The reaction of 2-methyl-3-hydroxy-4H-pyrane-4-one (maltol) with dialkyl acetylenedicarboxylates in the presence of triphenylphosphine in CH2Cl2 at room temperature leads to the unknown fused furan and cyclobutene derivatives, and functionalized olefins in fairly high yields.

[(4-Hydroxymethyl-2-methoxyphenyl)methyl]phosphonic acid di-tert-butyl ester (8) served as a key intermediate in the stereoselective preparation of N-Fmoc-3-methoxy-4-(di-tert-butyl)phosphonomethyl-L-phenylalanine (5). Reagent 5 may be useful for the solid-phase synthesis of phosphotyrosyl mimetic-containing peptides.

A mild and efficient synthesis of flavones was achieved by indium(III) chloride-mediated reactions of 1,3- diketones in good yields. As an application of this methodology, total synthesis of biologically interesting lanceolatin B was carried out.

A novel Michael addition of nitromethane to β-carbon of the benzimidazole chalcones 1 in the presence of K2CO3 and TBAB, under solvent-free conditions, by a simple physical mixing of compounds, leading to 1-(1-alkyl-1Hbenzimidazol- 2-yl)-4-nitro-3-aryl-butane-1-one 2 is described.

2-Amino-6-hydroxymethylpyridine (1) and 2-pivaloylamino-6-hydroxymethylpyridine (2) are important hydrogen bonding synthons as they are the very useful substrates which can be used for the synthesis of designed receptors in the field of molecular recognition [1] and supramolecular chemistry [2]. Here we report the compounds 1 and 2 as simple designers to create polymeric supramolecular three-dimensional assembly and self-complementary dimer respectively in solid-state crystal engineering.

Deprotection of aldehyde dimethylhydrazones was accomplished by stirring a biphasic mixture of the aldehyde dimethylhydrazone, 1M hydrochloric acid, and petroleum ether at room temperature for three to seven hours. The method works with α,β-unsaturated- and diene-aldehyde dimethylhydrazones, which are often difficult compounds to deprotect. Isolated yields ranged from 85% to 97%.