Torbjoern Frejd

Synthesis of fused tetrazole- and imidazole derivatives via iodocyclization

The possibility to prepare fused tetrazole- and imidazole derivatives by iodocyclization in moderate to excellent yields is demonstrated. In some examples the cyclizations were not following Baldwins rules entirely, i.e. exo-selectivity. Nucleophilic substitution of the formed iodides gave different results depending on the hardness of the nucleophile. Thus, elimination of the iodide could be a problem but a substitution reaction with ethyl potassium xanthate and a radical reaction using acrylonitrile were tolerated. In addition, we showed that it is possible to selectively use three iodo substituents individually in one of the fused imidazole derivatives.

Asymmetric Reduction of Ketones with Catecholborane Using 2,6‐BODOL Complexes of Titanium(IV) as Catalysts

Reductions performed with Ti(IV) complexes of ligands based on bicyclo[2.2.2]octane diols 5 and 6 are effective catalysts in the reduction of prochiral ketones to optically active alcohols, with catecholborane as the reducing agent. Methyl ketones are favored and enantiomeric excesses (ee) of < or =98% have been achieved with acetophenone as the substrate. Several other substrates were tested, among them 2-octanone, which gave 2-octanol in 87% ee. Further details of the method were examined, for example, temperature, solvent composition, amount of molecular sieves (4 A), and catecholborane quality, as well as the sensitivity of the ligands towards acids. NMR spectroscopic methods were used to gain some insight into the complexes formed between the ligands and [Ti(OiPr)4]. A dimeric structure is proposed for the pre-catalyst.

Spirobicyclo[2.2.2]octane derivatives: mimetics of baccatin III and paclitaxel (Taxol)

The formylated spirobyclic alcohol was computer modeled to be a mimetic of paclitaxel. In this model, the formyl group was used as a truncated paclitaxel side chain in order to reduce the computational work. Compound , carrying the paclitaxel side chain, was synthesized in six steps from optically active 1,3-diketone . Microtubule stabilization was not observed for , indicating that the model needs to be adjusted.

Phenylalanine Derivatives as Catalysts in the Enantioselective Addition of Diethylzinc to Benzaldehydes.

A series of mono and bis -amino alcohols derived from phenylalanine were synthesised and their application as chiral catalysts in the asymmetric ethylation of aromatic aldehydes in the presence of diethylzinc investigated.

Synthesis of a chiral dendrimer based on polyfunctional amino acids

A chiral, nonracemic dendrimer of generation two based on aromatic bis- and tris-amino acids has been synthesised.

On the Side-Chain Bromination of 3-Methylselenophene and 3-Methylthiophene

Abstract 3-Bromomethylselenophene can be prepared from 3-methyl-selenophene, N-bromosuccinimide and azo-bis-isobutyronitrile in carbon tetrachloride in 25% yield with the reversed addition method described in this paper. The method also gives consistently high yields of 3-bromomethylthiophene (70–75%) when applied on 3-methylthiophene.

Cyclisations with methacrylic acid in PPA. On the synthesis of cyclopenta[b]thiophenones

Abstract The reaction between some 2-substituted thiophen derivatives and methacrylic acid in PPA has been studied. Isomeric cyclopenta[b]thiophen ketones were formed in several cases, depending on the substituents. Features of their 13C and 1H NMR spectra are discussed and evidence is presented for ringclosure of 3(2-thienyl) propionic acids without rearrangement, in contrast to statements in the literature.

Spiro-bicyclo[2.2.2]octane derivatives as paclitaxel mimetics. Synthesis and toxicity evaluation in breast cancer cell lines

Paclitaxel is one of the most important anti-cancer agents introduced during the last 20 years. However, the use of paclitaxel is limited by undesirable side effects as well as the development of drug resistance. Here, we report a synthetic strategy towards spiro-bicyclo[2.2.2]octane derivatives, which includes double Michael addition and ring-closing metathesis as key synthetic steps. This strategy was used to synthesize a series of spiro-bicyclic compounds designed to be paclitaxel mimetics, which were evaluated in human breast-derived cell lines. One of these paclitaxel mimetics showed toxicity, although at higher concentrations than paclitaxel itself. In addition, two other spiro-bicyclic compounds, lacking the paclitaxel side chain, showed toxicity.

Ring opening reactions—XV : The reaction of some 2,5-disubstituted selenophenes with butyl- and phenyllithium

Abstract The reactions of 2,5-dimethoxyselenophene with butyl- and phenyllithium have been examined. In view of the formation of dibutyl- and diphenylselenide, respectively, together with some dienes, a reaction sequence could be formulated in which the first step is an attack on the selenium atom by the lithium reagent.

Novel, cyclic and bicyclic 1,3-diols as catalysts for the diethylzinc addition to aldehydes

A number of optically pure 1,3-diols have been synthesized and used as catalysts in the asymmetric addition of diethylzinc to aromatic aldehydes. Enantiomeric excesses of up to 92% of (R)-1-phenylpropan-1-ol were obtained with anisylbicyclo[2.2.2]octanediol (14) as a catalyst. Using 2-picolylbicyclo[2.2.2]ocatanediol (16) as the catalyst resulted in a reversal of the stereoselectivity, yielding (S)-1-phenylpropan-1-ol in 83% ee. A pronounced positive non-linear effect was observed when varying the enantiomeric purity of catalyst 14.