Marcel K. Eberle

Preparation of functionalized ketones via low temperature grignard reaction

Abstract δ-Chloroketones and 5-oxo-9-decenoic acid methyl ester were prepared from 5-chlorovaleryl chloride and methyl 4-(chloroformyl)-butyrate via Grignard reaction in tetrahydrofuran at −70°.

Preparation of functionalized ethers of cyclosporin A

Abstract Cyclosporin A ( 1 ) was O-alkylated selectively using phase transfer catalyzed reactions. With allyl chloride, metallyl chloride and propargyl bromide this lead to the ethers, 2 , 3 and 4 , respectively. With t-butyl bromoacetate the product was the ester 5 which was reduced to the alcohol 6 . With 2-(bromomethyl-propenoic acid methyl ester the ether 7 was obtained which was converted to 8 . The allylic ether alcohol 10 was prepared from 9 . This in turn was accessible from 1 and 1-chloro-2-chloromethyl-2-propene.

An Improved Preparation of Rp and Sp N6, N6, O2′ - Tri-Benzoyl-Adenosine-3′, 5′-Cyclic Phosphoranilidates

Abstract The conversion of the benzoylated cAMP (2) to the diastereomeric mixture of the anilidates (3) was improved. Replacing the triphenylphosphine/carbon tetrachloride mixture by oxalyl chloride in the presence of a catalytic amount of DMF followed by the addition of aniline not only increased the yield from 27 to 96% but rendered much easier the separation of the diastereoisomers (3), which were formed in approximately equal amounts. This greatly improved the accessability of Rp and Sp-cAMPS (1).

Neighboring Group Effects in Intramolecular Aldol Condensations. Rate Enhancement by γ Substituents1

The O-acetyl dieneol 1b, obtained from the Grignard addition of 2-(2-bromoethyl)-1,3-dioxolane to 2,4-hexadienal via 1a, and followed by an acetylation, was treated with maleic anhydride to give the crystalline Diels−Alder adduct 2b with good stereoselectivity. The acetal of 2b was selectively hydrolyzed to the acetoxy aldehyde 3b. This was treated with potassium hydride in tetrahydrofuran. A stereoselective intramolecular Aldol reaction resulted in the formation of the tricyclic lactone 4b. However, attempts to achieve an Aldol condensation under similar reaction conditions with the analogous aldehyde 3c, lacking the acetoxy group, failed, giving back the starting material 3c. On the other hand, the methoxy aldehyde 3d was cyclized to the tricyclic compound 4d.