Asymmetrische Synthese Delta 3a,4 -ungesättigter bicyclischer Prolin-Analoga und Festphasensynthese mit vinylischen Sulfoximinen

In the first part enantiomerically pure acyclic and cyclic allylic sulfoximines were transformed to the corresponding alpha-titanated compounds and reacted with N-tert-butylsulfonyl a-imino ethyl ester to give acyclic and monocyclic protected alpha-amino acid esters in yields of 32-97%. In all cases the alpha-amino acid esters were formed in a highly regio and diastereoselective fashion (>=98% de). The amino alkylation of cyclic allylic sulfoximines with N-tert-butylsulfonyl alpha-imino ethyl ester provided mixtures of E and Z-konfigured monocyclic alpha-amino acid derivatives. Both diastereomers were formed highly diastereoselective (>=98% de). The stereoselective formation of the products could be explained assuming a six-membered transition state model. The four step synthesis of N-tert-butylsulfonyl alpha-imino ethyl ester was optimized so that the overall yield could be raised from 20% to 63%. The E and Z-konfigured monocyclic alpha-amino acid derivatives were treated with Me3OBF4 to give the corresponding 1-alkenyl dimethylamino sulfoxonium salts in excellent yields of 93-96%. The obtained 1-alkenyl dimethylamino sulfoxonium salts were transformed via intramolecular nucleophilic substitution with either DBU or lithium-tert-butyl amide in good yields of 76-81% to D3a,4-unsaturated bicyclic proline analogues. The cyclization reaction starts with a base induced isomerization of the 1-alkenyl dimethylamino sulfoxonium salts to the novel 2-alkenyl dimethylamino sulfoxonium salts. Then the nucleophilic substitution occurs under formation of the unsaturated bicyclic proline derivatives and N,N-dimethylphenylsulfinamide of >=99% ee. The obtained yields were in a range of 74-76%. Finally, cleavage of the protecting group with anhydrous triflic acid furnished the fused bicyclic proline analogue containing an unsaturated six-membered ring in a high yield of 83%. In the second part the attempt to prepare an axial chiral vinylic sulfoximine on Merrifield resin failed because in all steps the conversion of the ...