Abstract EN:

This work deals with the enantioselective and diastereospecific 5-endo halogeno electrophilic cyclization reactions of betagamma ethylenic carboxylic acids and hydroxamates to give halolactones and halolactames. In the first part, the synthesis and screening of new chiral amine halogeno complexes were examined as halogen source for halogeno electrophilic cyclization reactions. Using these new complexes, moderate enantiomeric excesses were obtained in our best conditions (until 45% ee) for the iodo lactonizations. ( )(1R,2S) N-methylephedrine was found to be the best chiral amine tested, while the best enantiomeric excess was observed using 0. 4 equivalent of iodine. A presence of a chiral silver induce by the synthesis of the chiral halogeno complex was found to be crucial to obtain enantioselectivities. The mechanism of these enantioselective halogeno cyclizations was studied for the 5-endo cyclisations. In the second part, diastereospecific halo cyclizations of chiral beta,gamma ethylenic carboxylic acids were investigated. In a first step, chiral alphaalkyl betagamma-ethylenic carboxylic acids were prepared using Evans’ methodology. Then halo cyclizations of these different acids were carried out and only one diastereoisomer was isolated. This method allows us an easy preparation of enantiopur butyrolactones possessing a chiral quaternary carbon in gamma position. Furthemore, an application to a natural lactone synthesis, isolated from a sponge, was achieved. In the third part, butyrolactames were prepared using 5-endo halo cyclisation of beta,gamma-ethylenic hydroxamate. 5 phenyl 2H pyrrol-2-one was isolated from these cyclisations and its reactivity was examined.