Research Of Ireland-claisen Rearrangement Of Butenyl Trifluoroacetate And Asymmetric Syntheses Of α-fluoro-β-amino Acids

It is well established that the replacement of hydrogen by fluorine in biological compounds can have profound biological effects. Consequently, the development of new strategies for the introduction of fluorine into organic molecules has become a good challenge. The dissertation is divided into the following two parts:PartⅠ:Difluoromethylene compounds have become one of the most important synthetic targets because of their unique biological activity. Therefore, we want to introduce CF2 building blocks by (Z)-4-(benzyloxy)but-2-enyl 2,2,2-trifluoroacetate(2) through Mg(0)-promoted Ireland-Claisen rearrangement. Unfortunately, after different conditions have been tried, no defluorinative silylenolization of compound 2 was detected by 19F NMR analysis. It is probably due to the weak electron-withdrawing effect of compound 2.PartⅡ:Fluorinatedβ-amino acids have recently become of great interest in both medicinal and bioorganic chemistry and some good results have been achieved. In this part we used Ellman's N-tert-butylsulphinimines as a chiral auxiliary to afford nucleophilic addition product diastereoselectively. Treatment of N-tert-butylsulphinimine with ethyl bromofluoroacetate in the presence of activated Zn dust in boiling THF afforded the corresponding product in 70-86% yield and moderate diastereoselectivity (66:34 to 92:8). Finally all the protecting groups of product 10-A were removed with 6N HCl and get correspondingα-fluoro-β-amino acids in 70-93% yields.