Research On Stereoconvergent Halogenation Of Olefins And A New Synthetic Method Of Glycosides

Stereoconvergent chlorination and bromination of enamides and enamines controlled by electrostatic effect and the glycosylation of a series of carbohydrate donors and acceptors promoted by MeSCH₂Cl/KI are reported in this dissertation.The direct chlorination and bromination of（E）-enamines and（Z）-enamides to the corresponding（Z）-configuratedα-chloroenamines,α-bromoenaminesandα-chloroenamides have been realized using Ni Cl₂·6H₂O or tetrabutyl ammonium bromide as a halide source and（1,1-diacetoxyiodo）benzene as an oxidant.The high stereoselective reactions which produce products with only（Z）-configurations can be attributed to the structure of the intermediates,the conformations of which are controlled by the electrostatic attractions between the positively charged nitrogen atoms and the oxygen atoms of the carbonyl group.This type of electrostatic effect has never been reported in olefin halogenations.Two stereoconvergent experiments convertingunpurified（Z）/（E）-enamidestothesame（Z）-configuratedα-chloroenamides have been performed simplifying the procedure.The reactions were mild,fast,convenient and highly stereoselective with good to moderate yields for most products.These methods open pathways to prepareα-chloroenamines andα-chloroenamides,which are not accessible via the currently used methods.One obstacle for the practical glycosylations is the high costs of expensive promoters and low-temperature equipment.We have at least partially solved the problem by inventing new promoter MeSCH₂Cl/KI,whose estimated cost is<$1/mol,dramatically comparing to$1741/mol for AgOTf and$633/mol for TMSOTf.The promoter system is capable to activate various anomeric leaving group including F,Cl,trichloroacetimidate and acyloxy groups.Due to its stability and ease in preparation,anomeric benzoloxy carbohydrate donors were investigated in the glycosylations of carbohydrate,aliphatic alcohol,amino acid,steroid,and nucleoside acceptors.Among them,the diastereoselectivity of mannosylation is very high and the direct glycosylation of nucleoside using a benzoloxy leaving group is achieved for the first time in a heavy metal-free way.Zidovudine（AZT,a nucleoside）,the first clinic drug forHIV,was successfully glucosylated and mannosylated for the first time.A glycosylationmechanism is proposed based on control experiments.Most of the glycosylation are operationally simple,high in reaction rates and in medium yields（35-79%）.From the economic point of view,this glycosylation method is highly adaptable for industries.