Thiophilic promoters

Recently, a number of thiophilic activators that can activate thioglycosides of low reactivity at low temperature have been described. For example, thiophilic promoter systems, such as diphenylsulfoxide [87,99], S-(4-methoxyphenyl)benzenethiosulfinate... 

The addition of a second, reducing end acceptor and a thiophilic promoter (NIS) resulted in trisaccharide formation. Yields as high as 84% for the overall process were reahzed, showcasing the efficiency of this strategy as well as the promoter compatibility, which can be a problem (Fig. 3). The method has been extended to branched structures as well (34). Takahashi has advanced the orthogonal OPG strategy in an impressive synthesis of the heptasaccharide phytoalexin elicitor (HPE) in 24% overall yield (35). 

The capacity of these thioglycosides as glycosyl donors was evaluated using various thiophilic promoters and three different acceptors, one primary (66) and two secondary (67 and 68), the latter relevant for the synthesis of H. influenzae type e structures. The yields obtained were extraordinary, both with the benzoylated and the benzylated donor (1.5 equiv.) and with all three acceptors quantitative or nearly quantitative yields of disaccharide products were observ-... 

With two of the earlier acceptors, 66 and 68, together with 71 a in the presence of DDQ, the intermediate mixed acetals were obtained in high yields according to TLC. Work-up followed by immediate activation with different thiophilic promoters gave a reaction which was found to be as stereospecific for the fructo-furanosidic system as earlier for pyranosides (Scheme 25) [112]. 

Initially, the method was based on the differential reactivity conferred on each of the partners by the nature of the protecting groups and by the intrinsic nucleophilicity of the thioaryl leaving groups. However, as the method evolved, it became clear that the choice of the promoter was also an important factor to take into consideration. Indeed, it was demonstrated that a disarmed thioglycoside could be activated in the presence of powerful thiophilic promoters such as A-iodosuccinim-ide/trifluoromethanesulfonic acid (NIS/TfOH), whereas it remained inactivated in the presence of weak thiophilic reagent such as iodonium dicollidine perchlorate or methyl triflate [43,45]. 

Attempts to overcome this obstacle have included the use of ethyl 1,3,4,6-tetra-O-benzyl-2-thio-D-fructofuranoside as the glycosyl donor, and use of thiophilic promoters. Predictably, a,(3 mixtures were obtained, with the a anomers predominating. 

Similarly, reaction of a thioglycoside with a hydroxylic compound in the presence of an excess of a tetraalkylammonium bromide and the thiophilic promoter dimethyl(methylthio)sulfonium triflate (DMTST) proceeds with high stereoselectivity.131-133... 

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