Phenyl selenoglycosides

Disarmed as well as armed (see Section V and Scheme 9) phenyl selenoglycosides are reported to be activated by silver triflate in the presence of potassium or silver carbonate in the presence of armed ethyl thioglycoside acceptors, to produce ethyl thiodisaccharides in excellent yields. 

Such a synthesis is shown in Scheme 4.18a, in which a glycosyl bromide is coupled with the thioglycosyl acceptor to afford a thioglycosyl disaccharide. The glycosyl bromide was obtained from the corresponding 1-thioglycoside by treatment with Br2. It was shown [222-224] that phenyl selenoglycosides can be selectively activated in the... 

Cation-Based Activation Pinto s works not only described Ag0Tf/K2C03 as the promoter of choice for the activation of phenyl selenoglycosides but also indicated... 

Photochemical oxidation has been employed for the activation of O-glycosides [552], thioglycosides [553] and telluroglycosides [554], It is also effective for O-glycosylation with the phenyl selenoglycoside donors [555], although this approach has not been widely taken up for preparative use. 

In conclusion, the phenyl selenoglycosides are versatile building blocks for oligosaccharide synthesis. Through judicious choice of protecting groups, and particularly promoters, they can be exploited as either donors or acceptors in glycosylation... 

Entry Phenyl selenoglycoside Method Product Yield... 

As expected, such a selective activation of perbenzylated ( armed ) phenyl selenoglycoside 163 was also possible in the presence of the benzy-lated thioglycoside acceptor 162. In this case, an //3 mixture (ratio 2.5 1) of disaccharide 166 was obtained in excellent yield (Table III). 

The fact that phenyl selenoglycosides are rendered unreactive if an organic base such as collidine or 1,1,3,3-tetramethylurea is employed instead... 

The selective activation of glycoside trichloroacetimidates over phenyl selenoglycosides was also demonstrated by glycosidation of phenyl seleno-glycoside acceptors 168 and 169 with glycosyl trichloroacetimidate 172. In the presence of catalytic amounts of triethylsilyl trifluoromethanesulfonate at -78°C, the disaccharide derivatives 170 and 171 were obtained in respectively 84 and 90% yields. 

Glycosylation with perbenzylated armed phenyl selenoglycoside 183 of the same glycoside acceptors (174,175, and 176) was efficient and an a/ j8 mixture of disaccharides 184, 185, and 186 was obtained (Table IV). Since a weak thiophilic promotor (IDCP) was employed in this case, glycosylation of armed ethyl thioglycoside acceptor 187 was also possible, affording an alfi mixture of 188 (Table V). 

Furthermore, selective activation of differently protected selenoglycosides was also possible with IDCP as promoter. Perbenzylated armed phenyl selenoglycoside 183 was selectively activated in the presence of disarmed acceptor 189 and an < //3 mixture of disaccharide 190 was obtained. With the less-reactive secondary hydroxyl group of 191, the yield of 192 was lower. 

Some disappointing results were reported later by the same group in an attempt to use phenyl selenoglycoside donors for the synthesis of a tetrasaccharide.86 No glycosylation was possible with phenyl selenoglycoside 193 in the presence of NIS-TfOH, whereas 40% yield was obtained with the corresponding trichloroacetimidate 194. 

Mehta, S, Pinto, B M, Novel glycosidation methodology. The use of phenyl selenoglycosides as glycosyl donors and acceptors in oligosaccharide synthesis, J. Org. Chem., 58, 3269-3276, 1993. 

S. Mehta and B. M. Pinto, Phenyl selenoglycosides as novel, versatile glycosyl donors selective activation over thiglycosides, Tetrahedron Lett., 32 (1991) 4435-4438. 

S. Mehta and B. M. Pinto, Phenyl selenoglycosides as versatile glycosylating agents in oligosaccharide synthesis and the chemical synthesis of disaccharides containing sulfur and selenium, Front. Nat. Prod. Res., 1, Modern Methods in Carbohydrate Synthesis (S. H. Khan and R. A. O Neill, Eds.), and references therein. Harwood Academic Publishers (1996, pp. 107-129). 

Substitutive deselenenylation. The reagent and conditions for the substitution are sufficiently mild that functionalities such as the azido group are not affected. O-Olycosylation can be effected by treatment of phenyl selenoglycosides with alcohols acting as nucleophiles. 

Glycosylation. Phenyl selenoglycosides are activated by the iodinating agent. Dissacharides are formed at room temperature within minutes. 

Compounds of selenium are highly toxic and in addition have a tendency, like their sulfur analogues, to have an unpleasant odour. Care is therefore necessary when handling selenium reagents, and it is advisable to avoid the more pungent chemicals where an alternative is available. In particular, selenophenol itself is extremely noxious and should be avoided if possible. As phenyl selenoglycosides are stable to both basic [41] and acidic [40] conditions it is often possible for the functionality to be introduced early in a given synthesis. 

Scheme 3.4 Lewis acid catalysed phenyl selenoglycoside formation (i) PhSeH, BF3 Et20, DCM.

Scheme 3.6 Stick s phenyl selenoglycoside synthesis (i) PhSeSePh, NaBH4, EtOH, 2h,...

Another useful method for the preparation of phenyl selenoglycosides is the azidoselenation reaction, in which a glycal is reacted with sodium azide, diphenyldiselenide and (diacetoxyiodo)benzene to give a 2-azido-2-deoxy-seleno-glycoside. The reaction is believed to proceed through a radical mechanism, and... 

Generation of a phenyl selenoglycoside from 2,3,4,6-tetra-O-acetyl-a-D-galacto-pyranosyl bromide via displacement of the anomeric halide with a selenophenol anion generated by reduction of diphenyldiselenide [44]. 

Van Boom showed that the thiophilic reagents di-5 ym-collodine perchlorate [55] and V-iodosuccinimide with catalytic triflic acid [56] are both excellent activators of phenyl selenoglycosides [39]. A number of other reagents developed for the activation of thioglycosides have also been shown to be effective for the activation of phenyl selenoglycosides. These include methyl triflate [28] and V-iodosuccini-mide with catalytic trimethylsilyl triflate [79]. 

It has also been demonstrated that phenyl selenoglycosides can be activated by a single electron transfer reaction either chemically [80] or electrochemically [81]. However, these methods are yet to demonstrate the same synthetic utility as chemical activation. 

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