Synthesis of Glycosides by Addition Reactions

Besides nucleophilic substitutions, additions to the double bond of 1,2-unsaturated sugars (glycals) constitute an attractive route for the synthesis of glycosides. Glycals react in these reactions either by a 1,2-addition or by an allylic rearrangement. The following discusses these two reactions in turn. 

In later developments, the use of tin alkoxides of the acceptors to increase their nucleophilicity was introduced [591]. Danishefsky [592] expanded the use of IDCP-promoted reactions to oligosaccharide syntheses, showing that glycals are also amenable to armed-disarmed type glycosylations. 

Activation of glycals by selenylation was introduced by Sinay and coworkers [41] by the sequential addition of PhSeCl and the glycosyl acceptor. A two-step version of this activation with the isolation of the intermediate glycosyl acetate [596] has also been reported. 

Activation by alkylsulfenylation was reported by Ogawa [597], who used alkylsulfenylated acceptor derivatives in the presence of TMSOTf. In a two-step sequence, PhSCl was added to the 

The addition of hydrogen to C-2 (instead of the heteroatoms discussed so far) leads directly to 2-deoxyglycosides. Various sulfonic acids have been used as activators for this purpose, including MsOH [601], CSA [602-604], pTsOH [605], and dehydrated AG50 WX2 resin [606]. In addition to these, triphenylphosphine hydrobromide [607], BCI3 or BBr3 [608], and ceric ammonium nitrate (CAN) [609] are effective for this purpose. 

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The polymerization of 1 mentioned above should be compared with the enzymatic synthesis of chitin reported by Kobayashi and coworkers, in which an oxazoline derivative of A, A -diacetylchitobiose, the repeating unit of chitin was polymerized in the presence of chitinase enzyme via ring-opening addition process to give an artihcial chitin (Scheme 6) [5]. The method using an enzyme, however, may not enable synthesis of nonnatural-type aminopolysaccharide because the reaction catalyzed by chitinase enzyme is limited to the formation of (1 4)-P-glycosidic linkage. 

Maddaford reported the diastereoselective synthesis of C-glycosides 29 using conjugate addition catalyzed by cationic rhodium catalysts such as [Rh(COD)2]BF4 (Eq. 1) [24]. Addition of phosphine hgands to the reaction system inhibited the conjugate addition. It is likely that the enone 28 derived from the pyranose is less reactive toward the conjugate addition. 

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