Remote glycosylation reactions

The problem of the nucleophilicity of amides in glycosylation reactions is not limited to the sulfoxide method and has been shown to result in the formation of glycosyl imidates from intermolecular reaction with activated donors. It appears that this problem may be suppressed by the prior silylation of the amide [348,349]. Accordingly, it may be sufficient to operate the sulfoxide method with an excess of triflic anhydride when amides are present so as to convert all amides into O-triflyl imidates, which are then hydrolyzed on work-up. Despite these problems, several examples have been published of successful sulfoxide glycosylation reactions with acceptors carrying remote peptide bonds [344,345] and with donors coupled to resins via amide-based linkages [346,347], with no apparent problems reported. Sulfonamides and tertiary amides appear to be well tolerated by the sulfoxide method [340,350],... 

K. Koidc, M. Ohno, and S. Kobayashi, A new glycosylation reaction based on a remote activation concept Glycosyl 2-pyridinecarboxylate as a novel glycosyl donor. Tetrahedron Lett. 32 7065 (1991). 

Perhaps the best studied instance of stereospecificity in a glycosylation reaction that can be related to remote protecting groups is the -directing effect of 4,6-alkyl... 

Scheme 21. A possible remote acetyl group participation in a glycosylation reaction.

Tomono S, Kusumi S, Takahashi D, Toshima K. Armed-disarmed effect of remote protecting groups on the glycosylation reaction of 2,3-dideoxyglycosyl donors. Tetrahedron Lett. 2011 52 2399-2403. 

Carbamate glycosyl donors are another useful class of compounds, which pre sent significant variability in chemical structures (Scheme 3.24). In an early example by Kunz and Zimmer, the N-allyl carbamate donors were used in a remote activation protocol to furnish pyranoside and furanoside products. In this reaction, the N-allyl carbamate donor 146 is activated with dimethyl methylthiosulfonium... 

The chelating capacity of copper Lewis acids has been exploited in a variety of selective alcoholysis reactions. Kobayashi used Cu(OTf)2 to affect remote activation of the anomeric carbon for formation of a glycosyl bond (Sch. 13) [34]. The 2-pyridinecarboxylate group was crucial for success of the alcoholysis of 50 to afford disaccharides 51. The 4-pyridyl derivative and simple dialkylamino derivatives were unreactive. A chelating Lewis acid was required, because BF3 -OEt2 or TMSOTf were ineffective, whereas Sn(OTf)2 afforded a level of reactivity similar to that of Cu(OTf)2. 

The 3-0-diethylthiocarbamoyl libofuranosyl donor 140 was also utilized for the p-stereoselective C-glycosylation by Mukaiyama and co-workers the reaction of 140 and carbon nucleophile 144 produced the coupling product 145 (p/a = 96 4) with an excellent p-selectivity, which presumably resulted from the remote participation of the thiocarbamoyl group at 0-3 of 140 (Scheme 26) [78]. 

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