The Sulfonate Approach

A major development in the sulfonate approach was Crich s serendipitous observation that Kahne-activation of the mannosyl sulfoxide 30 with Tf20 in the presence of DTBMP, at —78°C in CH2CI2, followed by exposure of the intermedi- 

Hindered secondary and tertiary alcohols are also suitable acceptors [51, 103-107]. Mannosyl triflates can also be prepared from thiomannosides and mannosyl bromides by reaction with PhSOTf, or silver triflate, respectively. As in Schuerch s method [100], the order of the addition of the reactants is critical for the success. The intermediate triflates should be prepared first before addition of the alcohol to prevent attack by the latter at the initially formed oxocarbonium ion. Additional requirements are the presence in the mannosyl donors of non-participating (benzyl) groups at 0-2 and 3 and a benzylidene-acetal moiety at 0-4 and 0-6. Crich s method is likely to enjoy widespread popularity because of its simple experimental protocol combined with high yields and excellent P-stereoselectivity. 

Hindsgaul has proposed the isopropylidene acetal as an alternative, reactive tether between 0-2 of the mannosyl donor and the linkage oxygen of the aglycone 

Whereas both primary and secondary carbohydrate alcohols are suitable for the linking, the yield is very sensitive to structure and to experimental conditions. A further limitation is the acid-sensitivity of the acetal-tether this can lead to hydrolysis and transacetalization [114]. 

The 4-methoxybenzyl-assisted P-mannosylation is also suitable for the blockwise synthesis of higher-membered oligosaccharides [117, 118]. For example, DDQ- 

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