In situ anomerisation

The anomeric outcome of these glycosylations can also be discussed in more general mechanistic terms. First, the product ratio is governed by competing rates of formation of the a and P glycoside and therefore the glycosylation is kinetically controlled. Second, the Curtin-Hammett principle describes that when two reactants are in fast equilibrium, the 

It is essential that the in situ anomerisation is performed in a solvent of low polarity. In polar solvents, the reaction proceeds via an oxocarbenium ion and the anomeric selectivity is reduced. 

As mentioned above, it is very important that the equilibration between the two ion pairs be faster than the glycosylation, and many different parameters affect this requirement. Often many different reaction conditions have to be examined in order to obtain satisfactory results. Also, small changes in the constitution of the glycosyl donor or acceptor may have a dramatic effect on the stereochemical outcome of a glycosylation. 

---

A major breakthrough in a-glycosidic bond synthesis came with the introduction of the in situ anomerisation procedure.1 Lemieux and coworkers observed that a rapid equilibrium can be established between a and (3 halides by the addition of tetra-w-butyl ammonium bromide (Scheme 4.6). The anomerisation is believed to proceed through several intermediates. At equilibrium, there is a shift towards the a bromide since this compound is stabilised by an endoanomeric effect. Because, the p bromide is much more reactive towards nucleophilic attack by an alcohol,... 

Scheme 4.6 ot-Glycosidic bond synthesis by in situ anomerisation. 

The efficacy of the in situ anomerisation procedure was demonstrated by the condensation of a fucosyl bromide with a glycosyl acceptor in the presence of tetra-n-butyl ammonium bromide to give a trisaccharide mainly as the a anomer (Scheme 4.6). 

The in situ anomerisation procedure requires a fast equilibrium being set up between an ot and p halide or ion pairs. However, some glycosylation... 

Scheme 4.7 In situ anomerisation procedure using different donors.

---