With hindsight this result could have been predicted, inasmuch as Fraser-Reid's earlier experimental and computational work on the formation of oxacarbenium ions from pentenyl glycosides showed this to be more facile with a six-membered ring bridging the 3- and 4-positions than in the absence of such a ring, and certainly much more facile than in the case of 4,6-benzylidene protected systems [33]. Thus, this system also fits the general mechanistic scheme, with the a-selectivity being again due to a shift in the covalent triflate/ion pair equilibrium. Furthermore, the reversal of selectivity seen across the series 4,6-benzylidene/tetrabenzyl/3,4-bisacetal is in full agreement with the increasing stability of the oxacarbenium ions, as predicted computationally by Fraser-Reid in the glucose series [33].


Weiling Cai prepared a 4,6-O-benzylidene-2,3-di-O-benzyl-a-d-glucopyranosyl thio-glycoside 89 and oxidized it to the sulfoxide 90 in the expectation that activation under the standard conditions for ^-mannosylation would lead to the formation of ^-glucosides. Low-temperature studies in CD2Cl2 showed that both the sulfoxide and the thioglycoside, upon activation with Tf2O or PhSOTf, respectively, provided the a-glucosyl triflate 91 (SH1 = 6.3; ôC1 = 100.6; 3JHi,h2 = 3.5 Hz) in high yield (Scheme 18). However, all couplings except that to methanol were highly a-selective (Table 6) [44].

It is unlikely that this reversal of selectivity can be explained by reduced stability of the glucosyl triflate: variable temperature NMR studies showed that decomposition of the triflate did not set in until above 0°C (i.e., above the decomposition temperature of the corresponding mannosyl triflate). We believe that this result is a function of the differing extent of the anomeric effect in the two series. In effect it is known that the anomeric effect is considerably stronger in mannopyranose than glucopyranose derivatives [45,46]. Thus we suggest that the a- and ^-triflates are in dynamic equilibrium and that the reduced anomeric effect in the glucose series permits a population of the more reactive ^-triflate sufficient for it to serve as a donor in an SN2-like fashion, with Curtin-Hammett kinetics, leading preferentially to the a-glucosides observed. A similar rationale was advanced decades ago by Lemieux




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