Scheme 8

Scheme 8

the presence of the donor a la Brunckova, is trapped axially to give the anticipated a-mannoside (17a). On the other hand, we suggested that, under the Sun conditions, the oxacarbenium ion is trapped by triflate anion to give an a-mannosyl triflate 20. Then, on subsequent addition of the acceptor, an SN2-like process occurs with formation of the 0-mannoside (170) [27,28].

This mechanistic hypothesis also provided a reason for the poor ^-selectivity observed with secondary alcohol acceptors, even under the Sun conditions, namely, the well-known retardation of SN2 reactions by steric hindrance, leading to the interference of a dissociative mechanism via a Curtin-Hammett type of kinetic scheme. We predicted therefore that reducing the size of the O2 protecting group on mannose would accelerate the SN2 process for any given alcohol and so lead to increased ^-selectivity. We also predicted that a change in solvent from diethyl ether to dichloromethane would further shift any ion pair/covalent triflate equilibrium toward the covalent triflate and so similarly lead to enhanced ^-selectivity [27,28]. Both hypotheses were readily tested and confirmed. Thus, the series of sulfoxides 15, 21 and 22, with decreasing bulk of the O2 protecting group, were prepared and coupled to the rhamnosyl acceptor 23. As seen from Table 1, selectivity increases both as the size of the protecting group decreases and as the solvent is changed from diethyl ether to dichloromethane. Ultimately, with the 2-O-benzyl donor in dichloro-methane as solvent, the a anomer of the product was not detectable [28].

These conditions were then applied to the 0-mannosylation of a range of primary and secondary carbohydrate acceptors with considerable success (Table 2)

Attention was next focused on the use of alternative, nonparticipating protecting groups for the mannosyl donor, and the allyl group was found to be satisfactory at both O2 and O3 (Scheme 9) [27]. Indeed, Zongmin Dai and Greg Barba subsequently used a 2-O-allyl protected donor to form the 0-mannoside linkage in the Hyriopsis schlegelii trisaccharide and the caloporside disaccharide, respectively [2931]. Further work, however, revealed the 4,6-benzylidene group to be indispensable for high ^-selectivity, inasmuch as a 2,3,4,6-tetra-O-benzyl protected mannosyl donor gave very poor selectivity (Scheme 10) [27,28].

Table 1 Reaction of Glycosyl Donors with 23 in Ether and CH2Cl2


Product and yield (%)b Solvent Protocola $-Mannoside a-Mannoside $:a


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