Disarmed donor

Although glycosyl triflates have been demonstrated to be intermediates with a number of armed donors, and even with disarmed donors not capable of neighboring-group participation, such as the sulfonate esters, typical disarmed donors with esters in the 2-position function in the anticipated manner through anchimeric... 

Remarkably, armed glycosyl donor 160 preferred the secondary-OH of 159 (Scheme 5.37b). Disarmed donor 163 and NPO E108 both preferred the primary-0 H, but the NPOE furnished a single regioisomer 176 (Scheme 5.35c and d). 

The term semi-orthogonality between glycosyl donors (e. g. A and B, O Scheme 16) was introduced by Demchenko [79]. It indicates that whereas selective activation of armed and disarmed glycosyl donor A can be effected in the presence of either armed or disarmed donor B (O Scheme 16a), the opposite is not feasible. Thus, in semi-orthogonal donors, the selective activation of disarmed glycosyl donor B in the presence of glycosyl donor A can not be accomplished (O Scheme 16c). 

In order to confirm this assumption the authors performed the experiments inO Table 9 [113]. Equimolar amounts of armed and disarmed donors 64, and 200 or 202b were allowed to compete for one equivalent of acceptor 215 under the agency of NIS. When one equivalent of NIS was used the major product obtained was that of glycosylation of armed NPG 216, thus in agreement with a process of intermolecular halonium transfer and preferred reaction of the more reactive donor (O Table 9, entries i, iii). When the amount of NIS was increased to three equivalents, the observed ratio of compounds 216 and 217 indicated enhanced coupling of the disarmed donor (O Table 9, entries ii, iv), thus in agreement with the proposed rationalization for the regiopreferences observed in the three-component reactions. 

As expected the superarmed galacto derivative 770 was found to be significantly more reactive than the armed galacto derivative 772. Thus, disaccharides 111 and 775 were formed in 5 min (92 %) and 40 min (85 %), respectively. As in the case of D-glucose, no reaction took place with the perbenzoylated galactoside 114. Similar observations were made with mannosides 115-119 disaccharides 116 and 77S were formed in 50 min (79 %) and 90 min (79 %), respectively, whereas no glycosidation with the disarmed donor 119 took place. To this end, it was determined that not only did the 2-0-benzoyl-3,4,6-tri-0-benzyl donors 96,110, and 775 readily react, while disarmed glycosyl donors 94, 114, and 779 did not, but also, as postulated, they proved to be more reactive than their armed counterparts 93,112, and 777. 

The studies in Scheme IS indicate that selectivity between primary and secondary hydroxyls is donor dependent, NPOEs and disarmed donors fevoring primary, while armed donors favor secondary. 

We wished to extend the RDAS concept to acceptor diols 87 and 90, and for this, the NPOE 84 was used rather than disarmed donor 83, since the former gave much higher yields of the primary disaccharides 86 and 89 (see Scheme... 

The armed/disarmed chemoselectivity, although useful and serviceable, required further investigation to determine the limits of its effectiveness. From the earliest stages it had been evident that a disarmed donor was not inert, because it could be activated, probably under different conditions. Thus the disarmed partner, 10, on its own could serve as a glycosyl donor as will be exemplified in Scheme 6 [25]. However, this role was subjugated when it was forced to compete with the armed counterpart 9a in Scheme 3. 

The merit of such sidetracking can be envisaged in Scheme 6a where the desired product, 31b, could theoretically be obtained by glycosylating 28b with donor 30. However, such coupling would be contrary to the typical armed/disarmed protocol, summarized in option A (Fig. 1), where the disarmed partner functions as the acceptor. In contrast, the objective in Scheme 6a is to reverse this protocol, as in option B, where a disarmed donor, 30 (although more recent studies from Demchenko and coworkers [32] have demonstrated that 30 is indeed a superarmed donor, the validity of the approach remains unchanged), was required to glycosylate an armed acceptor, 28b. 

An additional value of sidetracking is seen in Scheme 6b where disarmed donor 30 was able to serve as both donor and acceptor. Thus routine processing of 30 gave... 

The history of this observation has been recounted elsewhere [91] but, in summary, the disarmed donor 79 was found to glycosylate the diol 80 at 06 to give disaccharide 78 as the only product, even when used in excess. In contrast, the armed counterpart 81 was promiscuous, although going to 02 mainly to give 82 as the major product (Scheme 13a). 

Scheme 12 Qiemoselective activation of disarmed donors 55 or 58 over superdisarmed acceptors 56 or 59. respectively...

Another disarmed donor 2 was activated with diphenyl sulfoxide and Tf20 and coupled with relatively unreactive acceptor 3 with excellent yield (eq 14). ... 

The p anomer spontaneously reacts with nucleophiles to give the desired a-fucoside. On the other hand, so-called disarmed donors such as AcaFucBr carrying electron-withdrawing protecting groups do not react under these eonditions. 

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