Donors, armed/disarmed chemoselectivity

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 concept of armed/disarmed glycosyl donors was subsequently extended by other groups to thioglycosides21 and selenoglycosides.64 A similar strategy has been used by Friesen and Danishefsky to achieve chemoselectivity in electrophilic addition to glycal double bonds.65... 

Ley and coworkers reported the one-pot synthesis of tetrasaccharide 176 by combining selective activation with reactivity-based armed-disarmed glycosylation [113]. As shown in Scheme 6.35, the first chemoselective coupling was achieved via selective activation of the fluoride donor 173 over the selenoglycoside acceptor 174. The resulting disaccharide intermediate was more armed than the bifunctional... 

The result is reminiscent of the original armed/disarmed experiment (Scheme 3) in that each reactant (75 or 76) can serve, separately, as a donor, but when they are forced to compete, one becomes the acceptor and the other the donor, thereby satisfying the condition for chemoselectivity. 

The role as glycosyl donor proceeds through the standard oxocarbenium intermediate 2, which can be trapped by nucleophiles. In aqueous medium the product is an aldose (1, Nu = OH). When such oxidative hydrolyses were probed it was found that with C2-OAcyl substrates the reaction occurs much more slowly than with C2-OAlkyl. This observation has been introduced into a chemoselective coupling [3] protocol that has come to be known as the armed-disarmed strategy. [4] Thus as illustrated in Scheme 4a, the partners 10 and 11 gave disaccharide 12a, with no evidence of the product of self-coupling of 11, nor of further reaction of disaccharide 12a with the acceptor 11, both of which would have occurred at disarmed anomeric... 

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