Chemoselectivity donor/acceptor coupling

Besides conformational disarming, one-pot methods also benefit from building blocks that are electronically disarmed. Biao Yu and coworkers utilized this effect in the one-pot assembly of the 19-membered macrolactone-containing tricolorin A (16) (Scheme 6.3) [13, 14], The key design of their synthesis is the chemoselective activation and coupling of the perbenzylated donor 7 to the bis-acyl-containing disarmed bifunctional acceptor 12. The subsequent glycosylation of macrolactone 14 in the same flask formed the protected tricolorin A15 in 43% overall yield, which was deprotected to provide tricolorin A (16). 

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... 

Mydock and Demchenko [48] studied whether the enhanced reactivity of superarmed donors 96, 110, and 775 was sufficient to allow for direct chemoselective couplings. As acceptors were chosen armed benzylated glycosides 725,124, and 125, all bearing the same leaving group (SBox) (Fig. 5.30). 

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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