Orthogonal activation

Use of orthogonal activation strategies in the synthesis of a disaccharide donor. 

SCHEME 3.23 Orthogonal activation of isomeric glycosyl phosphates. 

Gao ZG, Duong HT, Sonina T, Kim SK, Van Rompaey P, Van Calenbergh S, et al. Orthogonal activation of the reengineered A3 adenosine receptor (neoceptor) using tailored nucleoside agonists. 

Thus, we focused on identifying a compound which contained only one active electrophile and a second latent electrophile, which would require orthogonal activation to couple to the phosphoryl moiety. We identified two potential options capable of this type of reactivity (Scheme 6) (1) alkylation with chloromethyl acetate, which occurred with high selectively for the N1 position, followed by treatment with B-bromocatechol borane to provide bromide 25 and (2) alkylation with (chloromethyl)(4-chlorophenyl)sulfide (26) to produce a mixture of 27 and 28. Activation of sulfur with chlorine resulted in conversion of 27 to chloromethyl intermediate 22. Both 22 and 25 readily converted to 21 upon treatment with 18. 

This study provided one of the first demonstrations [24] that chiral secondary amines can integrate orthogonal activation modes of carbonyl compounds (enamine and iminium ion catalysis) into more elaborate reaction sequences, catalyzing more than one stereocontroUed bond-forming event As detailed in Section 42.2.2, this concept greatly permeated and boosted future developments in the field of asymmetric organocatalytic MCRs. 

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