Tuning Glycosyl Donor Reactivity via Nitroarene Protecting Groups: A Semiarmed Strategy for Selective Glycosylation

A modular strategy reports to tune glycosyl donor reactivity using nitroarene protecting groups. These groups suppress donor reactivity and can be chemically converted into activating groups, enabling a switchable system. This approach broadens the armed–disarmed glycosylation strategy and allows for efficient, selective oligosaccharide synthesis using precisely controlled donor reactivity.

Herein, a modular strategy for tuning the reactivity of glycosyl donors using nitroarene (NA) protecting groups such as 4-nitrobenzyl, 4-nitrobenzoyl, and 4-nitrophenyl. The electron-withdrawing nature of the nitro group markedly reduces donor reactivity, enabling selective activation. Notably, these NA groups can be readily transform into electron-donating pivaloylaminoarene (PA) and methoxycarbonylaminoarene (MCA) groups via nitro reduction followed by acylation or carbamation. This chemical conversion significantly enhances donor reactivity, offering a switchable reactivity platform. Relative reactivity values (RRVs), determined through competitive glycosylation, establish the reactivity trend: NA < arene < PA < MCA. Applying this strategy, an efficient synthesis of a series of disaccharides is achieved, demonstrating its utility in extending the conventional armed–disarmed approach in glycosylation chemistry.

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