Giese-type C-5 selective alkylation on fucoside substrates

The modification of carbohydrates plays a crucial role in drug design and development. However, while functionalization at the anomeric position is widely explored, C-H bond activation still remains underdeveloped. In this context, photocatalysis allows access to traditionally hindered reactivity1 and hydrogen atom transfer (HAT) reactions pave the way towards the direct editing of the sugar backbone.2 In the course of our research program on the fucose-specific bacterial lectin BC2L-C, we became interested in modifying the position 5 of β-fucosides. In this work, this is achieved using decatungstate anion (TBADT) as catalyst: the oxygen centers in TBADT excited state are highly electrophilic3 and, after deactivation by acetylation of fucose 1-4 positions, they generate an oxygen-stabilized tertiary nucleophilic radical in position 5, which undergoes a Giese-type reaction. The reaction was performed on a set of several β-fucosides, with variable yields, depending on the nature of the anomeric substituent. The most promising substrates were treated with several Giese acceptors, achieving full regio- and stereoselectivity. To the best of our knowledge, this work represents the first example of direct functionalization by C-H activation at position 5 of a monosaccharide.