Photocatalyzed site- and stereoselective functionalization of β-fucosides

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 reactivity[1] and hydrogen atom transfer (HAT) reactions pave the way towards the direct editing of the sugar backbone.[2] Here we present the photocatalyzed C-5 functionalization of β-fucosides. This is achieved using decatungstate anion (TBADT) as catalyst: the oxygen centers in its excited state are highly electrophilic[3] and, after deactivation of fucosides’ positions 1-4, they are able to generate an oxygen-stabilized tertiary nucleophilic radical in position 5. A scope of several fucosides was carried out, with different yields according to the nature of the substituent at the anomeric position. The most promising substrates were treated with several vinylic olefins, achieving full regio- and stereoselectivity. To the best of our knowledge, this work represents the first example of direct C-H functionalization at position 5 of monosaccharides. References 1. D.J. Gorelik, S.P. Desai, S. Jdanova, J.A. Turner, M.S. Taylor, Chem Sci 2024, 15, 1204. 2. L. Capaldo, D. Ravelli, M. Fagnoni, Chem. Rev. 2022, 122, 1875. 3. V. De Waele, O. Poizat, M. Fagnoni, A. Bagno, D. Ravelli, ACS Catal. 2016, 6, 7174.