Enzyme-like C–H Oxidation of Glucosides Promoted by Visible Light

Abstract

To match nature's prowess at using enzymes to make desired motifs in a regioselective fashion, we explore the use of visible light for the selective oxidation of the hydroxyl group to the corresponding ketosaccharide. This highly admirable approach offers several advantages over the enzymatic approach in terms of yields, the scope of substrates. Herein we report the development of a simple visible-light-promoted selective oxidation of unprotected glucosides that allows for inexpensive access to valuable ketosaccharides building blocks. The method is employed on a variety of different natural and artificial glucosides, is operationally simple and scalable, and is applied to access ketosaccharides rapidly and inexpensively.

Site-Selective Modification of (Oligo)Saccharides

“…These are illustrated for the conversion of methyl glucose into methyl allose (Scheme A, top part), although there are many more examples. The C3-hydroxy group of glucose can be oxidized regioselectively either using catalytic palladium/neocuproine in combination with oxygen or benzoquinone, or alternatively using a photoredox catalyst system in combination with oxygen. , An axial anomeric substituent blocks axial attack of the reducing agent. Therefore, the subsequent reduction leads, in the case of α-glucose derivatives, to the corresponding allose analogues (Scheme A).…”

Site-selective C–H alkylation of myo-inositol via organic photoredox catalysis

“…19 Our group also realized the siteselective modifications of glucosides via a HAT process. 20,21 Although the HAT process has been applied in the direct alkylation of unprotected sugars, it has never been performed on inositol substrates. In order to broaden the applications of HAT chemistry and to synthesize structurally diverse myo-inositol derivatives for drug discovery, herein we report a site-selective alkylation of myo-inositol 1 under a mild condition merging organic photoredox and HAT catalysis (Fig.…”

“…To increase the scope of the alkylating reagent, we commenced our study by utilizing an inactivated alkene 2a as a model substrate for the optimization of the reaction conditions. As our previous research demonstrated, the 4 Å molecular sieve (4 Å MS) plays an important role in the 4-CzIPNcatalyzed HAT process mediated by quinuclidine, 21,22 and we adopted this condition for the alkylation of 1 using 2a without O 2 . To our delight, a C-H alkylation product was successfully isolated in a 39% yield (Table 1, for more details, see ESI †).…”

“…16 The 1 J CH alteration revealed an equilibrium interaction between 1 and TBAP, indicating the presence of hydrogen-bonding interaction between them (for more details, see ESI †), but the exact mechanism of site selectivity is not yet fully understood and needs further exploration. 21 Table 2 Site-selective photoredox C-H alkylation a a Reaction conditions: 40 W Blue LEDs, 1 (0.4 mmol, 2.0 equiv. ), 2a-n (0.2 mmol, 1 equiv.…”

“…16 The 1 J CH alteration revealed an equilibrium interaction between 1 and TBAP, indicating the presence of hydrogen-bonding interaction between them (for more details, see ESI†), but the exact mechanism of site selectivity is not yet fully understood and needs further exploration. 21…”