Photocatalytic transformations of the anomeric carbon of monosaccharides

Photocatalysis has proved to be a valid instrument to overcome the classic problems related to functionalization of carbohydrates, enabling new pathways of reactivity and leading to high-value intermediates. In this context, we are focusing our attention on different structural modifications of monosaccharides that can be performed photochemically, such as arylation and reduction of OH groups. Inspired by a paper by MacMillan and co-workers on the metallaphotoredox deoxygenative arylation of alcohols using an Ir photocatalyst, we here report a cross-coupling process for the synthesis of aryl glycosides, whose applications are widespread in drug development, material science and biochemistry. These derivatives can be synthesized from monosaccharides unprotected at the anomeric position by employing organic dyes as photocatalysts and a Ni complex to promote the C-C bond formation between an aryl halide and the anomeric carbon of the substrate (in-situ activated by a N-heterocyclic carbene). A scope on carbohydrate derivatives and aryl halides will be shown in this contribution. A synthetic method for the reduction of lactols to pyranes has been also developed, exploiting hydrogen atom transfer (HAT) and specifically combining an Ir-based photocatalytic cycle with a thiol (R-SH)-mediated H atom donation. This approach represents a faster and greener alternative compared to tedious, multi-step and (often) heavy metal-based procedures to get important carbohydrate derivatives. The resulting products are 1-deoxy sugars, an important class of synthetic intermediates for the preparation of natural synthetic analogues, such as Aeruginosin 298-A core and Ophiocerin D.