Stereoselective β-C-aryl glycosylation through Ni-catalysed reductive cross-coupling

In comparison to the well-documented methods for accessing α-C-aryl glycosides, the stereoselective synthesis of β-anomers remains challenging, as reliable routes leading to β-functionalisation are much less documented. Metal-catalyzed cross-coupling is known as one of the most straightforward methods to afford stereoselectively β-C-aryl glycosides, however this strategy often requires the use of elaborated glycosyl donors or sensitive aryl metals along with the use of strict anhydrous and oxygen-free conditions. Herein, we report a robust and stereoselective synthesis of β-C-aryl glycosides by Ni-catalysed reductive cross-coupling using readily available and bench-stable materials. This reaction couples readily available glycosyl halides and aryl halides in the presence of an air stable Ni0 pre-catalyst and a mild reductant. The reaction exhibits excellent β-stereoselectivity with a broad range of carbohydrates and aryl moieties. Mechanistic studies, supported by DFT calculations were performed to provide a rationale for the observed β-stereoselectivity.