Palladium(0)-Catalysed Stereoselective Synthesis of Unsaturated Aryl β-O-Glycosides and Oligosaccharides: Influence of Protecting Groups and Reaction Conditions

The Pd(0)-catalysed aryloxylation of 6-O-tert-butyldimethylsilyl-3,4-di-O-isobutyloxycarbonyl-d-glucal (3) with a series of phenolic nucleophiles was investigated as an efficient approach to the synthesis of unsaturated aryl O-glycosides. Under the optimized reaction conditions, the corresponding 2,3- and 3,4-unsaturated O-glycosides were obtained in good to excellent yields and with high β-selectivity. In most cases, the reactions proceeded with a marked preference for the formation of 2,3-unsaturated β-glycosides, whereas chlorophenols exhibited distinct reactivity patterns, resulting in diminished regioselectivity and the additional formation of α-anomeric 2,3-unsaturated glycosides. Comparison with the previously reported reactions of 6-O-tert-butyldiphenylsilyl-3,4-di-O-isobutyloxycarbonyl-d-glucal demonstrated a pronounced influence of the silyl protecting group on the product yields and regioselectivity, with the TBDMS-protected donor generally affording higher yields and enhanced selectivity toward 2,3-unsaturated products. Furthermore, the developed methodology was successfully extended to carbohydrate nucleophiles, enabling the synthesis of model trisaccharides and demonstrating its applicability to oligosaccharide synthesis.