Protecting-group-free O-glysosidation using p-toluenesulfonohydrazide and glycosyl chloride donors

• N′-Glycosylsulfonohydrazides display good reactivity with moderate excesses of n-decanol.
• N′-Glycosylsulfonohydrazides may be a viable alternative to the Fischer glycosidation.
• Glucosyl chloride undergoes methanolysis with β-selectivity under halide exchange conditions.
• Glucosyl chloride is much more reactive than its tetra-O-benzyl analogue towards methanolysis.
• α-Glucosyl chloride may be displaced by methanol under halide exchange conditions.

A range of N′-glycosylsulfonohydrazides (GSHs) display good reactivity but poor stereoselectivity in protecting-group-free O-glycosidations when a moderate excess of the model acceptor n-decanol is employed. This stable, readily-accessed class of donor may be more tractable for the glycosylation of non-volatile acceptors than Fischer’s glycosidation conditions. It is possible to generate unprotected glycosyl chlorides from GSHs in situ. In an effort to find conditions to improve glycosidation stereoselectivity, methanolysis of unprotected glucosyl chloride under halide-ion exchange conditions was examined. Relative to its tetra-O-benzyl analogue, this donor displays moderate, inverted stereoselectivity and a significantly faster reaction rate.

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