A Convenient Synthesis Of 3,4-Di-O-Acetyl-Drhamnal (3,4-Di-O-Acetyl-6-Deoxy-D-Glucal)

1,5-Anhydro-2-deoxy-arabino-hex-1-enitols, such as the title compound, are versatile intermediates for the synthesis of a number of 2,6-dideoxy sugars commonly found in natural products. Part of their utility stems from the fact that they can be used directly in synthesis or converted into deoxy sugar hemiacetal donors for highly stereoselective glycosylation reactions. A number of methods for the preparation of these molecules have been described in the literature, which typically involve converting the C–6 oxygen of d-glucal into either a sulfonate ester or a halide, followed by reduction. Although powerful, these approaches suffer from limitations that become apparent on a larger scale. In the case of the sulfonate ester approach, reduction is typically carried out with an excess of LiAlH4, which has been reported to be problematic on scale-up. Alternatively, the sulfonate ester can be converted to a bromide or iodide, for radical dehalogenation. This latter approach adds a step to the synthetic sequence, and typically requires the use of stoichiometric amounts of highly toxic trialkyltin hydrides, which could be avoided using less-toxic alternatives.