Preparation and reactivity of iminoglycals: stereocontrolled, divergent approach to imino sugars

Abstract

The synthesis of 3,4,6-tri-O-acetyl imino D-glucal 2 from D-glucal is reported. This imino glycal participates in a variety of Lewis acid mediated carbon–carbon bond forming reactions by allylic displacement of the C-3 acetate group by added nucleophiles. Allyl silanes, trimethylsilyl enol ethers, alkenes and dialkyl zinc reagents serve as suitable reaction partners. In all the cases studied, the β-anomer is predominant. Using imino glycal 8, epimeric at C-5, it is established that the configuration at C-5 of the piperidine ring plays a major role in controlling the stereochemical outcome. These results are rationalised by invoking the intermediacy of a conjugated N-acyliminium ion. A short stereocontrolled synthesis of (+)-deoxoprosophylline is achieved using this chemistry. Additionally, imino glucal 2 is transformed into bromo piperidine 16, whose X-ray crystal structure is determined. Bromide 16 participates in palladium catalysed Stille and Suzuki cross-couplings allowing access to C-2 substituted imino sugars 17 and 18. In other studies, imino sugar C-glycosides 21 and 22 are made by combining the Lewis acid mediated carbon–carbon bond forming reactions with stereospecific dihydroxylations.