Formal Mixed Double Addition to N-Glycosyl Nitrones through Addition–Oxidation–Addition to N-Glycosylhydroxylamines

A protocol for the formal mixed addition of two different C-nucleophiles at C1 and C1'of N-glycosylnitrones has been developed. Addition of Grignard reagents to N-erythrosyl-N-benzylhydroxylamine I affords hydroxylamines 6 almost quantitatively with high diastereoselectivity. These compounds undergo regioselective oxidation to the corresponding C-phenyl nitrones 7, which in turn add a second Grignard reagent to give hydroxylamines 5. Synthetic usefulness of mixed bisadduct 5d has been proved by its enyne ring-closing metathesis to afford the densely functionalized unsaturated piperidine derivative 8