Domino Grignard Addition/Cope–House Reaction for the Synthesis of Polyhydroxylated 3-Methylindolizidines Analogous to Castanospermine

The first synthesis of polyhydroxylated 3-methylindolizidines is reported. A straightforward domino butenylmagnesium bromide addition/Cope-House reaction to carbohydrate-derived nitrones afforded efficiently the methyl pyrrolidine moiety with good stereoselectivity, which can be reversed by use of Lewis acids. A subsequent one-pot deprotection/deoxygenation/reductive amination step furnished the desired bicyclic architecture, allowing us to afford the desired final products in 3–4 steps from the starting nitrones and 18–30% overall yields.