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

多米诺格氏加成/科佩-豪斯反应合成与卡斯帕明类似的多羟基化3-甲基吲哚里西啶。

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Abstract

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.

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