Fully Stereoselective Nucleophilic Addition to a Novel Chiral Pyrroline N-Oxide: Total Syntheses of (2S,3R)-3-Hydroxy-3-methylproline and Its (2R) Epimer

A new total synthesis of (2S,3R)-3-hydroxy-3-methylproline has been performed via a key intermediate chiral pyrroline N-oxide, obtained from (R)-citramalic acid. This nitrone underwent nucleophilic addition of furyllithium with complete stereoselectivity through a preferential attack anti to the methoxymethoxy group. The correct stereochemistry was established through an oxidation−reduction sequence, which allowed inversion of configuration at C-2.