Chemoenzymatic syntheses of cis- and trans-3-hydroxy-5-methylpiperidin-2-ones

An approach to the enantioselective synthesis of cis- and trans-3-hydroxy-5-methylpiperidin-2-ones from racemic methyl 4-methyl-5-nitro-2-oxopentanonate 8 is described via the first example of a lactate dehydrogenase catalysed combined kinetic resolution and reduction of a 2-oxo acid. In an alternative approach, stereoselective conjugate addition of nitromethane to a crotonyl camphorsultam gave access to the enantiopure 2-oxo esters (S)-8 and (R)-8 which, in turn, may be converted to the 3-hydroxy-5-methyl δ-lactams.