Diastereoselective Synthesis of 4-Substituted 5-(p-Tolylsulfinyl)-5,6-dehydropiperidin-2-ones. A New Approach to Methyl L-(2S,4S)-4-Methyl-6-oxopipecolate.

Abstract The sulfoxide-mediated diastereoselective Michael reaction of homochiral α-sulfinylketimines 1a – d and β-substituted ene esters 2a – d (Hua's reaction) was explored. Straightforward cyclization of the open-chain adducts take place under the reaction conditions to provide the 4-substituted 5-( p -tolylsulfinyl)-5,6-dehydropiperidin-2-ones 3 and 7 – 12 , whose stereochemistry is formed in the prior step. Furthermore, the role of the metal ion of the aza-enolate reagents and the steric demands of the O -alkyl ester group have been examined. It seems that the anti -diastereoselectivity depends on metal chelation by the oxygen of the ester as well as the oxygen of the sulfinyl group and the nitrogen in the aza-enolate (( Z )-configuration). In addition, the synthesis of methyl l -(2 S ,4 S )-4-methyl-6-oxopipecolate has been achieved from the suitably functionalized 2-sulfinylketimine 1a (five steps; overall yield: 53–65%).