A Straightforward Synthesis of Enantiopure 2,6-Disubstituted Morpholines by Regioselective O-Protection/Activation Protocol

Enantiopure 2,6-disubstituted morpholines have been synthesized through the ring opening of chiral, nonracemic oxiranes with nitrogen nucleophiles, under solid-liquid phase-transfer catalysis (SL-PTC) conditions. The beta-hydroxytosyl amides resulting from the ring opening of a first epoxide with TsNH2 was used as nucleophile, after protection of the hydroxyl group, in the reaction with a second oxirane. The morpholine skeleton has been generated through standard functional group chemistry, followed by cyclization of the intermediate beta-hydroxy-beta'-tosyloxy-tosylamides carried out under SL-PTC conditions. N-Tosyl morpholines produced can be employed as building blocks in the synthesis of pharmaceuticals and as chiral tools