Regioselective O-Sulfonylation of N,N-Bis(2-hydroxyalkyl)tosylamides as a Synthetic Key Step to Enantiopure Morpholines

The synthesis of enantiopure 2,6-disubstituted morpholines was realized through sequential ring Opening of two different optically pure oxiranes by a tosylamide, under solid-liquid phase-transfer catalysis (SL-PTC) conditions, mono-O-sulfonylation of the resulting tosylamido-2,2'-diol, and Cyclization to the morpholine. The crucial step) the regioselective formation of the,monosulfonate, was controlled by taking advantage of the different stereo, electronic, and coordination properties of the oxirane-derived side chains in the backbone As an application of this protocol, a new morpholine-3-carboxamide was synthesized starting from threonine.