Synthesis of morpholinols, morpholines and benzoxazines starting from nitroepoxides

Abstract

Nitroepoxides are an underdeveloped class of compounds with wide potential for use in chemical synthesis. Nitroepoxides represent strained systems displaying two highly oxidized vicinal positions by nature of their chemical connectivity and hence are potentially exploitable as synthons with vicinal electrophilic centers. In 1991, Vankar reported the transformation of nitroepoxides into amino ketones.1d Nucleophilic attack of the amine to the β-position of the nitroepoxide followed by nitrite extrusion affords the amino ketone. In that work, nitroepoxides are easily transformed giving 2-hidroxymorpholines and 2-hidroxybenzoxazines. A properly reduction of that gives benzoxazines and morpholines in high diastereoselectivity. These transformations are efficient, provide access privileged, bioactive structures, and produce minimal waste.