Zinc chloride-catalyzed cyclizative 1,2-rearrangement enables facile access to morpholinones bearing aza-quaternary carbons.

Morpholines and morpholinones are important building blocks in organic synthesis and pharmacophores in medicinal chemistry, however, C3-disubstituted morpholines/morpholinones are extremely difficult to access. Here we show the ZnCl2-catalyzed cyclizative 1,2-rearrangement for the efficient synthesis of morpholinones bearing aza-quaternary stereocenters. A series of structurally diverse C3-disubstituted morpholin-2-ones which are difficultly accessible by existing methods were efficiently constructed from readily available two achiral linear compounds. Notably, mechanistic studies reveal that this reaction proceeds via an unusual sequence of direct formal [4 + 2] heteroannulation regioselectively delivering specific α-iminium/imine hemiacetals followed by a 1,2-esters or amides shift process, which is different from the reported mechanism of the aza-benzilic ester rearrangements.