Chemo- and Diastereoselective Synthesis of N‑Propargyl Oxazolidines through a Copper-Catalyzed Domino A3 Reaction

Herein we describe a highly chemoselective A3-coupling/annulation of amino alcohols, formaldehyde, two kinds of aldehydes and alkynes, catalyzed by copper­(II). This cascade reaction, employing readily available materials, provides a new and highly effective access to chiral N-propargyl oxazolidines with good diastereoselectivity (up to >20:1). In the case of ortho-substituted aromatic aldehydes, an intriguing steric effect is observed: a bulky group exhibits a remarkably adverse effect on the diastereoselectivity for the formation of the title molecule.