Copper-Catalyzed Three-Component Synthesis of Highly Substituted Morpholines

Unprotected, highly substituted morpholines were obtained through a copper-catalyzed three-component reaction utilizing amino alcohols, aldehydes, and diazomalonates. The transformation was effective for diversely substituted aldehydes and for a broad range of readily available vicinal amino alcohols, including those derived from glycine, alpha-substituted, and alpha,alpha-disubstituted amino acids. Epimerization of morpholines using light-mediated stereochemical editing was demonstrated, and the unprotected morpholine products were readily elaborated through efficient transformations.