Diastereoselective Synthesis of Secondary Propargylamines Exploiting CuI-Based Promoters and Determination of Their Relative Configuration by DFT-GIAO Conformational Analysis

The stereoselective synthesis of several secondary propargylamines by the copper-promoted A(3)-coupling reaction of aliphatic and aromatic aldehydes with phenylacetylene and (R)-(+)-phenylethyl-amine is here reported. Two different synthetic methodologies have been investigated in this study, involving CuSO4/NaI and CeCl(3)middot7H(2)O/CuI promoting systems. The reported methodologies were compared in terms of efficiency, diastereoselectivity, and toxicity, both showing advantages with respect to the current methodologies. The relative configurations of each of the obtained propargylamines, previ-ously unknown in the literature, were assigned by comparison of the H-1 NMR experimental chemical shifts with those theoretically predicted via the DFT-GIAO method.