Ligand-Controlled Diastereodivergency in Propargylic Alkylation of Vinylogous Aza-enamine: Construction of 1,3-Stereocenters

The first diastereodivergent propargylic alkylation reaction has been developed. This Cu(I)-catalyzed formal decarboxylative [4+2]-cycloaddition between ethynyl benzoxazinanone and vinylogous aza-enamine delivers tetrahydroquinoline derivatives, bearing 1,3-stereocenters. Access to each diastereomer of the product from the same set of starting materials is possible using either i-Pr-Pybox or BINAP as ligand under otherwise identical reaction conditions. This is the first application of vinylogous aza-enamines in a transition metal-catalyzed trans-formation and the first example of the creation of 1,3-stereocenters in a propargylic substitution reaction. Preliminary experiments with the aim to access each of the product stereoisomers showed promising enantioselectivities.