Photoinduced, Copper-Catalyzed Enantioconvergent Synthesis of β-Aminoalcohol Derivatives

In view of the frequent occurrence of carbon-nitrogen bonds in organic compounds, the development of powerful new methods for the construction of such bonds is expected to greatly impact many of the fields that utilize organic molecules. While the substitution of an alkyl electrophile by a nitrogen nucleophile is a seemingly straightforward approach to generating a carbon-nitrogen bond, in practice classical substitution pathways have very substantial limitations in the case of unactivated secondary and tertiary alkyl electrophiles. Recent reports that transition metals can catalyze certain substitution reactions of such electrophiles are therefore of considerable significance; however, virtually no methods have been developed wherein absolute stereochemistry is controlled together with carbon-nitrogen bond formation. Herein, we address this dual challenge of reactivity and enantioselectivity, describing a photoinduced, copper-catalyzed enantioconvergent synthesis of β-aminoalcohol derivatives via the coupling of anilines with racemic, unactivated β-haloethers. We apply this method to a catalytic asymmetric synthesis of metolachlor, and we report an array of mechanistic studies that are consistent with the reaction pathway that we propose.