| Description |
The prominence of N-containing molecules in pharmaceuticals and natural products has led the synthetic community to an interest in the formation of enantioselective C-N bonds. One efficient strategy for creating these bonds is the aza-Wacker reaction. Recently, aza-Wacker-type reactions have been developed to generate enantiomerically- enriched, N-heterocycles. Since Stahl and co-workers developed the first example of this in 2011, there have been numerous reports in the literature of enantioselective aza-Wacker cyclizations resulting in the efficient synthesis of enantiomerically-enriched heterocycles. However, to the best of our knowledge, enantioselective, intermolecular aza-Wacker reactions have not been reported. Forming N-C(sp3) bonds, enantioselectively, with the aza-Wacker reaction could provide an attractive approach for the synthesis of non-cyclic, nitrogen-containing organic compounds. With this in mind, a Pd-catalyzed coupling of allylic alcohols and oxygen nucleophiles was recently reported by the Sigman group, resulting in a Wacker-type coupling that is both enantioselective and intermolecular. A similar approach may be designed to perform an aza-Wacker type redox-relay reaction. Herein, a Pd-catalyzed coupling of indoles to alkenols is reported. This reaction not only creates a stereocenter at indole's less-nucleophilic N-1 position, but it is also is the first example of an enantioselective, intermolecular aza-Wacker type reaction. |
