Asymmetric Oxidative Coupling of 2-Hydroxycarbazoles

The biscarbazole skeleton is present in compounds produced by the plants of the Rutaceae family with over 20 naturally occurring molecules. Bishydroxycarbazoles, an important class of these alkaloids, are garnering increased interest for their potential antimalarial, cytotoxic, anti-HIV, and antimicrobial activity. Previous methods to form biscarbazoles are limited to racemic couplings to form the biaryl linkage. The goal of the project is to use a chiral vanadium catalyst and oxygen to achieve high enantioselectivity in a more efficient oxidative coupling. For a range of five substrates, enantioselectivies of 72-79% ee and yields up to 87% were obtained. This technique provides a potential route to various natural products, such as bismurrayfoline E. With the ability to synthesize these natural products, avenues are opened for further study of their biological activity.