Catalytic asymmetric additions of carbon-centered nucleophiles to nitrogen-containing aromatic heterocycles

Abstract

Nearly a century after the first report of the Reissert reaction the first catalytic, asymmetric example was published. Since then there have been a small number of reports of similar reaction types: activation of nitrogen-containing aromatic rings through alkylation or acylation, followed by the addition of a carbon-centered nucleophile to the ring. These reactions place great demands on catalyst design; many of the catalysts are bifunctional, simultaneously activating both nucleophiles and electrophiles. The structures obtained from such reactions may easily be derivatized into natural products or drug-like structures. Despite the elegance of the known examples, there are still many reaction types that have not been reported. In the last decade a small number of highly effective methods have been developed for the catalytic asymmetric addition ofcarbon-based nucleophiles to aromatic nitrogen heterocycles. The resulting structures are of wide potential utility in synthetic and medicinal chemistry. There is a great deal of room for discovery of new reactions in this class. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.