Asymmetric Cascade Reaction Sequences via Chiral Lithiated Intermediates

Abstract

The (-)-sparteine-mediated enantioselective intermolecular carbolithiation of (E)-2-propenylarylamines allows for the generation of chiral lithiated intermediates which have broad synthetic potential. These intermediates have been exploited in a series of further in situ reactions with electrophiles to generate a collection of products each containing a common stereogenic center. The stereogenic center, formed in high enantiomeric ratio in the first carbolithiation step, is carried through the cascade reaction sequence to the final products and is independent of electrophile used. The methodology is demonstrated by the synthesis of structurally diverse chiral anilines, indoles, and indolones all with an er of 92:8 (+/-1). The heterocyclic syntheses involve an enantioselective alkene carbolithiation and subsequent trapping of the intermediate organolithium with a suitable electrophile, followed by an in situ ring closure and dehydration to generate the indole or indolone rings.