Enantioselective Synthesis of Tryptophan Derivatives by a Tandem Friedel–Crafts Conjugate Addition/Asymmetric Protonation Reaction

Abstract

The tandem Friedel–Crafts conjugate addition/asymmetric protonation reaction between 2-substituted indoles and methyl 2-acetamidoacrylate is reported. The reaction is catalyzed by (<i>R</i>)-3,3′-dibromo-BINOL in the presence of stoichiometric SnCl₄, and is the first example of a tandem conjugate addition/asymmetric protonation reaction using a BINOL·SnCl₄ complex as the catalyst. A range of indoles furnished synthetic tryptophan derivatives in good yields and high levels of enantioselectivity, even on a preparative scale. The convergent nature of this transformation should lend itself to the preparation of unnatural tryptophan derivatives for use in a broad array of synthetic and biological applications