Journal of the American Chemical Society 2012-03-21

Enantioselective synthesis of tryptophan derivatives by a tandem Friedel-Crafts conjugate addition/asymmetric protonation reaction.

Madeleine E Kieffer, Lindsay M Repka, Sarah E Reisman

Index: J. Am. Chem. Soc. 134(11) , 5131-7, (2012)

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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 (R)-3,3'-dibromo-BINOL in the presence of stoichiometric SnCl(4), and is the first example of a tandem conjugate addition/asymmetric protonation reaction using a BINOL·SnCl(4) 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.