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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 (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.

SUBMITTER: Kieffer ME

PROVIDER: S-EPMC3310256 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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

Kieffer Madeleine E ME Repka Lindsay M LM Reisman Sarah E SE

Journal of the American Chemical Society 20120305 11

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, eve ...[more]

PMID: 22390403

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