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

• Published in: Journal of the American Chemical Society Vol. 134; no. 11; pp. 5131 - 5137
• Main Authors: Kieffer, Madeleine E, Repka, Lindsay M, Reisman, Sarah E
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 21.03.2012; Amer Chemical Soc
• Subjects: Acrylates - chemistry; Chemistry; Chemistry, Multidisciplinary; Indoles - chemistry; Molecular Structure; Physical Sciences; Protons; Science & Technology; Stereoisomerism; Tryptophan - chemical synthesis; Tryptophan - chemistry; CATALYSIS; ASYMMETRIC-SYNTHESIS; LEWIS-ACID; SILYL ENOL ETHERS; ALPHA-AMINO-ACIDS; CHIRAL BRONSTED ACID; BIS(OXAZOLINYL)PYRIDINE-SCANDIUM(III) TRIFLATE COMPLEXES; 1,4-ADDITION/ENANTIOSELECTIVE PROTONATION; ALKYLATIONS; INDOLES
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja209390d

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 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.