Synthesis of α-(3-Indolyl)glycine Derivatives via Spontaneous Friedel-Crafts Reaction between Indoles and Glyoxylate Imines

Abstract

Mannich-type Friedel-Crafts reaction between indoles and ethyl glyoxylate imines proceeded spontaneously in the absence of an acid catalyst. Ethyl α-(3-indolyl)glycinates were obtained in moderate to high yields. Reaction with (R)-α-methylbenzylamine derived imine afforded chiral α-(3-indolyl)glycinates with good diastereoselectivities (up to 96:4).

Key words

Friedel-Crafts reaction - indolyl glycine - indole derivative - glyoxylate imine - spontaneous reaction

References

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18

Although this reaction could be accelerated by a catalytic to stoichiometric amount of acid (CF₃CO₂H, MsOH, etc.), the yields were not improved and the diastereoselectivities were deteriorated in the following study.

19

Hydrogenation of N-[(R)-α-methylbenzyl] indolyl glycinate: 10% Pd(OH)₂ (20% on carbon), H₂ (5 atm), EtOH, r.t., 24 h, 41% yield of (+)-ethyl (3-indolyl)glycinate (21).