Synthesis of 3-Indolylglycine Derivatives via Dinuclear Zinc Catalytic Asymmetric Friedel-Crafts Alkylation Reaction

J Org Chem. 2016 Oct 7;81(19):9227-9234. doi: 10.1021/acs.joc.6b01805. Epub 2016 Sep 27.

Abstract

A direct asymmetric Friedel-Crafts (F-C) alkylation reaction between a wide range of indoles and ethyl 2-(4-methoxyphenylimino)acetate catalyzed by Trost's dinuclear complex is reported. A series of 3-indolylglycine derivatives were synthesized in enantioselectivity of up to >99% enantiomeric excess (ee) using 10 mol% catalyst loading under mild conditions. This atom economic reaction could be run on a gram scale without impacting its enantioselectivity. The absolute stereochemistry of catalytic products was determined by correlation with a known configuration compound. A possible mechanism was proposed for the asymmetric induction.

Publication types

  • Research Support, Non-U.S. Gov't