Synthesis of Unprotected 2-Arylglycines by Transamination of Arylglyoxylic Acids with 2-(2-Chlorophenyl)glycine

Abstract

The transamination of α-keto acids with 2-phenylglycine is an effective methodology for directly synthesizing unprotected α-amino acids. However, the synthesis of 2-arylglycines by transamination is problematic because the corresponding products, 2-arylglycines, transaminate the starting arylglyoxylic acids. Herein, we demonstrate the use of commercially available l-2-(2-chlorophenyl)­glycine as the nitrogen source in the transamination of arylglyoxylic acids, producing the corresponding 2-arylglycines without interference from the undesired self-transamination process.

Arylation of Diethyl Acetamidomalonate with Diaryliodonium Salts En Route to α-Arylglycines

“…Owing to the pharmaceutical relevance and synthetic importance of α-arylglycines, several methods have been developed to date to access them in both racemic and enantiomerically enriched forms from different starting materials. Among them are the classical Strecker synthesis, Petasis and Friedel–Crafts reactions, reduction of iminoesters, transition metal catalyzed α-arylation of glycine derivatives, transamination of α-keto acids, and others (Scheme B). While these methods are effective, they are often limited by several inherent disadvantages, such as the use of noncommercially available starting materials (imines, α-iminoesters), toxic (cyanide-anion sources), and expensive reagents (2-oxo-2-arylacetic acids) or transition metal-based catalysts.…”