Asymmetric Synthesis of (<i>S</i>)‐2‐Indolinecarboxylic Acid by Combining Biocatalysis and Homogeneous Catalysis

Abstract

A tale of two catalysts: (S)-2-Indolinecarboxylic acid, an intermediate for ACE inhibitors, was until recently produced by Fischer indole synthesis and classical resolution in seven steps. However, Perkin condensation to form ortho-chlorocinnamic acid, which is converted to (S)-ortho-chlorophenylalanine using the enzyme phenylalanine ammonia lyase prior to copper-catalyzed ring closure thereof delivers the enantiopure product in just three steps.