Asymmetric Synthesis of (S)-2-Indolinecarboxylic Acid by Combining Biocatalysis and Homogeneous Catalysis

(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.