Synthesis of Pharmaceutically Relevant 2‐Aminotetralin and 3‐Aminochroman Derivatives via Enzymatic Reductive Amination

Abstract

Abstract2‐Aminotetralin and 3‐aminochroman derivatives are key structural motifs present in a wide range of pharmaceutically important molecules. Herein, we report an effective biocatalytic approach towards these molecules through the enantioselective reductive coupling of 2‐tetralones and 3‐chromanones with a diverse range of primary amine partners. Metagenomic imine reductases (IREDs) were employed as the biocatalysts, obtaining high yields and enantiocomplementary selectivity for >15 examples at preparative scale, including the precursors to Ebalzotan, Robalzotan, Alnespirone and 5‐OH‐DPAT. We also present a convergent chemo‐enzymatic total synthesis of the Parkinson's disease therapy Rotigotine in 63 % overall yield and 92 % ee.