Biocatalytic Atroposelective Synthesis of Axially Chiral <i>N</i>-Arylindoles via Dynamic Kinetic Resolution
Patricia Rodríguez‐Salamanca, Gonzalo de Gonzalo, José A. Carmona, Joaquín López‐Serrano, Javier Iglesias‐Sigüenza, Rosario Fernández, José M. Lassaletta, Valentı́n Hornillos
Abstract
A highly enantioselective biocatalytic dynamic kinetic resolution (DKR) of configurationally labile N-arylindole aldehydes is described. The DKR proceeds by atroposelective bioreduction of the carbonyl group catalyzed by commercial ketoreductases (KREDs), thus affording the corresponding axially chiral N-arylindole aminoalcohols, with excellent conversions and optical purities. The strategy relies on the racemization of the stereogenic axis that takes place thanks to a transient Lewis pair interaction between the NMe2 and the aldehyde groups. This protocol features a broad substrate scope under very mild conditions.