Employing Small Polyfunctionalized Molecules for a Diastereoselective Synthesis of Highly Substituted Indolines

An efficient approach has been developed for the diastereoselective synthesis of 1,2,3‐trisubstituted indolines. The reaction sequence includes the highly diastereoselective reductive amination of 2‐oxo‐1,3‐propanediols, which are prepared by postfunctionalization of Morita–Baylis–Hillman (MBH) adducts, to give substituted 2‐amino‐1,3‐propanediols with an anti relative configuration. A subsequent intramolecular palladium‐catalyzed Buchwald coupling reaction provided the 1,2,3‐trisubstituted indolines in 47–82 % yield. The preference for the anti diastereomer was investigated by Gibbs free energy diagrams and applying theoretical calculations at the M06–2X/6‐31+G** level.