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. (AU)