Construction of C‐N Atropisomers by Aminocatalytic Enantioselective Addition of Indole‐2‐carboxaldehydes to <i>o</i>‐Quinone Derivatives
Vasco Corti, Mathias Kirk Thøgersen, Valdemar J. Enemærke, Nomaan M. Rezayee, Casper L. Barløse, Karl Anker Jørgensen
Abstract
Abstract The first atroposelective aminocatalytic methodology for the construction of C−N atropisomers is presented. The synthesis of this class of axially chiral molecules typically encompasses substrates in which the C−N bond is pre‐formed. In contrast, this work presents the direct coupling of indole‐2‐carboxaldehydes to ortho ‐quinones, to form the stereogenic C−N axis in an atroposelective way. Application of typical secondary amine catalysts furnished the desired product, however, in low yields and as a complex mixture arising from poor regiocontrol among the C 3 ‐ and N 1 ‐sites of the indole core. A new aminocatalyst was designed and synthesized with increased outer‐sphere steric bulk to address these challenges thereby providing good levels of regio‐ and enantioselectivity. A novel library of functionalized and enantioenriched C−N atropisomers was obtained and their synthetic utility was demonstrated by various transformations.