Enantioselective Synthesis of Atropisomeric Amides by Dynamic Resolution: Thermodynamic Control with a Proline-Derived Diamine Resolving Agent

By exploiting the thermal instability about the Ar-CO axis at high temperature, atropisomeric amides can be dynamically resolved to provide material with up to 96.5 % ee in 70-80 % overall yield from racemic starting material. The amides are coupled with a diamine resolving agent and equilibrated to single diastereoisomers. Hydrolysis returns enantiomerically enriched amide (see reaction scheme).