Practical catalytic enantioselective syntheses of 5-phenylbicyclo2.2.2oct-5-en-2-one A concise entry into chiral diene ligands

摘要

Chiral 5-phenylbicyclo[2.2.2]oct-5-en-2-one (1) was required as intermediate for the synthesis of an Active Pharmaceutical Ingredient. The published route1 afforded 1 in < 0.5% yield, following a long sequence with steps that are not acceptable for scale-up. Up to 90 kg of enantiomerically pure 1 had already been produced by a Diels-Alder approach, followed by a chiral separation of rac. 1.2 An enantioselective route was required for larger scales. Two practical routes to 1 are presented herein, both relying on catalytic enantioselective catalysis. Just two steps are required to synthesize chiral diene ligands (like Hayashi's bod* ligands)3 from now readily available 1. Eleven new chiral dienes are presented herein. As an efficient access to bod* ligands is still missing, this protocol should be beneficial for the widespread use of this new authoritative ligand class.