Asymmetric Total Synthesis of Nigerone and <i>ent</i>‐Nigerone: Enantioselective Oxidative Biaryl Coupling of Highly Hindered Naphthols

Abstract

Abstract An enantioselective synthesis of the chiral bisnaphthopyrone natural product nigerone and its enantiomer, ent ‐nigerone, has been realized. The use of constrained 2‐naphthol substrates was critical to producing highly functionalized chiral 1,1′‐binaphthols via asymmetric oxidative biaryl coupling with 1,5‐diaza‐ cis ‐decalin copper complexes. The final natural product was formed via a key eight‐step isomerization process of the coupling product, bisisonigerone, and proceeded with retention of the biaryl configuration. The axial configurations of bisisonigerone and nigerone were definitively established by a combination of circular dichroism (CD) measurements and quantum chemical CD calculations.