Palladium‐Catalyzed Enantioselective Desymmetrizing Aza‐Wacker Reaction: Development and Application to the Total Synthesis of (−)‐Mesembrane and (+)‐Crinane

Abstract

AbstractReported is an unprecedented catalytic enantioselective desymmetrizing aza‐Wacker reaction. In the presence of a catalytic amount of a newly developed Pd(CPA)2(MeCN)2 catalyst (CPA=chiral phosphoric acid), a pyrox ligand, and molecular oxygen, cyclization of properly functionalized prochiral 3,3‐disubstituted cyclohexa‐1,4‐dienes afforded enantioenriched cis‐3a‐substituted tetrahydroindoles in good yields with excellent enantioselectivities. A cooperative effect between the phosphoric acid and the pyrox ligand ensured efficient transformation. This reaction was tailor‐made for Amaryllidaceae and Sceletium alkaloids as illustrated by its application in the development of the concise and divergent total synthesis of (−)‐mesembrane and (+)‐crinane.