Concise asymmetric syntheses of novel phenanthroquinolizidines

Abstract

The first preparation of enantioenriched phenanthroquinolizidines with a quaternary center at C_14a was accomplished in seven steps from readily available starting materials. Key steps were an efficient dynamic kinetic allylation of a diastereomeric mixture of chiral tert-butylsulfinyl ketimines and the construction of a piperidine E ring by rhodium catalyzed hydroformylation. The Stevens rearrangement of the corresponding N-benzyl derivatives took place smoothly, allowing the installation of a benzyl moiety at C₉ in a trans relationship with the methyl group. The cytoxicity of the prepared phenanthroquinolizidines was evaluated against different human cancer cell lines.