Total Synthesis of Phenanthropiperidine Alkaloids by Sequential Alkylation of N,N‐Dibenzylaminoacetonitrile

Abstract Two representative members of the phenanthropiperidine alkaloid family, tylophorine ( 1 ) and cryptopleurine ( 2 ), were synthesized by a bidirectional alkylation strategy employing dibenzylaminoacetonitrile as a substrate. This approach relies on the unprecedented condensation of metallated α‐aminonitriles with bromomethylphenanthrenes to provide fully substituted α‐aminonitriles, which are subjected to a NaBH 4 ‐mediated reductive decyanation process to form homobenzylic amines. From these intermediates, a terminal leaving group was introduced by simple chemical manipulation, and its displacement by a free primary amine under two favorable cyclization processes led to the formation of the future E‐ring of both alkaloids in high yields. Finally, a late Pictet‐Spengler cyclization ensured the formation of a D‐ring for the alkaloids 1 and 2 .