Use of an electrocyclic reaction of o-quinodimethane and an intramolecular Mannich-type cyclisation in diterpene alkaloid synthesis: a synthesis of Nagata's intermediate for (±)-atisine

TLDR: In this paper, an electrocyclic reaction of Z-o-quinodimethane (10), generated in situ by thermolysis of the benzocyclobutene (9), leading to the dihydronaphthalene (8), was elaborated by an intramolecular Diels-Alder reaction of transient triene (6), which was produced from (8) via a nine-step sequence.

Abstract: A synthesis of the tetracyclic amine hydrochloride (2), a pivotal intermediate for Nagata's total synthesis of (±)-atisine, is described. The synthesis commenced with an electrocyclic reaction of the Z-o-quinodimethane (10), generated in situ by thermolysis of the benzocyclobutene (9), leading to the dihydronaphthalene (8). The hydrophenanthrene portion in (2) was elaborated by an intramolecular Diels-Alder reaction of the transient triene (6), which was produced from (8)via a nine-step sequence. The piperidine ring construction was accomplished by employing an intramolecular Mannich-type cyclisation (or an intramolecular iminium-ene reaction) of the hydrochloride (4); the resulting tetracycle (3) was then finally converted into (2) by catalytic hydrogenation. The cis-hydrochloride (27) was similarly converted into the cis-tetracycle (31)via(30), whose structure was established by a single-crystal X-ray analysis, by the same manner.