A Unified Approach for the Assembly of Atisine- and Hetidine-type Diterpenoid Alkaloids: Total Syntheses of Azitine and the Proposed Structure of Navirine C.

Abstract

A tetracyclic dinitrile was synthesized in twelve steps from cyclohex-2-en-1-one by using a chelation-triggered conjugate addition to a γ-hydroxy-substituted α,β-unsaturated nitrile and an oxidative dearomatization/Diels-Alder cycloaddition cascade as the key steps. The first total synthesis of azitine (in 17 steps) was achieved through a simple reductive cyclization of this intermediate and subsequent transformations while the total synthesis of the proposed structure of navirine C (in 19 steps) was accomplished by a hydrogen-atom-transfer reaction of the tetracyclic dinitrile, Pd/C-catalyzed reductive cyclization, and subsequent functional group manipulation.