Annulations of podocarpic acid derivatives via aryne intermediates

Abstract

Six-membered carbocyclic or five-membered heterocyclic rings were annulated onto ring-C of the podocarpane skeleton by trapping a diterpenoid aryne with cyclic dienes and l,3-dipolar species. The [4+2] epoxy adducts were converted regiospecifically into previously unavailable chrysen-4-ols. The anthranilic acid used to generate aryne at C 13 by nitrite treatment, was synthesised from the 14-amino compound. The latter was generated regiospecifically and in excellent yield via the same aryne by treatment of the 13-bromo compound with sodamide in liquid ammonia The amine was converted into the anthranilic acid by two separate synthetic routes; firstly by directed lithiation and trapping of the lithium species with a CO2 moiety, and secondly via oxidative cleavage of an isatin generated across positions 13 and 14. Attempts to convert the 14-amine into a 1-aminotriazole, an alternative aryne precursor, were unsuccessful. However this led to a new novel heterocyclic phenanthropyrazole ring system in high yield. In an unrelated project a novel procedure was developed for the regioselective hydroxylation of ring-C aromatic diterpenoids via their (η6-arene)tricarbonylchromium(0) complexes. Lithiation/cupration/oxidation gave high yields from methoxyarene complexes with an unhindered ortho position.