Atomatic Annulation Strategy for the Synthesis of Angularly-Fused Diterpenoid Quinones. Total Synthesis of (+)-Neocryptotanshinone, (-)-Cryptotanshinone, Tanshinone IIA, and (+/-)-Royleanone

Article abstract of DOI:10.1021/jo00131a006

The application of a photochemical aromatic annulation strategy in highly efficient total syntheses of several diterpenoid quinones isolated from the traditional Chinese medicine Dan Chen is reported.The pivotal step in each synthesis involves the assembly of the key tricyclic intermediate via the application of a recently developed "second generation" photochemical aromatic annulation method for the construction of highly substituted aromatic systems.In the total synthesis of neocryptotanchinone, the synthesis of the requisite diazo ketone anulation substrate 7 was achieved using paladium-mediated coupling reactions and an intramolecular Friedel-Crafts cyclization to form key carbon-carbon bonds.The pivotal aromatic annulation reaction was then accomplished by irradiating a solution of the diazo ketone 7 and the readily availabe siloxyalkyne 6 in benzene at room temperature.The desired tricyclic phenol 16 was produced in 58-65percent yield and was then converted to (+)-neocryptotanshinone (1) by treatment with tetra-n-butylammonium fluoride in the presence of oxygen.Cyclization to generate (-)-cryptotanshinone (2) was accomplished in high yield by brief exposure of 1 to an ethanolic solution of concentrated sulfuric acid, and dehydrogenation of 2 with DDQ furnished tanshinone IIA (3).As a further demonstration of the utility of the photochemical aromatic annulation strategy in the construction of angularly-fused diterpenes, the total synthesis of (+/-)-royleanone (4) was also investigated.Irradiation of a solution of the diazo ketone 18 and siloxyalkyne 25 produced the tricyclic intermediate 26, which was converted in two steps to royleanone by desilylation and oxidation.