Chemical Stimulation of Polycyclic Diterpenoid Biosynthesis Using Mercury(II) Triflate/N,N-dimethylaniline Complex: Mechanistic Aspects of a Biomimetic Olefin Cyclization

Article abstract of DOI:10.1021/jo00356a008

A new effective olefin cyclization reagent, mercury(II) triflate/N,N-dimethylaniline complex (1) has been developed.By use of 1, (E,E,E)-geranylgeranyl p-nitrobenzoate (4a) has been efficiently cyclized to give spongian (5) and labdane (6 and 7) type products.When acetate 4b is employed as the substrate, a unique hydroxylative cyclization takes place, affording C-13 hydroxylated products 14 and its stereoisomers.One of the stereoisomers is derived to 17, which is identified with a marine natural diterpenoid, isoaplysin-20, and the reported formula is corrected.On the cyclization of 4b with 1 in the presence of water (or methanol), intermediates in each stage can be trapped to give mono-, bi-, and tricyclic tertiary alcohols 19ab, 20ab, and 14.The structures of bicyclic alcohols 20a and 20b have been definitely established by completion of the total synthesis of (+/-)-(13E)-13-labdene-8,15-diol (21) and (+/-)-aplysin-20 (22b), respectively.These results provide clear experimental evidence on the mechanism of a biomimetic olefin cyclization which takes place in a stepwise manner via conformationally flexible cationic intermediates such as 27, 28 and 29.