Synthesis of carbocyclic attached ring systems by pinacol-terminated Prins cyclizations and studies toward a general strategy for the total synthesis of cladiellin, briarellin, and asbestinin diterpenes

Part I describes the first investigation of the use of pinacol-terminated Prins cyclizations to form carbocyclic attached ring systems. Treatment of triisopropylsilyl ethers of (Z)- or (E)-[2-(6,6-dimethoxyhexylidene)cyclohexanol with SnCl₄ provides bicyclic products having attached rings. The approach is synthetically useful in the Z alkylidenecyclohexane series, proceeding selectively by a pathway involving carbon migration in the pinacol rearrangement step, to provide methoxy epimers of 1-(2-methoxycyclohexyl)cyclopentylcarboxaldehyde. Reaction of the corresponding E stereoisomer is more complex and yields a mixture of products resulting from both hydride and carbon migration in the pinacol rearrangement step.; Part II describes the development of a general strategy for the total synthesis of cladiellin, briarellin, and asbestinin diterpenes. The key step of this strategy is condensation and pinacol-terminated Prins cyclization of an (E)- or (Z)-α,β-unsaturated aldehyde and a (S)-carvone-derived cyclohexadienyl diol to form, with complete stereocontrol, the hydroisobenzofuran core of these oxacyclic diterpenes. The formyl tetrahydroisobenzofuran intermediate bearing an isopropyl substituent was efficiently elaborated into the cladiellin diterpene sclerophytin A, whereas the formyl tetrahydroisobenzofuran bearing a 1(S )-methyl-2-(triisopropylsilyloxy)ethyl side chain was converted into an advanced tricyclic intermediate bearing the eight stereocenters common to the briarellin and asbestinin diterpenes.