Oxabicyclo[3.2.1]octadienes as Building Blocks in the Synthesis of Natural Products

Since the initial report by Diels and Alder in 1928, the [4+2] cycloaddition remains one of the most powerful and most frequently employed methods for the construction of six membered ring systems, generating a high degree of structural complexity in a single synthetic transformation. This cycloaddition process not only generates two new σ-bonds, but also establishes up to four new contiguous stereocenters in the process, owing to the high regio- and stereoselectivities displayed by this pericyclic reaction. In the decades following its discovery, Tobey and Law would report on the intriguing reaction of furan, substituted furans, and cyclopentadiene with both tetrachloro- and tetrabromocyclopropene. The two unsaturated systems reacted smoothly to directly produce cycloheptanoid systems, the products of a formal [4+3] cycloaddition reaction. The authors proposed in their early manuscripts that the tetrahalocyclopropenes under-went an initial thermal Diels-Alder cycloaddition to produce the cyclopropyl norbornene derivatives. However, these workers were unable to isolate or characterize the primary cycloadducts and instead observed a product which had spontaneously rearrange by way of a halogen atom migration to yield the bicyclo[3.2.1]octadiene nucleus. The majority of my research has been directed toward the application of this Diels-Alde