Studies of an Intramolecular Diels-Alder Approach to the Nargenicins: Involvement of Boatlike Transition States in the Cyclizations of Substituted 1,7,9-Decatrien-3-ones

Article abstract of DOI:10.1021/jo00265a036

The intramolecular Diels-Alder reactions of a series of substituted decatrienones were examined in connection with a planned synthesis of the decalin framework of the nargenicin antibiotic family.The cyclization of triene 7 provided cis-fused cycloadduct 9 with very high diastereoselectivity through transition state 7B_boat with a boatlike conformation of the connecting chain.The Diels-Alder reactions of trienes 19-23 generated mixtures of cycloadducts, but again a high preference for cyclization through boatlike transition states was observed.The involvement of boatlike transition states in decatrienone intramolecular Diels-Alder reactions appears to be general.A detailed analysis is presented that shows that, assuming the transition state is early as suggested by numerous other investigations, the boat decatrienone transition state is actually free of destabilizing eclipsing or other unfavorable nonbonded steric interactions.The boat transition state in the decatrienone cis-fused manifold is favored over the chairlike arrangement in part as a consequence of a stabilizing eclipsing sp³-sp² interaction between the diene and the allylic C-H bond, a relationship that is absent from the chair transition state.