Factors Affecting Regioselectivity in the Intramolecular Diyl Trapping Reaction

An account is presented detailing the nature of the factors which allow use of the intramolecular diyl trapping reaction for the selective construction of either linearly fused or bridged cycloadducts. A plan outlining the possible application of the results to the synthesis of the linearly fused tricyclopentanoid Δ^9.12-capnellene (1) and of aphidicolin (38), a tetracyclic anticancer agent possessing the bridged substructure, is also presented. 1. Introduction 2. First Evidence for Formation of the Bridged Ring System 3. Original Ideas Concerning Why the Bridged Cycloaddition Product was Obtained 4. Initial Attempts to Selectively Synthesize the Bridged System 4.1. A Frontier Molecular Orbital Argument 4.2. Return to a Reconsideration of the Importance of Geminal Alkyl Substitution 4.3. A Change of Plans - New Focus Upon the Diylophile Substituent 4.4. Intervention of Diyl Spin State Considerations and their Importance with Respect to Regioselectivity 4.5. Similarity Between Monoradical and Triplet Diyl Modes of Closure onto an Alkene 4.6. ESR Evidence for Intervention of the Triplet 4.7. Time to Think Again. How can Bridged Cycloadducts be Obtained Selectively? 4.8. Success at Last. Useful Generalizations Concerning How to Achieve Selectivity 4.9. Rationale 4.10. Application to Aphidicolin? 4.11. "Correction" of our Initial Analysis Error: Δ^9.12Capnellene Revisited 5. Concluding Remarks