Intramolecular Cyclopropanation/Thermal Fragmentation strategy: Intramolecular Reactions of Diazo Compounds in Natural Product Synthesis

The development of a novel methodology toward the construction of 5-7 ring systems. These ring systems are skeletons of a versatile class of many natural products with diverse biological activities. These structures are accessed starting with the preparation of functionalized cyclobutenes and applying a new intramolecular cyclopropanation/thermal fragmentation strategy. To expand the scope of these reactions to include additional functionality, a tethered diazo moiety has been attached onto the cyclobutene. The substrate is subjected to the transition metal- catalyzed diazo decomposition conditions to afford the desired intramolecular cyclopropanation product. The added functionality provides a handle for further manipulations for the synthesis of natural products with more structural complexity.