Executive Summary : | Terpenoids are diverse compounds with significant pharmacological properties. Cascade polyene cyclizations are efficient bioinspired transformations used in terpenoid synthesis, forming simultaneous multiple C-C bonds to generate complex polycyclic frameworks. In recent decades, total syntheses have been observed via cationic cyclizations and metal-catalyzed radical cyclizations, but these methods are less developed. The aim is to explore radical polyene cyclization to achieve structurally complex and chiral polycyclic terpene ring systems. Alkyl radicals have been widely used in natural product synthesis, with metal-mediated radical cascade reactions developed for various radical precursors from different functional groups. A halogen-atom transfer (XAT) method is proposed to generate alkyl radical reactive intermediates, which can be coupled with boronates using Cu- or Ni-catalyzed cross-coupling to access novel non-natural terpenoid frameworks. Different acyclic monoterpenoids and sesquiterpenoid units will be identified and converted to their corresponding primary/secondary alkyl iodides. These alkyl iodides will be converted into the corresponding alkyl radicals via XAT, which can trigger polyene cyclization to form a terpenoid skeleton. The radical intermediate will then be coupled with aryl, alkyl, vinyl, alkynyl, and allyl boronates using Cu- or Ni-catalyzed cross-coupling reactions, creating a new class of terpenoid motifs. These cross-coupled products can be further derivatized to afford novel functionalized polycyclic terpenoid scaffolds. |