Creation of Diversity in Polyquinane Synthesis Involving Metathesis as a Key Step

Polyquinanes are well known for their fused five-membered rings, and they represent structurally complex and biologically significant frameworks found in several natural products. This account highlights the use of norbornene derivatives as key building blocks in synthesizing various polyquinane scaffolds by employing advanced olefin metathesis (OM) strategies. Norbornene's reactivity is due to inherent strain energy and this reactivity promotes various synthetic transformations via ring-opening metathesis (ROM), ring-closing metathesis (RCM), and ring-rearrangement metathesis (RRM), enabling the precise bond reorganization that allows the construction of diverse linear, angular, and propellane types of polyquinane architects along with the higher order tetraquinanes and pentaquinanes. Diels-Alder adducts (DAA) derived from norbornene precursors further enhanced the modularity of these synthetic routes. Such approaches enabled an efficient assembly of cis-anti-cis and cis-syn-cis stereochemical motifs, overcoming challenges posed by strained ring systems and regioselective issues. Moreover, when the metathetic strategies are combined with Diels-Alder reaction (DAR), the complexity in the target molecules can rise quickly due to synergistic effect. These synthetic approaches efficiently construct tetraquinanes and pentaquinanes with intricate stereochemistry that allows the access of natural products and their analogs. These findings highlight the expanded use of alkene metathesis in constructing complex molecular architectures, emphasizing its crucial role in modern organic synthesis and drug development.