Synthetic Strategies for Oxygenated Cyclohexanoid Frameworks

Abstract

Highly oxygenated cyclohexanoid frameworks are key structural features in many natural products and remain challenging synthetic targets. Herein, we report investigations into two strategies for their preparation. A high-pressure Diels-Alder reaction enabled the construction of a temporary decalin scaffold, exploiting the stereochemistry established through ring formation, but was ultimately limited by unsuccessful alkene transposition. A semi-pinacol rearrangement strategy sought to introduce stereochemical information through functionalization of a monocyclic precursor but was limited by competing halide-mediated epoxide opening. Together, these studies illustrate two distinct strategies for stereochemical control, bicyclic ring formation and monocyclic functionalization, in the synthesis of oxygenated cyclohexanoid frameworks and highlight the challenges associated with their implementation.