Synthesis and Conformational Analysis of Parent Perhydroazulenes Reveal an Energetically Preferred cis Ring Fusion.

Perhydroazulenes are common structural motifs in various terpene natural products. Herein, we present the synthesis of parent cis- and trans-perhydroazulenes. Conformational analysis performed with density functional theory (DFT, e.g., B3LYP, M06-2X) and MP2 geometry optimizations with a cc-pVTZ basis set, followed by CCSD(T)/cc-pVTZ single-point energy computations reveals that the cis isomer is 0.7 kcal mol-1 more stable than the trans isomer. Steric and torsional strains present in the trans isomer are responsible for this unexpected relative cis/trans stability.