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

Fumito Saito; Jonathan Becker; Peter R Schreiner

doi:10.1021/acs.joc.0c00167

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

J Org Chem. 2020 Mar 20;85(6):4441-4447. doi: 10.1021/acs.joc.0c00167. Epub 2020 Mar 4.

Authors

Fumito Saito¹, Jonathan Becker², Peter R Schreiner¹

Affiliations

¹ Institute of Organic Chemistry, Justus Liebig University, Heinrich-Buff-Ring 17, 35392 Giessen, Germany.
² Institute of Inorganic and Analytical Chemistry, Justus Liebig University, Heinrich-Buff-Ring 17, 35392 Giessen, Germany.

PMID: 32073267
DOI: 10.1021/acs.joc.0c00167

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't