Selective Cross‐Metathesis Versus Ring‐Closing Metathesis of Terpenes, Taking the Path Less Travelled

• Published in: Angewandte Chemie International Edition 2024-12, Vol.63 (52), p.e202412430-n/a
• Main Authors: Iudanov, Keren, Nechmad, Noy B., Poater, Albert, Lemcoff, N. Gabriel
• Format: Article
• Language: English
• Subjects: cross-metathesis; Density functional theory; Dienes; iodide ligands; Metathesis; Natural products; olefin metathesis; Ruthenium; sulfur-chelated ruthenium; Terpenes
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202412430

A diiodo ruthenium olefin metathesis pre‐catalyst was employed to achieve remarkably selective cross‐metathesis reactions of prenylated 1,6‐dienes, effectively overcoming the entropically favored intramolecular ring‐closing metathesis. This reaction was investigated using Density Functional Theory (DFT) computations and fine‐tuned through the application of a Design of Experiments (DoE) approach. The potential of this innovative process was demonstrated through the unprecedented functionalization of various terpene natural products via cross‐metathesis, resulting in the synthesis of new derivatives in a single step. 1,6‐Heptadiene substrates readily ring‐close to form thermodynamically stable five‐membered rings in the presence of metathesis catalysts. However, the unique selectivity displayed by Ru−SCF3−I provides a distinct cross‐metathesis pathway with various prenylated 1,6‐heptadienes, including terpenes. This new methodology presents a promising opportunity for the modification of biologically active compounds.