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

Abstract

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.