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

Area of Science:

• Organic Chemistry
• Catalysis
• Natural Product Synthesis

Background:

• Olefin metathesis is a powerful tool for carbon-carbon bond formation.
• Prenylated dienes are prone to intramolecular cyclization, complicating cross-metathesis.
• Developing selective catalysts for complex substrates remains a challenge.

Purpose of the Study:

• To develop a highly selective cross-metathesis method for prenylated 1,6-dienes.
• To overcome the challenge of entropically favored intramolecular reactions.
• To demonstrate the utility of this method for functionalizing natural products.

Main Methods:

• Utilized a diiodo ruthenium olefin metathesis pre-catalyst.
• Employed Density Functional Theory (DFT) computations for mechanistic understanding.
• Applied a Design of Experiments (DoE) approach for reaction optimization.

Main Results:

• Achieved remarkably selective cross-metathesis of prenylated 1,6-dienes.
• Successfully suppressed the competing intramolecular ring-closing metathesis.
• Demonstrated unprecedented functionalization of diverse terpene natural products.
• Synthesized novel terpene derivatives in a single step.

Conclusions:

• The developed ruthenium-catalyzed cross-metathesis is highly effective for prenylated dienes.
• This method provides a new route for the efficient synthesis of functionalized terpenes.
• The combination of DFT and DoE facilitated the optimization and understanding of the catalytic system.