Stereodivergent Construction of trans-Decalin-Based Terpenoids

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Catalysis

Background:

• Many complex natural products feature a trans-decalin core with oxidized substituents.
• Controlling stereochemistry at the C(4) quaternary center is crucial for synthesizing these molecules.
• Existing methods often lack efficiency or versatility in accessing both equatorial and axial configurations.

Purpose of the Study:

• To develop an expedient and versatile route to a key terpenoid building block.
• To achieve diastereodivergent synthesis of functionalized trans-decalin intermediates.
• To demonstrate the utility of the developed method in natural product total synthesis.

Main Methods:

• A three-step synthesis starting from the chiral pool material (R)-carvone.
• A diastereoselective, intramolecular carboborylation reaction as the key transformation.
• Ligand screening using high-throughput experimentation (HTE) and in silico library design.
• Computational analysis to elucidate diastereoselectivity-determining interactions.

Main Results:

• A versatile terpenoid building block was synthesized efficiently.
• The method uniquely provides either equatorial or axial functionalized products from a single precursor.
• High diastereoselectivity was achieved, with an optimized axial-selective ligand identified.
• The synthetic utility was confirmed through the total synthesis of diterpenoid natural products.

Conclusions:

• A novel and efficient synthetic route to valuable terpenoid intermediates has been established.
• The diastereodivergent carboborylation offers unprecedented control over stereochemistry at the C(4) center.
• This methodology significantly advances the synthesis of complex oxygenated terpenoids and related natural products.