A Chalcogen Bonding Catalysis Platform for Isoprenoid Cyclization: Broad Scope and Diverse Product Frameworks

Area of Science:

• Organic Chemistry
• Natural Product Biosynthesis
• Catalysis

Background:

• Isoprenoid cyclization is crucial for synthesizing the largest class of natural products.
• Existing noncovalent catalysis and general synthetic methods for isoprenoid cyclization are limited.
• Developing artificial catalysts for diverse isoprenoid cyclizations is an ongoing challenge.

Purpose of the Study:

• To develop a novel noncovalent catalysis strategy for isoprenoid cyclization.
• To demonstrate the utility of chalcogen bonding in catalyzing these reactions.
• To explore the scope and limitations of this new catalytic platform.

Main Methods:

• Utilizing chalcogen bonding interactions between catalysts and isoprenoids.
• Employing a range of substrates with diverse functional groups (arenes, heteroarenes, carboxylic acids, alcohols, phenols, enols, sulfamides, esters, alkynes).
• Characterizing the resulting cyclized products and their structural diversity.

Main Results:

• Chalcogen bonding effectively catalyzes a wide array of isoprenoid cyclization reactions.
• The method accommodates diverse functional groups, yielding various product classes.
• Complex product frameworks, including seven-membered heterocycles and fused-, spiro-, and bridged-ring systems, were accessed.
• Unusual cyclizations involving prenyl and alkynes were achieved, forming seven-membered rings and six-membered allenes, distinct from gold catalysis outcomes.

Conclusions:

• Chalcogen bonding represents a powerful noncovalent strategy for isoprenoid cyclization.
• This platform offers a versatile and general synthetic method for accessing diverse natural product-like structures.
• The findings open new avenues for catalyst design and the synthesis of complex molecules.