A novel Prins cyclization through benzylic/allylic C-H activation.

Area of Science:

• Organic Chemistry
• Synthetic Methodology
• Catalysis

Background:

• Tetrahydropyran rings are prevalent structural motifs in natural products and pharmaceuticals.
• Efficient and stereoselective synthesis of substituted tetrahydropyrans remains a key challenge in organic chemistry.
• Current methods often require multiple steps or specialized reagents, limiting their applicability.

Purpose of the Study:

• To develop a step-economic and efficient method for constructing tetrahydropyran rings.
• To achieve high yield and stereochemical fidelity in the synthesis of equatorial-trisubstituted Prins products.
• To utilize sequential benzylic/allylic C-H bond activation and nucleophilic attack on unactivated olefins.

Main Methods:

• Employed sequential benzylic/allylic C-H bond activation via DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone) oxidation.
• Utilized nucleophilic attack of an unactivated olefin onto the activated intermediate.
• Applied the method to benzyl and allyl homoallylic ethers.

Main Results:

• Successfully constructed the tetrahydropyran ring in a step-economic manner.
• Obtained equatorial-trisubstituted Prins products with high yields.
• Demonstrated excellent stereochemical fidelity in the product formation.

Conclusions:

• The described method provides an efficient and stereoselective route to substituted tetrahydropyrans.
• This approach offers a valuable tool for accessing complex molecular architectures.
• The strategy highlights the potential of sequential C-H activation and olefin cyclization.