Chemoselective oxygen-centered radical cyclizations onto silyl enol ethers

Area of Science:

• Organic Chemistry
• Synthetic Methodology
• Radical Chemistry

Background:

• Oxygen-centered radical cyclizations are crucial for synthesizing oxygen-containing heterocycles.
• Accessing tetrahydropyrans via radical cyclization is often hindered by competing side reactions like 1,5-hydrogen abstraction.
• Silyl enol ethers offer unique reactivity profiles in radical reactions.

Purpose of the Study:

• To develop a new oxygen-centered radical cyclization reaction.
• To synthesize versatile siloxy-substituted tetrahydrofurans and tetrahydropyrans.
• To enhance chemoselectivity in radical cyclization reactions.

Main Methods:

• Development of an oxygen-centered radical cyclization protocol.
• Utilization of silyl enol ethers as cyclization substrates.
• Investigation of reaction pathways including alkene cyclization, hydrogen abstraction, and beta-fragmentation.

Main Results:

• Successful synthesis of siloxy-substituted tetrahydrofurans.
• Demonstration of excellent chemoselectivity for cyclization onto silyl enol ethers.
• Enabling the synthesis of tetrahydropyrans, previously challenging via this method.

Conclusions:

• The developed method provides a versatile route to substituted tetrahydrofurans and tetrahydropyrans.
• The high chemoselectivity overcomes limitations associated with competing radical pathways.
• This advancement expands the utility of oxygen-centered radical cyclizations in organic synthesis.