Microfluidic Photocatalytic Ring Expansion of Sulfonium Salts for the Synthesis of Cyclic Sulfides

微流控光催化硫鎓盐环扩展合成环状硫化物

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Abstract

Cyclic sulfides are relevant building blocks in medicinal and synthetic chemistry, with applications ranging from drug discovery to materials science. However, the synthesis of medium-sized cyclic sulfides (6-8-membered rings) remains largely underdeveloped. Herein, we report a photocatalytic ring-expansion strategy for sulfonium salts, granting access to six-, seven-, and eight-membered cyclic sulfides with very high regio- and diastereocontrol. The implementation of the method under continuous flow was key to increasing the efficiency and minimizing product decomposition. Mechanistic investigations revealed the formation of benzylic radicals and carbocation intermediates that control the high regio- and diastereoselectivity observed. Finally, the synthetic utility of this approach was demonstrated in the synthesis of cyclic sulfoxides and sulfones, which can be easily obtained from the corresponding sulfide products.

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