Defluorinative Multi-Functionalization by Fluorine-Assisted Temporary Dearomatization

Because of its unique physical properties, fluorine is often used to develop reaction processes that are difficult to achieve with fluorine-free compounds. For example, sulfur(VI)-fluorine displacement reaction, fluoroalkylation based on the negative effect of fluorine, etc. all exhibit the unique reactivity of fluorine-containing compounds. In addition, fluorine also has unique applications in aromatics chemistry. For example, the introduction of fluorine atoms into phenol derivatives can halt the original process of restoring aromaticity after electrophilic substitution at the dearomatization intermediate, and then introduce nucleophilic species to achieve difunctionalization of phenol derivatives.

Recently, some researchers, inspired by the fluorine-assisted temporary dearomatization strategy, envisioned introducing fluorine atoms into the sulfoxide substrate and constructing temporarily dearomatized sulfonium salt species through the [5,5]-rearrangement developed in the previous stage, and then explore the reactivity of this novel structure to develop the rearrangement-induced polyfunctionalization process of aromatic hydrocarbons.

Studies have shown that the temporarily dearomatized species constructed through rearrangement are unstable but can be derivatized at −95 °C and exhibit diverse reactivities. By using different types of nucleophiles, multi-substituted aromatic derivatives with various structures such as defluorination, desulfurization, and sulfur migration can be obtained through the reaction. Among them, α-substituted enol silyl ether is a nucleophile, and the reaction can obtain a defluorinated and desulfurized 1,2-bifunctional product. When Lewis acid AlCl₃ is introduced, the reaction can produce defluorination and sulfur migration products. In addition, allyl silicon, electron-rich heteroarenes, and organozinc reagents are nucleophiles, and defluorinated 3,4-bifunctional products can be obtained through the reaction. In the conjugated diene step, this intermediate forms a defluorinated 2,3,4-trifunctional product. Aromatic derivatives with various substitution forms lay the foundation for subsequent applications. In addition, the researchers revealed the irreplaceable role of fluorine in the reaction process through mechanism studies, and also gave a reasonable explanation for the rare sulfur migration process.

Reference

1. Defluorinative Multi-Functionalization of Fluoroaryl Sulfoxides Enabled by Fluorine-Assisted Temporary Dearomatization
   Angew. Chem. Int. Ed., 2023, 62