Nucleophilic and Radical Heptafluoroisopropoxylation with Redox‐Active Reagents

• Published in: Angewandte Chemie International Edition 2021-10, Vol.60 (42), p.22915-22924
• Main Authors: Tong, Chao‐Lai, Xu, Xiu‐Hua, Qing, Feng‐Ling
• Format: Article
• Language: English
• Subjects: Agrochemicals; conformation; heptafluoroisopropoxylation; Nitrogen; nucleophilic reactions; Phthalimide; Phthalimides; radical reactions; Reagents; redox-active reagents; Substrates
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202109572

The heptafluoroisopropyl group (CF(CF3)2) is prevalent in pharmaceuticals and agrichemicals. However, heptafluoroisopropoxylated (OCF(CF3)2) compounds remain largely underexplored, presumably due to the lack of efficient access to these compounds. Herein, we disclose the practical and efficient heptafluoroisopropoxylation reactions through the invention of a series of redox‐active N‐OCF(CF3)2 reagents. These reagents were readily prepared from the oxidative heptafluoroisopropylation of hydroxylamines with AgCF(CF3)2. The substitutions on the nitrogen atom significantly affected the properties and reactivities of N‐OCF(CF3)2 reagents. Accordingly, two types of N‐OCF(CF3)2 reagents including N‐OCF(CF3)2 phthalimide A and N‐OCF(CF3)2 benzotriazolium salt O′ were used as OCF(CF3)2 anion and radical precursors, respectively. This protocol enables the direct heptafluoroisopropoxylation of a range of substrates, delivering the corresponding products in moderate to excellent yields. Redox‐active heptafluoroisopropoxylating reagents were conveniently prepared from the oxidative heptafluoroisopropylation of hydroxylamines, and then were successfully used for the synthesis of a series of alkyl(aryl) heptafluoroisopropyl ethers.