Hexafluoroisopropanol-assisted selective intramolecular synthesis of heterocycles by single-electron transfer

Identifier:  imarina:9378022

Handle: https://hdl.handle.net/20.500.11797/imarina9378022

Authors:  Xie J; Zhang J; Kasemthaveechok S; López-Resano S; Cots E; Maseras F; Pérez-Temprano MH

Abstract:
Intramolecular amination of remote aliphatic C–H bonds via hydrogen-atom transfer reactions has become a powerful tool for accessing saturated nitrogen-containing heterocycles. However, the formation of six-membered rings or oxa-heterocycles remains a formidable challenge for Hofmann–Löffler–Freytag reactions. Here we show how by simply combining bench-stable (bis(trifluoroacetoxy)iodo)benzene and hexafluoroisopropanol (HFIP) we can switch from the well-established Hofmann–Löffler–Freytag mechanism to a different versatile reaction pathway that enables selective C(sp3)–H bond functionalization. We have exploited the facile formation of radical cations via single-electron transfer, in the presence or absence of light, to synthesize pyrrolidines and piperidines, including drug-type molecules, along with O-heterocycles. Experimental and computational mechanistic studies support two distinct mechanistic pathways, depending on the electron density of the substrate, in which the HFIP plays a multifunctional role. (Figure presented.)