Iron-catalyzed direct α-arylation of ethers with azoles

Abstract

The direct α-arylation of cyclic and acyclic ethers with azoles has been achieved, which features a novel iron-catalyzed cross-dehydrogenative coupling (CDC) process. This practical oxidative method allowed the efficient C2-alkylation of a variety of (benzo)azoles constituting straightforward access to heterocycles of utmost medicinal significance and highlighting the convenient use of feedstock substrates and iron catalysts. A preliminary mechanism supported by DFT calculations is discussed as well.

Using Minisci Reaction for Modification of the tris-Dioximate Metal Clathrochelates: Free-Radical Substitution at the Glyoximate Fragment of an Iron(II)-Encapsulating Cage Framework

“…This allowed minimizing the number of the possible reactive sites of the substrate molecule and, thus, the range of the possible reaction products, as well as to compare the reactivity of its glyoximate (methine) oxime functional group and its methyl substituted analog. The Fenton-type Fe 2+ -tertbutylhydroperoxide system was chosen for in situ generation of the reactive primary tert-butoxyl radicals: [6] they abstract hydrogen atom from 1,4-dioxane thus yielding the secondary 1,4-dioxan-2-yl radicals. These radicals further attack the glyoximate (methine) donor group of the macrobicyclic ligand, and the oxidation of the intermediate spin adduct by iron(III) ions completes this reaction (Scheme 2,i).…”

“…[6,7] Keeping in mind a pseudoaromatic character of the highly conjugated polyazomethine cage frameworks of the tris-dioximate metal clathrochelates and their electron-deficient nature stemming from the positive charge of the encapsulated metal ion, we aimed to apply the Minisci reaction for homolytic alkylation of these macrobicyclic substrates. Homolytic ribbed functionalization of the iron(II) cage tris-dioximates has been earlier performed using free radical substitution of the reactive chlorine atom of a dichloroclathrochelate precursor with carbon-centered radicals as shown in Scheme 1(i) [8][9][10][11][12][13] and by free-radical reductive double alkylation of the methyl substituted azomethine group of the corresponding cage framework as well [14,15] (Scheme 1,ii).…”

Recent Advances of Oxidative Radical Cross‐Coupling Reactions: Direct α‐C(sp3)–H Bond Functionalization of Ethers and Alcohols

“…The iron‐catalyzed C–H bond oxidative transformation is a valuable strategy for the construction of C–C bonds owing to its cheap and environmentally friendly features . In 2015, the group of Correa disclosed an iron‐catalyzed CDC of (benzo)azoles with ethers (Scheme ) . Under the optimized conditions, using FeF 2 as catalyst and tert ‐butyl hydroperoxide (TBHP) as oxidant, a variety of azoles such as substituted benzothiazoles, benzoxazoles, thiazoles and benzimidazoles were well tolerated, affording the coupling products in moderate to good yields.…”

Iron‐catalyzed C−H Activation

“…used iron‐catalyzed cross‐coupling radical reactions. The Correa group reported a novel CDC of azoles …”

“…used iron-catalyzed crosscoupling radical reactions. The Correa group reported a novel CDC of azoles 47. Iron catalytic activation of phenyl C-H with iodobenzene synthesis reaction of aryl compounds.…”