Stepwise Mechanism for the Bromination of Arenes by a Hypervalent Iodine Reagent

Abstract

A mild, metal-free bromination method of arenes has been developed using the combination of bis­(trifluoroacetoxy)­iodobencene and trimethylsilyl bromide. In situ-formed dibromo­(phenyl)-λ3-iodane (PhIBr2) is proposed as the reactive intermediate. This methodology using PIFA/TMSBr has been applied with success to a great number of substrates (25 examples). The treatment of mono-substituted activated arenes led to para-brominated products (2u–z) in excellent 83–96% yields. Density functional theory calculations indicate a stepwise mechanism involving a double bromine addition followed by a type II dyotropic reaction with concomitant re-aromatization of the six-membered ring.

para‐Selective Benzylation of Aryl Iodides by the in situ Preparation of ArIF2: a Hypervalent Iodine‐Guided Electrophilic Substitution

“…The C–C bond forming methodology described herein hints at, and provides increasing evidence for, a new class of reactions involving HIGES. Elegant synthetic pathways incorporating HIGES have resulted in tetraasubstituted benzenes via four C–C bond forming reactions from iodobenzene, the total synthesis of clopidogrel, the total synthesis of broussin, the synthesis of various heterocycles, and the selective bromination of arenes …”

Mechanistic Insights for Iodane Mediated Aromatic Halogenation Reactions

“…However, the detailed mechanism of iodane activation and subsequent aromatic substitution reactions still remains controversial. For example, either nucleophiles [11a,12] such as halide anions X − or electrophiles [11a,b,12b] TMSX (X=Cl, Br) seem to be directly involved in ligand exchange with stable iodanes such as PhI(OAc) 2 , followed by direct I−X bond cleavage of either non‐symmetric [11a] or symmetric [11b,12b] iodanes to induce radical [11a,12a] or electrophilic [11b,12b] aromatic substitution reactions. A clear and general mechanistic picture is thus highly desirable for such iodane‐mediated aromatic substitution reactions.…”

“…Experimentally, other electrophiles such as TMSX (X=Cl and Br) have also been identified as efficient activator of stable iodanes such as PhI(OAc) 2 [11a,b,12b] . As shown in Figure 2A, nucleophilic replacement at the Si‐center of TMSCl with a acetyl C=O group of PhI(OAc) 2 can easily release a chloride anion Cl − , which is only 10.1 kcal/mol endergonic to form the cation PhI(OAc) 2 TMS + .…”

DABCO as a practical catalyst for aromatic halogenation with N-halosuccinimides

“…Metal catalysed C–H activation strategies have also been developed in last decades 19–23 for the selective aromatic halogenation with NXS in which directing groups are usually necessary. In spite of the advantages of in situ formed electrophilic halogen intermediates from cheap halide ions in the oxidation process, 24–29 it requires stoichiometric oxidants or elevated temperatures. In addition, to address the problem that N -halosuccinimides, especially NCS, are substantially less reactive, other versatile catalysts have also been employed.…”