Cheap and Easy Synthesis of Highly Functionalized (Het)aryl Iodides via the Aromatic Finkelstein Reaction

Abstract

Aryl iodides are superior coupling partners in crosscoupling reactions compared to the corresponding chlorides or bromides. Unfortunately, the iodides are much more expensive, if commercially available at all, than the other halides. Thus, it is often mandatory to transform the available bromides into the corresponding iodides. The copper-catalyzed aromatic Finkelstein reaction turned out to be the method of choice to prepare a number of highly functionalized iodo(het)aryls, including pyridines, 2,2′-bipyridines, and chiral compounds.

Challenging cross couplings, in water, aided by in situ iodination of (hetero)aromatic bromides

“…Firstly, the rate at which equilibrium is reached usually requires less than eight hours which, by contrast, is dramatically faster than the 22 and 40 hours characteristic of prior conversions (Scheme 9). 2,3,11,[20][21][22] Also noteworthy is that the catalyst/solvent system developed accommodates important substrate functionality. Thus, in addition to increased tolerance of sensitive functional groups as documented in the Schemes shown earlier, as well as in Scheme 8, substrates bearing free O-H groups can now readily participate, unlike previous approaches that required considerable manipulation of the hydroxy group.…”

Metal-Mediated Halogen Exchange in Aryl and Vinyl Halides: A Review

“…The scope of the reaction was shown to be remarkably broad and this process clearly is one of the most efficient to date, as exemplified with representative synthetic application of this process that will be overviewed in section Synthetic Applications of Halogen Exchanges in Aryl Halides and its use in natural product synthesis (Fürstner and Kennedy, 2006 ; Carr et al, 2010 ). It was later on extended to other (hetero)aryl bromides (Lützen et al, 2014 ) and to continuous flow chemistry using a sodium iodide packed-bed reactor (Chen et al, 2014 ) and recent studies demonstrated that the reaction time could be shortened using microwave irradiation (Cannon et al, 2011 ) and that other diamines and some triamines (Jin and Davies, 2017 ) could also be used as ligands. Aryl chlorides are in general poor substrates in this reaction.…”

Improved Synthesis and Preparation of Analogues of a Pain-Relieving Pyridin-2(1H)-one

“…After Boc protection of the amino group of 4 , the aromatic Finkelstein reaction was performed to obtain a more reactive iodine intermediate. 7 This allowed us to carry out further Suzuki–Miyaura cross-coupling at lower temperature (60 °C) and then avoid reaction at the halogen position of the product 8 2-bromophenyl group. However, despite numerous attempts, we found that halogen exchange remained incomplete (~2:1 I/Br ratio from 6 ).…”