Hypervalent Iodonium Zwitterions and Nucleophilic Aromatic Substitution: A Multiple-Step Experiment in Organic Chemistry

Abstract

Iodonium zwitterions are hypervalent iodine compounds in which the iodine center binds to two substituents and carries a positive formal charge which is compensated by a negative charge within the same molecule. Under thermodynamic conditions, iodonium zwitterions allow concerted nucleophilic aromatic substitutions to be performed, followed by rearrangement reactions. In general, nucleophilic aromatic substitutions proceed stepwise, either via an elimination–addition or via an addition–elimination pathway. It has been suggested that nucleophilic aromatic substitutions occur through a transition state which reduces the activation barrier by charge delocalization. The laboratory experiments reported here aim to give students better insight into the concepts of nucleophilic aromatic substitutions and iodonium zwitterions. These experiments can be used to demonstrate a series of important topics and experimental skills in organic chemistry. In addition, they also teach students analytical techniques such as NMR spectroscopy, mass spectrometry, and X-ray diffraction.

Diversification of Complex Diaryl Ethers via Diaryliodonium Intramolecular Aryl Rearrangement

“…To our delight, the products 3a and 3a′ were obtained in yields of 55 and 31%, respectively. The reaction mechanism was proposed to go through a S N Ar pathway with a negatively charged Meisenheimer complex, which has been explained in our previous reports …”

“…Olofsson’s group described the rapid construction of diaryl ethers via ortho -fluoro-substituted diaryliodonium salts, which incorporated strong electron-withdrawing groups . We also synthesized a series of ortho -triflate-substituted diaryliodonium salts, successfully achieving site-selective O-arylation . While the current research on diaryliodonium salts has primarily focused on simple aromatic substrates due to their selectivity limitations imposed by the two aryl groups, a two-step strategy has been reported for the transition-metal-free C–H functionalization of arenes using unsymmetrical iodonium salts as synthetic linchpins, in which the 3,5-dimethyl-4-isoxazolyl group as a dummy ligand enables selective aryl transfer reaction .…”

Ionic Liquids as Organocatalysts for Nucleophilic Fluorination: Concepts and Perspectives

“…This class of nucleophilic fluorination has been under intensive study since the development of diaryliodonium salts as very useful substrates by Pike and coworkers [ 52 ] in 1998. The efficacy of solvent/promoter ILs for fluorination of diaryliodonium salts [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ], however, has not been systematically tested so far. There seems to be a great possibility that ILs could make a profound difference in the efficiency of this class of reaction, because the hypervalent I + in the substrates may directly interact with the IL anion by the strong Coulombic force.…”

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

“…Ortho-trimethylsilyl or boronic acidsubstituted diaryliodonium salts can serve as aryne precursors. Ortho-trifluoroborate-substituted diaryliodonium salts furnished iodonium zwitterions as bifunctional reagents [22][23][24][25]. Additionally, ortho-trifluoromethanesulfonate, N-sulfonyl, or tosylmethylene-substituted diaryliodonium salts can undergo intramolecular aryl migrations [26][27][28].…”