Breaking Down the Reactivity of λ³-Iodanes: The Impact of Structure and Bonding on Competing Reaction Mechanisms

Abstract

The functionalization of arenes via diaryliodonium salts has gained considerable attention in synthesis, as these compounds react under mild conditions. Mechanistic studies have shown that the formation of corresponding λ(3)-iodane intermediates takes a key role, as they determine the course and selectivity of the reaction. Bridged diaryliodonium salts, featuring a heterocyclic moiety involving the iodine atom, were shown to exhibit a distinctly different reactivity, leading to different products. These products are not just the result of reductive elimination reactions but may also arise via radical mechanisms. Our quantum chemical calculations reveal that the λ(3)-iodane intermediate is also the "gateway" for reactions that are observed only for strained bridged systems. At the same time, we find a remarkable affinity of the hypervalent region to planarity for all reaction mechanisms. This also explains the correlation between the size of the bridge connecting the aryl groups and the reaction products observed. Furthermore, the energetics of these competing reactions are examined by analysis of the mechanisms. Finally, using model compounds, some of the basic features governing the reactivity of λ(3)-iodanes are discussed.

Dividing a complex reaction involving a hypervalent iodine reagent into three limiting mechanisms by ab initio molecular dynamics

“…[12,13] The possibility of an SET mechanism is explored also for the trifluoromethylation of MeCN. Unlike the product of the first step of MeCN-trifluoromethylation, 2, phenyl trifluoromethyl thioether (7) does not represent a reactive intermediate.…”

“…). The electronic and structural properties leading to the distinct reactivity of reagent 1 have been the topic of earlier studies …”

“…The electronic and structural properties leading to the distinct reactivity of reagent 1 have been the topic of earlier studies. [4][5][6][7] The trifluoromethylation reaction with reagent 1 is assumed to occur via a reductive elimination (RE) [7,8] of the electrophilic CF 3 ligand and the nucleophile coordinated to the iodine atom. However, contrary to expectations, RE was shown to be challenged by an S N 2 mechanism on the basis of stationary computations in the gas phase.…”

S‐Trifluoromethylation of Thiols by Hypervalent Iodine Reagents: A Joint Experimental and Computational Study

“…This functional group displays a high degree of chemoselectivity, as demonstrated, for example, by an octapeptide derived from Sandostatin, or by co‐enzyme A . Although the chemistry of iodanes is well established, only recent computational studies revealed the mechanistic versatility of λ 3 ‐iodanes, reminiscent of that of transition metals . We previously investigated the electronic and structural properties leading to the distinct reactivity of reagent 1 as well as polar mechanistic details in combination with N ‐ and S ‐nucleophiles .…”

“…Although the chemistry of iodanes is well established, only recent computational studies revealed the mechanistic versatility of λ 3 ‐iodanes, reminiscent of that of transition metals . We previously investigated the electronic and structural properties leading to the distinct reactivity of reagent 1 as well as polar mechanistic details in combination with N ‐ and S ‐nucleophiles . Thus, the activation of reagent 1 by protonation is essential .…”