Alkyliodines in High Oxidation State: Enhanced Synthetic Possibilities and Accelerated Catalyst Turn‐Over

Abstract

In contrast to aryliodine(III) compounds, which have matured into a particularly attractive class of oxidants in modern synthesis, the synthetic potential of related alkyliodine(III) derivatives has remained widely underestimated. This is surprising since several unique synthetic possibilities arise directly from the low stability of their central carbon–iodine bond. In this respect, these high‐oxidation‐state iodine compounds resemble environmentally benign variants of the prominent metal counterparts such as those derived from palladium, nickel and copper. This Concept article summarizes the general reactivity trends in alkyliodine(III) chemistry and discusses selected examples of their strategic use as highly reactive, transient species in organic synthesis and homogeneous catalysis.

Iodine Catalysis for C(sp3)–H Fluorination with a Nucleophilic Fluorine Source

“…[16b] Compound 5 a was first reacted in an oxidation with xenon difluoride, which is known to convert alkyl iodides into their corresponding alkyldifluoroiodide(III) derivatives. [17,23] As expected, upon reaction between 5 a and XeF 2 , the corresponding fluorinated product 6 a was obtained in 58 % yield of isolated product from the fluorodeiodination reaction [Eq. (2)].…”

“…Subsequent reductive displacement of the IF 2 nucleofuge would concomitantly provide the fluoride anion for nucleophilic substitution. [17] To obtain a detailed picture, the compound TolIF 2 was prepared following a published procedure. [22] It was submitted together with the molecular iodine catalyst to the fluorination of 1 a.…”

“…Under circumstances that render aminative cyclization by the nitrogen group kinetically non-competent, the intermediary C À I bond can be intercepted by a suitable nucleophile. We envisioned taking advantage of this by generating an alkyliodine(III) intermediate as a super-nucleophuge [17] in order to enhance the rate for the desired fluorination and thereby accelerate the crucial turnover of the iodine catalyst. This strategy on an intermediary carbon-iodine bond would provide the additional advantage of an umpolung scenario, in which the final C À F bond formation becomes feasible through substitution by a nucleophilic fluorine source (Figure 1 C).…”

Iodine Catalysis for C(sp3)–H Fluorination with a Nucleophilic Fluorine Source

“…Under circumstances that render aminative cyclization by the nitrogen group kinetically non‐competent, the intermediary C−I bond can be intercepted by a suitable nucleophile. We envisioned taking advantage of this by generating an alkyliodine(III) intermediate as a super‐nucleophuge in order to enhance the rate for the desired fluorination and thereby accelerate the crucial turnover of the iodine catalyst. This strategy on an intermediary carbon–iodine bond would provide the additional advantage of an umpolung scenario, in which the final C−F bond formation becomes feasible through substitution by a nucleophilic fluorine source (Figure C).…”

Remote Fluorination and Fluoroalkyl(thiol)ation Reactions

“…Subsequent iodination and oxidation gave access to the alkyl iodine(III) intermediate I‐13 . This super‐nucleofuge might favor the key C−F bond formation process with fluoride to give the products [21b] . A broad scope of sulfamides 32 reacted at γ‐position to provide the 1,3‐fluoroamine compounds 34 , meanwhile sulfonamides 33 were fluorinated at δ‐position to give the 1,4‐fluoroamine compounds 35 .…”