Deconstructing the Catalytic, Vicinal Difluorination of Alkenes: HF-Free Synthesis and Structural Study of p-TolIF₂

Abstract

Recently, contemporaneous strategies to achieve the vicinal difluorination of alkenes via an I(I)/I(III) catalysis manifold were independently reported by this laboratory and by Jacobsen and co-workers. Both strategies proceed through a transient ArI(III)F species generated by oxidation of the ArI catalyst. Herein, an efficient synthesis of p-TolIF from p-TolI and Selectfluor is presented, together with a crystallographic and spectroscopic study. To mitigate safety concerns and simplify reaction execution, an HF-free protocol was devised employing CsF as a substitute fluoride source. The study provides insight into the initial I(I)→I(III) oxidation stage of the catalytic protocol using Selectfluor.

The Electrophilic Fluorination of Enol Esters Using SelectFluor: A Polar Two‐Electron Process

“…Reactions in MeCN(-d 3 )w ere often irreproduciblea nd typically did not reach completec onversion.A na uthentic sample of 2 was prepared through an independents ynthetic route to confirm the assignment. [38] High-quality,r eproducible kinetic data were obtained from 1 HNMR kinetice xperiments;t he use of a small excess of 1 (1.5equiv) led to ap seudo-first order in 3 for three or more half-lives. The reaction between 1 and 3 is first order in 1 as judged from plots of k obs versus [1] ( Figure 1).…”

“…Compounds 2 and [22]BF 4 were prepared according to literature methods. [38,43] Analysis NMR characterisation was carried out using Bruker AV3-400 equipped with al iquid nitrogen Prodigy cryoprobe, or aB ruker AV400 equipped with aB BFO-z-ATMA probe;k inetic data were obtained using aB ruker AVII-600 NMR spectrometer equipped with a BBO-z-ATMA probe. All NMR chemical shifts are quoted in units of parts per million (ppm).…”

Alkene Vicinal Difluorination: From Fluorine Gas to More Favoured Conditions

“…These studies were further developed by Gilmour, who, in 2017, reported HF-free conditions for the synthesis of aryl(difluoro)- 3 -iodanes by using caesium fluoride and Selectfluor ( Figure 8D). 44 The fact that HF is not required for this reaction renders this method the current procedure of choice. Difluoroiodane reagents 13 and 19 are troublesome to store and use because of their sensitivity to light, air, and heat.…”

“…Difluoroiodane reagents 13 and 19 are troublesome to store and use because of their sensitivity to light, air, and heat. [43][44][45] Therefore, conditions for their in situ preparation for alkene difluorination would clearly be advantageous. This problem was solved in 2016, with simultaneous reports from Jacobsen and Gilmour, who developed reaction conditions to generate aryl(difluoro)- 3 -iodanes in situ for alkene difluorination.…”

Enantioselective, Catalytic Vicinal Difluorination of Alkenes

“…Following Hara and Yonedass eminal disclosure of as toichiometric vicinal difluorination of alkenes using p- TolIF 2 , [19] contemporaneous studies by Jacobsen and coworkers [17a] and this laboratory [8,17b] translated the reaction to acatalytic paradigm. Common to both strategies was the in situ generation of ArIF 2 [20,21] using aterminal oxidant and an inexpensive fluoride source.E ncouraged by the efficiency of these closely similar platforms,i tw as envisaged that ac hiral resorcinol catalyst would promote enantioselectivity owing to the high degree of symmetry inherent to these scaffolds. [22,23] Full details of the catalyst and oxidant optimisation are provided in the Supporting Information.…”