PhI(OTf)2 Does Not Exist (Yet)**

Article abstract of DOI:10.1002/chem.202003819

PhI(OTf)₂ has been used for the past 30 years as a strong I(III) oxidant for organic and inorganic transformations. It has been reported to be generated in situ from the reactions of either PhI(OAc)₂ or PhI=O with two equivalents of trimethylsilyl trifluoromethanesulfonate (TMS-OTf). In this report it is shown that neither of these reactions generate a solution with spectroscopic data consistent with PhI(OTf)₂, with supporting theoretical calculations, and thus this compound should not be invoked as the species acting as the oxidant for transformations that have been associated with its use.

Full text of DOI:10.1002/chem.202003819

Accepted Article
Accepted Article
Title: PhI(OTf)2 Does Not Exist (Yet)
Authors: Jason Laurence Dutton, Sevan D. Houston, Lachlan Sharp-
Bucknall, Mohammad Albayer, Tania -, and Tiffany Poynder
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.202003819
Link to VoR: https://doi.org/10.1002/chem.202003819
01/2020

10.1002/chem.202003819
Chemistry - A European Journal
PhI(OTf)2 Does Not Exist (Yet)
Tania,+ Sevan D. Houston,+ Lachlan Sharp-Bucknall, Tiffany B. Poynder, Mohammad Albayer,
Jason L. Dutton*
Department of Chemistry and Physics, La Trobe University, Melbourne, Victoria, Australia
+ These authors contributed equally to the work
j.dutton@latrobe.edu.au
ABSTRACT
PhI(OTf)2 has been used for the past 30 years as a strong I(III) oxidant for organic and inorganic
transformations. It has been reported to be generated in situ from the reactions of either
PhI(OAc)2 or PhI=O with two equivalents of TMS-OTf. In this report it is shown that neither of
these reactions generate a solution with spectroscopic data consistent with PhI(OTf)2, with
supporting theoretical calculations, and thus this compound should not be invoked as the
species acting as the oxidant for transformations that have been associated with its use.
Keywords: Iodine, hypervalent, oxidants
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INTRODUCTION
Diacetoxyiodobenzene (PhI(OAc)2) and related species are versatile I(III) oxidants with
applications in organic and inorganic chemistry.[1] Replacement of the acetate ligands with
more electron poor fragments results in derivatives that are stronger oxidants.[2] One such
derivative with an increased oxidative capacity is PhI(OTf)2 which has had reported use as an
in situ generated species in solution by several groups, including our own. In organic chemistry
PhI(OTf)2 has purported use in formation of hydrazones,[3] oxyaminations,[4] dizaeniums,[5]
synthesis of functionalized cyclopropane rings,[6] cyclization of hydroxystilbenes or carboxylic
acids,[7] functionalization of acetylenes,[8] aryl C-H alkylations,[9] and alpha arylations.[10] We
have used it as a starting complex to form Weiss’ reagent, [PhI(Pyr)2]2+ via displacement of
the triflates.[11]
OAc
I
OTf
I
OAc
OTf
Syntheses of PhI(OTf)2 and a related derivative with methyl ester groups at the 3- and 5-
position have been reported by the reaction of two equivalents of TMS-OTf with PhI(OAc)2 or
two TMS-OTf with PhI=O,[3-4, 10, 11b, 12] with the first report coming from Zhdankin using TMS-
OTf and PhI=O.[13] It was postulated that two equivalents of triflic acid may react with PhI=O
to generate PhI(OTf)2 but was found in actuality to generate 1 which could be used to
generate bisiodonium salts.[14] Similarly it was suggested that triflic anhydride may react with
PhI=O in a 1:1 fashion to generate PhI(OTf)2, but experimental results were inconsistent with
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10.1002/chem.202003819
Chemistry - A European Journal
PhI(OTf)2 and more consistent with that of structure 1.[15] Reactions of PhI=O with half an
equivalent of triflic anhydride are known to give Zefirov’s reagent (2).[16]
OTf
I
OTf
I
2 HOTf
I
O
OH
1
Tf2O
2
I
O
I
TfO
O
2
I
OTf
Scheme 1. Reactions of PhI=O with triflic acid and triflic anhydride
While investigating the chemistry of “PhI(OTf)2” with tellurophenes we isolated the mixed
acetate/triflate Te(IV) species 3.[17] This led us to closely examine the CDCl3 proton NMR
spectrum of the mixture of the reaction of PhI(OAc)2 with two equivalents of TMS-OTf, which
clearly showed the species generated under these conditions is in fact PhI(OTf)(OAc) (Scheme
2). The identity of the PhI(OTf)(OAc) (generated from the reaction of equimolar amounts of
PhI(OAc)2 with TMS-OTf) was shortly thereafter confirmed in a remarkable piece of
crystallography on this reactive species by Shafir et al.[18]
OTf
AcO
Ph
OAc
I
Te
3
Te
Ph
Ph
Ph
2 TMS-OTf
OAc
OAc
I
OTf
I
2 TMS-OTf
- TMS-OAc
TMS-OTf
OAc
OAc
Scheme 2. Reaction of PhI(OAc)2 with two TMS-OTf stopping at PhI(OTf)(OAc).
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A series of recent papers published in The Journal of The American Chemical Society and
Angewandte Chemie from the Peng group has reported the arylation of 2-oxazolines or aryl
alkylations, and employs PhI(OAc)2/ 2 TMS-OTf as the oxidant (Scheme 3 for example), using
PhI(OTf)2 as a starting point for theoretical calculations on the reaction mechanism in each
study.[9-10] However, as detailed above, the reaction of PhI(OAc)2 with two equivalents of
TMS-OTf does not result in generation of PhI(OTf)2 either at room temperature or at -40 °C
as specified in the study. The outcomes of their syntheses are not at all in question here, but
rather the starting point of PhI(OTf)2 in their theoretical studies cannot be correct.
R
I
OAc
I
2 TMS-OTf
R
N
N
H
base
R
R
OAc
R
R
-40 deg C
Scheme 3. Reaction of PhI(OAc)2 with 2-oxazolines in the presence of two TMS-OTf, which
was proposed to proceed via PhI(OTf)2 as an intermediate.
Given the continued use of PhI(OAc)2/2 TMS-OTf as a purported method of generating
PhI(OTf)2 we decided it was timely for a detailed study on the possible synthesis and existence
of PhI(OTf)2 from both a synthetic and theoretical perspective using this method and the
original method from PhI=O and 2 TMS-OTf.
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RESULTS AND DISCUSSION
From PhI(OAc)2 and 2 TMS-OTf
Experimental reports on this reaction in CDCl3 are detailed in our previous paper,[17] which
show that this reaction stops at PhI(OTf)(OAc). The structure of PhI(OTf)(OAc) was later
corroborated in a separate study by Shafir and co-workers.[18] A referee for this report
suggested that performing the chemistry in acetonitrile solvent would promote metathesis
of the second acetate group with TMS-OTf. To probe this we isolated PhI(OTf)(OAc) as per
Shafir’s procedure and recorded a 1H proton NMR spectrum in CD3CN, which showed peaks
in the phenyl region at 8.37, 7.83 and 7.68 ppm as well as an acetate peak at 2.17 ppm.
Addition of one equivalent of TMS-OTf to this acetonitrile solution of PhI(OTf)(OAc) resulted
in no change to the chemical shifts and no generation of TMS-OAc.
Theoretical calculations on the free energy change for the reaction were performed at the
wPBE/def2-TZVP level of theory with an acetonitrile PCM solvent model. We found that many
common theoretical methods do a poor job of reproducing the geometry for bound triflate
in comparison to experimental reports. The wPBE/def2TZVP method gives results consistently
close to experimentally reported values across the species of interest in this study.
The calculated DG for the reaction PhI(OAc)2 + TMS-OTf à PhI(OTf)(OAc) + TMS-OAc is – 67
kJ/mol, consistent with experimental observation that this reaction proceeds to completion.
From this point however, the reaction of PhI(OTf)(OAc) + TMS-OTf à PhI(OTf)2 +TMS-OAc has
a calculated DG of + 30 kJ/mol. Considering the overall reaction PhI(OAc)2 + 2 TMS-OTf à
PhI(OTf)2 + 2 TMS-OAc gives a value of -37 kJ/mol. This theoretical data is consistent with our
experimental observation that the reaction stops at PhI(OTf)(OAc) and the 30 kJ/mol free
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energy well this product is in compared to PhI(OTf)2 solidly supports that PhI(OTf)2 should not
be invoked as a species in this reaction system.
DiMagno and co-workers reported isolation and use of a derivative of ArI(OTf)2 containing
methyl ester groups at the 3- and 5- positions of the phenyl ring.[12] Gas phase wPBE/def2TZVP
theoretical calculations on this system show the reaction of ArI(OAc)2 + TMS-OTf à
ArI(OAc)(OTf) + TMS-OAc is favourable with a DG of – 43 kJ/mol. A second metathesis giving
ArI(OTf)2 is also negative at – 58 kJ/mol, unlike the parent phenyl system most often used.
This indicates ArI(OTf)2 may be viable with these electron withdrawing groups present in the
backbone of the phenyl ring. It should however be noted that this species was not structurally
determined by X-ray crystallography in the report and only characterized by NMR
spectroscopy. In the 1H NMR spectrum in CD3CN a substantial unassigned peak at 2.18 ppm
is present, which is a virtually identical chemical shift to the 2.17 ppm observed for the acetate
resonance in PhI(OAc)(OTf). We repeated their synthetic procedure using only one equivalent
of TMS-OTf and obtained a spectroscopically identical material to what DiMagno and co-
workers reported, with the signal at 2.17 ppm integrating consistently with an acetate group,
and downfield from the signal in the starting ArI(OAc)2 material that is coincident with the
residual CHD2CN. Addition of another equivalent of TMS-OTf to this material resulted in no
change to the spectrum, with the exception of the full equivalent of TMS-OTf remaining
unreacted. Thus we conclude that this compound, reported as ArI(OTf)2, is in fact also
ArI(OAc)(OTf).
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From PhI=O
The reaction of 2 TMS-OTf with PhI=O in CH2Cl2, the original report of PhI(OTf)2, was described
to rapidly generate a yellow solution from which low melting crystals or oily substances of
PhI(OTf)2 could be isolated.[13] The byproduct was Me3Si-O-SiMe3 and the proton NMR
chemical shifts at 60 MHz in CD2Cl2 were reported to be multiplets at 8.2 (2H) and 7.5 ppm
(3H).
The calculated DG for the reaction is -41 kJ/mol, indicating the reaction is thermodynamically
feasible. It should however be noted the PhI=O is a polymeric, insoluble solid[19] and the
energy penalty for breaking up and solubilizing the polymer is not considered in the -41
kJ/mol. A referee suggested that using a model of the hydrated dimer of PhI=O, HO-I(Ph)-O-
I(Ph)-OH might better represent the polymer which is terminated by addition of water.[20]
Modelling of the reaction HO-I(Ph)-O-I(Ph)-OH + 4 TMS-OTf à 2 PhI(OTf)2 + 2 TMS-O-TMS +
H2O gives a DG of -100 kJ/mol. The limitation of this model is that more much water is present
in the modelled dimer than in the polymer and elimination of water provides a
thermodynamic sink. Given the experimental reports and negative DG values for both models
we revisited the reaction.
PhI=O was suspended in CD2Cl2 and two equivalents of TMS-OTf were added resulting in the
1
immediate generation of a colourless solution. A H NMR spectrum was taken which in the
upfield region of the spectrum Me3Si-O-SiMe3 and unreacted TMS-OTf were observed in an
approximate 3:1 ratio.[11a] In the aromatic region broad peaks in the locations Zhdankin
reported at 8.2 and 7.5 ppm were present. Iodobenzene, however, was the most abundant
species, with at least one other compound present. After 16 hours, the compound giving
broad signals at 8.2 and 7.5 ppm disappeared and was replaced with signals consistent with
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a disubstituted and a monosubstituted aryl group. A mass spectrum of a sample of the
reaction mixture added to CH3CN gave a signal with m/z at 406.9 in positive ion mode,
consistent with the cation [C6H5-I-C6H4-I]+, which is also consistent with signals in the 1H NMR
spectrum. A 1H NMR taken in DMSO-d6 to compare with literature data confirmed this cation
as the remaining product, with the iodobenzene also remaining present.[21]
Regarding the intermediate, which is consistent with the PhI(OTf)2 spectrum proposed by
Zhdankin, in both CDCl3 and CD2Cl2, the -ortho aryl protons in PhI(OAc)2 resonate at 8.10
ppm.[22] For PhI(OAc)(OTf) the -ortho protons resonate at a chemical shift of 8.25 ppm.[17] It
would be expected that another substitution of acetate for more electron poor triflate would
lead to a further downfield chemical shift for these protons, thus a signal at 8.2 ppm is not
consistent with PhI(OTf)2. The observation that not all the TMS-OTf is consumed in the
reaction is also inconsistent with formation of PhI(OTf)2. In summary, PhI=O reacted with two
equivalents of TMS-OTf does not generate a solution of PhI(OTf)2 based on 1H NMR data.
Triflic anhydride has been suggested to possibly react in equimolar quantities with PhI=O to
generate PhI(OTf)2,[15a] but it has also been found to actually give compound 1,[15b] and also
gives onward reactions consistent with that class of species. Reaction of half an equivalent of
triflic anhydride with PhI=O has been reported to give Zefirov’s reagent.[15a] The calculated
DG for the reaction of PhI=O with one equivalent of triflic anhydride giving PhI(OTf)2 is -166
kJ/mol. The calculated DG for the reaction with a half equivalent of triflic anhydride giving
Zefirov’s reagent is -233 kJ/mol, indicating stopping at this point should be the
thermodynamic sink for the reaction.
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These DG values considered, we decided to revisit the reaction of PhI=O and triflic anhydride
in CD2Cl2 in an equimolar ratio, to compare the results with our observations for PhI=O and
two TMS-OTf. The 1H NMR spectrum of the reaction mixture showed no peaks consistent with
the report of PhI(OTf)2 with no resonances around 8.2 ppm. At least two unique phenyl groups
were present in the mixture with the most downfield peak at 8.5 ppm, but being a minor
product. The 19F NMR spectrum contained unreacted triflic anhydride at -71 ppm and a
resonance at -78 ppm consistent with anionic triflate, and a minor resonance at -76 ppm,
which is consistent with a bound triflate and Zefirov’s reagent and 1 as previously reported.[15]
Reaction of 2 triflic acid with PhI=O to give PhI(OTf)2 is also calculated to be favourable at -69
kJ/mol, giving water as a byproduct. Reaction of PhI=O with 2 equivalents of TfOH in CD2Cl2
gave a 1H NMR spectrum similar to that of the reaction from triflic anhydride, with a mixture
of peaks in the aryl region in the in situ NMR spectrum consistent with the general structure
of 1 as previously described[14] and no evidence for the presence of PhI(OTf)2.
These observations, with triflic acid and triflic anhydride giving different products than the
reaction of PhI=O with 2 TMS-OTf, indicate that the intermediates generated in the TMS-OTf
reaction must differ. This is also consistent with reported reactions on the ring contraction of
alcohol appended cyclobutanes where reaction of PhI(OAc)2 with TMSOTf promoter gives a
substantially different yield than the reaction of PhI(OAc)2 or PhI=O with triflic anhydride as
the promoter.[6b]
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CONCLUSION
In this study we have shown that the methods reported to generate PhI(OTf)2 do not give
solutions of this species. The most common modern purported method, PhI(OAc)2 + 2 TMS-
OTf stops at one metathesis conclusively giving PhI(OTf)(OAc), and PhI(OTf)2 should not be
invoked from this mixture. For the reaction of 2 TMS-OTf with PhI=O, while calculated to be
thermodynamically feasible, we do not believe PhI(OTf)2 is generated and then decomposes
as only half of the TMS-OTf is consumed when the reaction ceases at room temperature and
the NMR data of the reaction mixture is not consistent with PhI(OTf)2. In summary, while
reactions using the above methods previously reported in the literature all result in
compounds containing oxidizing I(III) sources which have been used effectively for organic
transformations, the molecule PhI(OTf)2 itself does not (yet) exist. We would again clarify that
the organic transformations induced by the I(III) in these systems are not in question. Rather
the I(III) oxidant is incorrectly identified which impacts theoretical studies if the incorrect
starting energies are used due to an incorrect compound being used, as well as the potential
of the unintended presence of acetate possibly being a confounding factor in the desired
chemistry.
Acknowledgements
We thank La Trobe University and the Australian Research Council (FT16010007,
DP200100013) for their generous funding of this work. We thank Dr. Christian Hering-
Junghans for providing a 1H NMR of TMS-OAc in CD3CN.
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TOC Fig
PhI(OTf)2 has been invoked as an intermediate in I(III) mediated oxidations. In this
communication we show that the methods proposed to generate PhI(OTf)2 do not give
solutions spectroscopically consistent with this species.
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