New synthesis of diaryliodonium sulfonates from arylboronic acids

Article abstract of DOI:10.1016/S0040-4039(00)00861-3

Diaryliodonium salts, precursors to [¹⁸F]fluoroaromatics, have been prepared, in a regioselective manner, from readily available arylboronic acids eliminating the need for acid sensitive and toxic organotin intermediates. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00861-3

Tetrahedron Letters 41 (2000) 5393±5396
New synthesis of diaryliodonium sulfonates from
arylboronic acids
Michael A. Carroll,a Victor W. Pikeb and David A. Widdowsona,*
aDepartment of Chemistry, Imperial College of Science, Technology and Medicine, London SW7 2AY, UK
bChemistry and Engineering Group, MRC Cyclotron Unit, Imperial College School of Medicine,
Hammersmith Hospital, Ducane Road, London W12 0NN, UK
Received 8 May 2000; accepted 23 May 2000
Abstract
Diaryliodonium salts, precursors to [18F]¯uoroaromatics, have been prepared, in a regioselective man-
ner, from readily available arylboronic acids eliminating the need for acid sensitive and toxic organotin
intermediates. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: halogens and compounds; halogenation; hypervalent elements; boron and compounds.
Iodine, like the other halogens, is found typically in monovalent form (oxidation state: ^1).
However, due to its large size and polarisability, it is able to form stable polycoordinate, multi-
valent compounds. Compounds of this type, containing hypervalent iodine, have been known for
over a century and have received considerable attention. The ability of these compounds to act as
both selective reagents and intermediates has formed the basis for this interest.1 3
Our interest in the most numerous member of this group, the diaryliodonium salts, arose from
the demonstration that they are suitable precursors for the formation of ¯uoroarenes by the
action of ¯uoride ion.4,5 We have extended this methodology to the introduction of the ¯uorine-
18 label (t
1
ˆ 109:7 min) in the form of [18F]¯uoride ion.6,7 This methodology has distinct
advantages2 over conventional electrophilic procedures, which employ molecular [18F]F2, as
[18F]¯uoride can be produced in higher amounts and higher speci®c radioactivity by several
orders of magnitude.8 This is an important consideration for 18F-labelled organics employed as
radioligands for positron emission tomography (PET) ,9 a well established clinical research tool,
in for example, the use of l-6-[18F]¯uoro-DOPA10,11 in the study of brain dopaminergic neuron
density in movement disorders such as Parkinson's disease.
We have recently reported the regioselective preparation of diaryliodonium salts using aryl-
trialkylstannanes as intermediates.12,13 Although successful, this methodology raised a number of
concerns: the use of toxic organostannane intermediates in the production of radioligands for use
* Corresponding author. Tel: +44 (0) 20 75945779; fax: +44 (0) 20 75945804; e-mail: d.widdowson@ic.ac.uk
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00861-3

5394
in PET and the susceptibility of electron-rich aryltrialkylstannanes to protolysis which makes
their puri®cation arduous and also introduces a source of contamination by formation of the
diaryliodonium salt.
As a result, we sought an alternative procedure which would address these concerns, yet still
provide an ecient and highly regioselective method for the production of our targets. A recent
.
report demonstrated that treatment of PhI(OAc)2 with BF3 Et2O followed by the addition of a
vinylborane and then aqueous NaBF4 was an ecient method for the preparation of vinyl-
aryliodonium tetra¯uoroborates.14 It was also brie¯y mentioned that arylboronic acids may also
be employed under these conditions and we decided to investigate this class of substrate.
Unavoidable dilution of the isotopic ¯uorine label occurs when tetra¯uoroborate salts are used
and as such they are not appropriate precursors for the preparation of 18F-labelled compounds in
high speci®c activity.15,16 We therefore turned our attention to the preparation of salts which
possessed counter ions compatible with the radio¯uoridation process, in this case diaryliodonium
y
{
.
tri¯ates and tosylates. The reaction of phenylboronic acid with PhI(OAc)2 2TfOH, in dichloro-
methane at room temperature, gave diphenyliodonium tri¯ate in 92% yield (Table 1: entry 1).
Table 1
Preparation of aryl(phenyl)iodonium salts
y
Typical procedure for the formation of diaryliodonium tri¯ates: Tri¯uoromethanesulfonic acid (0.88 ml, 10 mmol) was
added dropwise, at ^30ꢀC, to a stirred suspension of diacetoxyiodobenzene (1.61 g, 5 mmol) in dichloromethane (50
ml). After 30 min the mixture was allowed to warm to room temperature and stirred for a further hour when it was
recooled (^30ꢀC) and the arylboronic acid (5 mmol) added. The resulting mixture was allowed to warm to room tem-
perature overnight when the solvent was removed in vacuo to give the crude product.
{
Typical procedure for the formation of diaryliodonium tosylates: The arylboronic acid (5 mmol) was added to a stirred
suspension of hydroxy(tosyloxy)iodobenzene±Koser's Reagent (1.96 g, 5 mmol) in dichloromethane (50 ml). The
resulting mixture was stirred at room temperature overnight when the solvent was removed in vacuo to give the crude
product.

5395
This success prompted us to determine the generality of the process and we found that a range of
diaryliodonium salts could indeed be prepared in good yield, from the appropriate arylboronic
acid, under these conditions (Scheme 1; Table 1). The eciency of the iodine±boron exchange was
evident as in all cases, analysis of the crude reaction mixture indicated near quantitative formation
of the desired diaryliodonium salt. However, small amounts of highly coloured by-products were
generated in the process making multiple recrystallisations necessary to obtain the products as
analytically pure white crystalline solids. This `darkening' of the reaction mixture was more pro-
nounced for the electron rich substrates (Table 1: entries 2 and 6) suggesting that the by-products
are a result of internal redox processes.
Scheme 1.
Our recent investigation, into the selectivity of the ¯uoridation process of heteroaryl(phenyl)-
iodonium salts, required the use of a range of heteroaryltrialkylstannanes as intermediates in their
formation.13 Although readily prepared using conventional procedures the sensitivity of these
materials as described above was a problem exacerbated by the electron rich nature of the
heteroaromatic ring. Electron rich arylboronic acids do not su€er from such pronounced sensi-
tivity and were therefore investigated as suitable precursors in the formation of heteroaryl(aryl)-
iodonium salts. In a manner analogous to that used above 2-thiopheneboronic acid was added to
.
PhI(OAc)2 2TfOH and gave 2-thienyl(phenyl)iodonium tri¯ate, however, as with the electron rich
examples above an analytical sample could not be obtained from the highly coloured reaction
Table 2
Preparation of heteroaryl(phenyl)iodonium salts

5396
mixture. Other heteroarylboronic acids behaved in a similar fashion and as a result the less reactive
hydroxy(tosyloxy)iodobenzene±Koser's reagent17 was studied. The use of this reagent greatly
reduced the level of contamination and thereby allowed the successful isolation of 2-thienyl-
(phenyl)iodonium tosylate (90% yield) and other heteroaryl(phenyl)iodonium tosylates (Table 2).
In summary we have demonstrated a mild and regioselective preparation of diaryliodonium
salts, including heteroaryl(phenyl)iodonium salts, from the appropriate arylboronic acids. This
eliminates the need for toxic and acid sensitive organostannanes as precursors to these materials.
We thank the EPSRC for ®nancial support and Mr. R. Sheppard for NOE measurements and
2D NMR.
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