Stabilization of zwitterionic aryltrifluoroborates against hydrolysis

Article abstract of DOI:10.1039/c0cc02117b

The presence of a proximal cationic group in zwitterionic aryltrifluoroborates such as o-(Ph₂MeP)C₆H ₄(BF₃) stabilizes these compounds against hydrolysis.

Full text of DOI:10.1039/c0cc02117b

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Stabilization of zwitterionic aryltrifluoroborates against hydrolysisw
Casey R. Wade, Haiyan Zhao and Franc¸ ois P. Gabbaı*
¨
Received 26th June 2010, Accepted 13th July 2010
DOI: 10.1039/c0cc02117b
The presence of a proximal cationic group in zwitterionic
aryltrifluoroborates such as o-(Ph2MeP)C6H4(BF3) stabilizes
these compounds against hydrolysis.
The discovery of novel fluorination reactions is attracting an
increasing interest because of their relevance to the preparation
of 18F-labeled radiotracers for PET imaging.1,2 An approach
that has gained interest in the past few years involves the
functionalization of a biomolecule with an arylboronic acid or
ester which is subsequently converted into a [18F]-aryltrifluoro-
borate prior to PET imaging.2–4 Such an approach is appealing
because time-consuming synthetic steps can be carried out
before introduction of the relatively short-lived 18F radio-
nuclide. Despite its attractive attributes, this method is
complicated by (i) the solvolysis of the aryltrifluoroborate at
physiological pH which will lead to deactivation of the
radiolabel;4 (ii) the acidic pH needed for the formation of
the aryltrifluoroborate which may limit compatibility with
proteins or other biomolecules that would denature under
these conditions.
Fig. 1 Structures of the zwitterionic trifluoroborates 1–3 synthesized
and evaluated in this study. For each compound, the relative
hydrolysis rate constant krel = kobs([PhBF3]À)/kobs(ArBF3) is provided.
The kinetic data were obtained at room temperature in D2O/CD3CN
(8/2 vol.) at pH 7.5 for 1, 2 and 3.
those of o-(i-Pr2PH)(BF3)C6H4 which has been recently
reported.8 While 1–3 do not decompose in organic solvents,
slow fluoride release is observed in D2O/CD3CN (8/2 vol.) at
pH 7.5 ([phosphate buffer] = 500 mM, [ArBF3] = 20 mM
with ArBF3 = 1, 2 or 3). This reaction, which is expected to
produce the corresponding [ArB(OH)2]+/ArB(OH)3 species,
can be easily monitored by 19F NMR spectroscopy. Although
the mechanism of fluoride dissociation involves multiple steps,
it has been previously demonstrated that dissociation of the
first fluoride anion is rate determining.4 In turn, the kinetics of
such reactions can be properly treated by a simple first order
rate law n = kobs[ArBF3]. Treatment of the data on the basis
of this equation affords kobs = 6.3 Â 10À5 minÀ1 for 1,
3.4 Â 10À6 minÀ1 for 2, and 1.2 Â 10À4 minÀ1 for 3 (Fig. 2).
Comparison of these rate constants with that obtained for
À
We have recently shown that the fluoride affinity of
organoboranes5 can be significantly increased by introduction
of a proximal cationic functionality as in I, II and III.6,7 In
addition to favorable inductive and coulombic effects which
promote fluoride ion capture, the resulting complexes are
stabilized by hydrogen bonding or donor–acceptor interactions
involving the proximal cationic functionality. Encouraged by
these results, we have now decided to determine whether a
similar approach could be used to stabilize aryltrifluoroborates
against solvolysis.
PhBF3 (kobs = 0.0245 minÀ1) under the same conditions
indicates that the presence of a cationic functionality in 1, 2,
and 3 passivates these compounds against hydrolysis. This
lowering of the reaction rate can be quantified by the relative
rate constant krel = kobs(PhBF3À)/kobs(ArBF3) presented in
Fig. 1 for each compound. Comparison of these results with
those obtained by Perrin et al. on anionic trifluoroborates4,9
suggests that the cationic substituents employed in 1–3 are
To explore this idea, we decided to synthesize 1, 2, and 3
(Fig. 1) by reaction of the boronic acid or ester precursors with
KHF2.w These compounds have been fully characterized. The
11B NMR spectra of these compounds display a sharp signal
around 3 ppm, characteristic of an aryltrifluoroborate species.
The trifluoroborate functionality of these compounds also
gives rise to a sharp 19F NMR resonance which appears around
À130 ppm. These spectroscopic features are reminiscent of
Department of Chemistry, Texas A&M University, College Station,
Texas 77843, USA. E-mail: francois@tamu.edu;
Fax: +1 979 845 4719; Tel: +1 979 862 2070
w Electronic supplementary information (ESI) available: Synthesis
and characterization of 1–3. CCDC: 782715–782717. For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/c0cc02117b
Fig. 2 Kinetic plots for the hydrolysis of 1, 2, and 3. The data were
obtained at room temperature in D2O/CD3CN (8/2 vol.) at pH 7.5.
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6380 Chem. Commun., 2010, 46, 6380–6381
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range for 1 and 2.974–3.145 A range for 2.13 Other possible
factors adding to the stability of 2 and 3 involve weak
F(lone pair) - E–C(s*) donor–acceptor interactions which
have been previously observed in compounds such as
7
o-(Ph2PMe)(Mes2BF)C6H4 and o-(i-Pr2PH)(Mes2BF)C6H4.8
The presence of such interactions can be proposed based on
the FÁ Á ÁE distances (FÁ Á ÁP = 3.003 A (molecule A) and 3.105
A (molecule B) in 2; FÁ Á ÁS = 3.013 A in 3) which are within
the sum of the van der Waals radii of the elements (rvdW = 1.5 A
for F, 1.95 A for P, 1.8 A for S).14 The presence of such
interactions is also supported by the linearity of the F–E–Ctrans
angle (av. F–P–Ctrans = 174.41 in 2; F2–S1–C7 = 175.861 in 3).
In conclusion, we have shown that zwitterionic aryltrifluoro-
borates are endowed by an unusual kinetic stability against
hydrolysis. These effects are most acute in the case of 2 which
is almoÀst four orders of magnitude more kinetically stable than
PhBF3
.
Fig. 3 Crystal structures of the zwitterionic aryltrifluoroborates 1, 2,
and 3. Ellipsoids are scaled to the 50% probability level and hydrogen
atoms have been omitted for clarity. Only one of the two independent
molecules of 2 is shown.
Notes and references
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functionality against hydrolysis. This stabilization is unequivocal
in the case of 2 whose hydrolysis is 7205 times slower than
that of [PhBF3]À. Comparison of the data obtained for 1
(krel = 389) with that of its para isomer (krel = 16)4 also
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its para isomer, is also in agreement with the observed
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This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 6380–6381 6381