Controlling the fluoridophilicity of sulfonium boranes via chelation, Coulombic and hydrophobic effects

Article abstract of DOI:10.1016/j.tet.2019.01.035

We describe the synthesis and properties of a series of sulfonium boranes featuring a dimesitylboryl unit and a dimethylsulfonium or methylphenyl sulfonium moiety connected by an ortho- or para-phenylene linker. Acid-base and fluoride anion tritration exp

Full text of DOI:10.1016/j.tet.2019.01.035

Tetrahedron 75 (2019) 1123e1129
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Controlling the fluoridophilicity of sulfonium boranes via chelation,
Coulombic and hydrophobic effects
Haiyan Zhao, Youngmin Kim, Gyeongjin Park, Francois P. Gabbai*
Department of Chemistry, Texas A&M University, College Station, TX, 77843, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
We describe the synthesis and properties of a series of sulfonium boranes featuring a dimesitylboryl unit
and a dimethylsulfonium or methylphenyl sulfonium moiety connected by an ortho- or para-phenylene
linker. Acid-base and fluoride anion tritration experiments carried out in aqueous media indicate that [o-
(Mes2B)C6H4(SMePh)]þ is the most Lewis acidic derivative. Structural and computational analysis indi-
cate that the favorable properties of this cationic borane derive from the proximity of the sulfonium and
boryl units which enhances the Coulombic stabilization of the ensuing zwitterions o-(Mes2XB)
C6H4(SMePh) with X ¼ OH or F. Another important factor is the overall hydrophobicity of the sulfonium
borane which, we propose, promotes anion desolvation, a factor also favoring B-X bond formation.
Finally, the crystal structure of o-(Mes2FB)C6H4(SMePh) shows that the zwitterion is further stabilized by
formation of a BeF/S chelate motif.
Received 14 December 2018
Received in revised form
12 January 2019
Accepted 16 January 2019
Available online 21 January 2019
© 2019 Elsevier Ltd. All rights reserved.
1. Introduction
This compound is however water sensitive thereby impeding an
investigation of the role played by hydrophobicity in these ortho-
Because of its inherent fluoridophilic properties, boron com-
pounds have emerged as uniquely suited for the design of fluoride
ion receptors [1]. Owing to applications in fluoride anion sensing
[1] and [18F]-fluoride anion capture for positron emission tomog-
raphy [2], this field of research has witnessed considerable growth
and maturation. Taking advantage of Coulombic effects, several
groups have investigated organoboranes whose Lewis acidity is
enhanced by the introduction of cationic moieties [1b,1k,3]. As part
of our contribution, we described phosphonium boranes such as
[I]þ, [II]þ, [III]þ and [IV]þ which are sufficiently acidic to capture
fluoride ions in aqueous solutions [4] (Scheme 1). A comparison of
the properties of these four boranes indicates that an increase in
the hydrophobicity of the derivative leads to an increase of their
anion affinity. By investigating the ortho-isomer of [I]þ, namely
[V]þ, we found that positioning the cationic group in the proximity
of the boron atom provided an additional gain in fluoridophilicity
[3i,5] (Scheme 1). This improvement was correlated to the
Coulombic stabilization of the ensuing zwitterion which features a
short fluoroborate phosphonium separation. Additional stabiliza-
tion was assigned to the formation of the BeF/P chelate motif.
phenylene phosphonium boranes. To advance our fundamental
understanding of the properties of these cationic boranes, we have
now chosen to investigate related sulfonium boranes which, based
on prior results, have better water tolerance than their phosphorus
analogs [6]. In this paper, we describe a series of results which
illustrate how chelation and hydrophobic effects inform the prop-
erties of these derivatives.
2. Results and discussion
2.1. Synthesis and characterization of the sulfonium boranes
Using a similar synthetic strategy to that employed in the case of
[1]þ [6a], we found that the related sulfonium boranes [2]þ, [3]þ
* Corresponding author.
E-mail address: francois@tamu.edu (F.P. Gabbai).
Scheme 1. Structure of previously investigated phosphonium boranes.
https://doi.org/10.1016/j.tet.2019.01.035
0040-4020/© 2019 Elsevier Ltd. All rights reserved.

1124
H. Zhao et al. / Tetrahedron 75 (2019) 1123e1129
to describe the process occurring during the acid-base titrations
[4a]. In the case of [2]þ (H2O/MeOH, 95:5 vol), when the pH reaches
a value of 6.1, around 9% of the absorbance is quenched. Achieving
the same extent of quenching with [1]þ necessitate a pH value of
6.9, indicating that [2]þ is more Lewis acidic than [1]þ. In both
cases, the acid-base titrations could not be completed due to the
precipitation of the hydroxide adducts. With the caveat that pre-
cipitation of the compound affects the accuracy of these acidity
measurements, fitting the available data to the equilibrium
described in eq. (1) affords pKR ¼ 7.02 ( 0.05) for [2]þ which can
þ
be compared to the value of 7.89 ( 0.05) for [1]þ established pre-
viously [6a]. The same experiments were performed for cations
[3]þ and [4]þ under similar conditions (H2O/MeOH, 95:5 vol).
Fittiþng of the titration data obtained forþthese two boranes affords
pKR ¼ 8.84 ( 0.05) for [3]þ, and pKR ¼ 8.54 ( 0.05) for [4]þ,
suggesting that the cation [4]þ is slightly more Lewis acidic than
[3]þ. In turn, comparison of the pKRþ between the ortho-phenylene
linked isomers ([1]þ and [2]þ) and the para-phenylene linked iso-
mers ([3]þ and [4]þ) supports the notion that the proximity of the
cationic moiety and the boron center increases the Lewis acidity of
the compounds.
Scheme 2. Synthesis of the sulfonium boranes [1]þ, [2]þ, [3]þ and [4]þ as their triflate
salts.
and [4]þ could be readily synthesized by reaction of 1-Li-2-SPh-
C6H4, 1-Li-4-SMe-C6H4 or 1-Li-4-SPh-C6H4 with Mes2BF and sub-
sequent methylation of the corresponding neutral thiophenyl bo-
ranes with MeOTf (Scheme 2). These triflate salts have been
characterized by multinuclear NMR spectroscopy. In all four cases,
the boron center remains trigonal planar in agreement with the
detection of a11B-NMR resonance in the 70e80 ppm range in CDCl3.
Like [1]þ, these new sulfonium boranes feature a low energy UV
absorption band detected at 334 nm for [2]þ, 325 nm for [3]þ, and
319 nm for [4]þ in H2O/MeOH (95:5 vol), which also confirms the
presence of a coordinatively unsaturated boron center [1s,7]. The
resulting boron-centered chromophores are fluorescent and give
rise to a broad emission band at 470 nm for [1]þ and [2]þ, 494 nm
for [3]þ and 499 nm for [4]þ in H2O/MeOH (95:5 vol), respectively,
when excited at 340 nm. These emissive properties are reminiscent
of those of ammonium and phosphonium boranes [4b,8].
KRþ
½R3Bꢀþ þ H O
R B ꢁ OH þ Hþ
(1)
ƒƒƒƒƒ!
2
3
To investigate the role played by solvation effects, we calculated
the n-octanol/water partition coefficient logKow where Kow ¼ [bor-
ane]octanol/[borane]water. These calculations were performed using
Density Functional Theory (DFT) and the SMD solvation model [9].
The results of these calculations show an increase in logKow through
replacement of a methyl group by a phenyl group for both the
ortho-phenylene linked isomers [1]þ and [2]þ as well as for the
para-phenylene linked isomers [3]þ and [4]þ (Table 1). These re-
sults show that the presence of a phenyl substituent on the sulfur
atom increases the hydrophobicity of the cationic borane.
Comparing these results with the experimentally determined
þ
pKR values illustrates the correlation that exists between Lewiþs
acidity and hydrophobicity. Interestingly, the difference in pKR
value between [1]þ and [2]þ (ca. 0.8) is larger than that between
[3]þ and [4]þ (ca. 0.3) suggesting that hydrophobic effects play a
more significant role when the hydrophobic group is in the
2.2. Lewis acidity and pH stability range studies
In order to compare the Lewis acidity of these four sulfonium
boranes and study their compatibility with aqueous environments,
we investigated their behavior in aqueous solution. Since hydroxide
binding is expected to quench the absorption of the low energy
band in the UVevis spectra of these boranes, we monitored the
absorbance as a function of pH (Fig. 1). In all cases, the absorption of
the low energy band is quenched as the pH of the solution in-
creases. Acidification of the solution results in a revival of the
absorbance, indicating that the hydroxide binding process is
reversible. Therefore, the equilibrium shown in eq (1) can be used
Table 1
Computed solvation energies and octanol-water partition coefficients.
Compound
D
Gw (Kcal/mol)
DGo (Kcal/mol)
-D
Gow, Kcal/mol
logKow
[1]þ
[2]þ
[3]þ
[4]þ
ꢁ39.8
ꢁ37.3
ꢁ43.8
ꢁ39.2
ꢁ46.6
ꢁ45.8
ꢁ51.0
ꢁ48.4
6.9
8.5
7.2
9.2
5.05
6.26
5.26
6.75
Fig. 1. Spectrophotometric acid-base titration curve of [2]þ, or [3]þ and [4]þ in H2O/MeOH (95:5 vol). The absorbance was measured at 334 nm for [2]þ, 325 nm for [3]þ and 319 nm
for [4]þ.The titrations of [2]þ and [4]þ could not be finished due to the precipitation of 2-OH and 4-OH.

H. Zhao et al. / Tetrahedron 75 (2019) 1123e1129
1125
immediate vicinity of the boron center. Equipped with this
knowledge, we turned our attention to the complexation of fluoride
anions.
donor-acceptor interaction involving a fluorine lone pair (lp) and
the * orbital of SeC bond. The fact that the B1eF1 bonds in 1-F
s
(1.491 (2) Å) and 2-F (1.482 (3) Å) are longer than in 4-F (1.466 (2)
Å) supports the view that the ortho-sulfonium unit participates in
fluoride anion chelation, a feature reminiscent of that displayed by
the phosphonium and stibonium analogs [3r,5a]. We note in
passing that this F/Sþ interaction can also be described as an
example of chalcogen bonding, a term that usually emphasizes the
Coulombic component of the interaction [10].
2.3. Fluoride ion complexation in MeOH
Since anion binding to the boron center of these sulfonium
boranes should result in a quenching of the low energy absorption
band observed in their UVevis spectra, we monitored the fluoride
binding process by UVevis spectroscopy. Addition of fluoride ions
to MeOH solution of these boranes quenches the low energy ab-
sorption band as a result of fluoride coordination to the boron atom.
Fitting of the resulting titration data to the 1:1 binding model
expressed in eq. (2) afforded the following fluoride binding con-
stants: K ¼ 4.0 ( 0.5) ꢂ 104 Mꢁ1 for [1]þ, K ¼ 8.5 ( 0.5) ꢂ 104 Mꢁ1
for [2]þ, K ¼ 260 ( 20) Mꢁ1 for [3]þ, and K ¼ 420 ( 40) Mꢁ1 for [4]þ.
These results show that in MeOH: i) the fluoride affinity increases
with the hydrophobic character of the boranes; ii) the ortho iso-
mers are more fluoridophilic. Last but not least, these four cationic
boranes do not bind other common anions such as Clꢁ, Brꢁ, Iꢁ, NO3ꢁ,
H2POꢁ4 , and HSOꢁ4 , suggesting that they are highly selective.
2.4. Fluoride ion complexation in water
Having established the pH stability range of these cationic bo-
ranes as well as their ability to bind fluoride in organic solvents,
their anion binding behavior was investigated in aqueous media
(H2O/MeOH, 95:5 vol). Titrations of [3]þ and [4]þ with fluoride ions
monitored by UVevis spectroscopy under dilute conditions
(0.052 mM for [3]þ and 0.042 mM for [4]þ) afforded K ¼ 8.5 ( 0.5)
Mꢁ1 for [3]þ and K ¼ 33 ( 1) Mꢁ1 for [4]þ (Fig. 3). The highest
fluoride anion affinity of [4]þ may be correlated to its increased
hydrophobicity, as speculated in the case of the phosphonium
½R3Bꢀþ þ Fꢁ R B ꢁ F
(2)
!
3
Attempts to isolate the fluoride adducts were also conducted.
Addition of excess KF to concentrated MeOH solutions of [1]þ, [2]þ,
[3]þ and [4]þ led to the precipitation of the corresponding fluoride
complexes 1-F, 2-F, 3-F, and 4-F, respectively. These compounds
have been characterized by multinuclear NMR spectroscopy. The
11B NMR resonances at
¼ 6.6 ppm for 3-F and
coordinate boron centers. The 19F NMR resonances
¼ ꢁ153.3 ppm for 1-F, ¼ ꢁ156.5 ppm for 2-F, ¼ ꢁ178.7 ppm
for 3-F and
¼ ꢁ178.8 ppm for 4-F) are also close to those observed
d
¼ 6.0 ppm for 1-F,
d
¼ 6.8 ppm for 2-F,
d
d
¼ 7.0 ppm for 4-F are consistent with four-
(d
d
d
d
in compounds featuring triarylfluoroborate moieties [4a,5a]. The
crystal structures of 1-F, 2-F and 4-F have been determined by
single crystal X-ray diffraction (Fig. 2). In all cases, the BeF bond
length (BeF ¼ 1.491 (2) Å for 1-F, BeF ¼ 1.482 (3) Å for 2-F and
BeF ¼ 1.466 (2) Å for 4-F) is comparable to those found in other
compounds with triarylfluoroborate moieties [4a,5a]. The boron
centers adopt a pyramidal geometry as indicated by the sum of the
C
aryl-B-Caryl angles (S(CeBeC) ¼ 340.1ꢃ for 1-F, S(CeBeC) ¼ 337.4ꢃ for
2-F and S(CeBeC) ¼ 338.6ꢃ for 4-F). In the case of 1-F and 2-F, the
separation between sulfur and fluoride (2.665 (2) Å in 1-F and 2.636
(2) Å in 2-F) is well within the sum of van der Waals radii of the two
elements and the F1eS1-Ctrans angle (170.5 (1)ꢃ for 1-F where
Ctrans ¼ C8 and 164.1 (1)ꢃ for 2-F with Ctrans ¼ C8) is close to line-
arity. These characteristics indicate the presence of a BeF/S
Fig. 3. Top: Experimental data and calculated 1:1 binding isotherm with K ¼ 8.5 ( 0.5)
Mꢁ1 for [3]þ using ε([3]þ) ¼ 8800 Mꢁ1 cmꢁ1, ε(3-F) ¼ 1000 Mꢁ1 cmꢁ1 at lmax ¼ 325 nm
(left), and K ¼ 33
(
1) Mꢁ1 for [4]þ using ε([4]þ) ¼ 8550 Mꢁ1 cmꢁ1
ε(4-F) ¼ 1900
,
Mꢁ1 cmꢁ1 at lmax ¼ 319 nm (right) monitored by UVevis spectroscopy. Bottom: Fluo-
rescence quenching titration data and calculated 1:1 binding isotherm with K ¼ 60
(
5) Mꢁ1 for [1]þ (left) and K ¼ 1670 ( 50) Mꢁ1 for [2]þ (right).
Fig. 2. ORTEP drawing of 1-F, 2-F and 4-F. (thermal ellipsoids drawn at 50%; for clarity purposes, the hydrogen atoms are omitted, and the mesityl ligands are represented by thin
lines). Pertinent metrical parameters are provided in the text and in the CIF files.

1126
H. Zhao et al. / Tetrahedron 75 (2019) 1123e1129
Fig. 4. Graphical summary of the favorable features displayed by [2]þ with respect to fluoride anion complexation.
analogs of these compounds [4a]. Considering the poor solubility of
the fluoride adducts 1-F and 2-F in aqueous environments, we
carried out fluorescence quenching titrations of [1]þ and [2]þ
monitored by fluorescence spectroscopy under more dilute con-
ditions. Fitting the data to a 1:1 binding isotherm using the Stern-
Volmer static quenching equation I0/I ¼ 1 þ K [Fꢁ] (I0: initial
fluorescence intensity in the absence of fluoride; I: fluorescence
intensity in the presence of fluoride) afforded K ¼ 60 ( 5) Mꢁ1 for
[1]þ and K ¼ 1670 ( 50) Mꢁ1 for [2]þ (Fig. 3). The fluoride affinity of
the latter cation [2]þ is almost 30 times higher than that of [1]þ,
again reinforcing the major role played by hydrophobic effects,
especially when the hydrophobic group is positioned near the
anion binding site. We propose that these hydrophobic effects
promote desolvation of the anion as it approaches the boron atom
thus strengthening its interaction with the Lewis acidic sites of the
receptor (Fig. 4).
[2]þ upon addition of fluoride ions (Fig. 5) could be fitted to a 1:1
binding isotherm affording binding constant of 2.65
a
( 0.2) ꢂ 104 Mꢁ1. As shown in Fig. 5, 0.76 and 1.52 ppm of fluoride
ions cause 32% and 56% quenching of the absorbance in the UVevis
spectra, respectively. In addition, this detection process is rapid and
only takes 1 min. To test the anion binding selectivity of [2]þ, its
absorption spectrum has been monitored upon the addition of
various anions including Clꢁ, Brꢁ, Iꢁ, NOꢁ3 , H2PO4ꢁ, and HSOꢁ4 . The
absorbance of [2]þ shows no or negligible quenching after the
addition of 5 equivalents of these anions, suggesting that [2]þ has
no or little affinity for these anions. Next, we tested the reversibility
of the fluoride binding process of [2]þ. Addition of an aqueous so-
lution of Al3þ to a solution containing 2-F led to a revival of the
absorbance of [2]þ showing that fluoride binding is reversible.
3. Conclusion
2.5. Lewis acidity and fluoride affinity of [2]þ in the presence of
cetyltrimethylammonium bromide (CTABr)
This study underscores some important principles that can be
used to optimize the properties of cationic boranes with respect to
their affinity for the fluoride anion. Indeed, the fluoridophilicity
order established in the paper indicates the prevalent role of three
essential parameters. First and foremost, the proximity of the
cationic center to the boron atom helps stabilize the resulting flu-
oroborate via Coulombic effects. Second, the sulfonium center is
Lewis acidic and stabilizes the fluoride complex by formation of a
BeF/S chelate motif. Third, the presence of a hydrophobic group
bound to the sulfur atom serves to increase the hydrophobic nature
of the anion binding pocket. These considerations lead us to pro-
pose that increasing the hydrophobicity of the sulfonium boranes
promotes dehydration of the approaching anion elevating the af-
finity of the latter for the boron center. These combined effects
culminate in the case of [2]þ which is sufficiently fluoridophilic to
Since the cation [2]þ is the strongest Lewis acid among the four
boranes investigated, we decided to investigate its fluoride affinity
in water in the presence of CTABr which is expected to increase the
solubility and fluoride affinity of the receptors in water [11]. We
first set out to determine the pKRþ of [2]þ by monitoring the
absorbance as a function of pH. The hydroxide binding process is
still reversible in H2O/MeOH (95:5 vol) with different concentra-
tions of CTABr. The acid-base titration of [2]þ afforded pKRþ ¼ 5.57
( 0.05) with 9.5 mM CTABr thus confirming the beneficial effects of
the ionic surfactant. Next, we decided to study the anion binding
properties of [2]þ in a H2O/MeOH (95:5 vol) solution containing
CTABr (9.5 mM). The changes observed in the UVevis spectrum of
Fig. 5. Left: Absorbance change of a solution of [2]þ after successive additions of fluoride anions in H2O/MeOH (95:5, vol.; 9.5 mM pyridine buffer, pH ¼ 4.6; CTABr, 9.5 mM). Right:
Experimental data and calculated 1:1 binding isotherm with K ¼ 2.65 ( 0.2) ꢂ 104 Mꢁ1 for [2]þ using ε([2]þ) ¼ 9200 Mꢁ1 cmꢁ1, ε(2-F) ¼ 0 Mꢁ1 cmꢁ1
.

H. Zhao et al. / Tetrahedron 75 (2019) 1123e1129
1127
bind fluoride at ppm levels in water.
4. Experimental section
3.05 mmol) in dichloromethane (20 ml). The resulting mixture was
heated to reflux overnight before being cooled to room tempera-
ture and brought to dryness by evacuation of the solvent. The
resulting foamy solid was washed by diethyl ether to afford [2]OTf
4.1. General considerations
as a white solid (1.2 g, 87% yield). 1H NMR (400 MHz, CDCl3)
d 2.11
(bs, 9H, Mes-CH3), 2.28 (s, 3H, Mes-CH3), 2.32 (s, 6H, Mes-CH3), 3.36
(bs, 3H, SeCH3), 6.87 (s, 4H, Mes-CH), 7.49 (d, 2H, JH-H ¼ 7.6 Hz, Ph-
CH), 7.60e7.73 (m, 5H, SPh-CH), 7.82e7.96 (m, 2H, Ph-CH). 13C NMR
(100 MHz, CDCl3) 21.32, 22.04, 27.88, 30.77, 120.15, 131.42, 134.14,
134.45, 135.65, 141.03, 141.64.11B NMR (128 MHz, CD3OD) 81.3 (bs).
Anal. Calcd for C32H34BF3O3S2: C, 64.21, H, 5.73. Found: C, 63.90, H,
5.68.
Methyl triflate and potassium fluoride were purchased from
Aldrich, diphenyl disulfide from TCI, n-butyllithium from Alfa Aesar.
Dimesitylboron fluoride and 1-dimesitylboryl-4-methylthio-ben-
zene were prepared by following the published steps [12]. Com-
pound [1]OTf was prepared as previously described [6a]. Solvents
were dried by passing through an alumina column (hexanes,
dichloromethane) or refluxing under N2 over Na/K (diethyl ether,
THF). UVevis spectra were recorded on an Ocean Optics USB4000
spectrometer with an Ocean Optics ISS light source. Elemental
analyses were performed by Atlantic Microlab (Norcross, GA). The
pH measurements were carried out with a Radiometer PHM290 pH
meter equipped with a VWR SympHony electrode. Fluorescence
measurements were carried out using a PTI, QuantaMaster spec-
trofluorometer. NMR spectra were recorded on Varian Unity Inova
400 FT NMR (399.59 MHz for 1H, 375.99 MHz for 19F,128.19 MHz for
11B, 100.45 MHz for 13C) spectrometers at ambient temperature.
Chemical shifts are given in ppm, and are referenced against
external BF3$Et2O (11B, 19F). The crystallographic measurements
were performed using a Bruker SMART1000 or APEX-II CCD area
4.4. Synthesis of 2-F
[2]OTf (0.050 g, 0.084 mmol) was dissolved in methanol and
treated with an excess of KF. After 15 min, the solid that precipi-
tated out of solution was isolated by filtration, dried under vacuum
to afford 2-F (0.035 g, 89% yield). Single crystals of 2-F were ob-
tained by slow evaporation of a dichloromethane solution. 1H NMR
(400 MHz, CDCl3)
d 1.95 (s, 6H, Mes-CH3), 2.00 (s, 6H, Mes-CH3),
2.24 (s, 3H, Mes-CH3), 2.26 (s, 3H, Mes-CH3), 3.19 (s, 3H, SeCH3),
6.71 (s, 2H, Mes-CH), 6.72 (s, 2H, Mes-CH), 6.96 (d, 1H, JH-H ¼ 8.0 Hz,
Ph-CH), 7.13 (t, 1H, JH-H ¼ 8.0 Hz, Ph-CH), 7.22 (t, 1H, JH-H ¼ 7.6 Hz,
Ph-CH), 7.38 (d, 1H, JH-H ¼ 7.6 Hz, ph-CH), 7.50 (d, 2H, JH-H ¼ 8.0 Hz,
SPh-CH), 7.56e7.66 (m, 3H, SPh-CH). 13C NMR (100 MHz, CDCl3)
detector diffractometers (Mo-Ka radiation,
l
¼ 0.71069 Å). In each
case, a specimen of suitable size and quality was selected and
mounted onto a nylon loop. The structures were solved by direct
methods, which successfully located most of the non-hydrogen
atoms. Subsequent refinement on F2 using the SHELXTL/PC pack-
age (version 5.1) allowed location of the remaining non-hydrogen
atoms.
d
20.91, 20.93, 24.73, 24.78, 24.91, 24.95, 28.74 (d, 1C, JH-C ¼ 6.1 Hz,
SeCH3), 126.23, 127.00, 128.66, 129.12, 130.55, 130.97, 132.64,
133.24, 133.39, 137.31, 137.37, 142.04, 142.37.11B NMR (128 MHz,
CDCl3)
d
þ7.0 (s). 19F NMR (375.9 MHz, CDCl3)
d
ꢁ156.5 (s). Anal.
Calcd for C31H34BFS: C, 79.48, H, 7.32. Found: C, 79.27, H, 7.40.
4.5. Synthesis of [3]OTf
4.2. Synthesis of 1-F
1-Dimesitylboryl-4-methylthio-benzene (0.20 g, 0.54 mmol)
was allowed to react with methyl triflate (0.10 g, 0.61 mmol) in
dichloromethane (5 ml). The resulting mixture was heated to reflux
overnight before being cooled to room temperature and brought to
dryness by evacuation of the solvent. The resulting foamy solid was
washed by diethyl ether to afford [3]OTf as a white solid (0.18 g, 62%
[1]OTf (0.08 g, 0.15 mmol) was dissolved in MeOH (5 mL) and
treated with an excess of KF which resulted in the formation of a
white solid. After 30 min, the solid was isolated by filtration,
washed with MeOH, and dried in vacuo to afford 1-F as a white solid
(65% yield). 1H NMR (400 MHz, CDCl3)
d
1.90 (s, 12H), 2.23 (s, 6H),
2.75 (s, 6H), 6.66 (s, 4H), 7.30e7.36 (m, 3H), 7.39e7.41 (m, 1H). 13
NMR (100 MHz, CDCl3) 21.03, 24.90, 29.24, 123.31, 127.14, 128.85,
C
yield). 1H NMR (400 MHz, CDCl3)
d 1.95 (s, 12H, Mes-CH3), 2.31 (s,
d
6H, Mes-CH3), 3.41 (s, 6H, SeCH3), 6.83 (s, 4H, Mes-CH), 7.73 (d, 2H,
128.94, 131.97, 133.41, 137.39 (d, JC-F ¼ 6.1 Hz), 141.87, 151.24 (bs),
JH-H ¼ 8.4 Hz, Ph-CH), 7.89 (d, 2H, JH-H ¼ 8.0 Hz, Ph-CH). 13C NMR
168.85 (bs). 11B NMR (128 MHz, CDCl3)
(376 MHz, CDCl3)
76.84; H, 7.94. Found: C, 75.47; H, 7.75.
d
þ6.02 (bs). 19F NMR
(100 MHz, CDCl3) d 21.26, 23.50, 29.30 (s, 2C, SeCH3), 121.17, 128.59,
d
ꢁ153.32 (s). Anal. Calcd for C26H32BFS (2-F): C,
128.74, 137.68, 140.04, 140.76.11B NMR (128 MHz, CD3OD)
d 82 (bs).
The purity of this compound was assessed using NMR spectroscopy.
4.3. Synthesis of [2]OTf
4.6. Synthesis of 3-F
o-Bromophenyl phenyl sulfide (2 g, 7.54 mmol) was allowed to
react with nBuLi (3.0 mL, 8.4 mmol, 2.8 M in hexanes) in diethyl
ether (60 mL) at ꢁ0 ꢃC. After stirring the reaction mixture for 3 h,
dimesitylboron fluoride (2.0 g, 7.46 mmol) was added to the
resulting solution. The reaction mixture was warmed to ambient
temperature and stirred overnight. The reaction was quenched
with water (40 mL) and extracted with dichloromethane. The
organic layer was separated, dried over MgSO4, filtered, and
concentrated in vacuo to afford a yellow solid. This solid was
washed with hexanes (10 mL) to afford 1-dimesitylboryl-2-
phenylthio-benzene as a pale solid (1.8 g, 55% yield). 1H NMR
[3]OTf (0.050 g, 0.093 mmol) was dissolved in methanol and
treated with an excess of KF. After 15 min, the solid that precipi-
tated out of solution was isolated by filtration, dried under vacuum
to afford 3-F (0.030 g, 79% yield). 1H NMR (400 MHz, DMSO‑d6)
d
1.78 (s, 12H, Mes-CH3), 2.06 (s, 6H, Mes-CH3), 3.14 (s, 6H, SeCH3),
6.38 (s, 4H, Mes-CH), 7.14 (bs, 1H, Ph-CH), 7.51 (bs, 1H, Ph-CH), 7.62
(bs, 1H, Ph-CH), 7.90 (bs, 1H, ph-CH). 13C NMR (100 MHz, DMSO‑d6)
d
20.96, 25.37, 25.41, 29.00, 119.16, 126.78, 128.51, 131.30, 140.90.11B
NMR (128 MHz, DMSO‑d6)
DMSO‑d6)
using NMR spectroscopy.
d
þ6.6 (bs). 19F NMR (375.9 MHz,
d
ꢁ178.7 (s). The purity of this compound was assessed
(400 MHz, CDCl3)
6.76 (s, 4H, Mes-CH), 7.07e7.13 (m, 2H, Ph-CH), 7.19e7.24 (m, 7H,
Ph-CH). 11B NMR (128 MHz, CDCl3)
81 (bs). Without additional
purification, 1-dimesitylboryl-2-phenylthio-benzene (1.0 g,
2.30 mmol) was allowed to react with methyl triflate (0.5 g,
d 2.04 (s, 12H, Mes-CH3), 2.28 (s, 6H, Mes-CH3),
4.7. Synthesis of [4]OTf
d
1-dimesitylboryl-4-phenylthio-benzene (0.50 g, 1.15 mmol) was
allowed to react with methyl triflate (0.23 g, 1.38 mmol) in

1128
H. Zhao et al. / Tetrahedron 75 (2019) 1123e1129
dichloromethane (20 ml). The resulting mixture was heated to
reflux overnight before being cooled to room temperature and
brought to dryness by evacuation of the solvent. The resulting
foamy solid was washed by diethyl ether to afford [4]OTf as a white
UVevis spectroscopy.
4.13. Acid-base titration of [2]þ in presence of CTABr in H2O/MeOH
(95:5, vol.)
solid (0.54 g, 78% yield). 1H NMR (400 MHz, CDCl3)
d 1.93 (s, 12H,
Mes-CH3), 2.29 (s, 6H, Mes-CH3), 3.73 (s, 3H, SeCH3), 6.81 (s, 4H,
Mes-CH), 7.63e7.74 (m, 5H, SPh-CH), 7.77 (d, 2H, JH-H ¼ 8.8 Hz, Ph-
CH), 7.90 (d, 2H, JH-H ¼ 8.0 Hz, Ph-CH). 13C NMR (100 MHz, CDCl3)
A solution of [2]OTf (3.0 ml, pyridine buffer, 9.5 mM) was
titrated by incremental addition of a solution of NaOH in water. The
resulting data was fitted to the equilibrium shown in eq. (1). Three
concentrations of CTABr were tested, 0.95 mM, 9.5 mM, and
47.5 mM. The titration was monitored by UVevis spectroscopy.
d
21.24, 23.48, 28.89, 125.44, 128.19, 128.56, 128.74, 130.13, 130.17,
131.48, 134.56, 137.65, 139.97, 140.74.11B NMR (128 MHz, CD3OD)
78 (bs). The purity of this compound was assessed using NMR
d
4.14. Fluoride titration of [2]þ with the concentration of CTABr at
9.5 mM
spectroscopy.
4.8. Synthesis of 4-F
A solution of [2]OTf (3.0 ml, 5.62 ꢂ 10ꢁ5 M, pyridine buffer,
9.5 mM) was titrated by incremental addition of a solution of KF in
water (0.06 M).
[4]OTf (0.050 g, 0.115 mmol) was dissolved in methanol and
treated with an excess of KF. After 15 min, the solid that precipi-
tated out of solution was isolated by filtration, dried under vacuum
to afford 4-F (0.046 g, 85% yield). 1H NMR (400 MHz, DMSO‑d6)
4.15. Computational details
d
1.74 (s, 12H, Mes-CH3), 2.04 (s, 6H, Mes-CH3), 3.67 (s, 3H, SeCH3),
6.37 (s, 4H, Mes-CH), 7.15 (bs, 1H, Ph-CH), 7.53 (bs, 1H, Ph-CH),
All calculations were carried out using density functional theory
as implemented in the Gaussian 09 program. All calculations were
conducted with the B3LYP functional and mixed basis sets:
6e31 þ g (d') for the boron, 6e31 þ g(d) for the sulfur atom, 6e31 g
for all carbon and hydrogen atoms. The SMD solvation model was
used to estimate the free energy of solvation of the boranes in water
7.63e7.71 (m, 5H, SPh-CH), 7.88 (d, 2H, JH-H ¼ 7.2 Hz, Ph-CH). 13C
NMR (100 MHz, DMSO‑d6)
d 20.95, 25.30, 25.33, 27.20, 119.51,
127.31, 128.54, 129.59, 129.66, 131.09, 131.36, 133.71, 135.80,
140.89.11
(375.9 MHz, DMSO‑d6)
was established by NMR spectroscopy.
B
NMR (128 MHz, DMSO‑d6)
d
þ7.0 (bs). 19F NMR
d
ꢁ178.8 (s). The purity of this compound
(DGw) and in n-octanol (DGo). Only the gas phase structures were
optimized. The energies of the solvated molecule were obtained via
single point calculations. The octanol-water partition coefficient
Kow was calculated with T ¼ 298 K using the following equation
4.9. Acid-base titration of [2]þ, [3]þ, and [4]þ in H2O/MeOH (95:5,
vol.)
logKow¼ (
D
Gw
-
DGo)/(2.303 ꢂ R ꢂ T).
A solution of [2]OTf (3.0 ml, 4.20 ꢂ 10ꢁ5 M; MES buffer, 9.5 mM),
[3]OTf (3.0 ml, 4.37 ꢂ 10ꢁ5 M; TRIS buffer, 9.5 mM), or [4]OTf
(3.0 ml, 4.27 ꢂ 10ꢁ5 M; TRIS buffer, 9.5 mM) was titrated by incre-
mental addition of a solution of NaOH in water. The resulting data
was fitted to the equilibrium shown in eq. (1). The titration was
monitored by UVevis spectroscopy.
Acknowledgments
This work was supported by the National Science Foundation
(CHE-1566474), the Welch Foundation (A-1423), and Texas A&M
University Texas A&M University (Arthur E. Martell Chair of
Chemistry). We thank Mengxi Yang and Nattamai Bhuvanesh for
their help with reprocessing some of the X-ray data.
4.10. Fluoride titration of [1]þ, [2]þ, [3]þ, and [4]þ in MeOH
A MeOH solution of [1]OTf (3.0 ml, 5.80 ꢂ 10ꢁ5 M), [2]OTf
(3.0 ml, 6.70 ꢂ 10ꢁ5 M), [3]OTf (3.0 ml, 5.20 ꢂ 10ꢁ5 M), or [4]OTf
(3.0 ml, 7.35 ꢂ 10ꢁ5 M) was titrated by incremental addition of a
MeOH solution of KF (0.0172 M for [1]OTf, 0.015 M for [2]OTf,
0.312 M for [3]OTf and [4]OTf). The titration was monitored by
UVevis spectroscopy.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2019.01.035.
References
4.11. Fluoride titration of [1]þ and [2]þ in H2O/MeOH (95:5 vol)
[1] (a) W.-J. Xu, Y.-Y. Qin, L.-W. Wei, K.Y. Zhang, S.-J. Liu, Q. Zhao, Eur. J. Inorg.
Chem. 2017 (2017) 4393;
A solution of [1]OTf (3.0 ml, 7.76 ꢂ 10ꢁ6 M, MES buffer, 9.5 mM)
or [2]OTf (3.0 ml, 6.95 ꢂ 10ꢁ6 M, MES buffer, 9.5 mM) was titrated
by incremental addition of a solution of KF in water (1.00 M for [1]
OTf, 0.30 M for [2]OTf). Because fluoride binding is slow at these
concentrations, each data point was obtained using a fresh solution
of the borane taken from the same stock solution. The fluorescence
spectra were collected before and after the fluoride addition, and
the intensity ratio I0/I at lmax with the fluoride concentration was
plotted.
(b) H. Zhao, L.A. Leamer, F.P. Gabbaï, Dalton Trans. 42 (2013) 8164;
(c) Z. Guo, I. Shin, J. Yoon, Chem. Commun. 48 (2012) 5956;
(d) T.S. De Vries, A. Prokofjevs, E. Vedejs, Chem. Rev. 112 (2012) 4246;
(e) F.P. Gabbaï, Angew. Chem. Int. Ed. 51 (2012) 6316;
(f) Z.M. Hudson, S. Wang, Dalton Trans. 40 (2011) 7805;
(g) E. Galbraith, T.D. James, Chem. Soc. Rev. 39 (2010) 3831;
(h) C.R. Wade, A.E.J. Broomsgrove, S. Aldridge, F.P. Gabbaï, Chem. Rev. 110
(2010) 3958;
(i) Z. Xu, X. Chen, H.N. Kim, J. Yoon, Chem. Soc. Rev. 39 (2010) 127;
(j) Z.M. Hudson, S. Wang, Acc. Chem. Res. 42 (2009) 1584;
(k) T.W. Hudnall, C.-W. Chiu, F.P. Gabbaï, Acc. Chem. Res. 42 (2009) 388;
€
(l) F. Jakle, Coord. Chem. Rev. 250 (2006) 1107;
(m) S. Yamaguchi, C. Xu, T. Okamoto, Pure Appl. Chem. 78 (2006) 721;
(n) H. Wang, S. Sole, F.P. Gabbaï, ACS Symp. Ser. 917 (2006) 208;
(o) F. Jakle, Boron: Organoboranes in Encyclopedia of Inorganic Chemistry,
4.12. Fluoride titration of [3]þ and [4]þ in H2O/MeOH (95:5, vol.)
€
second ed., Wiley, Chichester, 2005;
A solution of [3]OTf (3.0 ml, 5.20 ꢂ 10ꢁ5 M, pyridine buffer,
9.5 mM) or [4]OTf (3.0 ml, 4.18 ꢂ 10ꢁ5 M, pyridine buffer, 9.5 mM)
was titrated by incremental addition of a solution of KF in water
(1.00 M for [3]OTf and [4]OTf). The titration was monitored by
(p) M. Melaïmi, F.P. Gabbaï, Adv. Organomet. Chem. 53 (2005) 61;
(q) C.D. Entwistle, T.B. Marder, Chem. Mater. 16 (2004) 4574;
(r) S. Yamaguchi, S. Akiyama, K. Tamao, J. Organomet. Chem. 652 (2002) 3;
(s) C.D. Entwistle, T.B. Marder, Angew. Chem. Int. Ed. 41 (2002) 2927;
(t) J.D. Hoefelmeyer, M. Schulte, M. Tschinkl, F.P. Gabbaï, Coord. Chem. Rev.

H. Zhao et al. / Tetrahedron 75 (2019) 1123e1129
1129
235 (2002) 93;
(s) K.C. Song, K.M. Lee, H. Kim, Y.S. Lee, M.H. Lee, Y. Do, J. Organomet. Chem.
713 (2012) 89;
(t) K.C. Song, K.M. Lee, N.V. Nghia, W.Y. Sung, Y. Do, M.H. Lee, Organometallics
32 (2013) 817;
(u) Z. Yuan, J.C. Collings, N.J. Taylor, T.B. Marder, C. Jardin, J.-F. Halet, J. Solid
State Chem. 154 (2000) 5;
€
(v) F. Jakle, Chem. Rev. 110 (2010) 3985.
[2] (a) D.M. Perrin, Acc. Chem. Res. 49 (2016) 1333;
(u) K.M. Lee, Y. Kim, Y. Do, J. Lee, M.H. Lee, Bull. Korean Chem. Soc. 34 (2013)
1990.
[4] (a) Y. Kim, F.P. Gabbaï, J. Am. Chem. Soc. 131 (2009) 3363;
(b) M.H. Lee, T. Agou, J. Kobayashi, T. Kawashima, F.P. Gabbaï, Chem. Commun.
(2007) 1133.
[5] (a) T.W. Hudnall, Y.-M. Kim, M.W.P. Bebbington, D. Bourissou, F.P. Gabbaï,
J. Am. Chem. Soc. 130 (2008) 10890;
(b) C.R. Wade, H. Zhao, F.P. Gabbaï, Chem. Commun. (2010) 6380.
[6] (a) Y. Kim, H. Zhao, F.P. Gabbaï, Angew. Chem. Int. Ed. 48 (2009) 4957;
(b) H. Zhao, F.P. Gabbaï, Org. Lett. (2011) 1444, https://doi.org/10.1021/
ol200129q;
(c) H. Zhao, F.P. Gabbaï, Organometallics 31 (2012) 2327.
[7] (a) S. Yamaguchi, A. Wakamiya, Pure Appl. Chem. 78 (2006) 1413;
(b) M. Elbing, G.C. Bazan, Angew. Chem. Int. Ed. 47 (2008) 834.
[8] T.W. Hudnall, F.P. Gabbaï, J. Am. Chem. Soc. 129 (2007) 11978.
[9] (a) R.F. Ribeiro, A.V. Marenich, C.J. Cramer, D.G. Truhlar, J. Phys. Chem. B 115
(2011) 14556;
(b) K. Chansaenpak, B. Vabre, F.P. Gabbaï, Chem. Soc. Rev. 45 (2016) 954;
€
€
(c) V. Bernard-Gauthier, J.J. Bailey, Z. Liu, B. Wangler, C. Wangler, K. Jurkschat,
D.M. Perrin, R. Schirrmacher, Bioconjug. Chem. 27 (2016) 267.
[3] (a) C. Dusemund, K.R.A.S. Sandanayake, S. Shinkai, Chem. Commun. (1995)
333;
(b) C.R. Cooper, N. Spencer, T.D. James, Chem. Commun. (1998) 1365;
(c) C. Bresner, S. Aldridge, I.A. Fallis, C. Jones, L.-L. Ooi, Angew. Chem. Int. Ed.
44 (2005) 3606;
(d) R. Badugu, J.R. Lakowicz, C.D. Geddes, Sens. Actuators, B B104 (2005) 103;
(e) R. Badugu, J.R. Lakowicz, C.D. Geddes, Curr. Anal. Chem. 1 (2005) 157;
(f) T. Agou, J. Kobayashi, T. Kawashima, Inorg. Chem. 45 (2006) 9137;
(g) C.-W. Chiu, F.P. Gabbaï, J. Am. Chem. Soc. 128 (2006) 14248;
(h) Y. Sun, N. Ross, S.B. Zhao, K. Huszarik, W.L. Jia, R.Y. Wang, D. Macartney,
S. Wang, J. Am. Chem. Soc. 129 (2007) 7510;
(i) T. Agou, J. Kobayashi, Y. Kim, F.P. Gabbaï, T. Kawashima, Chem. Lett. 36
(2007) 976;
€
(j) K. Venkatasubbaiah, I. Nowik, R.H. Herber, F. Jakle, Chem. Commun. (2007)
(b) M. Kolar, J. Fanfrlik, M. Lepsik, F. Forti, F.J. Luque, P. Hobza, J. Phys. Chem. B
117 (2013) 5950;
2154;
(k) G.C. Welch, L. Cabrera, P.A. Chase, E. Hollink, J.D. Masuda, P. Wei,
D.W. Stephan, Dalton Trans. (2007) 3407;
(c) F. Vlahovic, S. Ivanovic, M. Zlatar, M. Gruden, J. Serb. Chem. Soc. 82 (2017)
1369.
(l) M.H. Lee, F.P. Gabbaï, Inorg. Chem. 46 (2007) 8132;
(m) Q. Zhao, F. Li, S. Liu, M. Yu, Z. Liu, T. Yi, C. Huang, Inorg. Chem. 47 (2008)
9256;
(n) T. Agou, M. Sekine, J. Kobayashi, T. Kawashima, Chem. Eur J. 15 (2009)
5056;
(o) H.Y. Zhao, F.P. Gabbaï, Nat. Chem. 2 (2010) 984;
(p) A.E.J. Broomsgrove, D.A. Addy, A. Di Paolo, I.R. Morgan, C. Bresner,
V. Chislett, I.A. Fallis, A.L. Thompson, D. Vidovic, S. Aldridge, Inorg. Chem. 49
(2010) 157;
(q) Y. Sun, S. Wang, Inorg. Chem. 49 (2010) 4394;
(r) C.R. Wade, F.P. Gabbaï, Organometallics 30 (2011) 4479;
[10] D.J. Pascoe, K.B. Ling, S.L. Cockroft, J. Am. Chem. Soc. 139 (2017) 15160.
[11] (a) M. Cametti, A. Dalla Cort, K. Bartik, ChemPhysChem 9 (2008) 2168;
(b) M. Hirai, M. Myahkostupov, F.N. Castellano, F.P. Gabbaï, Organometallics
35 (2016) 1854;
(c) I.-S. Ke, M. Myahkostupov, F.N. Castellano, F.P. Gabbaï, J. Am. Chem. Soc.
134 (2012) 15309.
[12] (a) H.C. Brown, V.H. Dodson, J. Am. Chem. Soc. 79 (1957) 2302;
(b) Z. Yuan, C.D. Entwistle, J.C. Collings, D. Albesa-Jove, A.S. Batsanov,
J.A.K. Howard, N.J. Taylor, H.M. Kaiser, D.E. Kaufmann, S.-Y. Poon, W.-Y. Wong,
C. Jardin, S. Fathallah, A. Boucekkine, J.-F. Halet, T.B. Marder, Chem. Eur J. 12
(2006) 2758.