Mechanistic Study of Arylsilane Oxidation through 19F NMR Spectroscopy

Article abstract of DOI:10.1021/jacs.7b00357

The mechanism of the oxidation of arylsilanes to phenols has been investigated using¹⁹F NMR spectroscopy. The formation of silanols in these reactions results from a rapid background equilibrium between silanol and alkoxysilane; the relative rates of reaction of these species was evaluated by modeling of concentration profiles obtained through ¹⁹F NMR spectroscopic reaction monitoring. Combining these results with a study of initial rates of phenol formation, and of substituent electronic effects, a mechanistic picture involving rapid and reversible formation of a pentavalent peroxide ate complex, prior to rate-limiting aryl migration, has evolved.

Full text of DOI:10.1021/jacs.7b00357

Article
pubs.acs.org/JACS
19
Mechanistic Study of Arylsilane Oxidation through F NMR
Spectroscopy
Elizabeth J. Rayment,† Aroonroj Mekareeya,† Nick Summerhill,‡,§ and Edward A. Anderson*,†
†Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, United Kingdom
‡Worldwide Medicinal Chemistry, Pfizer, Sandwich, Kent CT13 9NJ, United Kingdom
S
* Supporting Information
ABSTRACT: The mechanism of the oxidation of arylsilanes to
phenols has been investigated using 19F NMR spectroscopy. The
formation of silanols in these reactions results from a rapid
background equilibrium between silanol and alkoxysilane; the
relative rates of reaction of these species was evaluated by
modeling of concentration profiles obtained through 19F NMR
spectroscopic reaction monitoring. Combining these results with
a study of initial rates of phenol formation, and of substituent
electronic effects, a mechanistic picture involving rapid and
reversible formation of a pentavalent peroxide ate complex, prior
to rate-limiting aryl migration, has evolved.
Scheme 1. Mechanistic Paradigms in the Tamao Oxidation,
and Previous Work from Our Group
INTRODUCTION
■
Arylsilanes are highly versatile intermediates in organic
synthesis, with a number of methods having recently been
disclosed for both their preparation1 and transformations.2
Among these, the oxidation of arylsilanes to phenols is
relatively underexploited compared to the equivalent con-
version of alkyl and alkenylsilanes into aliphatic alcohols and
ketones, respectively,3,4 and has only recently been developed
as an efficient and general methodology.5,6 Despite the
demonstrated synthetic utility of this oxidation,5g,7 mechanistic
explorations of this phenol synthesis are limited to a study of
arylfluorosilane oxidation by Tamao and co-workers,3h and
theoretical investigations on the oxidation of alkylfluorosilanes,8
and alkylalkoxysilanes (and mixed alkoxyfluorosilane deriva-
tives)9 by Mader and Norrby. Here we describe an
experimental study of the mechanism of the H2O2-mediated
oxidation of arylalkoxysilanes, a reaction that proceeds in the
presence or absence3g,5a,10 of fluoride. In addition to shedding
new light on the dynamic behavior of alkoxysilanes, this work
explores the effects of low concentrations of fluoride ion on the
oxidation, which can be rationalized by consideration of the
relative reactivity of different organosilane intermediates.
The Tamao group’s seminal mechanistic studies on the
hydrogen peroxide-mediated oxidation of fluorosilanes (and
their corresponding fluoride ate complexes) led to their
proposal (Scheme 1a) of a rate-limiting addition of hydrogen
peroxide or hydroperoxide anion, under neutral or basic
conditions respectively, to pentacoordinate ate complex 1
(formed by rapid and reversible addition of fluoride ion to 2).3h
This peroxide association step was proposed to be rate-limiting,
as the reaction was found to be first order with respect to H2O2.
Each pathway leads to a hexacoordinate species (3 or 4), and
then to pentacoordinate aryloxysilane 5 via aryl migration; a
concerted peroxide association/migration was not excluded.
Tamao found that aryl groups migrate in preference to alkyl
Received: January 11, 2017
© XXXX American Chemical Society
A
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groups,11 and proposed that the addition of fluoride ion is
necessary for the oxidation to proceed.
(ArMe2SiH), substrates which do not contain an electro-
negative substituent as has previously been thought to be
crucial for Tamao oxidation. The conversion of 4-
(dimethylsilyl)benzonitrile 9a, a substrate we had found to be
among the more reactive toward oxidation, was monitored by
1H NMR spectroscopy (Figure 1). To reproduce “standard”
Mader and Norrby subsequently calculated (Scheme 1b) that
anionic substitution of anionic pentavalent silicates (e.g., 6) is
rapid,12 and that hydroperoxide anion is more likely to attack
pentacoordinate silicon (6) than the neutral species (7).8,9
They also proposed that addition of fluoride ions is not
essential for the oxidation to proceed, but increases the rate of
hydroperoxide attack at silicon via formation of a greater
proportion of pentavalent trifluorosiliconate species, which are
more reactive toward substitution of F− by HOO− than neutral
tetravalent difluorosilanes. Importantly, these authors con-
cluded that alkyl migration from conformer 8b, and not
peroxide ion attack to generate hexacoordinate species such as
3 or 4, is the rate-limiting step. Our own experimental work
(Scheme 1c)5a had shown that the oxidation of arylhydrosilanes
9,5d and arylalkoxysilanes 10, proceeds under fluoride-
promoted or fluoride-free conditions, thus supporting the
notion that fluoride ion is a nonessential (but generally
beneficial) component of the reaction.
Several points arise from this previous work. First, there is a
general acceptance that stoichiometric amounts of fluoride are
required for successful oxidation (albeit that fluoride ion may
not be coordinated to silicon in the migration step itself), and
that fluoride is sequestered in the course of the reaction by
liberated silanes. Second, the peroxide-mediated oxidation of
silanes featuring only one, or even no electronegative
substituents, has not been studied from a mechanistic
perspective. Third, no experimental correlation of Mader and
Norrby’s calculations on alkoxysilane oxidation has been
achieved. Finally, the observation of silanols and disiloxanes,
as intermediates or byproducts, has not been considered in
detail. In this work, we disclose investigations of arylsilane
oxidation which unite the various experimental and computa-
tional studies in the field, and provide a comprehensive picture
of the equilibria that are at play during oxidation, as well as the
influence of fluoride.
1
Figure 1. H NMR spectroscopic reaction profiles of the oxidation of
hydrosilane 9a to phenol 12a. (a) Reaction evolution as monitored by
1H NMR spectroscopy. (b) Depiction of variation of concentration of
9a, 12a, and silanol 11a with time. (c) Oxidation of a 4:1 mixture of
hydrosilane 9a and authentic silanol 11a. Reactions run in 1:1 d4-
MeOH/d8-THF (1:1, 0.3 M) at 298 K.
Tamao oxidation conditions, this experiment was performed in
a mixed deuterated solvent system of d4-MeOD/d8-THF (1:1),
with 6.0 equiv H2O2 (30% aq.) and 1.6 equiv KHCO3.
Although monitoring of the reaction was complicated by a
broad water peak at 3.5−5.5 ppm, two regions of the spectrum
proved informative (Figure 1a): the aromatic region (>6.5
ppm), where oxidation is characterized by an upfield shift of the
aromatic protons; and the silane region (<0.5 ppm), where the
silane substituents are characterized by their multiplicity (the
methyl signals appear as a doublet in the hydrosilane, but as a
singlet in compounds that do not contain Si−H). The profile of
this reaction is shown in Figure 1b. This revealed a smooth
consumption of hydrosilane 9a, and the formation of a
nonoxidized arylsilane species assigned as silanol 11a,16 which
was converted to phenol 12a as the reaction proceeded. The
identity of 11a was confirmed through independent syn-
thesis,17,18 and submission of a mixture of authentic 11a and
hydrosilane 9a to the oxidation. Identical chemical shifts and a
similar reaction profile were observed for this mixture as had
been seen in the first oxidation, which confirmed the identity of
11a in the mixed NMR solvent system.
RESULTS AND DISCUSSION
■
In earlier work,5a,b we had found that the addition of a fluoride
source was not essential to achieve full conversion of arylsilanes
to phenols, but that even substoichiometric amounts increase
the overall efficiency of oxidation. This observation is mirrored
in studies by Phillips and co-workers on the deprotection of
silyl ethers using catalytic amounts of TBAF (0.1 equiv),13
which also demonstrate that fluoride ion can be recycled from
fluorosilane byproducts (that fluorosilanes are formed irrever-
sibly is an understandable assumption based on the strength of
the Si−F bond, ∼135 kcal mol−1).14 Phillips found the
deprotection of arylsilyl ethers to be especially rapid, under-
lining that these ethers are particularly susceptible to
nucleophilic attack, and thus potentially more amenable to
fluoride recycling as is also required in a fluoride-catalyzed
oxidation manifold.15 Both our group and the Phillips group
found the predominant fate of the organosilane to be the
formation of a silanol (rather than fluorosilane, alkoxysilane, or
disiloxane), again supporting the release of fluoride at some
point after silyl ether cleavage.5a With these observations in
mind, we set out to study the processes at play during the
oxidation of arylhydrosilanes and arylalkoxysilanes, under
fluoride-free and fluoride-catalyzed reaction conditions.
We questioned whether the silanol observed in this oxidation
was a necessary intermediate, or if direct hydrosilane oxidation
could compete. Due to the limitations of observing the
oxidation by 1H NMR spectroscopy, we turned to p-
fluorodimethylsilane (9b, Figure 2), which enabled reaction
Oxidation of Arylhydrosilanes in THF/MeOH. We began
this work by examining the oxidation of arylhydrosilanes
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Figure 2. 1H NMR spectroscopic reaction profiling of the oxidation of
hydrosilane 9b to phenol 12b. (a) Reaction run in the absence of
fluoride. (b) Reaction run in the presence of 0.1 equiv TBAF.
Reactions run in 1:1 d4-MeOH/d8-THF (1:1, 0.3 M) at 298 K.
monitoring by 19F NMR spectroscopy. 9b is significantly less
reactive than benzonitrilesilane 9a, but nonetheless revealed a
similar trend of reactivity (Graph a), and allowed us to observe
subtle details of the early phase of the oxidation, where a
significant lag in the production of phenol was apparent until
appreciable quantities of silanol had formed.18 This supports
the intermediacy of the silanol in the oxidation, rather than a
direct oxidation of the hydrosilane (i.e., migration of H is
favored over Ar in the initial oxidation).
Figure 3. 1H NMR spectroscopic reaction profiling in the oxidation of
silanol 11b and methoxysilane 10b to phenol 12b. Reactions run in d4-
MeOH/d8-THF (1:1, 0.1 M) at 298 K. (a) Fluoride-free oxidation of
silanol 11b. (b) Fluoride-free oxidation of methoxysilane 10b. (c)
Fluoride-promoted (0.1 equiv. TBAF) oxidation of methoxysilane 10b.
Interestingly, small amounts of methoxysilane 10b were
observed throughout the reaction. As expected, the equivalent
oxidation of 9b under fluoride-promoted conditions proceeded
more rapidly (0.1 equiv TBAF, Graph b), although a delay in
the production of phenol was again observed, with silanol 11b
being produced alongside small amounts of methoxysilane 10b
throughout the reaction.19 This suggests that an equivalent (but
accelerated) reaction pathway operates in the presence of
fluoride.
basic conditions (KHCO3) in deuterated THF/MeOH (1:1,
plus a volume of water equivalent to that of the 30% aq. H2O2
used in the oxidations), in the presence and absence of TBAF.
Under fluoride- and peroxide-free conditions (Figure 4, Graph
Oxidation of Silanols and Methoxysilanes in THF/
MeOH. Although silanols were clearly intermediates in the
oxidation of arylhydrosilanes under either fluoride-free or
fluoride-promoted conditions, their reactivity relative to
methoxysilanes, and the importance of exchange between
these two species, was as yet unclear. To probe this, the
fluoride-free oxidations of (4-fluorophenyl)dimethylsilanol 11b
and (4-fluorophenyl) methoxydimethylsilane 10b were studied
(Figure 3). We immediately noticed that oxidation of silanol
11b (Figure 3a) proceeded at a much reduced rate compared to
methoxysilane 10b (Figure 3b), and that the latter oxidation
featured significant quantities of silanol. Oxidation of 10b under
fluoride-promoted conditions (0.1 equiv TBAF, Figure 3c)
proceeded at an overall rate broadly similar to that of the
fluoride-free reaction. However, the composition of the various
reaction intermediates was rather different, with silanol 11b
produced to a much greater extent, in addition to small
amounts of a further silicon-containing species which was
identified as disiloxane 13b.18
1
Figure 4. H NMR spectroscopic profiling of the equilibria between
methoxysilane 10b and silanol 11b. (a) Fluoride-free equilibrium. (b)
Fluoride-promoted equilibrium (0.1 equiv TBAF). Reactions run in d4-
MeOH/d8-THF (1:1, 0.1 M substrate) at 298 K.
a), an equilibrium between 10b and 11b was established over
∼48 h, which stabilized with an equilibrium constant of Keq
=
2.48 (in favor of silanol 11b). The addition of TBAF greatly
increased the rate at which equilibrium was reached, but not its
position (Graph b, ∼3 h, Keq = 2.57; see the Supporting
Information (SI) for further details on this equilibrium and the
negligible effect of fluoride ion concentration). In both
experiments, significant amounts of disiloxane 13b were formed
at the expense of the equilibrium mixture of silanol and
methoxysilane; this side-reaction, which is to the detriment of
oxidation,20 was clearly promoted by fluoride. Under “true”
oxidation conditions, the rate of equilibration could also be
While both the methoxysilane and silanol could potentially
serve as substrates for oxidation, it was not clear whether both
indeed did, given that these two components likely exist in
equilibrium. To study this, methoxysilane 10b was subjected to
C
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affected by the nucleophilic hydroperoxide anion, particularly in
the case of fluoride-free Graph 4a.
(unimolecular) oxidation than (bimolecular) substitution.
Equilibrium between methoxysilane and silanol is not reached
until ∼5 h reaction time (Figure 3b), such that a greater
proportion of more reactive methoxysilane is present in the
reaction before this time point. However, in the presence of
TBAF (Figure 3c), the rate of substitution at silicon (i.e., the
interconversion of methoxysilane and silanol) is increased to
such an extent that it now outpaces the rate of oxidation (k1 >
k−1 > k2). This seems reasonable, in that the interconversion of
the methoxysilane and silanol would benefit significantly from
fluoride (c.f. Figure 4b), and the rapid establishment of this
equilibrium is to the detriment of methoxysilane oxidation.8,9
The culmination of these effects is that fluoride-free and
fluoride-promoted methoxysilane oxidations proceed at similar
overall rates, but by different compositions of intermediates.
Attempts to fit reaction parameters to the slower oxidation of
the silanol (i.e., Figure 3a) proved more challenging: although
these oxidations gave reproducible trends in 1:1 THF/MeOH,
they did not afford reproducible relative rates of reaction, which
prevented reliable parameter fitting. The reactions were found
to be highly susceptible to agitation, with a momentary
effervescence being observed which coincided with a marked
“spike” (increase) in the rate of reaction. We surmised that this
corresponded to release of carbon dioxide (from KHCO3/
H2CO3 decomposition), the evolution of which would have a
dramatic effect on the acid−base equilibria of the reaction
system and therefore presumably on the concentration of
peroxide (or other) anions. This could be circumvented to an
extent by purging the reaction mixture with argon, which
displaced solubilized CO2. However, the most significant
improvement was gained through the use of methanol alone
as solvent, which now gave reproducible kinetic profiles.24
The oxidations of the methoxysilane 10b and silanol 11b
were monitored under these modified conditions (Figure 6),
and the profiles modeled using Berkeley Madonna.21
Considering the fluoride-free oxidations of 10b (Graph a)
and 11b (Graph b), it was immediately apparent that the rate of
nucleophilic substitution at silicon was significantly enhanced in
pure MeOH compared to MeOH/THF mixtures:25 after initial
rapid equilibration of silanol and methoxysilane (perhaps
promoted by the higher solubility of KHCO3 in MeOH), the
two reaction profiles were very similar. Due to the high
reproducibility of the reactions,24 we were able to fit identical
rate coefficients to the oxidation of both the silanol and
methoxysilane, indicating that these oxidations operate under a
Curtin−Hammett situation where rapid interconversion of 10b
and 11b precedes rate-limiting oxidationin other words, near
identical reaction pathways operate from both arylsilanol and
arylmethoxysilane substrates. The oxidation rate coefficients
evaluated in the modeling suggest that although the silanol
predominates at equilibrium, the vast majority of oxidation
proceeds via the methoxysilane (i.e., k1 > k−1 ≫ k2 ≫ k3).
The reaction profile of the fluoride-catalyzed oxidation of
methoxysilane 10b (0.1 equiv TBAF, Graph c) also revealed
broadly similar kinetics, with a rapid equilibrium of
methoxysilane and silanol compared to methoxysilane
oxidation. TBAF might be expected to further enhance the
rate of methoxysilane−silanol exchange, but no accompanying
acceleration of oxidation was apparent. The reason for this was
soon to become clear.
This suggested that under both sets of oxidation conditions, a
dynamic equilibrium between the silanol and methoxysilane
operates alongside the oxidation of either or both species,
which is consistent with the exchange of ligands between
different ate complexes. To elucidate the relative rates of these
various processes, we modeled the timecourse kinetic data of
the oxidation of methoxysilane 10b in THF/MeOH using
Berkeley Madonna software, based on the reaction scheme in
Figure 5a. Graph b illustrates the experimental and modeled
Figure 5. Modeling of kinetic data for oxidations of methoxysilane
10b, as shown in Figure 3, using Berkeley Madonna. The model is
based on experimental data up to 50% conversion (data points
shown). (a) Modeled reaction pathways; (b) model for fluoride-free
oxidation. (c) model for fluoride-promoted oxidation (0.1 equiv
TBAF). Values are normalized relative to k3. Experimental data
obtained at 0.1 M substrate, 0.6 M H2O2, 1.8 equiv KHCO3 in d4-
MeOH/d8-THF (1:1). Relative rate coefficients were obtained by best
fit of parameters to the reaction profile a.
data for the fluoride-free oxidation of 10b, and Graph c
illustrates the data for fluoride-promoted oxidation.21 Best-fit
correlations of the experimental data with the illustrated
reaction scheme were obtained, which led to the relative rate
coefficients depicted in the Table (Figure 5).22
The modeling led to an excellent fit between experiment and
theory, suggesting that the reaction scheme adopted is a valid
depiction of the processes at play during the oxidation. Both
models correlate with the equilibrium constants obtained
experimentally (Keq ≈ 2.5, c.f. Figure 4), and give a qualitative
indication that the rate of methoxysilane oxidation is around
10-fold that of silanol oxidation (i.e., k2 ≫ k3). This may reflect
the propensity of the silanol to form hydrogen bonds with
methanol (Si−O−H···O(H)Me), which could increase electron
density at the silicon atom and therefore deactivate it toward
attack by hydroperoxide anion.23 In the absence of TBAF, the
rate of methoxysilane oxidation appears significantly faster than
substitution at silicon by water/hydroxide (k2 ≫ k1 > k−1).
Although hydroperoxide presumably serves as a highly
competent nucleophile for ate complex formation (as
evidenced by the more rapid interconversion of methoxysilane
and silanol in its presence compared to the peroxide-free
equilibrium experiment in Figure 4a), the peroxide ate complex
formed from the methoxysilane seems more prone to undergo
Influence of Reagent Concentration on Initial Rate of
Reaction. The influence of the concentration of the various
reagents was evaluated by measurement of initial rates of
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Figure 7. Order of reaction for the oxidation of methoxysilane 10b
with respect to reagents. Reactions run 0.1 M in substrate, in MeOH.
Variation of concentration of (a) H2O2 (0.1 equiv TBAF, 0.1 equiv
KHCO3); (b) KHCO3 (0.1 equiv TBAF, 6.0 equiv H2O2); (c) TBAF
(0.1 equiv KHCO3, 6.0 equiv H2O2). Data points represent the mean
rate coefficient of three reactions. Error bars indicate one standard
deviation from the mean. See the SI for raw data sets.
reaction, we suggest that this effect is offset by an increased rate
of interconversion of the various tetracoordinate and
pentacoordinate silicon species, including the possibility that
fluoride could retard the overall rate of oxidation by
competitive displacement of hydroperoxide from preoxidation
ate complexes, thereby decreasing the overall rate of reaction.
Finally, the effect of water present in the reaction was
examined, as this would likely also affect the concentration of
the two silane species, and hence the rate of oxidation. Figure 8
illustrates the influence of water on the methoxysilane−silanol
equilibrium constant. Not only is there a clear correlation
between Kobs and the concentration of water, but also with the
nature of the cosolvent, with a higher proportion of silanol
being observed in THF/MeOH mixtures (Series A) compared
Figure 6. 19F NMR spectroscopic observation, and modeled reaction
parameters, for oxidations in MeOH. (a) Fluoride-free oxidation of
methoxysilane 10b; (b) fluoride-free oxidation of silanol 11b; and (c)
fluoride-promoted oxidation of 10b. Experimental data obtained under
the conditions indicated in d4-MeOH. Relative rate coefficients were
obtained by best fit of parameters to the illustrated reaction profiles.
phenol formation in MeOH (Figure 7, experiments run in
triplicate for each data point). Graph a shows the variation in
initial rate of phenol formation with hydrogen peroxide
concentration. As expected, the reaction shows a linear
relationship to [H2O2], but at higher concentrations a plateau
effect is seen. We propose that this arises from the limiting
concentration of KHCO3 present in the reaction, which in turn
limits the maximum concentration of active hydroperoxide
anion. Similar results were obtained when the concentration of
KHCO3 was varied (Graph b): an increase in rate can again be
seen with increasing concentration of base, with plateauing
observed as the reaction mixture approaches a limit of base
solubility at 0.3 equiv. KHCO3 (i.e., 0.03 M).
The effect of TBAF concentration was next examined. Here
we were surprised to observe an overall inhibitory effect of
fluoride in the initial rate profiles (Graph c). Fluoride ions
increase the rate of nucleophilic substitution around tetravalent
silicon by increasing the electrophilicity of the silicon center in
a pentavalent silicon-fluoride ate complex, where negative
charge is dispersed onto the electronegative apical ligands;
nucleophilic attack at pentavalent silicon can be up to 150 times
faster than at tetravalent silicon.12b,26 However, in the oxidation
Figure 8. Effect of water on the methoxysilane/silanol equilibrium. All
experiments employed 0.05 mmol 10b and 0.1 equiv KHCO3. Series
A: THF/MeOH (1:1). Series B: MeOH. Series C: MeOH, 1 equiv
TBAF.
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to MeOH alone (Series B, C). It is again notable in the latter
solvent that fluoride does not affect the position of equilibrium.
These results suggest that increasing amounts of water are likely
to inhibit oxidation, albeit the inorganic base will be better
solubilized.
Aryldimethylfluorosilane Intermediacy. The impor-
tance of fluoride ions in silicon chemistry merited a search
for fluorosilane intermediates, which we expected would likely
be present during the oxidation. To study this, we prepared the
p-fluorophenyl dimethylfluorosilane (4-FC6H4SiMe2F), and
recorded its 19F NMR spectrum, which showed two signals at
−113.5 (C−F) and −165.1 (Si−F)27 ppm (in MeOH, Figure
9a).28 Close inspection of the reaction profiles of the oxidation
mixture of two silanes in the presence of 6 equiv H2O2. Five
arylsilanes were investigated (p-OMe, Me, F, Br, CN), each run
in competition with the p-F arylsilane. In each case, the
1
proportion of products was measured by H NMR spectro-
scopic monitoring of the reaction (experiments run in triplicate,
ratios, which were consistent, were taken up to ∼50%
conversion). To compare solvent effects, each set of experi-
ments was performed in THF/MeOH (1:1), and MeOH.
The resultant LFER plots are depicted in Figure 10. Graph a
shows the Hammett plot in 1:1 THF/MeOH, and Graph b the
Figure 9. 19F NMR spectra of 4-FC6H4SiMe2F, and oxidation of 10b,
in MeOH. (a) Authentic sample of fluorosilane. (b) Oxidation of 10b
after 4 h reaction time. (c) Spectrum of reaction mixture of oxidation
of 10b at completion (36 h), showing consumption of the fluorosilane.
Figure 10. LFER plots for the oxidations of p-substituted
ArSiMe2OMe. (a) Hammett plot in 1:1 d8-THF/d4-MeOH; (b)
Hammett plot in d4-MeOH; (c) Swain−Lupton plot in 1:1 d8-THF/
d4-MeOH; (d) Swain−Lupton plot in d4-MeOH. All reactions run
with 1.0 equiv each of two arylsilanes, 6 equiv H2O2, 16 h, rt, with (a)
0.5 equiv. KHCO3, 0.1 M in THF/MeOH (1:1); (b) 0.5 equiv.
of methoxysilane 10b in MeOH, using 0.1 equiv TBAF and 3
or 6 equiv of H2O2, revealed a small amount of this fluorosilane
to be rapidly formed in these reactions (Figure 9b, 6 equiv
H2O2). The proportion of fluorosilane observed was inversely
proportional to the concentration of H2O2, and the fluorosilane
peak completely disappeared in the reaction using 6 equiv of
H2O2 once this reaction reached completion (Figure 9c).29
These observations substantiate the notion that fluorosilane
formation is indeed influential on reaction progress, and that
fluoride ion can be recycled from silane intermediates.
1
KHCO3, 0.1 M MeOH, reaction progress monitored by H NMR
spectroscopy. All reactions run in competition with 4-
FC6H4SiMe2OMe. krel = [p-XC6H4OH]/[p-FC6H4OH], as deter-
mined by 1H NMR spectroscopic analysis of each reaction. Error bars
show one standard deviation from the mean.
Charge Development in the Rate-Limiting Step. The
experimental data obtained supports a rapid exchange of
electronegative ligands around silicon (methoxide, hydroxide,
hydroperoxide, and fluoride) as a prelude to a slower, rate-
determining migration. In methanol, the rate of ligand exchange
approaches a Curtin−Hammett situation, with the majority of
the oxidation proceeding via the less abundant, but far more
reactive methoxysilane. Given its greater intrinsic nucleophil-
icity, the reaction of tetravalent silicon with hydroperoxide
anion itself is likely to be significantly faster than methoxide or
hydroxide.
To further investigate this, we compared the relative rates of
oxidation of a variety of para-substituted arylmethoxysilanes,
which would enable the construction of linear free-energy
relationship (LFER) plots and evaluation of associated reaction
parameters. The relative rates of oxidation of these
arylmethoxysilanes were measured by reaction of an equimolar
Hammett plot in MeOH, which pleasingly show an excellent
straight line fit, with reaction constants of ρ = +0.60 and ρ =
+0.45 for Graphs a and b, respectively. Mindful that mesomeric
effects might play a limited role during a rate-limiting migration
step, we also explored Swain−Lupton plots of these data;30
Graph c shows the Swain−Lupton plot in 1:1 THF/MeOH
(ρSL = 1.17), and Graph d in MeOH (ρSL = 0.77). Of great
intrigue is the balance of Swain−Lupton sensitivity factors f
(field/inductive) and r (resonance), which were obtained using
Dual Obligation Vector Evaluation (DOVE) as reported by
Swain et al.30 In MeOH/THF, f = 0.491, r = 0.509; while in
MeOH, f = 0.459, r = 0.541. These values show that mesomeric
and inductive effects play an equal role in the rate-determining
step of the oxidation.
Despite a significant change in the rates of nucleophilic
substitution at silicon when the solvent system is changed from
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THF/MeOH to pure MeOH (Compare Figures 4 and 6,
respectively), the somewhat similar ρ values observed for these
two reactions under both Hammett and Swain−Lupton
analyses further argues against nucleophilic attack of hydrogen
peroxide at silicon being rate-determining, albeit H2O2
concentration clearly has a rate-influencing effect. These values
are, nonetheless, indicative of modest negative charge develop-
ment in the transition state of the rate-limiting step, which may
reflect a positioning of the migrating group in the (charge
dense) apical position around pentacoordinate silicon prior to/
during the migration step itself. The balance of inductive and
mesomeric effects is harder to interpret, as these could affect
both migration, or HOO− coordination to the silane, but
provide an additional interesting insight into the electronic
characteristics of the RDS. The effect of the solvent on the
extent of negative charge development adjacent to the arene in
the RDS may reflect a change in the position of the transition
state. For instance, it seems reasonable to suppose that O−O
bond breaking may be more advanced in MeOH due to better
solvation of the hydroxide leaving group.
these studies offer new insight into organosilane reactivity for
the design of silicon-based organic reactions.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.7b00357.
■
S
Experimental procedures and data sets for NMR
timecourse experiments. Characterization data and
copies of NMR spectra for reaction intermediates
(PDF)
AUTHOR INFORMATION
Corresponding Author
*edward.anderson@chem.ox.ac.uk.
■
ORCID
Edward A. Anderson: 0000-0002-4149-0494
Present Address
§Quotient Bioresearch, The Old Glassworks, Nettlefold Road,
Cardiff, CF24 5JQ, U.K.
Finally, we note that these reaction constants are similar in
magnitude to the results of an intramolecular competition study
of aryl migration conducted by the Tamao group (Scheme 2, eq
Notes
The authors declare no competing financial interest.
Scheme 2. Summary of Results of Linear Free Energy
Relationship Experiments
ACKNOWLEDGMENTS
■
E.J.R. thanks Pfizer (U.K.) for a CASE studentship award. A.M.
thanks the Royal Thai Government and the DPST project for a
studentship. E.A.A. thanks the EPSRC for an Advanced
Research Fellowship (EP/E055273/1), and for additional
funding (EP/M019195/1). We thank Dr. John M. Brown for
insightful discussions on kinetic data.
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■
By observing the oxidation of arylsilanes using 19F NMR
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H
DOI: 10.1021/jacs.7b00357
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX