Organocatalytic oxidation of organosilanes to silanols

Article abstract of DOI:10.1021/cs400515w

The oxidation of organosilanes to silanols constitutes an attractive transformation for both industry and academia. Bypassing the need for stoichiometric oxidants or precious metal catalytic complexes, the first organocatalytic oxidation of silanes has been accomplished. Catalytic amounts of 2,2,2-trifluoroacetophenone, in combination with the green oxidant H ₂O₂, lead to excellent to quantitative yields in a short reaction time. A variety of alkyl, aryl, alkenyl, and alkynyl substituents can be tolerated, providing an easy, cheap, efficient, and practical solution to a highly desirable transformation.

Full text of DOI:10.1021/cs400515w

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Article
Organocatalytic Oxidation of Organosilanes to Silanols
Dimitris Limnios, and Christoforos George Kokotos
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/cs400515w • Publication Date (Web): 26 Aug 2013
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Organocatalytic Oxidation of Organosilanes to
Silanols
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Dimitris Limnios and Christoforos G. Kokotos*
Laboratory of Organic Chemistry, Department of Chemistry, University of Athens,
Panepistimiopolis 15771, Athens, Greece
KEYWORDS : Green Chemistry, Hydrogen peroxide, Organocatalysis, Oxidation,
Perfluoroketones, Silanols
ABSTRACT : The oxidation of organosilanes to silanols constitutes an attractive transformation
both for industry and academia. Bypassing the need for stoichiometric oxidants or precious metal
catalytic complexes, the first organocatalytic oxidation of silanes has been accomplished.
Catalytic amounts of 2,2,2,ꢀtrifluoroacetophenone, in combination with the green oxidant H2O2,
leads to excellent to quantitative yields in short reaction time. A variety of alkyl, aryl, alkenyl
and alkynyl substituents can be tolerated providing an easy, cheap, efficient and practical
solution to a highly desirable transformation.
INTRODUCTION
Organosilicon compounds are of high interest because they find wide applications as versatile
building blocks both in industry and academia.1 In particular, silanols have been utilized in
industry for the production of siliconꢀbased polymeric materials,2 for the derivatization of
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functional groups and as nucleophilic partners in metalꢀcatalyzed crossꢀcoupling reactions in
organic synthesis.3 Organosilanols have been also identified as challenging bioactive agents in
experimental pharmacology.4 Very recently, organosilanols have been employed in catalysis,5
due to their anion recognition ability.6 Although the wide application of silanols requires
efficient preparative protocols from readily available precursors, current synthetic approaches are
only limited to hydrolysis of chlorosilanes, alkali treatment of siloxanes and oxidation of silanes
(Figure 1).7 The latter approach has stimulated the scientific community and early attempts
utilized stoichiometric oxidants like peracids,8a permanganates,8b dioxiranes8c,d and
oxaziridines.8e However, these methods suffer from low yields and selectivities, since
undesirable byꢀproducts, like disiloxanes are formed. Transition metal catalysis has provided
elegant solutions by employing a diverse set of catalytic conditions minimizing the byꢀproduct
formation. Among the various metals utilized, Rh,9a,b Cu,9c Re,9d,e Pd,9f Ir9g and W9h have been
demonstrated to provide efficiently the oxidation of silanes. More recently, Tiꢀbased,10a goldꢀ10b,c
and silverꢀ10d,e nanoparticles have been synthesized and employed in the same transformation.
Since 2000, organocatalysis, the use of small organic molecules as catalysts for organic
transformations, has grown to such an extent that is nowadays considered the third major branch
of asymmetric catalysis along with transition metal catalysis and biocatalysis.11,12 Although
much effort has been devoted to invent novel reactivities, researchers on organocatalysis have
not been so actively involved in oxidation reactions. Only a number of examples exist in the
literature, dealing mainly with the epoxidation reaction.13ꢀ16 Due to their better environmental
acceptance and their ability to act without requiring special reaction conditions, nonꢀmetal
organic oxidants have become available and have been employed in oxidation reactions.
Furthermore, in pharmaceutical industry, any contamination in the active pharmaceutical
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ingredients coming from metal catalysts is not usually acceptable [very low levels of metals
(ppm to ppb) are sometimes tolerated]. Along these lines, we became interested in developing
the first organocatalytic protocol that could be efficiently applied in the catalytic oxidation of
organosilanes.
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(FIGURE 1)
RESULTS AND DISCUSSION
Among the most promising organic oxidants are perhydrates and dioxiranes.13a,b These reagents
derive from ketones in conjunction with an oxygen source. Although, in principle, the aboveꢀ
mentioned oxidants can be used catalytically, the vast majority of the literature utilize, in the best
case scenario, stoichiometric quantities. In most cases, large excess (over 5 equivalents) is
required in order oxidations to reach completion. Attempts to reduce the amount of the reaction
promoter to substoichiometric quantities have met with limited success. Indeed, some excellent
contributions from the groups of Denmark,14 Yang15 and Shi16 have provided elegant solutions
both to racemic and asymmetric epoxidation reactions. To fulfill our expectations for a process
that would be acceptable for both academia and industry, we have focused on the development of
a general strategy that enables the use of substoichiometric amounts (10 mol%) of a compound
as a synthetically versatile and operationally trivial mode of activation of a green oxidant like
H2O2. Today there is an increasing demand to use oxidants such as H2O2, which are
environmentally friendly and do not give rise to any waste products. We have been previously
involved in the synthesis of activated ketones as potent and selective enzyme inhibitors.17,18
Coupled with our own previous experience in organocatalysis,19 we envisaged the use of
activated ketones as catalysts. Hydrogen peroxide by itself is a poor oxidant for organic
oxidations. Thus, it has to be coupled with a catalyst in order to create a reactive intermediate
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that will accelerate the oxidation. We anticipated that an activated ketone has the ability to
perform in a similar way to a metal and react with hydrogen peroxide. This intermediate will
perform the oxidation of the substrate and will regenerate the catalyst.
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A variety of activated ketones were tested as catalysts for the oxidation of triethyl silane to
triethyl silanol using H2O2 as the oxidant (Scheme 1). Initially, ketoacids A and B, and ketoester
C were employed as activated ketones. However, they led to low to moderate yields. Isatin D
and strained 1,2ꢀdiketone E did not furnish the desirable results. One of the most important
classes of activated ketones is polyfluoroalkyl ketones. These ketones are known to be more
activated than ketoacids and ketoesters and they exist in equilibrium with their hydrate form in
aqueous environment. From this class of compounds, only some trifluoromethyl ketones have
been employed in epoxidation reactions as catalysts. However, more than stoichiometric
quantities are usually employed or when substoichiometric amounts are used, lower yields, harsh
reaction conditions and longer reaction times are employed.13 Once 2,2,2ꢀtrifluorolacetophenone
F was employed, excellent yield was obtained after short reaction time (97% yield, 1.5 h).
Prolonged reaction time led to quantitative yield. Similar results were obtained, when
pentafluoroethyl (G) or heptafluoropropyl acetophenone were employed.20 Decreasing the
potency of activation on the carbonyl, either by substituting one fluorine by one chlorine or
utilizing a benzyl moiety instead of a phenyl, led to diminished reaction yields. Acetophenone
(J) or the use of no catalyst led to very low conversions underlying the role of the activated
ketone for the catalytic activity.
(Scheme 1)
After optimization,20 we concluded that 10 mol% of the catalyst F in a tertꢀbutanolꢀaqueous
buffer reaction medium can lead to excellent yields after 24 h utilizing 1.1 equivalents of
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MeCN:H2O2. The substrate scope of the protocol was then explored (Scheme 2). Initially,
trialkyl and mixed alkyl silanes were efficiently employed (silanols 2ꢀ7). Unsaturated
organosilanes bearing triple or double bonds can be utilized once the reaction medium is slightly
altered in order to avoid product decomposition (EtOAc instead of tertꢀbutanol). Both aromatic
and aliphatic alkynyl substrates were employed leading to high yields (silanols 8 and 9).
Substituting the alkynyl moiety with an alkene led to the isolation of silanol 10 in high yield.
Aromatic moieties are also well tolerated. The substitution of an aliphatic alkyl moiety by either
a phenyl ring or a heteroaromatic thiophene moiety led to the isolation of silanols 11 and 12 in
excellent yields. It has to be highlighted that prolonged reaction time led to decreased yields via
decomposition pathways. Further substitution of additional alkyl moieties by aromatic phenyl
substituents led to faster reaction, leading to silanols 13 and 14 in almost quantitative yields. An
organosilane bearing three TMS moieties was also employed successfully leading to good yield
(15), although in this case longer reaction time was necessary. Finally, the versatility of this
method was also highlighted using diphenylsilane. This substrate usually suffers from the
propensity upon oxidation utilizing metal oxidants to form not only the desired silanol 16 but
also a mixture of disiloxanes, because a number of reaction pathways can be followed after the
first oxidation. Our organocatalytic protocol led to a high yield of silanol 16 and no other byꢀ
product could be identified both by NMR and GCꢀMS analysis of the reaction mixture, although
the reaction time and medium were quite crucial for the reaction outcome. Longer reaction time
led to decreased yields due to product decomposition to phenol.
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(Scheme 2)
We then turned our attention in elucidating the reaction mechanism. A number of experiments
were performed in order to shed more light on the reactive intermediates and keyꢀactive species.
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In the absence of H2O2, no reaction occurred. H2O2 was not capable by itself or in the
combination with the catalyst to perform the oxidation, because in the absence of MeCN,
oxidation did not take place (Scheme 3, A). Furthermore, when only 0.5 equivalent of MeCN
was employed, then only 48% of the oxidation occurs.20 We assume that there is an intermediate
oxidant, which is a peroxycarboximidic acid, similar to the intermediate that Payne and
coworkers have proposed in their epoxidation reaction.21 Furthermore, this intermediate oxidant
is also not capable of promoting the reaction by itself, since in the absence of the catalyst only
29% yield is obtained (Scheme 3, A). In our belief, H2O2 which is not capable of performing the
oxidation by itself, has to react with acetonitrile to afford the more reactive oxidant intermediate,
which in turn is not capable of performing the full oxidation but in the presence of the hydrate
form of the catalyst can react and form the final oxidant which performs the reaction. Evidence
that supports the peroxycarboximic acid intermediate is the observation of acetamide formation
at the end of the reaction both by GCꢀMS analysis and 1HꢀNMR. At this stage, the crucial role of
the pH of the solution has to be highlighted in order the peroxycarboximic acid intermediate to
be generated (see Supporting Information). The reaction outcome was independent from the
addition of the radical traps, like Tempo, AIBN and BHT, indicating that this protocol does not
contain any radical intermediates (Scheme 3, B). Stemming from previous knowledge acquired
in our laboratory for fluoroketones,17 19F NMR experiments showed that although in organic
solvents the equilibrium lied towards the ketone form, in the aqueous medium of the reaction, the
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hydrate was the main form (Scheme 3, C, see also SI). Following the reaction mixture by Fꢀ
NMR, IR and MS spectroscopy, new species containing fluorine were identified (Scheme 3, C).
Although 2,2,2ꢀtrilfuoroacetophenone exists in the keto form in organic solvents, in the D2Oꢀ
buffer solution, the hydrate form is the predominant species (Scheme 3, C). Upon addition of tꢀ
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BuOH and MeCN, no change was observed. Once H2O2 was added, immediately a new peak was
observed in 19FꢀNMR. This is presumably compound IV, a perhydrate since the same compound
was obtained when no MeCN was added in the reaction mixture (Scheme 3, C, bottom). It seems
that MeCN has a dual role in the oxidation via the formation of the peroxycarboxymidic acid.
First, it helps in the formation of higher concentrations of the perhydrate via oxidation and
secondly the perhydrate with the peroxycarboximidic acid forms the active oxidant species. If no
silane was added, the perhydrate was slowly transformed to a new compound, which is assumed
to be the corresponding dihydroperoxide. This compound is capable of promoting the oxidation,
but its oxidation reaction rate is slower (24% yield, 1 h; 94% yield, 24 h). Monitoring the
reaction mixture leads to the conclusion that the perhydrate is decaying while the concentration
of the dihydroperoxide increases.
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(Scheme 3)
Taking into consideration these data, the following catalytic cycle is proposed (Figure 2).
Initially the perfluoroalkyl ketone is hydrated in the presence of water leading to its hydrate form
I. Once the optimum pH is utilized, acetonitrile and H2O2 react to form peroxycarboximidic acid
II. The hydrate form of the perfluoroalkyl ketone is oxidized by H2O2 and II forming perhydrate
IV and leaving as byꢀproduct from the peroxycarboximidic acid, acetamide III. The presence of
a new intermediate after addition of acetonitrile and H2O2 in the solution of the catalyst in the
reaction medium was identified by 19FꢀNMR (see SI). Perhydrate IV then reacts with II forming
the active oxidant species of the oxidation.22 Upon addition of the silane, the oxidation occurs to
the corresponding silanol. Finally, the silanol derivative is obtained and at the same time
recycling of the catalyst occurs through generation of the hydrate I. If no silane is added in the
reaction medium, perhydrate is transformed to another species, the dihydroperoxide, which is
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capable of promoting the oxidation but in a slower rate (based on the observation of FꢀNMR,
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see SI).
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(Figure 2)
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Conclusions
In conclusion, the first highly selective organocatalytic oxidation protocol of organosilanes to
silanols is described. Perfluoroalkyl aryl ketones can be employed as catalysts (10 mol%) in a
such a reaction leading to excellent to quantitative yields in short reaction times. To our
knowledge, this is the first example of such a catalytic oxidation utilizing a cheap and
commercially available metalꢀfree organic molecule. The substrate scope of the reaction is very
general and a variety of alkyl, alkenyl, alkynyl, aryl and heteroaryl substituents can be tolerated.
The mechanism of the reaction was studied and active intermediates are proposed.
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Figure 1. Approaches for the synthesis of silanols.
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Figure 2. Proposed catalytic cycle of the oxidation.
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Scheme 1. Catalyst screening for the organocatalytic oxidation of triethyl silane to silanol.
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Scheme 2. Substrate scope of the organocatalytic oxidation of organosilanes.
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Et
Et
Et Si OH
Et Si H
Et
2
Et
1
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F
10% mol , MeCN, H2O2, t-BuOH, Buffer
No
>99% yield (24 h)
0% yield (24 h)
1% yield (24 h)
A
F
10% mol , MeCN,
H2O2, t-BuOH, Buffer
F No
F 50 mol%
No catalyst,
10% mol
,
MeCN, H2O2, t-BuOH, Buffer
10% mol
,
MeCN, H2O2, t-BuOH, Buffer 48% yield (24 h)
MeCN, H2O2, t-BuOH, Buffer
29% yield (24 h)
10% mol F, MeCN, H2O2, t-BuOH, Buffer
Reaction Conditions and Tempo (1equiv.)
Reaction Conditions and AIBN (1equiv.)
99% yield (2 h)
B
C
99% yield (2 h)
99% yield (2 h)
99% yield (2 h)
BHT
Reaction Conditions and
(1equiv.)
Scheme 3. A. Control experiments to probe the reaction mechanism. B. Experiments to rule out
the possibility of radical intermediates. C. 19FꢀNMR experiments to probe the active oxidant
species.
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AUTHOR INFORMATION
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Corresponding Author
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* Tel: +30 210 7274281. Eꢀmail: ckokotos@chem.uoa.gr
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
The authors gratefully acknowledge the Operational Program “Education and Lifelong Learning”
for financial support through the NSRF program “ΕΝΙΣΧΥΣΗ ΜΕΤΑꢁΙꢁΑΚΤΟΡꢂΝ
ΕΡΕΥΝΗΤꢂΝ” (PE 2431)” coꢀfinanced by ESF and the Greek State.
ASSOCIATED CONTENT
Supporting Information
Experimental Procedures, Catalyst and Conditions Optimization including NMR and GC data, as
well as mechanistic investigations. This information is available free of charge via the Internet at
htpp://pubs.acs.org/.
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REFERENCES
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(1) For books, see: (a) Ojima, I., Li, Z., Zhu, J. In The Chemistry of Organic Silicon
Compounds, Rappoport, S., Apeloig, Y., Eds.; Wiley: New York, 1998; (b) Colvin, E. W. In
Silicon Reagents in Organic Synthesis, Academic Press, London, 1988.
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(2) Lickiss, P. D. Adv. Inorg. Chem., 1995, 42, 147ꢀ262.
(3) For a book, see: Denmark, S. E., Sweis, R. F. In Metal-Catalyzed Cross-Coupling Reactions,
de Meijere, A., Diederich, F., Eds; WileyꢀVHC: Weinheim, 2004; (b) For a recent use of silanols
as crossꢀcoupling partner, see: Zhou, H.; Moberg, C. J. Am. Chem. Soc., 2012, 134, 15992ꢀ
15999.
(4) For a recent review, see: Franz, A. K.; Wilson, S. O. J. Med. Chem., 2013, 56, 388ꢀ405.
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Table of Contents (TOC) and Abstract Graphic
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O
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Ph
CF3
10%
Si
H
Si OH
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H2O2, MeCN,
t-BuOH, Buffer
alkyl, aryl, alkenyl, alkynyl
high to quantitative yields
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