Silylation of O-H bonds by catalytic dehydrogenative and decarboxylative coupling of alcohols with silyl formates

Article abstract of DOI:10.1039/c7cc05212j

The silylation of O-H bonds is a useful methodology in organic synthesis and materials science. While this transformation is commonly achieved by reacting alcohols with reactive chlorosilanes or hydrosilanes, we show herein for the first time that silylformates HCO₂SiR₃ are efficient silylating agents for alcohols, in the presence of a ruthenium molecular catalyst.

Full text of DOI:10.1039/c7cc05212j

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Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
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Silylation of O–H Bonds by Catalytic Dehydrogenative and
Decarboxylative Coupling of Alcohols with Silyl Formates
Clément Chauvier, Timothé Godou and Thibault Cantat*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
The silylation of O–H bonds is a useful methodology in organic
synthesis and materials science. While this transformation is
commonly achieved by reacting alcohols with reactive
chlorosilanes or hydrosilanes, we show herein for the first time that
silylformates HCO2SiR3 are efficient silylating agents for alcohols, in
the presence of a ruthenium molecular catalyst.
The replacement of polar O–H bonds in alcohols and
phenols with the O–Si linkage is of great importance across the
chemical sciences. For example, in synthetic organic chemistry,
the silyl ether functionality is frequently installed for the
temporary protection of otherwise reactive hydroxyl groups.1 In
this respect, the wide availability of various silyl groups with
tunable stereo-electronic properties has considerably
facilitated the total synthesis of complex natural products.2 In
addition, silyl ethers generally display increased thermal
stability and volatility as well as decreased polarity compared to
their parent alcohols. Trimethylsilylation of the latter has thus
become an invaluable tool for their derivatisation prior to GC
analysis.3
The silylation of hydroxyl groups commonly relies on the use
of silyl chlorides or silyl triflates in the presence of a
stoichiometric amount of a Brønsted base (Scheme 1, top).4
While the implementation of this protocol is generally
straightforward, the separation of the salt (typically an
ammonium hydrochloride salt) from the product may be
tedious. To circumvent this limitation, salt-free silylation
methods based either on hydrosilanes or on sophisticated
Scheme 1. Overview of the prototypical methodologies for the silylation of alcohols (Eqs.
1 and 2) and the new protocols based on silyl group transfer reagents (Eq. 3 and 4).
Nevertheless, the lightest hydrosilanes, e.g. Me3SiH, are
gaseous and/or pyrophoric reagents, and not suitable for
practical organic syntheses. This issue has been tackled via the
use of surrogates of hydrosilanes as shown by Oestreich and
coworkers, with silylated cyclohexa-1,4-dienes (1,4-CHDN). In
the presence of catalytic amounts of B(C6F5)3, the authors were
able to promote the transfer hydrosilylation of a variety of
unsaturated functional groups9 as well as the dehydrogenative
silylation of alcohols (Scheme 1, Eq. 3).10 Recently, we
demonstrated that silylformates, HCO2SiR3, could serve as a
new class of hydrosilane surrogates in the transfer
hydrosilylation of aldehydes, by formal decarboxylation of the
formate ligand in the presence of a metal catalyst.11 This
approach has the advantage of utilizing formic acid, a mild
reductant derived from biomass or CO2, as a hydride source.12
In comparison, hydrosilanes are classically formed from
chlorosilanes and LiAlH4 as an energy intensive hydride donor.13
Herein we report the successful silylation of O–H bonds by
catalytic dehydrogenative and decarboxylative coupling of
alcohols and phenols with silyl formates (Scheme 1, Eq. 4).
We started our study with the silylation of 4-methoxyphenol
trimethylsilyl
(TMS)
group
donors
such
as
bis(trimethylsilyl)acetamide (BSA)5 or N-trimethylsilylimidazole
(TMSIM)6 have been devised. Hydrosilanes are particularly
attractive in this context as gaseous H2 is the sole byproduct in
the dehydrogenative Si–O coupling, and a plethora of transition
metal-7 and main-group-based8 catalysts has been reported for
this reaction (Scheme 1).
(2) in the presence of triethylsilyl formate (Et3SiOCHO, 1a) as a
surrogate of the widely used triethylsilane (Et3SiH). Because a
NIMBE, CEA, CNRS, Université Paris-Saclay, Gif-sur-Yvette, France.
E-mail: thibault.cantat@cea.fr
†Electronic Supplementary Information (ESI) available: [experimental details and
procedures]. See DOI: 10.1039/x0xx00000x
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catalyst is seemingly required to promote the decarboxylation
of the formate moiety in 1a, we initially selected the ruthenium- evaluated with a variety of alcohols featuring diverse functional
based complex [Ru(κ1-OAc)(κ2-OAc)(κ3-triphos)] (triphos: 1,1,1- groups (Scheme 4 and ESI). Phenols substituted with bromo,
Journal Name
The generality of the dehydrogenative coupling was further
View Article Online
DOI: 10.1039/C7CC05212J
tris(diphenylphosphinomethyl)ethane) (
complex has indeed proven competent to generate reactive reacted analogously to
hydride-containing ruthenium complexes via decarboxylation
of 1a under catalytic conditions.11
4
) (Scheme 2). This benzyloxy, dimethylamino, amino and acetamido (ESI) groups
and the corresponding silyl ethers
6a and 7a) were obtained in excellent yields. A similar
outcome is seen for primary alcohols ( 17) that are fully
2
(5b-d,
8
-
converted into their silyl-protected analogues within 1 h at
70 °C. For example, the silylation of benzyl alcohol with the silyl
formates 1a
, 1b or bulkier 1d yields the corresponding ethers
(8a-b and 8d) quantitatively. In contrast, the B(C6F5)3-catalyzed
silylation of benzyl alcohol with silylated 1,4-CHDN leads to
substantial amounts of toluene via deoxygenation. Importantly,
fragile or reducible functional groups are also well-tolerated
under our reaction conditions as the nitro, iodo and C=C groups
are preserved in the silyl ethers 9a, 10a and 16a as well as the
Scheme 2. Catalytic dehydrogenative and decarboxylative silylation of phenol 2.
epoxide, imine of alkynyl functionalities.14 The clean three-fold
transfer of the TMS group from 1b (3.5 equiv.) to 2-
methylglycerol, a reaction potentially relevant to biodiesel
quality assessment, was also noted and 17b was obtained in
excellent yield (> 99 %) after 3 h at 70 °C.
After optimisation of the nature of the solvent, the
temperature and the catalyst loading (see ESI), we found that
phenol
formate 1a (1.2 molar equiv.) after 40 min at 70 °C, with 1 mol%
of complex . While the formation of silyl ether 3a is
2 is quantitatively silylated by a slight excess of silyl
4
conveniently monitored by 13C NMR spectroscopy, we also
confirmed the co-generation of H2 (δH = 4.57 ppm in CD3CN) and
CO2 (δC = 125.9 ppm in CD3CN) during the course of the
reaction. In contrast, in the absence of catalyst, only traces
amounts of 3a were detected (<2 %) after 1.5 h at 70 °C. The
formation of 3a from 1a and
2 represents the first example of
the utilization of a silylformate reagent for the silylation of an
O–H bond.
In order to evaluate the influence of the silyl group on the
reactivity, the silylation of phenol
2 was carried out with various
silylformates substituted with alkyl and aryl groups (1b-e
)
(Scheme 3). Notably, the TMS group is efficiently transferred
from trimethylsilyl formate (1b) as the silyl ether 3b was
obtained in quantitative yield after 30 min. 1b thus behaves as
a new liquid surrogate of Me3SiH (b.p. 86 °C for 1b vs. 6.7 °C for
Me3SiH) and it complements the trimethylsilylated CHDN
derivative developed by the group of Oestreich. Bulky TBDMS
(tert-butyldimethylsilyl) and TIPS (triisopropylsilyl) groups were
also successfully introduced without altering the optimized
conditions. Conversely, the silylation with triethoxysilyl formate
1f is somewhat less efficient and silylether 3f was obtained in
62 %
yield
after
2.5 h.
Scheme 4. Scope of the transfer dehydrogenative silylation of alcohols with silyl
formates. Reaction conditions: alcohol (0.1 mmol); silyl formate (0.14 mmol); complex 4
(1 mol%); MeCN (0.4 mL; 0.2 M); 1 h at 70 °C. Yields determined by 1H NMR analysis using
mesitylene (10 µL) as an internal standard. Isolated yields from upscaled experiments
(0.5 mmol scale) in brackets. [a] 2 mol% 4 used. [b] Yield determined after 5.5 h.
Scheme 3. Dehydrogenative silylation of phenol 2 with various silyl formates. Isolated
yields in brackets
2 | Chem. Commun., 2017, 00, 1-3
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Secondary alcohols are likewise prone to undergo the reaction mixture must therefore be delayed by atVlieewaAsrttic3le0Omnlinine
10
catalytic transfer dehydrogenative coupling with either 1a or 1b to prevent the deactivation of the catalysDt.OI: 10.1039/C7CC05212J
providing the corresponding silyl ethers in high yields (> 90 %
for 18-21). For example, 1-phenylethanol (18) was silylated with
1a and 2 mol%
quantitative yield after 1 h. A competition experiment carried
out between 18 and the related primary benzyl alcohol (
4 affording the corresponding silyl ether 18a in
8
)
In contrast, formic acid (FA) was the only intermediate
revealed that the latter reacted with 1a ca. 3 times faster than
the secondary alcohol 18 (see ESI). The silylation of the allylic
alcohol 1-hexen-3-ol (22) with Et3SiOCHO afforded 22a with a
moderate yield of 54 %, presumably because of the competing
catalytic 1,3-hydrogen transfer yielding the saturated 3-
hexanone (observed by 1H NMR). The utility and practicality of
our method was further established with naturally-occurring
testosterone that was chemoselectively trimethylsilylated
within 2 h at 70 °C. Owing to the gaseous nature of the
byproducts, the corresponding silyl ether 24b was isolated in
97 % yield merely after the removal of the catalyst onto a short
plug of silica gel. The transfer of the TES group to bicyclic 2-
adamantanol also proceeded with ease providing 25a
quantitatively, while its tertiary congener, 1-adamantanol,
remained unchanged even under forcing conditions (100 °C,
24 h). The transfer of the less hindered TMS group to 1-
adamantanol was nonetheless possible and 26b was formed in
82 % yield after 5.5 h at 70 °C.
1
observed by H and 13C NMR spectroscopy upon silylation of
phenol
2 with triethylsilyl formate 1a, in the presence of catalyst
4
. In the absence of catalyst, an equilibrium is slowly established
within 110 h at 70 °C between the free phenol and the
corresponding silyl ether, with concomitant release of FA (black
curve in Fig. 1, 퐾3043퐾 = 1.7).18 In contrast, no reaction occurs
between the bulky triisopropylsilyl formate 1e and phenol
2
after 7 days at 70 °C, although 1e is able to transfer the TIPS
group to phenols under catalytic conditions (see Scheme 3).
According to these observations, the ruthenium complex
4
plays a dual role in the reaction (Scheme 6). At the outset, the
catalyst facilitates the exchange of formate and phenolate
anions at the silicon center (blue curve in Fig. 1), leading to the
formation of FA. It also catalyses the irreversible decomposition
of FA into H2 and CO2, thereby shifting the aforementioned
equilibrium to the right (green curve in Fig. 1).
Based on the successful results obtained with alcohols, the
transfer hydrosilylation of
a few carboxylic acids was
attempted. While silyl esters find applications in material
science and in organic synthesis,15 their preparation by catalytic
dehydrogenative coupling with hydrosilanes has only been
scarcely investigated.16 We were thus pleased to observe the
clean formation of triethylsilyl acetate (27a) and benzoate (28a
)
in excellent yields after respectively 2.5 h and 2 h at 70 °C
(Scheme 5). Additionally, levulinic acid, a biogenic carboxylic
acid obtained from cellulosic materials, was chemoselectively
silylated in good yield (29a, 85 % after 3 h at 70 °C), as the keto
group remained untouched.17 To the best of our knowledge,
these examples constitute the first report of silylation of
carboxylic acids with a surrogate of a hydrosilane.
Figure 1. Silylation of phenol 2 with silyl formate 1a in the presence (♦ at 70 °C and ▲at
RT) or in the absence (■ at 70 °C and • at RT) of catalyst 4.
Scheme 5. Silyl esters obtained by dehydrogenative silylation of carboxylic acids with 1a.
From a mechanistic standpoint, triethysilane (Et3SiH), which
Scheme 6. Proposed mechanism for the dehydrogenative and decarboxylative silylation
may be generated by catalytic decarboxylation of triethylsilyl of alcohols with silyl formates.
formate 1a, could not be detected in solution. In fact, phenol
2
The ability of ruthenium complex
4 to promote the
did not react with Et3SiH under the optimized reaction
conditions, even after 30 h at 70 °C (Eq. 5), thereby ruling out its
involvement as a competent intermediate. In this respect, silyl
formates radically differ from silylated 1,4-CHDN that have been
shown to act as precursors of hydrosilanes. The latter indeed
releases the free hydrosilane upon catalysis with B(C6F5)3 prior
to the dehydrocoupling with the alcohol whose addition to the
acceptorless dehydrogenation of FA (ADH) was further
assessed: an acetonitrile solution of FA was fully decomposed
into CO2 and H2 within 1 h at 70 °C with 1 mol% of the complex
4
(Eq. 6). This result demonstrates that 4 is a competent catalyst
for the base-free dehydrogenation of FA under mild
conditions.19 In line with the well-established positive influence
of bases on the rate of FA decomposition,20 we also observed a
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Journal Name
Am. Chem. Soc., 1989, 111
Mukherjee, R. R. Thompson, A. EDllOerI:n10a.n10d3V9Aie/w.CDA7rC.tiCcSlae0d5O2on1lwi2nJe,
ACS Catal., 2011, , 698-702; (i) S. Vijjamarri, V. K.
Chidara, J. Rousova and G. Du, Catal. Sci. Technol., 2016,
, 3886-3892.
(a) J. M. Blackwell, K. L. Foster, V. H. Beck and W. E. Piers,
J. Org. Chem., 1999, 64, 4887-4892; (b) D. Gao and C.
Cui, Chem. Eur. J., 2013, 19, 11143-11147; (c) V.
Gevorgyan, J.-X. Liu, M. Rubin, S. Benson and Y.
Yamamoto, Tetrahedron Lett., 1999, 40, 8919-8922; (d)
A. A. Toutov, K. N. Betz, M. C. Haibach, A. M. Romine and
R. H. Grubbs, Org. Lett., 2016, 18, 5776-5779; (e) A.
Weickgenannt and M. Oestreich, Chem. Asian J., 2009,
, 2527-2535; (h) D.
rate enhancement of our transfer dehydrocoupling protocol by
the addition of a catalytic amount of triethylamine (10 mol%)
(Eq. 7). This result suggests that the decarboxylation of a
formate anion at the ruthenium center, which precedes the
formation of H2, is the rate determining step of the transfer
1
6
8
9
dehydrocoupling of phenol 2 with triethylsilyl formate 1a.
4
, 406-410.
M. Oestreich, Angew. Chem. Int. Ed., 2016, 55, 494-499.
10 A. Simonneau, J. Friebel and M. Oestreich, Eur. J. Org.
Chem., 2014, 2014, 2077-2083.
11 C. Chauvier, P. Thuéry and T. Cantat, Angew. Chem. Int.
Ed., 2016, 55, 14096-14100.
12 (a) C. Chauvier and T. Cantat, ACS Catal., 2017,
2115; (b) X. Lu, D. Y. C. Leung, H. Wang, M. K. H. Leung
and J. Xuan, ChemElectroChem, 2014, , 836-849; (c) R.
Wolfel, N. Taccardi, A. Bosmann and P. Wasserscheid,
Green Chem., 2011, 13, 2759-2763.
13 (a) V. N. Gevorgyan, L. M. Ignatovich and E. Lukevics, J.
Organomet. Chem., 1985, 284, C31-C32; (b) M. Ito, M.
7, 2107-
In conclusion, silyl formates have been shown to serve as
salt-free silylating agents for O–H bonds, for the first time,
leading to gaseous CO2 and H2 as the only by-products. Using
1
the ruthenium(II) complex
4, supported by a triphosphine
ligand, a variety of silyl formates were used as surrogates of
hydrosilanes for the silylation of alcohols and carboxylic acids.
The decarboxylative and dehydrogenative coupling between
alcohols and silyl formates was shown to rely on a catalytic
sequence based on a trans-silylation equilibrium, affording the
desired silyl ether along with HCO2H, and the subsequent
irreversible base-free dehydrogenation of formic acid.
Itazaki, T. Abe and H. Nakazawa, Chem. Lett., 2016, 45
1434-1436.
,
14 For further illustrations of the functional group
tolerance of our transfer dehydrogenative silylation
protocol, see the ESI.
15 (a) J. Tan, M. Akakura and H. Yamamoto, Angew. Chem.
Int. Ed., 2013, 52, 7198-7202; (b) J. M. Weinberg, S. P.
Gitto and K. L. Wooley, Macromolecules, 1998, 31, 15-
21.
16 (a) M. Chauhan, B. P. S. Chauhan and P. Boudjouk, Org.
Notes and references
Lett., 2000, 2, 1027-1029; (b) G. B. Liu, H. Y. Zhao and T.
1
P. G. M. Wuts and T. W. Greene, in Greene's Protective
Groups in Organic Synthesis, John Wiley & Sons, Inc.,
2006, pp. 16-366.
For recent total syntheses involving at least one silyl
ether protecting group, see: (a) T. Maehara, K.
Motoyama, T. Toma, S. Yokoshima and T. Fukuyama,
Angew. Chem. Int. Ed., 2017, 56, 1549-1552; (b) A. W.
Schuppe and T. R. Newhouse, J. Am. Chem. Soc., 2017,
139, 631-634.
J. M. Halket and V. G. Zaikin, Eur. J. Mass Spectrom.,
2003, 9, 1-21.
(a) E. J. Corey and A. Venkateswarlu, J. Am. Chem. Soc.,
1972, 94, 6190-6191; (b) P. Patschinski, C. Zhang and H.
Zipse, J. Org. Chem., 2014, 79, 8348-8357; (c) E. J. Corey,
H. Cho, C. Rücker and D. H. Hua, Tetrahedron Lett., 1981,
22, 3455-3458.
Thiemann, Synth. Commun., 2007, 37, 2717-2727; (c) Y.
Ojima, K. Yamaguchi and N. Mizuno, Adv. Synth. Catal.,
2009, 351, 1405-1411.
2
17 Nevertheless, prolonged heating of the crude reaction
mixture after completion of the reaction lead to some
reduction of the keto group, presumably by
hydrogenation
with
H2
generated
by
the
dehydrogenative coupling.
18 Equilibria between carboxylic acids and acyloxysilanes
are known, see: S. Kozuka, T. Kitamura, N. Kobayashi
and K. Ogino, Bull. Chem. Soc. Jpn., 1979, 52, 1950-1952.
19 For examples of base-free dehydrogenation of FA, see:
(a) A. Boddien, D. Mellmann, F. Gärtner, R. Jackstell, H.
Junge, P. J. Dyson, G. Laurenczy, R. Ludwig and M. Beller,
Science, 2011, 333, 1733; (b) S. Oldenhof, B. de Bruin, M.
Lutz, M. A. Siegler, F. W. Patureau, J. I. van der Vlugt and
J. N. H. Reek, Chem. Eur. J., 2013, 19, 11507-11511.
20 B. Loges, A. Boddien, H. Junge and M. Beller, Angew.
Chem. Int. Ed. Engl., 2008, 47, 3962-3965; C. Fellay, P. J.
Dyson, G. Laurenczy, Angew. Chem. Int. Ed. 2008, 47,
3966-3968; C. Guan, D. D. Zhang, Y. P. Pan, M. Iguchi, M.
J. Ajitha, J. S. Hu, H. F. Li, C. G. Yao, M. H. Huang, S. X.
Ming, J. R. Zheng, Y. Himeda, H. Kawanami, K. W. Huang,
Inorg. Chem. 2017, 56, 438-445.
3
4
5
6
7
J. F. Klebe, H. Finkbeiner and D. M. White, J. Am. Chem.
Soc., 1966, 88, 3390-3395.
L. Birkofer and A. Ritter, Angew. Chem. Int. Ed., 1965, 4,
417-429.
(a) D. E. Barber, Z. Lu, T. Richardson and R. H. Crabtree,
Inorg. Chem., 1992, 31, 4709-4711; (b) J. M. S. Cardoso,
R. Lopes and B. Royo, J. Organomet. Chem., 2015, 775
,
173-177; (c) S. Chang, E. Scharrer and M. Brookhart, J.
Mol. Catal. A: Chem., 1998, 130, 107-119; (d) K. Garcés,
F. J. Fernández-Alvarez, V. Polo, R. Lalrempuia, J. J.
Pérez-Torrente and L. A. Oro, ChemCatChem, 2014, 6,
1691-1697; (e) H. Ito, T. Saito, T. Miyahara, C. Zhong and
M. Sawamura, Organometallics, 2009, 28, 4829-4840;
(f) H. Ito, A. Watanabe and M. Sawamura, Org. Lett.,
2005, 7, 1869-1871; (g) X. L. Luo and R. H. Crabtree, J.
4 | Chem. Commun., 2017, 00, 1-3
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TOC GRAPHIC FOR
Silylation of O–H Bonds by Catalytic Dehydrogenative and Decarboxylative Coupling of
Alcohols with Silyl Formates
Clément Chauvier, Timothé Godou and Thibault Cantat*
NIMBE, CEA, CNRS, Université Paris-Saclay, Gif-sur-Yvette, France
E-mail: thibault.cantat@cea.fr
PPh2
Ph2P
O
cat.
Ru
P
O
O
Ph2
OAc
OH
OSi
+ CO2 + H2
+
Si
R
R
H
O
• alcohol (I, II & III)
• carboxylic acids
• High yields
Dehydrogenative
& Decarboxylative
• High selectivity
• Salt-free
S1