Base-catalyzed dehydrogenative Si-o coupling of dihydrosilanes: Silylene protection of diols

Article abstract of DOI:10.1055/s-0030-1258055

The direct dehydrogenative coupling of 1,3- and 1,4-diols and dihydrosilanes is efficiently catalyzed by CsO(10 mol%), cleanly affording six- and seven-membered 1,3-dioxo-2-silacycles with dihydrogen as the sole by-product. Conversely, 1,2-diols do not yield the expected 1,3-dioxo-2- silacyclopentanes, essentially forming cyclic disiloxanes instead. Aside from the synthetic convenience, the procedure itself is also useful for straight-forward diol derivatization prior to GLC analysis. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0030-1258055

2482
LETTER
Base-Catalyzed Dehydrogenative Si–O Coupling of Dihydrosilanes:
Silylene Protection of Diols
Diol
Protection gnieszka Grajewska, Martin Oestreich*
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität, Corrensstr. 40, 48149 Münster, Germany
Fax +49(251)8336501; E-mail: martin.oestreich@uni-muenster.de
Received 9 July 2010
broad scope.11 We had serendipitously identified this tran-
sition-metal-free dehydrogenative coupling as the unse-
lective background reaction of our enantioselective Cu–
H-catalyzed silicon–oxygen coupling.12 Those investiga-
Abstract: The direct dehydrogenative coupling of 1,3- and 1,4-di-
ols and dihydrosilanes is efficiently catalyzed by Cs2CO3 (10
mol%), cleanly affording six- and seven-membered 1,3-dioxo-2-si-
lacycles with dihydrogen as the sole by-product. Conversely, 1,2-
diols do not yield the expected 1,3-dioxo-2-silacyclopentanes, es- tions were initially limited to monohydrosilanes but we
sentially forming cyclic disiloxanes instead. Aside from the synthet-
ic convenience, the procedure itself is also useful for straight-
forward diol derivatization prior to GLC analysis.
soon learned that dihydrosilanes also react with alcohols
in the presence of tert-butoxide. This observation prompt-
ed us to further elaborate on silylene protection of diols.
Here, we report a facile base-catalyzed silicon–oxygen
Key words: coupling, dehydrogenation, diols, protecting groups,
silicon
coupling of dihydrosilanes and diols, which also shows
potential for practical derivatization prior to GLC analy-
sis.13
Protection of diol motifs is commonly achieved through
Catalytic amounts (5.0 mol%) of t-BuOK or t-BuONa in
the formation of cyclic systems involving both hydroxy
THF, THF–DMF mixtures or DMF were optimal to effect
groups.1 Brønsted and Lewis acid catalyzed acetalization
dehydrogenative couplings in our previous study.11 We
of 1,2- and 1,3-diols is still the prevalent method, and con-
therefore tested t-BuOK (10 mol%) as well as t-BuONa
densation of these diols with, for example, acetone pro-
Table 1 Base-Catalyzed Silylene Protection: Base Identificationa
duces acid-labile but base-stable acetonides. Acetonides
are equivalent to cyclic silylene ethers. The established
procedure for silylene protection of diols is their reaction
with dichlorosilanes in the presence of double stoichio-
metric amounts of a hydrochloric acid scavenger, usually
pyridines or tertiary amines.2 Aside from twice equimolar
formation of pyridinium or ammonium chlorides, this
method is afflicted with a few more drawbacks. The di-
tert-butylsilylene group is commonly used but its precur-
sor t-Bu2SiCl2 is relatively unreactive, often requiring
harsher reaction conditions.3 For protection of sterically
hindered substrates, t-Bu2SiCl2 is replaced by either the
Ph Ph
base
(10 mol%)
OH OH
Si
Ph Ph
Si
O
O
+
Ph
THF
r.t.
H
H
Ph
1a
2a
(1.5 equiv)
3aa
Entry
Base
Time (h)
Conv. (%)b
1
KOt-Bu
NaOt-Bu
NaHCO3
KHCO3
K2CO3
Cs2CO3
Et3N
1
1
100
100
0
2
5
expensive t-Bu2Si(OTf)2 reagent4 or the toxic t-Bu2Si(CN)2
3
24
24
24
1
reagent.
4
0
Another attractive method for the formation of silicon–
oxygen bonds is based on the dehydrogenative coupling
of hydrosilanes and alcohols.6 The significant advantage
of this approach is that only dihydrogen is generated as
waste instead of stoichiometric amounts of hydrochloride
salts. A few transition-metal-mediated protocols are avail-
able for the direct coupling of dihydrosilanes and diols
5
88c
100
33
0
6d
7
24
24
8e
imidazole
7
using Cp2TiPh2 and Cp2TiCl2–n-BuLi8 as well as
a Unless otherwise noted, all reactions were conducted using the indi-
cated base (10 mol%) and Ph2SiH2 (2a, 1.5 equiv) with a substrate
concentration of 0.11 M in THF at r.t.
[Ph3PCuH]6.9 The strong Lewis acid B(C6F5)3 also cata-
lyzes that silylene formation.10
b Conversion determined by GLC analysis using n-decane as internal
standard.
Our laboratory recently disclosed a remarkable tert-but-
oxide-catalyzed silicon–oxygen coupling of exceptionally
c Conversion was drastically lower at short reactions times, and pro-
longed heating at reflux as well as using double stoichiometric
amounts of the base were ineffective to obtain full conversion.
d Full conversion was also seen in CH2Cl2 (1 h) and toluene (1 h) as
solvents.
SYNLETT 2010, No. 16, pp 2482–2484
x
x
.x
x
.2
0
1
0
Advanced online publication: 19.08.2010
DOI: 10.1055/s-0030-1258055; Art ID: G19810ST
e Using 50 mol% of the base yielded 30% conversion after 24 h.
© Georg Thieme Verlag Stuttgart · New York

LETTER
Diol Protection
2483
Table 2 Cs2CO3-Catalyzed Silylene Protection: Silane Screeninga
(10 mol%) in the silylene protection of a model 1,3-diol
with Ph2SiH2 (2a), and clean conversion was detected af-
ter one hour (1a → 3aa, Table 1, entries 1 and 2). Traces
of water were particularly problematic with these bases,
resulting in rapid formation of siloxanes. We then contin-
ued screening different bases. No reaction occurred in the
presence of bicarbonates (Table 1, entries 3 and 4) while
carbonates were able to promote the catalysis (Table 1,
entries 5 and 6). K2CO3 yielded good conversion at ex-
tended reaction times but full conversion was obtained af-
ter one hour with Cs2CO3. Nitrogen bases performed
poorly (Table 1, entries 7 and 8).
R
R
Cs2CO3
(10 mol%)
OH OH
Si
R
R
O
O
+
Si
Ph
THF
1 h at r.t.
H
H
Ph
1a
2a–f
(1.5 equiv)
3aa–af
Entry
Dihydrosilaneb
Silylene Conv. (%)c Yield (%)d
2
R
1
2
3
4
5
6f
2a
2b
2c
2d
2e
2f
Ph
3aa
3ab
3ac
3ad
3ae
3af
100
100
100
100e
0
89
70
70
68
–
4-anisyl
3,5-xylyl
2-tolyl
mesityl
t-Bu
The bases NaOt-Bu and Cs2CO3 were equally effective in
THF, and Cs2CO3 also mediated the silylene protection in
CH2Cl2 and toluene. The solvent independence seen with
the Ph2SiH2–Cs2CO3 combination stands in contrast to the
transition-metal-free coupling of less reactive monohy-
drosilanes; tert-butoxide would only catalyze silicon–
oxygen bond formation in THF but not toluene,11 and
0
–
Cs2CO3 alone would not even promote the dehydrogena- a Unless otherwise noted, all reactions were conducted using Cs2CO3
(10 mol%) and the indicated R2SiH2 (2, 1.5 equiv) with a substrate
tive coupling in THF, requiring a transition-metal cata-
lyst.12 Another striking difference between the KOt-Bu11
concentration of 0.11 M in THF at r.t.
b Ar2SiH2 were prepared from the reaction of trichlorosilane and
and Cs2CO3 catalysts is the pronounced effect of added
ArMgBr followed by reduction (see Supporting Information for de-
molecular sieves: KOt-Bu (5.0 mol%) tolerates its
tails).
presence11 while Cs2CO3 (10 mol%) is not sufficient to
catalyze the coupling. In that case, Cs2CO3 (50 mol%)
must be added in substoichiometric amounts but the reac-
tion rate is still significantly slowed down by molecular
sieves (for unknown reasons).
c Conversion determined by GLC analysis using n-decane as internal
standard.
d Isolated yield of analytically pure material after purification by flash
chromatography on silica gel (cf. Supporting Information).
e Five hours were needed for full conversion (80% conversion after
1 h).
f Considerable conversion was observed at higher Cs2CO3 loadings
(cf. Scheme 1).
We then screened several dihydrosilanes 2a–f in the
Cs2CO3-catalyzed reaction (1a → 3aa–af, Table 2). As
expected, dihydrosilanes 2a–c substituted with electron-
rich aryl groups were of comparable reactivity (Table 2,
entries 1–3). Conversely, sterically hindered dihydrosi-
lanes 2d–f were either rather unreactive or even inert
(Table 2, entry 4 vs. entries 5 and 6). It ought to be men-
tioned that 2f reacted when using 50 mol% of Cs2CO3 to
afford 3af along with noncyclized 4af (Scheme 1).
phy on silica gel or distillation. Dimer formation, as de-
scribed in the protection of 5a with Ph2SiCl2,15 was not
observed.
An obvious advantage of these base-catalyzed dehydroge-
native couplings is the formation of dihydrogen as the sole
by-product. This clearly simplifies purification proce-
dures, which mainly require separation of the solid base.
Another potentially useful aspect is the fact that GLC
analysis of these reactions is diagnostically conclusive.
When employing dichlorosilane–nitrogen base combina-
tions, the GLC analysis might be complicated by peak
overlapping and by-products. In any of our silylene pro-
tections (Tables 2 and 3), there was no evidence of such
by-products, as verified by GLC–MS and NMR measure-
ments. The base-catalyzed silylene protection of diols
might therefore be a convenient derivatization method for
GLC analysis.13
Cs2CO3
(50 mol%)
t-Bu t-Bu
Si
t-Bu t-Bu
Si
2f
OH OH
(1.5 equiv)
O
O
OH
O
H
+
Ph
THF
Ph
Ph
40 h at r.t.
72% conversion
1a
3af
4af
3:1
Scheme 1 Reaction of t-Bu2SiH2 (2f) at higher catalyst loading
We finally applied this protocol using Cs2CO3 (10 mol%)
and less Ph2SiH2 (1.2 equiv)14 to the protection of selected
1,3-diols 1a–c and 1,4-diols 5a,b (Table 3). Reactions are
generally clean and fast, showing full conversion in less
than one hour (Table 3, entries 1, 2, 4 and 5), and that in-
cludes protection of an extremely congested tertiary alco-
hol (Table 3, entry 3). The six- and seven-membered 1,3-
dioxo-2-silacycles 3aa–ca and 6aa–ba, respectively were
isolated in good chemical yields after flash chromatogra-
It must be mentioned that the reaction of Ph2SiH2 with
traces of water16 in the presence of Cs2CO3 generates oc-
taphenylcyclotetrasiloxane, and minor amounts of this
compound were detected even when using meticulously
dried substrates and solvents. The use of molecular sieves
for moisture removal11 thwarts turnover in the Cs2CO3 ca-
talysis (vide supra).
Synlett 2010, No. 16, 2482–2484 © Thieme Stuttgart · New York

2484
A. Grajewska et al.
LETTER
simple methodology is effective for the silylene protec-
tion of 1,3- and 1,4- but not 1,2-diols. The reaction condi-
tions are usually mild, also making it a practical tool for
GLC derivatization. The chemical stability of diphenyl-
silylene-protected diols is however not as good as that of
diols protected with a di-tert-butylsilylene group, and we
observed hydrolysis upon extended exposure to silica gel
during purification by flash chromatography.
Table 3 Cs2CO3-Catalyzed Silylene Protection of Selected 1,3- and
1,4-Diolsa
Ph Ph
Cs2CO3
(10 mol%)
OH OH
Si
Ph Ph
Si
O
O
+
R1
R2
THF
r.t.
H
H
n
R1
R2
n
1a–c (n = 1)
5a–b (n = 2)
2a
(1.2 equiv)
3aa–ca (n = 1)
6aa–ba (n = 2)
Entry Diol R1
R2
n
Silylene Time Conv. Yield
(h) (%)b (%)c
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
1
2
3
4
5
1a
1b
1c
5a
5b
Ph
Ph
Ph
H
Me
Ph
1
1
3aa
3ba
3ca
6aa
6ba
1
1
1
1
1
100
100
100
100
100
89
74
80
55d
70
Acknowledgment
t-Bu
H
1
2
2
A.G. thanks the Alexander von Humboldt-Foundation for a post-
doctoral fellowship (2009–2010).
Ph
H
References and Notes
a All reactions were conducted using Cs2CO3 (10 mol%) and Ph2SiH2
(2a, 1.2 equiv) with a substrate concentration of 0.11 M in THF at r.t.
b Conversion determined by 1H NMR analysis.
(1) (a) Wuts, P. G. M.; Greene, T. W. Greene´s Protective
Groups in Organic Synthesis, 4th ed.; Wiley: New York,
2007, 299. (b) Kocieński, P. J. Protecting Groups, 3rd ed.;
Thieme: Stuttgart, 2004, 119.
(2) Cragg, R. H.; Lane, R. D. J. Organomet. Chem. 1984, 267, 1.
(3) Trost, B. M.; Caldwell, C. G. Tetrahedron Lett. 1981, 22,
4999.
c Isolated yield of analytically pure material after purification by flash
chromatography on silica gel (cf. Supporting Information).
d Extended exposure to silica gel during purification by flash chroma-
tography resulted in decomposition. A sufficiently pure sample of 6aa
was obtained by evaporation of unreacted 5a under reduced pressure
(octaphenylcyclotetrasiloxane was a minor impurity).
(4) Corey, E. J.; Hopkins, P. B. Tetrahedron Lett. 1982, 23,
4871.
(5) Mai, K.; Patil, G. J. Org. Chem. 1986, 51, 3545.
(6) (a) For late-transition-metal catalysis, see: Corey, J. Y. In
Advances in Silicon Chemistry, Vol. 1; Larson, G., Ed.; JAI
Press: Greenwich, 1991, 327. (b) For Brønsted and Lewis
acid/base catalysis, see: Lukevics, E.; Dzintara, M.
J. Organomet. Chem. 1985, 295, 265.
(7) Nakano, T.; Nagai, Y. Chem. Express 1990, 5, 21.
(8) Bedard, T. C.; Corey, J. Y. J. Organomet. Chem. 1992, 428,
315.
(9) Lorenz, C.; Schubert, U. Chem. Ber. 1995, 128, 1267.
(10) Blackwell, J. M.; Foster, K. L.; Beck, V. H.; Piers, W. E.
J. Org. Chem. 1999, 64, 4887.
(11) Weickgenannt, A.; Oestreich, M. Chem. Asian J. 2009, 4,
406.
We also tested 1,2-diols but the reaction outcome was
quite different from that of the 1,3- and 1,4-diols. For ex-
ample, protection of 7a appeared to be low-yielding under
standard reaction conditions, forming only traces of de-
sired 8aa. However, a two-fold excess of Ph2SiH2 (2a) in
the same reaction produced a seven-membered ring in
good isolated yield (7a → 9aa, Scheme 2). Compound
9aa is considerably more stable than 8aa,17 which decom-
posed during purification on silica gel. The routine setup
[Cs2CO3 (10 mol%) without molecular sieves] is however
complicated by the formation of appreciable quantities of
octaphenylcyclotetrasiloxane, which is why the use of
molecular sieves with Cs2CO3 (50 mol%) is recommend-
ed (vide supra). We explain the origin of the silicon-bridg-
ing oxygen atom in 9aa by the presence of water, despite
its rigorous exclusion and the use of molecular sieves.
Sterically more hindered diols, e.g., pinacol, yielded in-
tractable product mixtures (not shown).
(12) Weickgenannt, A.; Mewald, M.; Muesmann, T. W. T.;
Oestreich, M. Angew. Chem. Int. Ed. 2010, 49, 2223; Angew.
Chem. 2010, 122, 2269.
(13) van Look, G.; Simchen, G.; Heberle, J. Silylating Agents;
Fluka Chemie AG: Buchs, 1995, 111.
(14) General Procedure for Silylene Protection A flame-dried
Schlenk flask was charged with Cs2CO3 (10 mol%). The
flask was evacuated and backfilled with argon prior to the
successive addition of the diol (1.0 equiv) dissolved in THF
(0.15 M) and the dihydrosilane (1.2 equiv) dissolved in THF
(0.50 M). The reaction mixture was maintained at r.t. for the
indicated time, and the base was then filtered off. The filtrate
was evaporated under reduced pressure, affording the crude
silylene-protected diols, which were purified by flash
column chromatography on silica gel.
Cs2CO3
(50 mol%)
Ph
Ph
Ph
O
2a
Ph
OH
Si
(2.1 equiv)
Si
O
O
Ph
Ph
+
OH
O
Ph
Si
3 Å
THF
12 h at r.t.
H
Ph
Ph
O
H
H
7a
8aa (traces)
9aa (70%)
(15) Cragg, R. H.; Lane, R. D. J. Organomet. Chem. 1985, 289,
23.
(16) The reaction of Ph2SiH2 with H2O in the absence of base
yields disiloxane (Ph2HSi)2O (cf. ref. 8).
Scheme 2 Cs2CO3-catalyzed protection of a 1,2-diol
In summary, we have demonstrated that Cs2CO3 catalyzes
the dehydrogenative silicon–oxygen coupling of dihy-
drosilanes and diols to form 1,3-dioxo-2-silacycles. This
(17) (a) Silcox, C. M.; Zuckerman, J. J. J. Organomet. Chem.
1966, 5, 483. (b) Yang, M.-H.; Yeh, F.-J. J. Chin. Chem.
Soc. 1991, 38, 57.
Synlett 2010, No. 16, 2482–2484 © Thieme Stuttgart · New York