Photolabile arylsilyl group: application to the oxidation of C-Si bonds

Article abstract of DOI:10.1016/j.tetlet.2007.10.057

(2,6-Dimethoxyphenyl)-dimethylsilyl group constitutes a new orthogonal masked hydroxyl group. Protodesilylation of this arylsilane occurs under photochemical conditions in the presence of alcohols such as hexafluoroisopropanol (HFIP) or isopropanol. These mild and neutral conditions thus allowed the oxidation of organosilicon compounds such as β-hydroxysilanes that are known to be prone to Peterson elimination.

Full text of DOI:10.1016/j.tetlet.2007.10.057

Available online at www.sciencedirect.com
Tetrahedron Letters 48 (2007) 8909–8913
Photolabile arylsilyl group: application to the oxidation of
C–Si bonds
*
´ ´
Susen Werle, Frederic Robert, Henri Bouas-Laurent and Yannick Landais
Universite´ Bordeaux 1, Institut des Sciences Mole´culaires, ISM—UMR 5255, 351 Cours de la Libe´ration,
33405 Talence Cedex, France
Received 24 July 2007; accepted 10 October 2007
Available online 14 October 2007
Abstract—(2,6-Dimethoxyphenyl)-dimethylsilyl group constitutes a new orthogonal masked hydroxyl group. Protodesilylation of
this arylsilane occurs under photochemical conditions in the presence of alcohols such as hexafluoroisopropanol (HFIP) or isopro-
panol. These mild and neutral conditions thus allowed the oxidation of organosilicon compounds such as b-hydroxysilanes that are
known to be prone to Peterson elimination.
ꢀ 2007 Elsevier Ltd. All rights reserved.
The oxidative cleavage of carbon–silicon bonds, discov-
ered some twenty years ago is now part of the organic
chemist armory and has enjoyed a widespread interest
as illustrated by numerous examples in total synthesis
of natural compounds.1,2 The unmasking of a silicon
group into the corresponding hydroxy group occurs
with retention of configuration. The nature of the sub-
stituents at silicon dictates the outcome of the oxidation.
Halo- and alkoxysilanes are easily oxidized using H2O2
in the presence of a fluorine source and such a transfor-
mation is usually compatible with many functionalities
(Tamao conditions).1a,b Unfortunately, such organosi-
lanes, although readily oxidized under mild conditions
are sensitive, and not compatible with long synthetic
sequences. In contrast, arylsilanes such as 1 are more
robust and thus stable to a wide range of reaction con-
ditions, but in turn, their oxidation requires more drastic
conditions (Scheme 1).1c,d,2a Oxidation of arylsilanes is
usually carried out through a two-step sequence involv-
ing a removal of the aryl group through protodesilyla-
tion, followed by peracid or H2O2 oxidation of the
remaining activated organosilanes 2 (X = F, OR,
OAc,. . .) (Fleming conditions). Protodesilylation which
occurs under acidic conditions is usually the critical step,
which may, depending on the substrate, lead to unde-
sired by-products. Various solutions to this problem
have been proposed, including the use of buffered condi-
tions1d or the design of more labile arylsilanes.2b,c
The need for new generation of masked hydroxyl groups
thus prompts us to report here our preliminary studies
on the development of arylsilane 1 that can be converted
into 2 using light under neutral conditions (ROH).
While several photocleavable OH protecting groups
have been developed,3 oxidation of the C–Si bond based
on a photochemical removal of a substituent at silicon (a
furyl group) has been exploited only once by Kocienski
et al.4 to carry out a critical oxidation of the C–Si bond
of an allylsilane. During this oxidation, the furyl group
was lost upon photooxygenation. The methodology we
planned to develop is quite different since the arene at
silicon would be removed through photoprotonation
and thus theoretically reusable. Based on some early
work by Desvergne5 and McClelland,6 it was anticipated
that light-sensitive aromatic groups (Ar* in 1) on the
silicon center might be cleaved selectively through pro-
todesilylation under photochemical activation in the
presence of alcohols.7 Using photoactivation, it was
SiMe2Ar*
(SiMe2Ar*)1
R2
SiMe2X
hυ
ROH
+ Ar*H (1)
R1
R2
R1
R1
R2
1
2
SiMe2X
OH
H2O2 or
(2)
R1
R2
peracid
KF
R1
R2
2
3
*
Corresponding author. Tel.: +33 5 4000 2289; fax: +33 5 4000
6286; e-mail: y.landais@ism.u-bordeaux1.fr
Scheme 1.
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.10.057

8910
S. Werle et al. / Tetrahedron Letters 48 (2007) 8909–8913
K2OsO4, 2 H2O
Arenes 4a–d were easily coupled through metallation
with commercially available allyldimethylchlorosilane
to provide the desired arylallylsilanes 5a–e in good yield
(Table 1).9 With arene 4a, metallation then silylation
occurred regioselectively between the two methoxy
groups.9a With dibenzofurane, mono- and bissilylation
occurred (i.e., 5d–e), as reported, ortho to the furanyl
group.9d Dihydroxylation of the latter under sharpless
conditions10 led to the corresponding diols 6a–e that
were then protected as their acetonides 7b, 7d–e or bis-
acetates 7a, 7c, using standard procedures.
K3Fe(CN)6
K2CO3
OH
1. n-BuLi
2.
Ar
Ar
ArX
Si
Si
SiMe2Cl
t-BuOH-H2O 1:1
quinuclidine
Me2
Me2
OH
X=H,Br
MeSO2NH2
4a-d
6a-e
5a-e
Ac2O
Et3N
OAc
Me2C(OMe)2
Ar
Ar
Si
6a-e
Si
Me2
O
DMAP
p-TsOH
(87-91%)
Me2
O
OAc
(60-77%)
7b-7d-7e
7a-7c
Irradiation of precursors 7a–e was carried out in quartz
glassware using a medium pressure mercury lamp in var-
ious non degassed alcohols (distilled prior to irradiation)
at room temperature under an air atmosphere. A cool-
ing bath was generally used to maintain the temperature
close to 20 ꢁC. The product of the reaction was then
simply recovered after evaporation of the solvent under
reduced pressure. Preliminary experiments (Table 2,
entries 1 and 2) were carried out using 7a, which upon
irradiation in HFIP, unexpectedly provided disiloxane
8a (PG = OAc) and none of the desired alkoxysilane,
MeO
OMe
a
b
c
Ar :
O
O
d
e
Scheme 2.
1
as indicated by H NMR and mass spectrometry.11 It
effectively shown that alcohols such as MeOH, t-BuOH
or hexafluoroisopropanol (HFIP) were acidic enough to
protonate an arene in its singlet excited state, and at the
same time nucleophilic enough to finally form the
alkoxysilane intermediate 2 (Scheme 1, X = OR). The
authors suggested that protodesilylation involved an
associative process in which the cleavage of the C–Si
bond and the formation of the Si–OR bond were
concerted.
is worthy of note that 1,3-dimethoxybenzene could also
be recovered and may thus be recycled. In some cases,
small amounts of silanol 9 (9a, PG = OAc) were
detected, indicating that water was present in the
medium.12 Different attempts to remove water using
˚
3 A molecular sieves and a nitrogen atmosphere were
however unsuccessful. On the contrary, addition of
10% (vol.) of water led to similar results, indicating that
water likely catalyzes the formation of siloxane 8a13
through dimerization of silanol 9a (PG = OAc).
Several arenes 4a–d were thus chosen as potent photola-
bile aryl silicon substituents (Scheme 2). Polynuclear
arenes 4b–c and heteroarenes 4d–e were selected based
on the known stability of their silicon derivatives and
their UV absorption at longer wavelengths. b-hydroxy-
silanes were used as model compounds for our oxidation
as their C–Si bond oxidation is often difficult, due to
Peterson b-elimination8 that may occur under both
acidic and basic conditions.2a,b
Although we were able to recover expensive HFIP
through distillation, other solvents were tested as possi-
ble alternatives. Isopropanol led to encouraging results
(entries 4 and 5), although the reaction was much slower
than that with HFIP. Methanol led to mixtures of 8a
and starting material (entry 3) and trifluoroethanol
(entry 6) led to decomposition. Under these conditions,
a- and b-naphthylsilanes 7b and 7c led to no reaction
Table 1. Preparation of model compounds 5a–e and 6a–e (Scheme 2)
Entry
1
ArX
Conditionsa
% Yieldc 5a–e
5a (84)
% Yieldc 6a–e
6a (99)
4a
(X = H)
4b
n-BuLi (1 equiv), TMEDA
Hexane, 0 ꢁC to rt, 22 h
t-BuLi (2 equiv), THF
À78 ꢁC, 5 h
2
3
4
5
5b (75)
5c (99)
5d (77)d
5e (35)e
6b (98)
6c (91)
6d (100)f
6e (95)f
(X = Br)
4c
t-BuLi (2 equiv), THF
À78 ꢁC, 5 h
(X = Br)
4d
n-BuLi (1 equiv), THF
rt,b 22 h
(X = H)
4d
n-BuLi (2 equiv), THF
rt,b 22 h
(X = H)
a Allyldimethylchlorosilane was added after metallation and the reaction mixture stirred for the period reported above.
b The reaction mixture was refluxed after the addition of allyldimethylchlorosilane.
c Isolated yields unless otherwise mentioned.
d 11% of bissilylated product 5e was also isolated.
e 57% of monosilylated product 5d was also isolated.
f Crude yield.

S. Werle et al. / Tetrahedron Letters 48 (2007) 8909–8913
Table 2. Irradiation of model compounds 7a–e
8911
SiMe2OH
O
hυ
Ar
Si
Si
OPG
OPG
OPG
ROH
Me2
Me2
2
OPG
OPG
OPG
8
7a-e
9
Entry
Arylsilane
ROHa
HFIP
HFIP–MeOH (22 equiv)
MeOH
i-PrOH
i-PrOH
CF3CH2OH
HFIP
HFIP (40 equiv)–MeOH
HFIP
Time (h)b
% Yieldc
1
2
3
4
5
6
7
8
9
7a
7a
7a
7a
7a
7a
7b
7c
7d
7e
14
44
26
25
56
27
48
26
28
28
8a (quant.)
8a (quant.)
d
—
e
8a (quant.)
decomp.
7b (quant.)
7c (quant.)
7d (quant.)
7e (quant.)
10
HFIP
a Arylsilanes 7a–e were dissolved in the indicated solvent (C = 10–20 mmol/l) and irradiated at 20 ꢁC using a medium pressure mercury lamp.
b Irradiation time.
c Crude yields after evaporation of the solvent.
d A 56:44 mixture of 7a/8a was estimated from 1H NMR of the crude reaction mixture.
e A 58:42 mixture of 7a/8a was estimated from 1H NMR of the crude reaction mixture.
and surprisingly starting materials were recovered
unchanged, whatever the conditions (entries 7 and 8).
Similarly, dibenzofuranylsilanes 7d and 7e were also
recovered unchanged after irradiation for 28 h in HFIP
(entries 9 and 10).
30% H2O2
OAc
OAc
Ac2O (3 eq.)
SiMe2)2O
OH
KF, DMF
OAc
OAc
12
60 °C, 37 h
40%
8a
As water likely assists the protodesilylation6 to form the
silanol (i.e., 9) which then dimerizes, it was decided to
carry out the reaction on a precursor such as 6a, having
an hydroxyl group close to silicon that could approach
the silicon center to form siloxane 10 and thus prevent
the nucleophilic attack by water (Scheme 3). Irradiation
of 6a was thus carried out as above, but disiloxane 11
was the only product of the reaction with none of the
expected cyclic siloxane 10 formed.
Scheme 4.
reactions under the usual Tamao conditions probably
lead to siloxanes and polysiloxanes, through dimeriza-
tion of silanols formed in situ. Acetic anhydride might
react with the latter and thus prevent the formation of
siloxanes, through the formation of acetoxysilanes
which are easier to oxidize.
The study was then extended to related hydroxycar-
bamate 13 which is also prone to Peterson elimination.
13 was prepared from allylsilane 5a using sharpless
amino-hydroxylation (AA) protocol.14 This led to a
2.5:1 mixture of regioisomers 13 and 14 (Scheme 5),
These results suggest that disiloxanes are the thermo-
dynamically favored compounds due to the formation
of two strong Si–O bonds. Therefore, it was decided to
test the oxidation on 8a as it is easily obtained in quan-
titative yield. Different conditions were thus tested that
led consistently to complex mixtures of polysiloxanes.
Finally, when the oxidation was conducted in the pres-
ence of acetic anhydride, 30% H2O2 and KF in
DMF,1a,b the desired alcohol 12 was obtained, albeit
in modest yield (Scheme 4). The role of acetic anhydride
is not clear. Siloxanes are difficult to oxidize and their
K2OsO4, 2 H2O
NaClNCO2Et
ArMe2Si
ArMe2Si
OH
NHCO2Et
+
5a
n-PrOH-H2O 1:1
(DHQ)2PYR
OH
13
NHCO2Et
2.5 : 1 (67%)
14
OH
HFIP, hυ
quartz, 7 h
OMe
OH
Me2
Si
Me2Si
OH
O
30% H2O2
10
OH
OH
hυ
OH
Ac2O (3 eq.)
OH
SiMe2)2O
HFIP
KF, DMF
OMe
NHCO2Et
NHCO2Et
SiMe2)2O
60˚C, 22 h
quant.
67%
6a
11 (quant.)
16
OH
15
Scheme 3.
Scheme 5.

8912
S. Werle et al. / Tetrahedron Letters 48 (2007) 8909–8913
which were easily separated by chromatography.15 13
was then irradiated as above to provide disiloxane 1516
in quantitative yield. Oxidation of crude 15 under the
optimized conditions above led to diol 1615,17 in a satis-
fying 67% yield.
Bonneau, R.; Do¨rr, G.; Bouas-Laurent, H. Photochem.
Photobiol. Sci. 2003, 2, 289–296.
6. Lew, C. S. Q.; McClelland, R. A. J. Am. Chem. Soc. 1993,
115, 11516–11520.
7. For a review on organosilane photochemistry, see: Stein-
metz, M. G. Chem. Rev. 1995, 95, 1527–1588.
8. (a) Peterson, D. J. J. Org. Chem. 1968, 33, 780–784; (b)
Jager, D. J. Org. React. 1990, 38, 1–223; (c) van Staden, L.
F.; Gravestock, D.; Ager, D. J. Chem. Soc. Rev. 2002, 31,
195–200; (d) Hudrlick, P. F.; Peterson, D. J. Am. Chem.
Soc. 1975, 97, 1464–1468.
9. For silylation of 4a, see: (a) Bennetau, B.; Rajarison, F.;
Dunogues, J.; Babin, P. Tetrahedron 1993, 49, 10843–
10854; 4b, see: (b) Lee, Y.; Silverman, R. B. Tetrahedron
2001, 57, 5339–5352; 4c, see: (c) Katz, T. J.; Sudhakar, A.;
Teasley, M. F.; Gilbert, A. M.; Geiger, W. E.; Robben, M.
P.; Wuensch, M.; Ward, M. D. J. Am. Chem. Soc. 1993,
115, 3182–3198; 4d–e, see: (d) Bekele, H.; Nesloney, C. L.;
McWilliams, K. W.; Zacharias, N. M.; Chitnumsub, P.;
Kelly, J. W. J. Org. Chem. 1997, 62, 2259–2262.
10. Kolb, H. C.; vanNieuwenhze, M. S.; Sharpless, K. B.
Chem. Rev 1994, 94, 2483–2547.
11. Stirring of the organosilanes in HFIP in the absence of
irradiation led to no reaction, indicating that the conjunc-
tion of alcohol and the irradiation was necessary for the
protodesilylation to occur.
12. Alkoxysilanes may be isolated under strictly anhydrous
conditions,6 which are not really suitable for preparative
chemistry.
These results thus unambiguously show that the 2,6-
dimethoxyphenylsilyl group can be considered as a
new potent masked hydroxyl group. It is stable under
basic conditions and in mildly acidic medium.18 It is
cleaved under neutral conditions which should be com-
patible with the presence of other arylsilyl groups. One
could then envisage a selective oxidation of this aryl
group in the presence of other aryldimethylsilanes such
as PhMe2Si,2a,b p-TolMe2Si19 or the recently developed
(Ph2CH)Me2Si group.20 Interestingly, when treated
under buffered Fleming conditions1c,d (AcOOH, AcO-
Na, KBr, rt, 88 h), 7a led to 12 with only 50% conver-
sion and did not produce the desired alcohol under
Tamao conditions1a,b (30% H2O2, K2CO3, KF, THF–
MeOH, rt, 73 h).
In summary, we devised a photolabile arylsilicon group
that can be used for the C–Si bond oxidation. Pro-
todesilylation occurs under neutral conditions, generat-
ing a siloxane that may then be oxidized under
standard conditions. Our preliminary results demon-
strate that the methodology is useful for the oxidation
of acid and base sensitive organosilanes. Application
of this sequence to more complex organosilanes is under
way and will be reported in due course.
13. General procedure for photoprotonation of 2,6-dimethoxy-
phenylsilyl group: The solution of the arylsilane (0.3 mmol)
in HFIP (14 ml) was irradiated over a period of 14 h. After
evaporation of the solvent and 1,3-dimethoxybenzene, the
crude siloxane was obtained as a yellow oil that was not
1
purified further, but used directly in the next step. 8a: H
NMR (300 MHz, CDCl3): d 5.26–5.14 (m, 1H), 4.24–4.19
(m, 1H), 3.91 (dd, J = 7.0 Hz, 11.9 Hz, 1H), 2.02 (s, 3H),
2.00 (s, 3H), 1.01–0.86 (m, 2H), 0.11 (s, 3H), 0.09 ppm (s,
3H). 13C NMR: (75.5 MHz, CDCl3): d 170.8, 70.4, 69.6,
66.9, 21.3, 20.9, 20.8, 1.4, 0.9 ppm. MS (LSIMS, FAB+)
m/z: 235 (34%); 265 (8%); 281 (6%); 413 (10%); 473
([M+Na]+, 100%).
Acknowledgements
The authors gratefully acknowledged the CNRS,
Region Aquitaine and the Institut Universitaire de
France for financial support. We also thank Dr. Dario
´
14. (a) Li, G.; Chang, H.-T.; Sharpless, K. B. Angew. Chem.,
Int. Ed. 1996, 35, 451–454; (b) Rudolph, J.; Sennhenn, P.
C.; Vlaar, C. P.; Sharpless, K. B. Angew. Chem., Int. Ed.
1996, 35, 2810–2813; (c) Li, G.; Angert, H. H.; Sharpless,
K. B. Angew. Chem., Int. Ed. 1996, 35, 2813–2817; (d)
Angelaud, R.; Babot, O.; Charvat, T.; Landais, Y. J. Org.
Chem. 1999, 64, 9613–9624.
´
Bassani and Dr. Jean-Pierre Desvergne (Universite
Bordeaux 1, ISM) for fruitful discussions.
References and notes
15. Angelaud, R.; Landais, Y. Tetrahedron 2000, 56, 2025–
2036.
16. Compound 15: H NMR (250 MHz, CDCl3): d 5.38 (br s,
1. (a) Tamao, K.; Kakui, T.; Akita, M.; Iwahara, T.;
Kanatani, R.; Yoshida, J.; Kumada, M. Tetrahedron
1983, 39, 983–990; (b) Tamao, K.; Ishida, N.; Tanaka, T.;
Kumada, M. Organometallics 1983, 2, 1694–1696; (c)
Fleming, I.; Henning, R.; Plaut, H. J. Chem. Soc., Chem.
Commun. 1984, 29–31; (d) Fleming, I.; Henning, R.;
Parker, D. C.; Plaut, H.; Sanderson, P. E. J. J. Chem. Soc.,
Perkin Trans. 1 1995, 317–337.
1
1H), 4.08 (quart, J = 6.8 Hz, 2H), 3.94–3.90 (m, 1H),
3.33–3.24 (m, 1H), 3.03–2.91 (m, 1H), 1.21 (t, J = 7.0 Hz,
3H), 1.06–0.71 (m, 2H), 0.26 (d, 3H), 0.18–0.05 ppm (m,
3H). 13C NMR: (75.5 MHz, CDCl3): d 157.6, 68.8, 61.1,
49.6, 24.9, 14.7, 1.6, 1.2 ppm.
17. General procedure for the disiloxane oxidation: To a
solution of disiloxane (0.2 mmol) in DMF (2.2 ml) was
added at room temperature, KF (1 mmol) and then at 0 ꢁC
acetic anhydride (1 mmol) and a 30% aqueous solution of
H2O2 (10 mmol). The reaction mixture was stirred at 60 ꢁC
for 36 h, then quenched with a 25% Na2S2O3 solution.
After the addition of a 0.5% solution of HCl (5 ml), the
reaction mixture was extracted with diethylether (3·) and
dried over Na2SO4. Evaporation of the solvent in vacuo
and purification of the residue by column chromatography
led to the desired alcohol. Compound 16:15 1H NMR
(250 MHz, CDCl3): d 5.56 (br s, 1H), 4.11 (quart,
2. For reviews, see: (a) Fleming, I. Chemtracts: Org. Chem.
1996, 1–64; (b) Landais, Y.; Jones, G. Tetrahedron 1996,
52, 7599–7662; (c) Tamao, K. In Advances in Silicon
Chemistry; Jai Press, 1996; Vol. 3, p 1.
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Chem. Soc. 2001, 123, 3638–3643; (b) Pirrung, M. C.; Lee,
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77–78.
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Soc., Chem. Commun. 1986, 82–84; (b) Desvergne, J.-P.;

S. Werle et al. / Tetrahedron Letters 48 (2007) 8909–8913
8913
J = 7.0 Hz, 2H), 3.95 (s, 1H), 3.74 (m, 2H), 3.65–3.49 (m,
2H), 3.37–3.16 (m, 2H), 1.23 ppm (t, J = 7.0 Hz, 3H).
13C NMR: (62.4 MHz, CDCl3): d 158.1, 71.4, 63.9, 61.4,
43.3, 14.7 ppm.
(a) Ollivier, C.; Renaud, P. J. Am. Chem. Soc. 2001, 123,
4717–4727; (b) Ollivier, C.; Renaud, P. Angew. Chem., Int.
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18. The 2,6-dimethoxyphenylsilyl group is also stable to
thermal radical conditions as illustrated by the carboaz-
idation of allylsilane 5a:
19. (a) Fleming, I.; Ghosh, S. K. J. Chem. Soc., Chem.
Commun. 1994, 2285–2286; (b) Fleming, I.; Ghosh, S. K.
J. Chem. Soc., Chem. Commun. 1994, 2287–2288.
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621–623; (b) Peng, Z.-H.; Woerpel, K. A. Org. Lett. 2000,
2, 1379–1381.
S
EtO2C
S
OEt
OMe
N3 CO2Et
Me2
Si
t-BuO-N=N-Ot-Bu
5a
Bu6Sn2, PyrSO3N3
Benzene, reflux, 1.5 h
17 (82%)
OMe