Radical addition of silanes to alkenes followed by oxidation

Article abstract of DOI:10.1055/s-0031-1289568

Phenyldimethylsilane and trichlorosilane are shown to undergo efficient radical hydrosilylation reactions, on reaction with various alkenes, using triethylborane as the initiator. Adducts from the trichlorosilane reactions can be oxidised to afford alcohols in good yields. This two-step process leads to the anti-Markovnikov hydration of alkenes. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1289568

LETTER
2811
Radical Addition of Silanes to Alkenes Followed by Oxidation
A
ddition of Silanes atthew J. Palframan,a Andrew F. Parsons,*a Paul Johnsonb
a
b
Received 8 September 2011
terminal C=C bonds, in the presence of a range of func-
tional groups, to afford adducts 1a–j in 81–97% yield af-
ter column chromatography.6,7
Abstract: Phenyldimethylsilane and trichlorosilane are shown to
undergo efficient radical hydrosilylation reactions, on reaction with
various alkenes, using triethylborane as the initiator. Adducts from
the trichlorosilane reactions can be oxidised to afford alcohols in
good yields. This two-step process leads to the anti-Markovnikov
hydration of alkenes.
Attention then turned to oxidative removal of the silyl
group using oxidation conditions developed by Fleming2
(Scheme 2). Cleavage of the Si–Ph bond of 1a–c was ef-
ficiently accomplished using boron trifluoride acetic acid
complex to form the fluorosilanes 2a–c in 75–88% yield.8
Subsequent oxidation using MCPBA and potassium fluo-
ride gave the desired alcohols 3a–c, but in our hands, in
only moderate yields of 25–31%.9 Unfortunately, when
treating the phenyldimethylsilanes with MCPBA and po-
tassium fluoride in alternative solvents to DMF, or using
AcOOH/Et3N as the oxidising agent, there was no im-
provement in the yields of the alcohols. In addition, a one-
pot conversion of the phenyldimethylsilanes 1a–c into al-
cohols 3a–c was explored, using various oxidising condi-
tions (including KBr, AcOOH, NaOAc, AcOH or Br2,
AcOOH, NaOAc, AcOH), but these also gave the alco-
hols in low yield (typically less than 10%).
Key words: addition reaction, alcohol, alkene, radical reaction,
silane
Organosilanes are useful intermediates in synthesis, and
their reactivity has been exploited in synthetically impor-
tant reactions including the Peterson olefination to form
alkenes,1 and the Fleming–Tamao or Tamao–Kumada ox-
idations to form alcohols.2 One particularly mild synthetic
approach to organosilanes involves the addition of silicon
hydrides to alkenes, via regioselective addition of silyl
radical intermediates to C=C bonds.3 Although this radi-
cal hydrosilylation reaction has been reported in the liter-
ature, subsequent transformations of the organosilane
adducts, to form useful synthetic targets, has rarely been
exploited.4 Consequently, this paper describes our novel
results on the radical addition reactions of a range of sili-
con hydrides, to various alkenes under mild conditions,
and their subsequent oxidation using different reagents to
form alcohols. Overall, this method leads to the anti-
Markovnikov hydration of a C=C bond and it comple-
ments the classical hydroboration followed by oxidation
methodology.
PhMe2SiH (1.2 equiv),
i-Pr3SiSH (0.05 equiv)
SiMe2Ph
R
R
Et3B (1 equiv), THF, r.t.
SiMe2Ph
1a–j, 81–97%
C6H13
SiMe2Ph
1b, 88%
MeO
1a, 97%
O
Our initial studies focussed on the development of a mild
and efficient method of hydrosilylation. Previous work by
Roberts5 had shown that, in conjunction with a thiol cata-
lyst, alkyl- or arylsilanes efficiently add to C=C bonds,
typically using di-tert-butyl hyponitrite as the initiator at
60 °C. To develop a milder method of hydrosilylation, our
studies investigated the use of triethylborane as initiator at
room temperature, and we explored the addition of phe-
nyldimethylsilane (1.2 equiv) to alkenes (1 equiv) using
triisopropylsilanethiol (0.05 equiv) as the catalyst. Opti-
misation studies showed that for efficient addition of the
silane to the C=C bond, one equivalent of triethylborane
(added in two equal portions) was required, as shown in
Scheme 1. Under these conditions it was found that phe-
nyldimethylsilane adds regioselectivity to electron-rich
PhO
SiMe2Ph
SiMe2Ph
1c, 88%
1e, 88%
1d, 88%
O
O
SiMe2Ph
SiMe2Ph
SiMe2Ph
1f, 95%
EtO2C
EtO2C
SiMe2Ph
OH
1g, 95%
1h, 81%
MeO
MeO
SiMe2Ph
O
SiMe2Ph
1i, 85%
1j, 94%
Scheme 1
SYNLETT 2011, No. 19, pp 2811–2814
x
x
.x
x
.2
0
1
1
Advanced online publication: 09.11.2011
DOI: 10.1055/s-0031-1289568; Art ID: D28811ST
© Georg Thieme Verlag Stuttgart · New York
In an attempt to increase the efficiency of the transforma-
tion, the radical addition of ethoxysilanes and methoxy-

2812
M. J. Palframan et al.
LETTER
silanes [including (EtO)3SiH, (EtO)2MeSiH, (MeO)3SiH, Following the successful addition of trichlorosilane to ter-
and (MeO)2MeSiH] to alkenes, to give alkoxysilanes, minal alkenes, the cyclisation of 1,6-dienes, followed by
which are precursors of the Tamao oxidation, were inves- oxidation, was attempted (Scheme 4). It was found that,
tigated. However, it was found that initiation using Et3B under the standard conditions used for the terminal al-
and a thiol catalyst resulted in mainly recovered starting kenes, the radical addition of trichlorosilane to diallyl
material. Even when using t-BuOOt-Bu as initiator, and ether 4a or hepta-1,6-diene 4b resulted in polymerisation.
heating in a sealed tube, only starting alkene was recov- However, efficient cyclisation was found to occur under
ered.
increased dilution to afford the corresponding trichlorosi-
lyl adducts in reasonable yields. Subsequent oxidation of
the unpurified cyclic adducts resulted in the isolation of
the expected alcohols 5a,b (as predominantly the cis dia-
stereomers).
BF3⋅(AcOH)2
SiMe2Ph
SiMe2F
R
R
CH2Cl2
1a (R = 4-MeOC6H4CH2)
1b (R = C6H13
1c (R = PhOCH2)
2a, 75%
2b, 78%
2c, 88%
)
MCPBA, KF,
DMF
(i) Cl3SiH (2 equiv),
Et3B (3⋅0.4 equiv),
THF, 0 °C to r.t.
OH
3a, 31%
3b, 25%
3c, 26%
OH
R
X
(ii) KF, NaHCO3,
X
MeOH–THF, 0 °C, 1 h
then H2O2, r.t., 48 h
4a, X = O
4b, X = CH2
5a, X = O (29%, dr = 4:1)
5b, X = CH2 (27%, dr = 2.8:1)
Scheme 2
Scheme 4
It was then decided to investigate the radical addition of
trichlorosilane to a C=C bond10 using triethylborane as the
initiator. Pleasingly, it was found that reaction of trichlo-
rosilane (2 equiv) and triethylborane (3 × 0.4 equiv) with
1-allyl-4-methoxybenzene (1 equiv), in an ice-bath and in
the absence of a thiol catalyst, resulted in complete con-
version of the alkene into the trichlorosilane adduct (as in-
In conclusion, this paper has shown that phenyldimethyl-
silane adds efficiently to a range of terminal alkenes under
mild conditions using triethylborane as the radical initia-
tor in the presence of triisopropylsilanethiol. Oxidative re-
moval of the phenyldimethylsilyl group from the adducts
was then examined, and although efficient conversion to
the fluorosilanes was possible, subsequent oxidation gave
the desired alcohols in only low yields.
1
dicated by the H NMR spectrum of the unpurified
reaction mixture).11 Due to the high reactivity of the
trichlorosilane adduct, isolation and purification was not
straightforward and so the unpurified adduct was immedi-
ately treated under Tamao oxidation conditions, with po-
tassium fluoride and sodium hydrogen carbonate,
followed by the addition of hydrogen peroxide. This two-
step sequence afforded the desired alcohol 3-(4-meth-
oxyphenyl)propan-1-ol (3a) in 51% overall yield
(Scheme 3).12 This novel radical addition–oxidation se-
quence was successfully applied to the synthesis of alco-
hols 3b–f in similar yields.
Pleasingly, it was also found that trichlorosilane adds ef-
ficiently to terminal C=C bonds in the presence of trieth-
ylborane as radical initiator (but in the absence of a thiol
catalyst). The unpurified adducts were then subjected to
the Tamao oxidation conditions to afford the desired
alcohols in good yields. A combined radical addition–
cyclisation–oxidation sequence is also possible.
Acknowledgment
We thank AstraZeneca and the EPSRC for funding.
Cl3SiH (2 equiv),
Et3B (3 × 0.4 equiv),
THF, 12 h, 0 °C to r.t.
SiCl3
R
R
References and Notes
(1) (a) Peterson, D. J. J. Org. Chem. 1968, 33, 780. (b) Ager,
D. J. Synthesis 1984, 384. (c) Iguchi, M.; Tomioka, K. Org.
Lett. 2002, 4, 4329. (d) Barbero, A.; Blanco, Y.; Garcia, C.
Synthesis 2000, 1223.
KF, NaHCO3,
MeOH–THF, 0 °C, 1 h
then H2O2, 48 h, r.t.
OH
R
3a–f, 39–51%
(2) (a) Fleming, I.; Henning, R.; Parker, D. C.; Plaut, H. E.;
Sanderson, P. E. J. J. Chem. Soc., Perkin Trans. 1 1995,
317. (b) Tamao, K.; Ishida, N. J. Organomet. Chem. 1984,
269, c37. (c) Tamao, K.; Kumada, M.; Maeda, K.
OH
C6H13
OH
MeO
3b, 39%
Tetrahedron Lett. 1984, 25, 321. (d) Tamao, K.; Maeda, K.
Tetrahedron Lett. 1986, 27, 65. (e) Jones, G. R.; Landais, Y.
Tetrahedron 1996, 52, 7599. (f) Sunderhaus, J. D.; Lam, H.;
Dudley, G. B. Org. Lett. 2003, 8, 4571. (g) Jensen, J. F.;
Svendsen, B. Y.; la Cour, T. V.; Pedersen, H. L.; Johannsen,
M. J. Am. Chem. Soc. 2002, 124, 4558. (h) Shimada, T.;
Mukaide, K.; Shinohara, A.; Han, J. W.; Hayashi, T. J. Am.
Chem. Soc. 2002, 124, 1584.
3a, 51%
3c, 49%
PhO
Ph
OH
Ph
OH
3d, 47%
MeO
OH
OH
MeO
(3) (a) Walton, J. C.; Studer, A. Acc. Chem. Res. 2005, 38, 794.
(b) Amrein, S.; Studer, A. Helv. Chim. Acta 2002, 85, 3559.
(c) Amrein, S.; Studer, A. Chem. Commun. 2002, 1592.
(d) Chatgilialoglu, C.; Griller, D.; Lesage, M. J. Org. Chem.
1988, 53, 3641. (e) Kopping, B.; Chatgilialoglu, C.;
3e, 47%
3f, 49%
Scheme 3
Synlett 2011, No. 19, 2811–2814 © Thieme Stuttgart · New York

LETTER
Zehnder, M.; Giese, B. J. Org. Chem. 1992, 57, 3994.
Addition of Silanes
2813
NMR (100 MHz, CDCl3): d = 148.7 (ArCO), 147.1 (ArCO),
139.3 (ArC), 135.3 (ArC), 133.7 (2 × ArCH), 128.9 (ArCH),
127.8 (2 × ArCH), 120.4 (ArCH), 111.7 (ArCH), 111.1 (ArCH),
56.0 (OCH3), 55.9 (OCH3), 39.3 (ArCH2), 26.1 (CH2), 15.4
(SiCH2), –3.0 [2 × Si(CH3)2]. ESI-MS: m/z (%) = 315 (20),
314 (100) [M+], 283 (30), 237 (15).
(f) Miura, K.; Oshima, K.; Utimoto, K. Bull. Chem. Soc. Jpn.
1993, 66, 2348. (g) Postigo, A.; Nudelman, N. S. J. Phys.
Org. Chem. 2010, 23, 910.
(4) For an example of radical hydrosilylation and oxidation of a
silane adduct using Hg(OAc)2/AcOOH, see: Amrein, S.;
Timmermann, A.; Studer, A. Org. Lett. 2001, 3, 2357.
(5) (a) Cai, Y.; Roberts, B. P. J. Chem. Soc., Perkin Trans. 1
1998, 467. (b) Roberts, B. P. Chem. Soc. Rev. 1999, 28, 25.
(c) Haque, M. B.; Roberts, B. P. Tetrahedron Lett. 1996, 37,
9123.
(6) All new compounds gave spectroscopic and HRMS data in
accord with their structures.
(7) Typical Procedure for the Addition of
(8) Typical Procedure for the Oxidation of
Phenyldimethylsilanes 1a–c
To a stirred solution of the dimethylphenylsilane 1a–c (5.0
mmol, 1 equiv) in dry CH2Cl2 (15 mL) at r.t. was added BF3–
AcOH complex (1.4 mL, 10.0 mmol, 2 equiv), and the
resulting solution was stirred for 6 h, during which time the
solution turned orange. The reaction mixture was quenched
by being poured slowly into a stirred solution of 1 M
NaHCO3 (100 mL), the aqueous layer was extracted with
CH2Cl2 (2 × 75 mL), the combined organic extracts were
dried over MgSO4 and evaporated under reduced pressure to
afford the fluorosilanes 2a–c as a pale yellow oil (0.71–0.93
g, 75–88%). No further purification was carried out, and the
resulting oil was subjected to the oxidation conditions.
(9) Typical Procedure for the Oxidation of Fluorosilanes 2a–c
To a stirred solution of the unpurified fluorosilane 2a–c
(3.4–4.0 mmol, 1 equiv) and anhyd KF (0.39–0.46 g, 6.8–8.0
mmol, 2 equiv) in dry DMF (5 mL) at r.t. was added drop-
wise a solution of MCPBA (1.38–1.62 g, 85%, 6.8–8.0
mmol, 2 equiv) in dry DMF (10 mL). The resulting solution
was stirred for 4 h at r.t. The reaction mixture was diluted
with CH2Cl2 (75 mL) and washed successively with aq
Na2S2O3 (2 × 50 mL), aq Na2CO3 (2 × 50 mL), brine (50
mL), then dried over MgSO4 and purified by flash chroma-
tography (PE–Et2O = 10:1) to afford alcohols 3a–c as
colourless oils (0.11–0.18 g, 25–31%).
Phenyldimethylsilane to Alkenes
To a stirred solution of the alkene (10 mmol, 1 equiv),
phenyldimethylsilane (2.0 g, 15 mmol, 1.5 equiv) in THF (3
mL) was added Et3B in THF (0.5 mL, 1 M solution, 5 mmol,
0.5 equiv) and, shortly after, triisopropylsilane thiol (105 mL,
0.5 mmol, 5 mol%, care required due to noxious smell).
After stirring at r.t. for 1 h, a further portion of Et3B in THF
(0.5 mL, 1 M solution 5 mmol, 0.5 equiv) was added and the
mixture was left stirring overnight. Removal of the solvent
under reduced pressure afforded the crude product which
was purified by flash silica chromatography (elution
gradient PE to PE–EtOAc = 5:1) to afford the silane addition
products 1a–j (81–97%).
Representative Analytical Data
[3-(4-Methoxyphenyl)propyl]dimethyl(phenyl)silane
(1a)
Rf = 0.45 (PE–EtOAc = 10:1). IR (thin film): nmax = 3010
(w), 2988 (w), 2959 (w), 2837 (w), 1743 (m), 1503 (w), 1512
(s), 1466 (m) cm–1. 1H NMR (400 MHz, CDCl3): d = 7.57–
7.53 (2 H, m, ArCH), 7.42–7.38 (3 H, m, ArCH), 7.11 (2 H,
app dd, J = 8.6, 2.1 Hz, ArCH), 6.87 (2 H, app dd, J = 8.6, 2.1
Hz, ArCH), 3.81 (3 H, s, OCH3), 2.61 (2 H, t, J = 7.7 Hz,
ArCH2), 1.71–1.63 (2 H, m, CH2), 0.86–0.79 (2 H, m, SiCH2),
0.29 [6 H, s, Si(CH3)2]. 13C NMR (100 MHz, CDCl3): d =
157.9 (ArCO), 139.6 (ArC), 134.4 (ArC), 133.7 (2 × ArCH),
129.5 (2 × ArCH), 128.9 (ArCH), 127.9 (2 × ArCH), 113.7
(2 × ArCH), 55.0 (OCH3), 38.5 (ArCH2), 25.8 (CH2), 15.0
(SiCH2), –3.5 [2 × Si(CH3)2]. ESI-MS: m/z (%) = 285 (20),
284 (100) [M+], 207 (10).
(10) For the addition of trichlorosilane to alkenes using a
peroxide initiator see, for example: (a) Speier, J. L.;
Webster, J. A. J. Org. Chem. 1956, 21, 1044. (b) Sommer,
L. H.; Pietrusza, E. W.; Whitmore, F. C. J. Am. Chem. Soc.
1947, 69, 188.
(11) Typical Procedure for the Addition of Trichlorosilane to
Alkenes 1a–c
To a stirred solution of the alkene (5.0 mmol, 1 equiv) in
THF (5 mL) at 0 °C, under air, was added Cl3SiH (1.0 mL,
10.0 mmol, 2 equiv) followed by the slow dropwise addition
of Et3B (2.0 mL, 1 M solution in THF, 2.0 mmol, 0.4 equiv).
The resulting solution was stirred at 0 °C for 1 h, after which
a further portion of Et3B (2.0 mL, 1 M solution in THF, 2.0
mmol, 0.4 equiv) was added, and the mixture was stirred for
a further 1 h at 0 °C followed by addition of a further portion
of Et3B (2.0 mL, 1 M solution in THF, 2.0 mmol, 0.4 equiv).
The resulting solution was stirred at 0 °C for 1 h then
warmed to r.t. and stirred for a further 4 h. Removal of the
solvent under reduced pressure afforded the crude
trichlorosilane addition product, as an oil.
Octyl(dimethyl)(phenyl)silane (1b)
Rf = 0.80 (PE). IR (thin film): nmax = 3058 (w), 2918 (s), 2857
(s), 2120 (w), 1470 (m), 1431 (m) cm–1. 1H NMR (400 MHz,
CDCl3): d = 7.55–7.45 (2 H, m, ArCH), 7.38–7.30 (3 H, m,
ArCH), 1.33–1.20 (12 H, m, CH2), 0.91 (3 H, t, J = 7.0 Hz,
CH3), 0.77 (2 H, t, J = 8.1 Hz, SiCH2), 0.29 [6 H, s,
Si(CH3)2]. 13C NMR (100 MHz, CDCl3): d = 139.7 (ArC),
133.5 (2 × ArCH), 128.7 (ArCH), 127.7 (2 × ArCH), 33.6
(CH2), 31.9 (CH2), 29.3 (2 × CH2), 23.8 (CH2), 22.6 (CH2),
18.2 (CH2), 15.7 (CH2), 14.1 (CH3), –3.0 [Si(CH3)2]. ESI-
MS: m/z (%) = 250 (20), 249 (100) [MH+], 233 (30), 171
(20)
(12) Typical Procedure for the Oxidation of Trichlorosilanes
to Give Alcohols 3a–f
The crude trichlorosilane addition product was taken up in
THF (75 mL), and the solution was stirred at r.t. (under air)
while MeOH (75 mL) was slowly added, after which KF (2.6
g, 45.0 mmol, 9 equiv) and KHCO3 (9.00 g, 90.0 mmol 18
equiv) were added, and the suspension was stirred for 1 h. To
the resulting white suspension was added H2O2 (5.1 mL,
30% solution, 45.0 mmol, 9 equiv), and the reaction mixture
was vigorously stirred for 24 h; after which Na2S2O3·5H2O
(7.4 g, 30.0 mmol, 6 equiv) was added, and the mixture was
stirred for 1 h. The mixture was filtered through a Celite
plug, and the filter cake was rinsed with Et2O (50 mL). The
[3-(3,4-Dimethoxyphenyl)propyl]dimethyl(phenyl)-
silane (1j)
Rf = 0.30 (PE–EtOAc = 10:1). IR (thin film): nmax = 3004
(w), 2990 (w), 2952 (w), 2929 (w), 2833 (w), 1739 (m), 1509
(w), 1514 (s), 1464 (m) cm–1. 1H NMR (400 MHz, CDCl3):
d = 7.53–7.44 (2 H, m, ArCH), 7.37–7.34 (3 H, m, ArCH),
6.79 (1 H, d, J = 8.0 Hz, ArCH), 6.69 (1 H, dd, J = 8.0, 1.9
Hz, ArCH), 6.66 (1 H, d, J = 1.9 Hz, ArCH), 3.86 (6 H, s,
OCH3), 2.57 (2 H, t, J = 7.6 Hz, ArCH2), 1.68–1.56 (2 H, m,
CH2), 0.83–0.77 (2 H, m, SiCH2), 0.26 [6 H, s, Si(CH3)2]. 13
C
Synlett 2011, No. 19, 2811–2814 © Thieme Stuttgart · New York

2814
M. J. Palframan et al.
LETTER
filtrate was concentrated under vacuum, the resulting residue
was dissolved in CH2Cl2 (50 mL), dried over MgSO4, and
the solvent was removed in vacuo to afford the crude
product. This was purified by flash silica chromatography
(elution gradient PE to PE–EtOAc = 2:1) to afford alcohols
3a–f (39–51%).
Synlett 2011, No. 19, 2811–2814 © Thieme Stuttgart · New York

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