Anilinosilanes/TBAF catalyst: Mild and powerful agent for the silylation of sterically hindered alcohols

Article abstract of DOI:10.1055/s-2005-872098

We developed an efficient method for the silylation of alcohols using anilinosilane with tetrabutylammonium fluoride (TBAF) catalyst, wherein TMS, TES and TBS groups were smoothly introduced into silylation-resistant hindered alcohols under mild condition

Full text of DOI:10.1055/s-2005-872098

PAPER
2677
Anilinosilanes/TBAF Catalyst: Mild and Powerful Agent for the Silylation of
Sterically Hindered Alcohols
A
nilinosilanes/T
B
k
A
F
Catalyst ira Iida, Atsushi Horii, Tomonori Misaki, Yoo Tanabe*
Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyougo 669-1337, Japan
Fax +81(79)5659077; E-mail: tanabe@kwansei.ac.jp
Received 4 April 2005; revised 9 May 2005
NSi
H
NH2
cat. TBAF (0.02 equiv)
DMF
Abstract: We developed an efficient method for the silylation of al-
cohols using anilinosilane with tetrabutylammonium fluoride
(TBAF) catalyst, wherein TMS, TES and TBS groups were smooth-
ly introduced into silylation-resistant hindered alcohols under mild
conditions.
+
ROSi +
ROH
Si = TMS 1a
TES 1b
TBS 1c
Key words: alcohols, silylation, anilinosilane, TBAF, catalyst
Scheme 1
nosilanes 1–TBAF catalyst (Scheme 1). The present
method covers three types of silylation (TMS, TES, TBS)
against sterically uncrowded and crowded alcohols under
mild conditions.
The silylation of alcohols is an essential process in the
various organic synthesis fields, especially as the most re-
liable protective method.1 Silyl ethers are commonly ob-
tained by the reacting parent alcohols with the
corresponding trialkylsilyl halides or triflates in the pres-
ence of stoichiometric amounts of bases, such as trialkyl-
amine and imidazole. Despite these well-established
methods, there remains a need for improved efficiency in
view of process chemistry and natural product synthesis.
Our and Johnson’s groups independently reported a near-
ly neutral and effective method for silylation systems us-
ing silazanes,2a,3 hydrosilanes or disilanes2b together with
catalytic tetrabutylammonium fluoride (TBAF). Silazanes
are also efficient silylation agents for alcohols or phenols
promoted by the PyH+·OTf– catalyst,4 and for ketones or
aldehydes giving enol silyl ethers catalyzed by NaH or
DBU.5
Initially, trimethylsilylation was examined using 1-oc-
tanol to check the inherent reactivity of several available
silazanes with gas chromatography monitoring. (Table 1,
Method A). Silazanes are placed in the order of reactivity
(entries 1–14) except anilinotrimethylsilane 1a (entries 15
and 16). Next, comparable experiment was guided using
very sterically crowded (silylation-resistant) terpine-4-ol
in the presence of TBAF catalyst (0.02 equiv) (Method
B), because this catalytic method was generally very pow-
erful due to the utilization of reactive hypervalent silicate
intermediates.2a Scheme 2 illustrates the relative order of
reactivity of methods A and B. It should be noted that this
order is not necessarily same and the case using 1a exhib-
its clear contrast. This result indicates that TBAF acts as a
highly effective trigger for the present trimethylsilylation
using 1a (the reaction completed within 30 min even at
–20 °C (entry 16).
Consistent with the study of these mild, catalytic, and
practical silylations systems, we report herein a nearly
neutral and powerful method utilizing a novel agent, anili-
< Without TBAF for the trimethylsilylation of 1-octanol>
TMS
O
NTMS
H
OTMS
NTMS
O
O
N
N
NTMS
(TMS)2NH
NTMS
Me
F3C
NTMS
Me
TMSN
H
NTMS
H
1a
O
Reactivity
< With TBAF for the trimethylsilylation of terpinen-4-ol>
TMS
O
O
N
NTMS
O
OTMS
NTMS
H
N
NTMS
(TMS)2NH
TMSN
H
NTMS F3C
H
NTMS
Me
1a
NTMS
Me
O
Reactivity
Scheme 2
SYNTHESIS 2005, No. 16, pp 2677–2682
x
x.
x
x
.
2
0
0
5
Advanced online publication: 22.07.2005
DOI: 10.1055/s-2005-872098; Art ID: F06305SS
© Georg Thieme Verlag Stuttgart · New York

2678
A. Iida et al.
PAPER
Table 1 Trimethylsilylation Ability of Several Silazanes in the Ab-
sence or Presence of TBAF Catalyst
yields (entries 1–20). Cl atom, THP and methyl ester
functions tolerated the reaction conditions (entries 21–
26). p-Cresol was also trimethylsilylated, however, with a
much lower reaction speed (entry 27). TES and TBS were
not introduced into p-cresol.
Method A
No catalyst
TMS
+
OH
6
OTMS
Silazanes
6
DMF
TBAF (0.02 equiv)
DMF
Method B
TMS
+
PhNHSi
Silazanes
OH
OTMS
1
TBAF
Entry TMS-Silazane
Method Temp (°C) /
Time (min)
Yield (%)a
–
NHPh
Si
Si OR
1
2
(TMS)2NH
A
B
r.t./1
r.t./60
trace
trace
F
ROH
A
3
4
A
B
r.t./1
r.t./60
trace
trace
O
1
TMSN
H
NTMS
H
5
6
A
B
r.t./30
r.t./60
15
95
O
–
–
NHPh
Si OR
Si OR
NTMS
Me
H
F
F
B
7
8
A
B
r.t./1
r.t./60
39
51
O
NTMS
OTMS
NTMS
PhNH2
9
10
A
B
r.t./1
r.t./30
95
69
Scheme 4
11
12
A
B
r.t./1
r.t./30
99
trace
O
A plausible reaction mechanism is shown in Scheme 4,
which is similar to a previously reported method.2a The
TBAF catalyst first attacks the anilinosilane to form the
reactive pentavalent silicate A,7 which in turn condenses
with an alcohol to form alkoxy(fluoro)silicate B with
eliminating aniline. The fluoride anion is transferred from
B to the remaining anilinosilane to release the silyl ether
by reforming A. A slight excess of anilinosilane com-
pletes the catalytic cycle.
F3C
N
NTMS
Me
13
14
A
B
r.t./1
r.t./30
99
78
NTMS
15
16
A
B
r.t./1
–20/30
18
100
NTMS
H
1a
a GC analysis.
In conclusion, we developed a mild, practical, and power-
ful method for the preparation of various silyl (TMS, TES,
TBS) ethers using readily available anilinosilanes and cat-
alytic TBAF.
Anilinosilanes 1 are commercially available (TMS; 1a) or
easily prepared (TES; 1b and TBS; 1c) by the reported
method6 from aniline and the corresponding hydrosilanes
with a Pd/C catalyst in good yields (Scheme 3).
NMR spectra were recorded on a JEOL DELTA 300 spectrometer,
1
operating at 300 MHz for H NMR and 75 MHz for 13C NMR.
Chemical shifts (d) in CDCl3 are reported downfield from TMS (0
1
ppm) or CHCl3 (7.26 ppm) for H NMR. For 13C NMR, chemical
NH2
+
NSi
H
10% Pd/C (0.05 equiv)
toluene, 110 °C
SiH
shifts (d) were reported in the scale relative to CDCl3 (77.00 ppm)
as an internal reference. IR spectra were recorded on JASCO
FT/IR-5300 spectrophotometer. Flash column chromatography
analyses were performed with silica gel Merck 60 (230–400 mesh
ASTM) according to the method of Still.8 GC data were obtained on
a Simazu GC-17A [column: Widebore DB-1701; ∆ : 0.53 mm × 30
m; oven temperature: 50 °C–250 °C (20 °C/min); injection/detec-
tion (FID) temperature: 250 °C; carrier gas: N2].
+
H2
1b, 1c
Scheme 3
This hydrosilylation method to give 1b and 1c was origi-
nally utilized for silyl protection of amino groups and per-
formed in gram-scale preparation. TBS analog 1c is
considerably moisture-insensitive (see experimental sec-
tion).
Anilinotriethylsilane (1b)
Aniline (5.0 g, 50 mmol) and Et3SiH (7.6 g, 65 mmol) were succes-
sively added to a stirred suspension of 10% Pd-C (3.5 g, 2.5 mmol)
in toluene (100 mL) at 25 °C under an Ar atmosphere. After stirring
at reflux for 12 h, the mixture was filtered through the celite with
glass filter and the filtrate was concentrated in reduced pressure.
The obtained crude product was purified by distillation to give the
Table 2 lists the results of the silylations (TMS, TES, and
TBS) for various alcohols. Not only primary and second-
ary alcohols, but also sterically crowded tertiary alcohols
were successfully silylated in good to excellent isolated
Synthesis 2005, No. 16, 2677–2682 © Thieme Stuttgart · New York

PAPER
Anilinosilanes/TBAF Catalyst
2679
Table 2 Silylations of Various Alcohols Using Anilinosilanes (1a,b,c) with TBAF Catalyst
NSi
H
1a Si = TMS
1b Si = TES
1c Si = TBS
cat. TBAF (0.02 equiv)
DMF, r.t.
ROSi
ROH
+
Entry
Alcohol
Anilinosilane Time (min)
Silyl ether
Yield (%)a
96
96
99
OH
OSi
1
2
3
1a
1b
1c
5
5
5
2a
2b
2c
4
5
6
1a
1b
1c
5
5
5
3a
3b
3b
96
94
99
OH
OSi
7
8
9
1a
1b
1c
5
5
10
4a
4b
4c
95
99
99
OH
OSi
10
11
1b
1c
5
5
5b
5c
99
99
OH
OSi
12
13
1b
1c
5
5
6b
6c
99
99
OH
OSi
14
15
16
1a
1b
1c
5
10
20
7a
7b
7c
95
92
94
OH
OSi
17
18
1b
1c
30
180
8b
8c
91
92
OH
OSi
19
20
1a
1c
10
20
9a
9c
98
86
OH
OSi
21
22
1a
1c
5
5
10a
10c
99
99
OH
OH
OSi
OSi
Cl
Cl
23
24
1a
1c
5
60
11a
11c
95
99
HO
SiO
25
26
1c
1c
30
10
12c
13c
83
86
OTBS
OH
THPO
O
THPO
O
OTBS
OH
MeO
MeO
81b
OTMS
27
1a
210
14a
OH
a Isolated yield.
b Anilinosilane 1a (2.5 equiv) was used.
desired product (9.44 g, 91%); colorless oil; bp 96–97 °C/2.1
mmHg.
Anilino(tert-butyldimethyl)silane (1c)9
Colorless oil.
IR (neat): 3381, 2953, 1601, 1499, 1292, 889 cm–1.
IR (neat): 3399, 2955, 1603, 1499, 1292, 897 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.72–0.82 (m, 6 H), 0.94–1.03 (m,
9 H), 3.34 (br s, 1 H), 6.65–6.74 (m, 3 H), 7.10–7.18 (m, 2 H).
1H NMR (300 MHz, CDCl3): d = 0.27 (s, 6 H), 0.98 (s, 9 H), 3.34
(br s, 1 H), 6.62–6.77 (m, 3 H), 7.09–7.20 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 4.63, 7.00, 116.03, 117.35, 129.18,
147.73.
13C NMR (75 MHz, CDCl3): d = –4.23, 17.95, 26.37, 116.54,
117.52, 129.14, 147.65.
Anal. Calcd for C12H21NSi: C, 69.5; H, 10.2; N, 6.8. Found: C, 69.1;
H, 9.9; N, 6.6.
Synthesis 2005, No. 16, 2677–2682 © Thieme Stuttgart · New York

2680
A. Iida et al.
PAPER
Silylations of 1-Octanol Using Anilinotrimethylsilane (1a); Typ-
ical Procedure
13C NMR (75 MHz, CDCl3): d = –4.71, –4.40, 14.11, 18.18, 22.66,
23.82, 25.70, 25.93, 29.41, 31.91, 39.79, 68.68.
TBAF (1 M THF solution; 0.02 mL, 0.02 mmol) was added to a
stirred solution of 1-octanol (130 mg, 1.0 mmol) and PhNHTMS
(1a; 248 mg, 1.5 mmol) in DMF (2.0 mL) at 20–25 °C under an Ar
atmosphere. After stirring at the same temperature for 5 min, the
mixture was quenched with water (5.0 mL), which was extracted
with Et2O. The combined organic phase was washed with water,
brine, dried (Na2SO4) and concentrated. The obtained crude product
was purified by SiO2 column chromatography (hexane) to give 1-
(trimethylsiloxy)octane (2a)10 (194 mg, 96%); colorless oil.
1-(Trimethylsiloxy)-3,7-dimethyl-2,6-octadiene (4a)14
Colorless oil.
IR (neat): 2926, 1445, 1381, 1250, 1065, 842 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.13 (s, 9 H), 1.60 (s, 3 H), 1.64
(s, 3 H), 1.68 (s, 3 H) 1.98–2.14 (m, 4 H), 4.15 (t, J = 6.5 Hz, 2 H),
5.06–5.13 (m, 1 H), 5.30–5.45 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = –0.31, 16.27, 17.65, 25.66, 26.35,
39.58, 59.53, 123.79, 124.08, 131.55, 137.65.
IR (neat): 2930, 1252, 1100, 841, 748 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.11 (s, 9 H), 0.87 (t, J = 6.5 Hz,
3 H), 1.21–1.33 (m, 10 H), 1.47–1.57 (m, 2 H), 3.56 (t, J = 6.5 Hz,
2 H).
13C NMR (75 MHz, CDCl3): d = –0.46, 14.09, 22.68, 25.85, 29.31,
29.43, 31.86, 32.77.
1-(Triethylsiloxy)-3,7-dimethyl-2,6-octadiene (4b)15
Colorless oil.
IR (neat): 2957, 1458, 1379, 1067, 1008, 745 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.62 (q, J = 7.9 Hz, 6 H), 0.97 (t,
J = 7.9 Hz, 9 H), 1.60 (s, 3 H), 1.63 (s, 3 H), 1.68 (s, 3 H), 1.98–2.13
(m, 4 H), 4.18 (d, J = 6.5 Hz, 2 H), 5.07–5.12 (m, 1 H), 5.31–5.35
(m, 1 H).
13C NMR (75 MHz, CDCl3): d = 4.51, 6.77, 16.29, 17.65, 25.66,
26.35, 39.56, 59.81, 124.10, 124.19, 131.52, 137.12.
1-(Triethylsiloxy)octane (2b)11
Colorless oil.
IR (neat): 1475, 1245, 1160, 1015 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.60 (q, J = 7.9 Hz, 6 H), 0.85–
0.99 (m, 3 H), 0.96 (t, J = 7.9 Hz, 9 H), 1.19–1.38 (m, 10 H), 1.47–
1.58 (m, 2 H), 3.59 (t, J = 6.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 4.45, 6.76, 14.09, 22.68, 25.85,
29.33, 29.45, 31.85, 32.96, 63.00.
1-(tert-Butyldimethylsiloxy)-3,7-dimethyl-2,6-octadiene (4c)16
Colorless oil.
IR (neat): 1265, 1120, 1080, 845 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.07 (s, 6 H), 0.91 (s, 9 H), 1.61
(s, 3 H), 1.62 (s, 3 H), 1.68 (s, 3 H), 1.98–2.13 (m, 4 H), 4.20 (d,
J = 6.6 Hz, 2 H), 5.07–5.12 (m, 1 H), 5.28–5.33 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = –5.05, 16.33, 17.67, 18.43, 25.68,
26.02, 26.37, 39.52, 60.35, 124.12, 124.42, 131.52, 136.83.
1-(tert-Butyldimethylsiloxy)octane (2c)12
Colorless oil.
IR (neat): 2932, 1464, 1253, 1101, 846, 783 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.05 (s, 6 H), 0.87–0.91 (m, 3 H),
0.88 (s, 9 H), 1.24–1.33 (m, 10 H), 1.46–1.56 (m, 2 H), 3.60 (t, J =
6.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = –5.24, 14.11, 18.39, 22.68, 25.70,
26.00, 29.33, 29.43, 31.85, 32.91, 63.37.
2-(Triethylsiloxy)-1,7,7-trimethylbicyclo[2.2.1]heptane (5b)17
Colorless oil.
IR (neat): 2953, 1458, 1115, 1086, 1017, 741 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.54 (q, J = 7.9 Hz, 6 H), 0.79 (s,
3 H), 0.83 (s, 3 H), 0.91–0.96 (m, 2 H), 0.95 (t, J = 7.9 Hz, 9 H),
1.01 (s, 3 H), 1.41–1.53 (m, 1 H), 1.58–1.75 (m, 4 H), 3.52–3.56 (m,
1 H).
13C NMR (75 MHz, CDCl3): d = 4.91, 6.90, 11.87, 20.11, 20.57,
27.37, 33.96, 42.37, 45.28, 46.48, 49.10, 79.56.
2-(Trimethylsiloxy)octane (3a)13
Colorless oil.
IR (neat): 2930, 2858, 1250, 1082, 841 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.11 (s, 9 H), 0.85–0.91 (m, 3 H),
1.12 (d, J = 6.2 Hz, 3 H), 1.19–1.46 (m, 10 H), 3.70–3.80 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 0.25, 14.09, 22.66, 23.90, 25.97,
29.35, 31.91, 39.66, 68.61.
2-(tert-Butyldimethylsiloxy)-1,7,7-timethylbicyclo[2.2.1]heptan
(5c)18
Colorless oil.
IR (neat): 2953, 1256, 1115, 1086, 837, 776 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.01 (s, 6 H), 0.79 (s, 3 H), 0.82
(s, 3 H), 0.86–0.88 (m, 2 H), 0.87 (s, 9 H), 1.01 (s, 3 H), 1.41–1.53
(m, 1 H), 1.58–1.75 (m, 4 H), 3.52–3.56 (m, 1 H).
2-(Triethylsiloxy)octane (3b)11
Colorless oil.
IR (neat): 2957, 1460, 1075, 1013, 739 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.59 (q, J = 7.9 Hz, 6 H), 0.85–
0.99 (m, 3 H), 0.96 (t, J = 7.9 Hz, 9 H), 1.13 (d, J = 6.2 Hz, 3 H),
1.23–1.41 (m, 10 H), 3.72–3.82 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 4.69, 6.88, 14.09, 22.64, 23.84,
25.81, 29.41, 31.91, 39.87, 68.53.
13C NMR (75 MHz, CDCl3): d = –5.08, –4.61, 11.99, 17.95, 20.13,
20.57, 25.81, 27.36, 33.88, 42.12, 45.26, 46.50, 49.10, 79.68.
1-(Triethylsiloxy)-3-phenylpropane (6b)19
Colorless oil.
IR (neat): 3029, 1456, 1238, 1102, 737 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.61 (q, J = 8.3 Hz, 6 H), 0.98 (t,
J = 8.3 Hz, 9 H), 1.81–1.91 (m, 2 H), 2.66–2.72 (m, 2 H), 3.65 (t,
J = 6.5 Hz, 2 H), 7.16–7.31 (m, 5 H).
2-(tert-Butyldimethylsiloxy)octane (3c)12
Colorless oil.
IR (neat): 1260, 1095, 845, 785 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.05 (s, 6 H), 0.86–0.90 (m, 3 H),
0.89 (s, 9 H), 1.11 (d, J = 6.2 Hz, 3 H), 1.24–1.46 (m, 10 H), 3.71–
3.82 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 4.45, 6.79, 32.14, 34.47, 62.14,
125.64, 128.26, 128.42, 142.24.
Synthesis 2005, No. 16, 2677–2682 © Thieme Stuttgart · New York

PAPER
Anilinosilanes/TBAF Catalyst
2681
1-(tert-Butyldimethylsiloxy)-3-phenylpropane (6c)6
Colorless oil.
1-(Trimethylsiloxy)tricyclo[3.3.1.1]decane (9a)22
Colorless oil.
IR (neat): 2955, 1472, 1254, 1103, 837, 777 cm–1.
IR (neat): 2901, 1354, 1453, 1249, 1017, 831 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.60 (s, 6 H), 0.92 (s, 9 H), 1.80–
1.89 (m, 2 H), 2.66–2.71 (m, 2 H), 3.64 (t, J = 6.5 Hz, 2 H), 7.15–
7.31 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = –5.28, 18.33, 25.97, 32.10, 34.47,
62.37, 125.66, 128.26, 128.47, 142.28.
1H NMR (300 MHz, CDCl3): d = 0.12 (s, 9 H), 1.58–1.60 (m, 6 H),
1.76–1.77 (m, 6 H), 2.05–2.14 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 2.98, 30.92, 36.23, 46.04, 71.40.
1-(tert-Butyldimethylsiloxy)tricyclo[3.3.1.1]decane (9c)23
Colorless oil.
3,7-Dimethyl-3-(trimethylsiloxy)-1,6-octadiene (7a)20
Colorless oil.
IR (neat): 2964, 2930, 1252, 1049, 841 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.12 (s, 9 H), 1.31 (s, 3 H), 1.46–
1.52 (m, 2 H), 1.59 (s, 3 H), 1.67 (s, 3 H), 1.87–2.07 (m, 2 H), 4.98
(dd, J = 1.7, 10.7 Hz, 1 H), 5.07–5.12 (m, 1 H), 5.13 (dd, J = 1.7,
17.5 Hz, 1 H), 5.86 (dd, J = 10.7, 17.5 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 2.50, 17.57, 22.79, 25.68, 27.28,
43.48, 75.87, 111.65, 124.71, 131.09, 145.53.
IR (neat): 2900, 1355, 1255, 1160, 1094, 1016, 830 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.07 (s, 6 H), 0.86 (s, 9 H), 1.57–
1.61 (m, 6 H), 1.70–1.74 (m, 6 H), 2.04–2.12 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = –1.65, 17.95, 25.83, 30.92, 36.33,
46.14, 70.69.
8-Chloro-1-(trimethylsiloxy)octane (10a)24
Colorless oil.
IR (neat): 2934, 2859, 1250, 1098, 843 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.01 (s, 9 H), 1.25–1.59 (m, 10 H),
3-(Triethylsiloxy)-3,7-dimethyl-1,6-octadiene (7b)11
Colorless oil.
IR (neat): 2955, 2878, 1051, 1013, 743 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.58 (q, J = 7.9 Hz, 6 H), 0.96 (t,
J = 7.9 Hz, 9 H), 1.30 (s, 3 H), 1.44–1.54 (m, 2 H), 1.59 (s, 3 H),
1.68 (s, 3 H), 1.90–2.10 (m, 2 H), 4.99 (dd, J = 1.7, 10.7 Hz, 1 H),
5.06–5.13 (m, 1 H), 5.14 (dd, J = 1.7, 17.3 Hz, 1 H), 5.86 (dd, J =
10.7, 17.3 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 6.81, 7.11, 17.55, 22.83, 25.68,
27.34, 43.80, 75.34, 111.61, 124.80, 131.10, 145.55.
1.71–1.81 (m, 2 H), 3.51 (t, J = 6.9 Hz, 2 H), 3.56 (t, J = 6.9 Hz, 2
H).
13C NMR (75 MHz, CDCl3): d = –0.48, 25.72, 26.83, 28.85, 29.24,
32.62, 32.68, 45.13, 62.64.
1-(tert-Butyldimethylsiloxy)-8-chlorooctane (10c)25
Colorless oil.
IR (neat): 2932, 2859, 1462, 1254, 1105, 835 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.43 (s, 6 H), 0.89 (s, 9 H), 1.25–
1.55 (m, 10 H), 1.71–1.81 (m, 2 H), 3.52 (t, J = 6.5 Hz, 2 H), 3.56
(t, J = 6.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = –5.28, 18.36, 25.70, 25.97, 26.83,
28.85, 29.24, 32.62, 32.81, 45.11, 63.21.
3-(tert-Butyldimethylsiloxy)-3,7-dimethyl-1,6-octadiene (7c)21
Colorless oil.
IR (neat): 2932, 2859, 1254, 1049, 837, 774 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.06 (s, 3 H), 0.08 (s, 3 H), 0.89
(s, 9 H), 1.29 (s, 3 H), 1.42–1.52 (m, 2 H), 1.59 (s, 3 H), 1.67 (s, 3
H), 1.90–2.10 (m, 2 H), 4.98 (dd, J = 1.7, 10.7 Hz, 1 H), 5.05–5.13
(m, 1 H), 5.14 (dd, J = 1.7, 17.3 Hz, 1 H), 5.84 (dd, J = 10.7, 17.3
Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = –2.05, 17.57, 22.80, 25.70, 25.95,
27.44, 43.79, 75.51, 111.55, 124.78, 131.09, 125.67.
1,8-Bis(trimethylsiloxy)octane (11a)26
Colorless oil.
IR (neat): 2936, 2861, 1252, 1098, 841 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.10 (s, 18 H), 1.27–1.34 (m, 8 H),
1.45–1.58 (m, 4 H), 3.56 (t, J = 6.5 Hz, 4 H).
13C NMR (75 MHz, CDCl3): d = –0.48, 25.77, 29.40, 32.72, 62.72.
1-(Triethylsiloxy)-1-isopropyl-4-methyl-3-cyclohexene (8b)4
Colorless oil.
IR (neat): 2961, 2878, 1130, 1071, 1009, 739 cm–1.
1,8-Bis(tert-butyldimethylsiloxy)octane (11c)27
Colorless oil.
IR (neat): 2930, 2859, 1256, 1102, 837, 776 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.56 (q, J = 7.9 Hz, 6 H), 0.88 (d,
J = 6.8 Hz, 3 H), 0.88 (d, J = 6.8 Hz, 3 H), 0.94 (t, J = 7.9 Hz, 9 H),
1.61–2.29 (m, 10 H), 5.19–5.25 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 6.92, 7.26, 17.03, 17.20, 23.09,
28.77, 32.18, 33.89, 36.14, 75.52, 119.34, 133.49.
1H NMR (300 MHz, CDCl3): d = 0.05 (s, 12 H), 0.89 (s, 18 H),
1.26–1.33 (m, 8 H), 1.43–1.57 (m, 4 H), 3.60 (t, J = 6.5 Hz, 4 H).
13C NMR (75 MHz, CDCl3): d = –5.26, 18.39, 25.72, 26.00, 29.45,
32.89, 63.33.
1-(tert-Butyldimethylsiloxy)-8-(tetrahydropyranyloxy)hexane
(12c)28
1-(tert-Butyldimethylsiloxy)-1-isopropyl-4-methyl-3-cyclohex-
ene (8c)4
Colorless oil.
IR (neat): 2932, 2859, 1464, 1256, 1100, 837 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.04 (s, 6 H), 0.89 (s, 9 H), 1.28–
1.43 (m, 4 H), 1.48–1.91 (m, 10 H), 3.38 (dt, J = 6.9, 9.6 Hz, 1 H),
3.46–3.54 (m, 1 H), 3.60 (t, J = 6.9, 2 H), 4.56–4.58 (m, 1 H), 3.73
(dt, J = 6.9, 9.6 Hz, 1 H), 3.82–3.91 (m, 1 H).
Colorless oil.
IR (neat): 2959, 2859, 1472, 1254, 1071, 835 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.03 (s, 3 H), 0.06 (s, 3 H), 0.87
(s, 9 H), 0.88 (d, J = 6.7 Hz, 3 H), 0.89 (d, J = 6.7 Hz, 3 H), 1.61–
2.30 (m, 10 H), 5.20–5.25 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = –2.33, –2.04, 17.06, 17.15, 18.65,
23.07, 26.00, 28.78, 32.23, 33.79, 35.92, 75.72, 119.40, 133.49.
13C NMR (75 MHz, CDCl3): d = –5.26, 18.37, 19.69, 25.51, 25.70,
25.98, 26.08, 29.77, 30.78, 32.83, 62.33, 63.23, 67.59, 98.84.
Synthesis 2005, No. 16, 2677–2682 © Thieme Stuttgart · New York

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A. Iida et al.
PAPER
1-Methyl-6-(tert-butyldimethylsiloxy)hexanoate (13c)29
Colorless oil.
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2923.
IR (neat): 2955, 2932, 2361, 1746, 1472, 1256, 1073, 837 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.04 (s, 6 H), 0.89 (s, 9 H), 1.22–
1.41 (m, 2 H), 1.46–1.69 (m, 4 H), 2.31 (t, J = 7.6 Hz, 2 H), 3.60 (t,
J = 6.5 Hz, 2 H), 3.66 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = –5.30, 18.34, 24.78, 25.43, 25.95,
32.45, 34.09, 51.44, 62.95, 174.19.
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4-Methyl-1-(trimethylsiloxy)benzene (14a)30
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Colorless oil.
IR (neat): 2961, 1613, 1510, 1250, 918, 845 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.03 (s, 9 H), 2.28 (s, 3 H) 6.71–
6.75 (m, 2 H), 7.00–7.06 (m, 2 H).
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130.64, 152.82.
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Acknowledgment
This research was partially supported by a Grant-in-Aid for Scien-
tific Research on Priority Areas (A) ‘Creation of Biologically
Functional Molecules’ and on Basic Areas (C) from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
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Synthesis 2005, No. 16, 2677–2682 © Thieme Stuttgart · New York