The study of intramolecular tandem radical cyclizations of acylsilanes with radicalphiles attached on silicon

Article abstract of DOI:10.1016/j.tet.2004.12.053

Radical cyclizations of acylsilanes with radicalphilic pendant introduced on silicon proceeded in a tandem fashion to give spiro products containing a cyclic silyl ether skeleton. Because the alkoxysilyl group can be replaced with a hydroxy group through

Full text of DOI:10.1016/j.tet.2004.12.053

Tetrahedron 61 (2005) 2037–2045
The study of intramolecular tandem radical cyclizations of
acylsilanes with radicalphiles attached on silicon
*
Kuo-Hsiang Tang, Fang-Yu Liao and Yeun-Min Tsai
Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan, ROC
Received 4 December 2004; revised 22 December 2004; accepted 22 December 2004
Available online 13 January 2005
Abstract—Radical cyclizations of acylsilanes with radicalphilic pendant introduced on silicon proceeded in a tandem fashion to give spiro
products containing a cyclic silyl ether skeleton. Because the alkoxysilyl group can be replaced with a hydroxy group through oxidation, the
spiro silyl ethers can be converted into diols. In the case with a radical intermediate carrying 2-oxa-3-sila-6-heptenyl skeleton, products
derived from 1,7-endo cyclization were obtained in good yields.
q 2004 Elsevier Ltd. All rights reserved.
1
5,16
1. Introduction
rearrangement
In this fashion, the radical carbonyl cyclization reaction
occurs to afford an a-silyloxy radical 3.
Radical reactions are now widely used as important tools to
1
construct carbon–carbon bonds. Among various radical
can also be driven irreversibly towards ring formation.
Depending on the reaction conditions
features
13c
and structural
the intermediate a-silyloxy radical 3 can be
1
3b,d,f,j
reactions, radical additions to carbonyl generate alkoxy
radicals that are prone to undergo b-scission to regenerate
converted to different products. One possibility (Scheme 2)
involves the design of a radicalphile tethered to the silicon
atom in such a way that the a-silyloxy radical can undergo
2
the carbonyl functionality. Yet this seemingly deleterious
3
property can be manipulated to yield ring-expansion and
,4
4
–7
13f
acylation
also be trapped intermolecularly or intramolecularly by
products. The cyclized alkoxy radicals can
further cyclization.
The alkoxy silane moiety in the
resulting silacycles can be considered as a hydroxy group
8
hydrogen, phosphorous, boron and tin.
9
10
11,12
17
equivalent. Through oxidative hydrolysis, the silacycles
can be opened to give diols. Now we wish to report the full
investigation of this approach.
Several years ago, we initiated a study of intramolecular
1
radical cyclizations of acylsilanes (Scheme 1). In this type
3
of cyclizations, radical 1 adds intramolecularly to the
1
4
carbonyl of the acylsilane functionality to give a b-silyl
substituted alkoxy radical 2. A facile radical-Brook
Scheme 2.
2. Results and discussion
As shown in Scheme 3, we choose to synthesize acylsilanes
and 9. These acylsilanes contain allyl and homoallyl group
attached on silicon. The strategy developed by Brook and
8
1
8
Scheme 1.
1
9
Corey was used in the synthesis. We first prepared 2-silyl-
,3-dithianes 5a (83%), 5b (64%) and 5c (68%) from the
1
Keywords: Acylsilanes; Tandem radical cyclizations; Alkoxysilane; Brook
rearrangement.
silylation of 1,3-dithiane (4) with the corresponding
chlorosilanes. However when we used the same method
for the preparation of dithiane 5d, small amount of double
*
Corresponding author. Tel.: C886 22 369 0152x117; fax: C886 22 363
359; e-mail: ymtsai@ntu.edu.tw
6
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.12.053

2038
K.-H. Tang et al. / Tetrahedron 61 (2005) 2037–2045
bond positional isomerization product was always present
and difficult to remove. This was probably caused by the
presence of small amount of hydrochloric acid in chloro-
dimethyl(3-methyl-3-butenyl)silane. We therefore switched
to use an in situ generation method for the preparation of the
chlorosilane under a slightly basic condition. The
Grignard reagent prepared from 4-bromo-2-methylbutene
in THF was treated with chlorodimethyl(dimethylamino)-
silane followed by the addition of acetyl chloride. To the
chlorodimethyl(3-methyl-3-butenyl)silane solution thus
prepared was added the anion generated from 1,3-dithiane
to afford pure 2-silyldithiane 5d in 38% without the
formation of its double bond positional isomer.
respectively. The yields for the preparation of acylsilanes 8
are lower. This probably reflects the lower stability of the
corresponding bromides 6 because in these compounds
intramolecular attack of sulfur at the bromo-substituted
carbon goes through a favored six-membered ring transition
state. In contrast, the homologous bromides 7 contain one
more methylene unit and the intramolecular nucleophilic
attack by sulfur is more difficult.
2
0
The radical cyclization of acylsilane 8a (Scheme 4) was
performed by slow addition (1 h) of a benzene solution of
tributyltin hydride (1.2 equiv) and AIBN (0.05 equiv) to a
solution of 8a in refluxing benzene. The concentration with
respect to 8a was 0.05 M. Although there may be four
possible products 10–13, acylsilane 10, derived from
hydrogen abstraction of the initial radical 14, was not
observed. This is expected, because radical 1,5-cyclizations
of acylsilanes are very fast processes, and straight reduction
1
3h,i
products are generally not observed.
Cyclopentyl ether
1
1
1 derived from hydrogen abstraction of a-silyloxy radical
5 was observed in 8% by GC analysis. For the purpose of
GC comparison, an authentic sample of ether 11 was
prepared from the silylation of cyclopentyl alcohol with
allyldimethylsilyl chloride. Radical intermediate 15 can
undergo endo- and exo-cyclization to give spiro silyl ethers
1
2 and 13, respectively. However, due to the volatility of
these silyl ethers, we were only able to isolate the major
product 12 in 46% yield. We believe some portion of 12 was
lost during concentration. As mentioned earlier, the C–Si
bond of the alkoxysilyl group can be oxidatively cleaved to
result in the replacement of the silyl group with a hydroxy
1
7
group. Therefore, we decided to treat the crude cyclization
product mixture directly with hydrogen peroxide and
potassium hydrogen carbonate in a mixture of methanol
Scheme 3. Reagents and conditions: (a) BuLi, THF, 0 8C; (b) (CH
CHCH )Me SiCl for 5a (83%), (CH ]CHCH CH )Me SiCl for 5b (64%),
and (CH ]CMeCH )Me SiCl for 5c (68%); (c) (i) Mg, THF, (ii)
Me NSiMe Cl, (iii) AcCl, (iv) 4, BuLi (5d, 39%); (d) Br(CH Br,
K20 8C, 1 h, for 6c (52%), 6d (51%), 7c (66%), and 7d (85%); (e)
CAN (4 equiv), H O/MeOH/CH Cl , K20 8C, for 8a (33% from 5a); CAN
O/CH CN, NaHCO , 0 8C, 10 min, for 8c (37%), 8d (80%), 9c
38%), and 9d (64%); (f) (CF COO) IPh (1.7 equiv), NaHCO , CH CN/
O, K20 8C, for 8b (36% from 5b), 9a (52% from 5a), and 9b (43% from
b).
2
]
2
2
2
2
2
2
2
2
2
2
2
2 m
)
2
2
2
(3 equiv), H
2
3
3
(
3
2
3
3
H
2
5
The 2-silyl-1,3-dithianes were then alkylated with 1,4-
dibromobutane or 1,5-dibromopentane to afford bromides 6
and 7. Due to the presence of nucleophilic sulfur atoms in
the molecule, the bromides are not stable. Although these
bromides can be isolated and purified, it is best to hydrolyze
the dithiane moiety once the crude bromides are obtained. In
the case of the hydrolysis of 6a, 6c, 6d, 7c, and 7d, ceric
2
1
ammonium nitrate (CAN) in wet methanol or acetonitrile
was used as the reagent to give acylsilane 8a, 8c, 8d, 9c, and
2
d. Iodobenzene bistrifluoroacetate was used in the
2
9
hydrolysis of 6b, 7a, and 7b to give 8b, 9a, and 9b,
Scheme 4.

K.-H. Tang et al. / Tetrahedron 61 (2005) 2037–2045
2039
2
3
and THF. In this way, we isolated 38% of diol 16 and 20%
of diol 17. Since diols 16 and 17 must be derived from silyl
ethers 12 and 13, respectively, this result showed that the
endo-cyclization mode is the preferred process for the
cyclization of a-silyloxy radical 15. The ratio of the yields
of the two diols, 16/17Z1.9/1, then reflects the endo/exo
cyclization rate ratio of radical 15.
23 in 55 and 25% yields, respectively. Gas chromatographic
analysis of the crude cyclization mixture showed the straight
reduction product 18 was present in about 7%, and the
monocyclic product 19 was present in about 5%. For the
purpose of comparison, authentic sample of 18 was isolated
in 51% yield by performing the cyclization reaction at a
more concentrated condition of 0.5 M. The silyl ether 19
was prepared from the reaction of cyclohexanol with
allyldimethylsilyl chloride.
In the cyclization of 5-hexenyl radical it is well-known that
5
1
-exo cyclization is preferred over 6-endo cyclization. In
contrast, it was found that the replacement of C-3 of 5-
hexenyl radical with a silicon atom directed the cyclization
For the cyclization of acylsilane 9a, the ratio of endo/exo
cyclizations of the intermediate a-silyloxy substituted
radical extrapolated from the ratio of diols 22/23 is 2.2/1.
This endo/exo cyclization ratio is about the same as in the
case of the cyclization of acylsilane 8a. Therefore, the
regioselectivity of the second ring formation is not strongly
influenced by the pre-existing five- or six-membered ring. In
the cyclization of 9a, more straight reduction product was
obtained. This reflects the slower 1,6-cyclization rate for
2
4
to 6-endo cyclization almost exclusively. This preference
is actually derived from the diminished 5-endo cyclization
2
4a
rate of the b-dimethylsilyl substituted radical.
It was
2
4a
proposed by Wilt et al. that this phenomenon was due to
the longer Si–C bond and the preferred ground state
conformation making the radical more difficult to approach
the internal carbon of the olefin. Our cyclization belongs to a
1
3i
2
-oxa-3-sila-5-hexenyl radical system that is rarely found in
acylsilanes as observed previously.
the literature. The cyclization results of acylsilane 8a
indicate that the presence of the silicon atom in this system
also affects the mode of ring closure in favor of 6-endo
cyclization albeit in a lower endo/exo ratio comparing with
the 3-sila-5-hexenyl radical system. Although there is no
adequate information in the literature to estimate the effect
of the conformation of the silyloxy substituted radical, it can
be speculated that the shorter C–O and Si–O bonds have
important contribution influencing the endo/exo cyclization
ratio of 2-oxa-3-sila-5-hexenyl radical.
With a homoallyl group attached to the silicon atom, the
two-step radical cyclization–oxidation sequences performed
on acylsilanes 8b and 9b (Scheme 6) gave diols 24 (67%)
and 26 (78%), respectively, as the major products. Small
amount of diol 25 (3%) was isolated for the reaction of
acylsilane 8b. For the homologous acylsilane 9b, diol 27
was not detected. These results indicate that the 2-oxa-3-
sila-6-heptenyl radical intermediates 28 undergo 1,7-endo
cyclization in preference. In the case of acylsilane 9b, GC
analysis of the crude radical cyclization product indicated
the presence of 10% of straight reduction product and 12%
of monocyclic silyl ether. Since the amount of monocyclic
product is not much different from those obtained in the case
of 8a and 9a, the 1,7-endo cyclization appears to be quite
efficient. Previously, a similar 2,4-dioxa-3-sila-6-heptenyl
radical system has also been reported by Myers, Gin and
Similarly, the reaction of acylsilane 9a (Scheme 5) with
tributyltin hydride at a concentration of 0.05 M gave a
mixture of straight reduction product 18, monocyclic
product 19, and two tandem cyclization products 20 and
21. Direct treatment of the crude cyclization mixture under
the oxidation conditions stated above afforded diols 22 and
2
5
Rogers to give 1,7-endo cyclization predominantly.
We also studied the cyclization of acylsilane 8c (Scheme 6)
having 2-methylallyl substituent on silicon. The methyl
group attached on the internal carbon of the olefin directed
the radical cyclization of 8c to afford the spiro silyl ether 30
in 74% yield as the only product. We did not detect the
presence of monocyclic ether 31 or acylsilane 32.
Apparently the methyl group on the allyl moiety retarded
the attack of the radical appreciably such that the 5-exo
2
6
cyclization mode was completely suppressed. In addition,
the 6-endo cyclization led to the formation of a more
stabilized tertiary radical. This factor may contribute an
acceleration effect that makes this tandem cyclization so
efficient.
In comparison, the homologous acylsilane 9c under our
standard radical cyclization condition gave 23% of the
tandem cyclization product 33. Again, 6-endo cyclization of
the second cyclization step was the predominate process.
1
Analysis of the crude cyclization mixture via H NMR
revealed the presence of monocyclic product 34 and straight
reduction product 35. The ratio of 33/34/35 determined by
NMR integration was 87/8/5. The low yield of the spiro
product 33 was due to the volatility and the extensive
chromatographic processes for its purification. When the
Scheme 5.

2040
K.-H. Tang et al. / Tetrahedron 61 (2005) 2037–2045
With a 3-methyl-3-butenyl group attached on silicon, the
cyclizations of acylsilanes 8d and 9d gave exclusively
-endo cyclization product for the second cyclization step.
7
In the case of acylsilane 8d, spiro silyl ether 37 was isolated
in 69% yield in addition to 7% of monocyclic product 38.
Analysis of the crude product by H NMR showed that
1
straight reduction product 39 was not formed. The ratio of
spiro silyl ether 37 and monocyclic silyl ether 38 in the
crude product was 9/1 (37/38). The reaction of acylsilane 9d
with tributyltin hydride gave a 74/10/9 crude mixture of
spiro silyl ether 40, monocyclic silyl ether 41 and straight
reduction product 42, respectively. The spiro silyl ether 40
was isolated in 40% through silica gel column chroma-
tography in addition to 6% of monocyclic product 41 and
7
% of straight reduction product 42. The presence of 42
reflected the slower rate of the initial 1,6-cyclization as
described above. The lower ratio of spiro product 40 and
monocyclic product 41 (74/10 by NMR) also showed that
the pre-existing six-membered ring might influence the
second 7-endo cyclization.
In summary, we have demonstrated that by introducing
radicalphilic pendant on silicon, the radical cyclizations of
acylsilanes can proceed in a tandem fashion. Because the
alkoxysilyl group can be replaced with a hydroxy group
through oxidation, the final cyclization products can be
converted to give diols. In the case with a radical
intermediate carrying 2-oxa-3-sila-6-heptenyl skeleton,
products derived from 1,7-endo cyclization were obtained
in good yields.
3. Experimental
3
.1. General
1
Melting points are uncorrected. H NMR spectra were
1
recorded at 200, 300 or 400 MHz; C NMR spectra were
3
recorded at 50, 75 or 100 MHz. Tetramethysilane (dZ
0
standards and CDCl was used as the solvent. Benzene and
ppm) or CHCl3 (dZ7.24 ppm) were used as internal
Scheme 6.
3
THF were distilled from sodium benzophenone ketyl under
N . Diisopropylamine and acetonitrile were dried with
CaH2 and distilled. The benzene used for cyclization
reactions was deoxygenated by passing a gentle stream of
argon through for 0.5 h before use. All reactions were
2
crude product of the cyclization of 9c was directly oxidized
2
3
under the Tamao oxidation condition, we were able to
obtain the diol 36 in 62% yield. The formation of small
amount of monocyclic silyl ether 34 in this system seems to
indicate that the cyclization rate of the intermediate
cyclohexyl radical is slightly slower than the corresponding
cyclopentyl radical as in the case of acylsilane 8c. We
suspect that the allylic methyl group may exhibit repulsive
interaction with the C(3)-methylene unit of the cyclohexyl
group in the transition state (Fig. 1) of the second
cyclization and thus slows down the rate.
performed under a blanket of N or Ar. Lobar LiChroprep Si
2
60 (40–63 mm) pre-packed columns purchased from
Merck were used for medium pressure liquid chroma-
tography (MPLC). Gas chromatography was performed on
a Shimadzu GC-8A apparatus with TCD using a 3.3 mm!
2 m column of 10% SE-30 on Chromosorb W (AW-
DMCS), 80–100 mesh, and hydrogen as carrier gas.
3.1.1. 2-(Allyldimethylsilyl)-1,3-dithiane (5a). To a solu-
tion of 0.800 g (6.67 mmol) of 1,3-dithiane in 4.7 mL of dry
THF cooled at 0 8C was added dropwise over 20 min a
1
8
.64 N solution of butyllithium in hexane (5.29 mL,
.67 mmol). The resulting solution was stirred at the same
temperature for 40 min and then added over 30 min to a
solution of 1.08 mL (7.38 mmol) of allylchlorodimethyl-
silane in 4.0 mL of dry THF cooled at 0 8C. The reaction
mixture was stirred at the same temperature for 1 h and then
Figure 1. The proposed 1,6-endo cyclization transition state of the (2-
methylallyl)silyloxy substituted cyclohexyl radical.

K.-H. Tang et al. / Tetrahedron 61 (2005) 2037–2045
2041
partitioned between 100 mL of ether and 50 mL of water.
The organic layer was washed with brine (50 mL), dried
(MgSO ), and concentrated in vacuo. The residue was
4
chromatographed with MPLC using Lobar size B column
prepared above at 0 8C over a period of 20 min, and the
reaction mixture was stirred for 1.5 h at room temperature.
The resulting mixture was poured into 20 mL of sat.
ammonium chloride solution and extracted with 100 mL of
ether. The organic layer was washed with water (100 mL!
(
(
eluted with hexane/ethyl acetate, 99/1) to give 1.20 g
83%) of 5a as a pale yellow liquid: IR (neat) 1625 cm
K1
;
2), brine (100 mL), dried (MgSO ) and concentrated in
4
1
H NMR (CDCl , 300 MHz) d 0.11 (s, 6H), 1.65 (d, JZ
vacuo to give 2.31 g of a yellow residue. The residue was
chromatographed with MPLC using Lobar size B column
(eluted with hexane/ethyl acetate, 98/2) to give 0.659 g
3
8
2
1
8
3
2
Hz, 2H), 1.88–2.15 (m, 2H), 2.68 (dt, JZ14, 4 Hz, 2H),
.84 (td, JZ14, 4 Hz, 2H), 3.71 (s, 1H), 4.85 (br d, JZ
0 Hz, 1H), 4.90 (br d, JZ18 Hz, 1H), 5.76 (ddt, JZ18, 10,
K1
1
(39%) of 5d as a colorless liquid: IR (neat) 1652 cm ; H
NMR (CDCl , 400 MHz) d 0.14 (s, 6H, SiCH ), 0.80–0.85
1
3
Hz, 1H); C NMR (CDCl , 75 MHz) d K5.4, 21.0, 26.1,
1.0, 33.0, 114.0, 133.7; HRMS calcd for C H S Si m/z
3
3
3
(m, 2H, SiCH ), 1.72 (s, 3H, ]CCH ), 1.95–2.14 (m, 4H,
2 3
9
18
2
18.0619, found 218.0621.
SCH CH CH S, and ]CCH ), 2.71 (dt, JZ14, 4 Hz, 2H,
2 2 2 2
SCH2(eq)), 2.86 (td, JZ14, 2.8 Hz, 2H, SCH2(ax)), 3.73 (s,
1H, SCHS), 4.66 (br s, 1H, ]CH ), 4.70 (br s, 1H, ]CH );
, 100 MHz) d K4.8 (CH ), 11.6 (CH ),
), 26.3 (CH ), 31.2 (CH ), 31.5 (CH ), 33.6 (CH),
108.6 (CH ), 147.7 (C); HRMS (FAB) calcd for C11 Si
m/z 246.0932, found 246.0928.
3.1.2. 2-((3-Buten-1-yl)dimethylsilyl)-1,3-dithiane (5b).
According to the procedure for the preparation of 5a, 1,3-
dithiane (0.48 g, 4.0 mmol) reacted with 0.65 mL
2
2
1
3
C NMR (CDCl
22.3 (CH
3
3
2
3
2
2
2
2
7
4.0 mmol) of (3-buten-1-yl)chlorodimethylsilane to
(
afford 595 mg (64%) of 5b as a pale yellow liquid: IR
2
H S
22 2
K1
1
(
neat) 1633 cm ; H NMR (CDCl , 300 MHz) d 0.12 (s,
3
6
4
H), 0.70–0.82 (m, 2H), 1.88–2.15 (m, 4H), 2.68 (dt, JZ14,
Hz, 2H), 2.85 (td, JZ14, 4 Hz, 2H), 3.70 (s, 1H), 4.87 (br
3.1.5. 5-Bromo-1-(allyldimethylsilyl)-1-pentanone (8a).
To a solution of 300 mg (1.38 mmol) of 5a in 4.0 mL of dry
THF cooled at 0 8C was added dropwise over 10 min a
1.46 N solution of butyllithium in hexane (1.23 mL,
1.79 mmol). The resulting solution was stirred at the same
temperature for another 40 min and then added dropwise
over 40 min to a solution of 0.33 mL (2.8 mmol) of 1,4-
dibromobutane in 4.0 mL of dry THF cooled at K20 8C.
The reaction mixture was stirred at K20 8C for 1 h and then
partitioned between ether (60 mL) and water (30 mL). The
organic layer was washed with brine (30 mL), dried
d, JZ11 Hz, 1H), 4.98 (br d, JZ17 Hz, 1H), 5.84 (ddt, JZ
1
12.5, 26.2, 27.6, 31.1, 33.5, 113.0, 141.0; HRMS calcd for
C H S Si m/z 232.0775, found 232.0785.
1
3
7, 11, 6 Hz, 1H); C NMR (CDCl , 75 MHz) d K4.8,
3
1
0 20 2
3
.1.3.
2-[Dimethyl(2-methyl-2-propenyl)silyl]-1,3-
dithiane (5c). According to the procedure for the prepa-
ration of 5a, 1,3-dithiane (0.217 g, 1.81 mmol) reacted with
0
1
.35 mL (2.0 mmol) of chlorodimethyl(2-methyl-2-propen-
-yl)silane to afford 275 mg (65%) of 5c as a colorless
2
8
(MgSO ), and concentrated in vacuo. The residue was
4
K1 1
liquid: IR (neat) 1639 cm ; H NMR (CDCl , 400 MHz) d
3
dissolved in a mixture of 2 mL of methanol and 2 mL of
dichloromethane. To the resulting solution cooled at
K20 8C was added over 7 min a solution of 3.10 g
(5.66 mmol) of CAN in 6 mL of methanol and 0.31 mL of
water. The resulting mixture was stirred at the same
temperature for 5 min and then diluted with ether. The
resulting mixture was filtered, and the filtrate was
partitioned between 80 mL of ether and 35 mL of water.
The organic phase was washed with brine (35 mL), dried
0.14 (s, 6H, SiCH ), 1.70 (s, 2H, SiCH ), 1.72 (s, 3H,
3 2
]
CCH ), 1.93–2.16 (m, 2H, SCH CH CH S), 2.71 (dt, JZ
3 2 2 2
4, 4 Hz, 2H, SCH2(eq)), 2.87 (td, JZ14, 2.4 Hz, 2H,
1
SCH2(ax)), 3.73 (s, 1H, SCHS), 4.55 (br s, 1H, ]CH ), 4.63
2
1
br s, 1H, ]CH2); C NMR (CDCl , 100 MHz) d K4.5
CH ), 24.8 (CH ), 25.4 (CH ), 26.3 (CH ), 31.2 (CH ), 33.6
2
3
(
(
(
3
3
2
3
2
CH), 109.4 (CH ), 142.3 (C); HRMS (FAB) calcd for
2
C
C H S Si (MCH) m/z 233.0854, found 233.0836.
10 21 2
(MgSO ), and concentrated in vacuo to give 658 mg of a
4
3
(
.1.4. 2-[Dimethyl(3-methyl-3-butenyl)silyl]-1,3-dithiane
5d). A mixture of 0.358 g (14.9 mmol) of magnesium
residual oil. The oil was chromatographed with MPLC
over a Lobar size B column (eluted with hexane/ethyl
acetate, 98/2) to give 120 mg (33%) of 8a as a pale yellow
turnings and a few crystals of iodine in 1 mL of dry THF
was stirred under argon until the iodine color disappeared. A
solution of 1.38 mL (11.1 mmol) of 4-bromo-2-methyl-1-
butene in 10 mL of dry THF was added to the mixture over a
period of 25 min and stirred for another 15 min. The
Grignard reagent prepared above was added dropwise over a
period of 15 min to a cooled (0 8C) solution of 1.2 mL
K1 1
liquid: IR (neat) 1637 cm ; H NMR (CDCl , 300 MHz) d
3
0.19 (s, 6H), 1.53–1.72 (m, 4H), 1.72–1.87 (m, 2H), 2.60 (t,
JZ7 Hz, 2H), 3.36 (t, JZ6.5 Hz, 2H), 4.81–4.93 (m, 2H),
1
3
5.72 (ddt, JZ18, 10, 8 Hz, 1H); C NMR (CDCl
75 MHz) d K5.2, 20.5, 21.1, 32.2, 33.4, 48.0, 114.5,
,
3
8
H19 BrOSi m/z
1
133.0, 246.2; HRMS calcd for C10
264.0368, found 264.0357.
(
8
6.93 mmol) of chlorodimethyl(dimethylamino)silane in
mL of dry THF. The reaction mixture was stirred for
another 10 min at 0 8C followed by the addition of a solution
of 0.50 mL (6.9 mmol) of acetyl chloride in 7 mL of dry
THF over a period of 20 min at the same temperature. The
resulting mixture was stirred for another 2.5 h at 0 8C to
furnish a solution of dimethyl(3-methyl-3-buten-1-yl)silyl
chloride. To another solution of 1.42 g (11.9 mmol) of 1,3-
dithiane in 13 mL of dry THF cooled in an ice-water bath
was added dropwise over 20 min a 1.5 N solution of
butyllithium in hexane (9.40 mL, 14.1 mmol). This anion
solution was then added to the silyl chloride solution
3.2. General procedure for the preparation of acylsilanes
8b, 9a and 9b using iodobenzenebistrifluoroacetate for
hydrolysis: 5-bromo-1-((3-buten-1-yl)dimethylsilyl)-1-
pentanone (8b)
According to the procedure for the synthesis of 8a, 0.70 g of
5b (3.0 mmol) was alkylated with 0.72 mL (6.0 mmol) of
1,4-dibromobutane. The crude alkylation product was
mixed with 1.76 g of sodium bicarbonate, 10 mL of
acetonitrile, and 3 mL of water. To the resulting mixture

2042
K.-H. Tang et al. / Tetrahedron 61 (2005) 2037–2045
cooled at K20 8C was added slowly a solution of 2.2 g
5.1 mmol) of iodobenzenebistrifluoroacetate in 10 mL of
acetonitrile. The reaction mixture was stirred at the same
temperature for 5 min and then partitioned between 100 mL
of ether and 50 mL of water. The organic layer was washed
organic layer was dried (MgSO ) and concentrated in vacuo
4
(
to give 0.428 g of a residual oil. The oil was chromato-
graphed with MPLC over a Lobar size B column (eluted
with hexane/ethyl acetate, 98/2) to give 109 mg (37%) of 8c
K1 1
as a pale yellow oil: IR (neat) 1645 cm ; H NMR (CDCl3,
400 MHz) d 0.18 (s, 6H, SiCH ), 1.60–1.72 (m overlapped
with brine (50 mL), dried (MgSO ), and concentrated in
4
3
vacuo to give 1.7 g of a residual oil. The oil was
chromatographed with MPLC over a Lobar size B column
with two s at 1.67 and 1.70, 7H, ]CCH , SiCH and
2
3
others), 1.76–1.85 (m, 2H), 2.62 (t, JZ7 Hz, 2H, COCH2),
3.37 (t, JZ6.8 Hz, 2H, CH Br), 4.50 (br s, 1H, ]CH ), 4.62
(
(
eluted with hexane/ethyl acetate, 97/3) to give 298 mg
36%) of 8b as a pale yellow oil: IR (neat) 1642 cm ; H
2
2
K1
1
13
(br s, 1H, ]CH2); C NMR (CDCl , 100 MHz) d K0.92
3
NMR (CDCl , 200 MHz) d 0.16 (s, 6H), 0.70–0.85 (m, 2H),
3
(CH ), 20.8 (CH ), 24.3 (CH ), 32.3 (CH ), 33.5 (CH ), 46.7
2
3
2
3
2
1
2
.51–1.87 (m, 4H), 1.93–2.13 (m, 2H), 2.59 (t, JZ7 Hz,
H), 3.34 (t, JZ7 Hz, 2H), 4.70–5.03 (m, 2H), 5.79 (ddt,
(CH ), 110.3 (CH ), 142.2 (C), 244.5 (C); MS (rel intensity)
2 2
C
m/z 277 (M , 2), 263 (6), 211 (11), 157 (24), 139 (38),
1
3
JZ17, 11, 6 Hz, 1H); C NMR (CDCl , 50 MHz) d K4.8,
1
HRMS calcd for C H BrOSi m/z 278.0524, found
1 21
113 (90), 85 (40), 75 (100), 59 (92); HRMS calcd for
C H
3
8
1
C
BrOSi (MCH) m/z 279.0597, found 279.0602.
2.5, 20.6, 27.5, 32.2, 33.3, 47.6, 113.5, 140.4, 246.9;
1
1
22
8
1
1
2
78.0524.
3.2.5. 2-(4-Bromobutyl)-2-[dimethyl(3-methyl-3-butenyl)-
silyl]-1,3-dithiane (6d). According to the procedure for the
synthesis of 8a, 1.56 g (6.34 mmol) of 5d was alkylated
with 5.00 mL (37.3 mmol) of 1,4-dibromobutane to give
1.23 g (51%) of 6d as a pale yellow liquid: IR (neat)
3.2.1. 6-Bromo-1-(allyldimethylsilyl)-1-hexanone (9a). A
pale yellow oil: IR (neat) 1635 cm ; H NMR (CDCl ,
K1
1
3
2
00 MHz) d 0.18 (s, 6H), 1.25–1.73 (m overlapped with d,
JZ8 Hz, 6H), 1.82 (quintet, JZ7 Hz, 2H), 2.58 (t, JZ7 Hz,
H), 3.37 (t, JZ7 Hz, 2H), 4.80–4.93 (m, 2H), 5.70 (ddt,
K1
1
1651 cm ; H NMR (CDCl , 400 MHz) d 0.19 (s, 6H,
3
2
SiCH ), 0.84–0.92 (m, 2H, SiCH ), 1.60–1.73 (m, 2H), 1.73
3
2
1
3
JZ18, 10, 8 Hz, 1H); C NMR (CDCl , 50 MHz) d K5.2,
(s, 3H, ]CCH ), 1.85–1.96 (m, 3H), 2.02–2.08 (m, 3H),
3
3
2
1.0, 21.2, 27.8, 32.6, 33.5, 48.8, 114.4, 133.1, 246.6;
2.17–2.24 (m, 2H, ]CCH ), 2.43 (dt, JZ14, 3.6 Hz, 2H,
2
8
1
HRMS calcd for C H BrOSi m/z 278.0525, found
1 21
SCH2(eq)), 3.00 (td, JZ14, 2.8 Hz, 2H, SCH2(ax)), 3.44 (t,
JZ6.4 Hz, 2H, CH Br), 4.66 (br s, 1H, ]CH ), 4.70 (br s,
1
2
78.0512.
2
2
1
H, ]CH2); C NMR (CDCl , 100 MHz) d K4.2 (CH ),
3
1
11.8 (CH
3
3
3.2.2. 6-Bromo-1-((3-buten-1-yl)dimethylsilyl)-1-hexa-
none (9b). A pale yellow oil: IR (neat) 1642 cm ; H
NMR (CDCl , 200 MHz) d 0.16 (s, 6H), 0.70–0.82 (m, 2H),
3
2
), 22.4 (CH
32.1 (CH ), 33.2 (CH
(C), 108.6 (CH
3
), 23.6 (CH
2
), 25.2 (CH
), 36.6 (CH
), 148.0 (C); HRMS (FAB) calcd for
2
), 26.4 (CH
2
),
K1
1
), 33.6 (CH
), 38.8
2
2
2
2
2
7
9
C
1
.27–1.59 (m, 4H), 1.81 (quintet, JZ7 Hz, 2H), 1.97–2.12
C H30 BrS Si (MCH) m/z 381.0742, found 381.0741.
15 2
(
5
m, 2H), 2.57 (t, JZ7 Hz, 2H), 3.36 (t, JZ7 Hz, 2H), 4.80–
.03 (m, 2H), 5.79 (ddt, JZ16, 10, 6 Hz, 1H); C NMR
1
3
3.2.6. 5-Bromo-1-[dimethyl(3-methyl-3-butenyl)silyl]-
pentan-1-one (8d). According to the procedure for the
synthesis of 8c, 0.12 g (0.31 mmol) of 6d was hydrolyzed
with 0.52 g (0.95 mmol) of ceric ammonium nitrate to give
(
CDCl , 50 MHz) d K4.7, 12.6, 21.0, 27.5, 27.8, 32.6, 33.5,
3
8
1
4
m/z 292.0681, found 292.0691.
8.5, 113.5, 140.5, 247.4; HRMS calcd for C H
1
BrOSi
2
23
7
1645 cm ; H NMR (CDCl , 400 MHz) d 0.18 (s, 6H,
2.3 mg (80%) of 8d as a pale yellow liquid: IR (neat)
K1
1
3
.2.3. 2-(4-Bromobutyl)-2-[dimethyl(2-methyl-2-pro-
3
penyl)silyl]-1,3-dithiane (6c). According to the procedure
for the synthesis of 8a, 3.0 g (13 mmol) of 5c was alkylated
with 3.85 mL (32.3 mmol) of 1,4-dibromobutane to give
SiCH ), 0.81–0.87 (m, 2H, SiCH ), 1.60–1.71 (m over-
3
lapped with a s at 1.70, 5H, CCH and others), 1.76–1.84
3
2
(m, 2H), 1.95–2.01 (m, 2H, ]CCH ), 2.61 (t, JZ7 Hz, 2H,
2
2
.5 g (52%) of 6c as a pale yellow liquid: IR (neat)
COCH ), 3.37 (t, JZ6.8 Hz, 2H, CH Br), 4.67 (br s, 2H,
2
2
K1
639 cm ; H NMR (CDCl , 400 MHz) d 0.20 (s, 6H,
1
13
]CH2); C NMR (CDCl , 100 MHz) d K4.6 (CH ), 11.7
1
SiCH ), 1.60–1.69 (m, 2H), 1.71 (s, 3H, ]CCH ), 1.79 (s,
3
3 3
(CH ), 20.8 (CH ), 22.2 (CH ), 31.5 (CH ), 32.3 (CH ), 33.5
2 2 3 2 2
3
3
2
2
H, SiCH ), 1.81–1.94 (m, 3H), 1.99–2.08 (m, 1H), 2.16–
2
.25 (m, 2H), 2.44 (dt, JZ14, 3.6 Hz, 2H, SCH2(eq)), 3.00
(CH ), 47.7 (CH ), 109.0 (CH ), 147.2 (C), 246.6 (C);
2 2 2
7
9
C
HRMS (FAB) calcd for C H
12
BrOSi (MCH) m/z
24
(
CH Br), 4.53 (br s, 1H, ]CH ), 4.63 (br s, 1H, ]CH );
td, JZ14, 2.8 Hz, 2H, SCH2(ax)), 3.44 (t, JZ6.8 Hz, 2H,
291.0780, found 291.0785.
1
3
C
NMR (CDCl , 100 MHz) d K4.0 (CH ), 23.6 (CH ), 24.6
2
2
2
3
3
2
3.2.7. 2-(5-Bromopentyl)-2-[dimethyl(2-methyl-2-pro-
penyl)silyl]-1,3-dithiane (7c). According to the procedure
for the synthesis of 8a, 3.1 g (13.3 mmol) of 5c was
alkylated with 5.00 mL (37.3 mmol) of 1,5-dibromopentane
to give 3.36 g (66%) of 7c as a pale yellow liquid: IR (neat)
(
(
CH ), 25.1 (CH ), 25.5 (CH ), 26.4 (CH ), 33.1 (CH ), 33.6
2 2 3 2 2
CH ), 38.7 (C), 109.6 (CH ), 142.6 (C); HRMS (FAB)
2
2
7
9
calcd for C H
1
BrS Si m/z 366.0507, found 366.0500.
2
4
27
K1
1
3
.2.4. 5-Bromo-1-[dimethyl(2-methyl-2-propenyl)silyl]-
1651 cm ; H NMR (CDCl , 400 MHz) d 0.18 (s, 6H,
3
pentan-1-one (8c). To a vigorously stirred cold (0 8C)
mixture of 0.392 g (1.07 mmol) of 6c and 0.553 g
SiCH ), 1.42–1.55 (m, 4H), 1.70 (s, 3H, ]CCH ), 1.76 (s,
3
2H, SiCH ), 1.86–1.95 (m, 3H), 1.98–2.06 (m, 1H), 2.15–
2
3
(
6.59 mmol) of sodium bicarbonate in 10 mL of acetonitrile
2.21 (m, 2H), 2.43 (dt, JZ14, 3.2 Hz, 2H, SCH2(eq)), 2.99
(td, JZ14, 2.8 Hz, 2H, SCH2(ax)), 3.41 (t, JZ7.2 Hz, 2H,
and 1 mL of water was added 1.47 g (2.69 mmol) of ceric
ammonium nitrate in one portion. The resulting mixture was
stirred for another 3 min at the same temperature and then
quickly filtered over Celite. The filtrate was partitioned
between 100 mL of ethyl acetate and 100 mL of water. The
1
3
CH Br), 4.51 (br s, 1H, ]CH ), 4.62 (br s, 1H, ]CH );
C
NMR (CDCl , 100 MHz) d K4.0 (CH ), 23.6 (CH ), 24.6
2
2
2
3
3
2
(CH ), 25.1 (CH ), 25.5 (CH ), 27.1 (CH ), 28.8 (CH ), 32.7
2
2
3
2
2
(CH ), 33.9 (CH ), 37.5 (CH ), 38.8 (C), 109.5 (CH ), 142.6
2
2
2
2

K.-H. Tang et al. / Tetrahedron 61 (2005) 2037–2045
2043
7
9
(
found 380.0663.
C); HRMS (FAB) calcd for C H
1
BrS Si m/z 380.0663,
2
cooled to room temperature. Gas chromatographic analysis
(oven tempertatureZ130 8C; flow rateZ28 mL/min) of the
5
29
reaction mixture showed the presence of 11 (t Z6.4 min),
R
3
.2.8. 6-Bromo-1-[dimethyl(2-methyl-2-propenyl)silyl]-
13 (t Z7.3 min), and 12 (t Z8.1 min) in a ratio of 1:3:8.3,
R R
hexan-1-one (9c). According to the procedure for the
synthesis of 8c, 3.31 g (8.68 mmol) of 7c was hydrolyzed
with 12.2 g (22.3 mmol) of ceric ammonium nitrate to give
respectively. The reaction mixture was concentrated in
vacuo. The residue was mixed with 626 mg (6.26 mmol) of
potassium bicarbonate, 0.68 mL (23 mmol) of hydrogen
peroxide, 8 mL of methanol, and 8 mL of THF. The
resulting mixture was stirred at 66 8C for 19 h and then
partitioned between 50 mL of dichloromethane and 30 mL
of water. The aqueous phase was extracted with dichlor-
omethane (50 mL), and the combined organic layers were
0
.97 g (38%) of 9c as a pale yellow liquid: IR (neat)
K1
644 cm ; H NMR (CDCl , 400 MHz) d 0.19 (s, 6H,
1
1
SiCH ), 1.33–1.42 (m, 2H), 1.47–1.57 (m, 3H), 1.66 (s, 3H,
3
3
]
CCH ), 1.69 (s, 2H, SiCH ), 1.83 (quintet, JZ7.2 Hz,
3 2
2
H), 2.60 (t, JZ7 Hz, 2H, COCH ), 3.37 (t, JZ6.8 Hz, 2H,
2
13
CH Br), 4.48 (br s, 1H, ]CH ), 4.61 (br s, 1H, ]CH );
C
dried (MgSO ), and concentrated in vacuo. The residue was
4
2
2
2
NMR (CDCl , 100 MHz) d K4.3 (CH ), 21.2 (CH ), 25.1
3
chromatographed over silica gel (eluted with hexane/ethyl
acetate, 7/3, 6/4, 4/6 in sequence) to give 16 mg (20%) of
3
2
(
(
CH ), 25.2 (CH ), 27.9 (CH ), 32.7 (CH ), 33.7 (CH ), 48.8
2
3
2
2
2
K1
CH ), 109.6 (CH ), 141.7 (C), 246.4 (C); HRMS (FAB)
2
the less polar 17 as a colorless oil: IR (neat) 3431 (br) cm
H NMR (CDCl
;
2
7
9
C
1
calcd for C H BrOSi (MCH) m/z 291.0780, found
2 24
, 200 MHz) d 0.98 (d, JZ7 Hz, 3H), 1.38–
3
1
2
91.0774.
1.95 (m, 9H), 3.00 (br s, 2H), 3.62 (dd, JZ10.5, 5 Hz, 1H),
1
3
3
.84 (dd, JZ10.5, 4 Hz, 1H); C NMR (CDCl , 50 MHz) d
3
3
.2.9. 2-(5-Bromopentyl)-2-[dimethyl(3-methyl-3-bute-
12.8, 23.5, 23.8, 37.2, 39.2, 42.3, 66.9, 86.1; HRMS calcd
for C m/z 144.1150, found 144.1140. Continued
elution gave 31 mg (38%) of the more polar 16 as a pale
nyl)-silyl]-1,3-dithiane (7d). According to the procedure
for the synthesis of 8a, 1.44 g (5.84 mmol) of 5c was
alkylated with 2.2 mL (16 mmol) of 1,5-dibromopentane to
give 1.97 g (85%) of 7d as a pale yellow liquid: IR (neat)
1653 cm ; H NMR (CDCl , 400 MHz) d 0.17 (s, 6H,
SiCH ), 0.85–0.91 (m, 2H, SiCH ), 1.44–1.56 (m, 4H), 1.72
H O
8 16 2
1
2
yellow oil.
K1
1
3.3.1. Cyclization of 9a followed by oxidation: 1-(3-
hydroxypropyl)cyclohexanol (22) and 1-(2-hydroxy-1-
methylethyl)cyclohexanol (23). According to the general
procedure for cyclization and oxidation, the reaction of
100 mg (0.36 mmol) of 9a afforded 14 mg (25%) of 23 as a
3
3
2
(
s, 3H, ]CCH ), 1.85–1.94 (m, 3H), 1.95–2.07 (m, 3H),
3
2
.16–2.22 (m, 2H, ]CCH ), 2.43 (dt, JZ13.5, 4 Hz, 2H,
2
SCH2(eq)), 3.00 (td, JZ13.5, 2.8 Hz, 2H, SCH2(ax)), 3.41 (t,
JZ6.8 Hz, 2H, CH Br), 4.66 (br s, 1H, ]CH ), 4.70 (br s,
2
9
colorless oil, and 31 mg (55%) of the more polar 22. 22:
2
2
1
H, ]CH2); C NMR (CDCl , 100 MHz) d K4.1 (CH ),
3
13
1
C NMR (CDCl
63.3, 71.1. 23: IR (neat) 3347 (br) cm ; H NMR (CDCl ,
3
3
, 50 MHz) d 22.3, 25.8, 26.1, 37.5, 38.8,
3
3
K1
1
1
1.9 (28), 22.3 (CH ), 23.6 (CH ), 25.2 (CH ), 27.1 (CH ),
3
2
2
2
2
8.8 (CH ), 32.1 (CH ), 32.7 (CH ), 33.9 (CH ), 37.5 (CH ),
2
200 MHz) d 0.91 (d, JZ7 Hz, 3H), 1.02–1.75 (m, 11H),
2
2
2
2
3
C H
8.9 (C), 108.6 (CH ), 148.0 (C); HRMS (FAB) calcd for
2.56 (br s, 2H), 3.66 (dd, JZ11, 6 Hz, 1H), 3.77 (dd, JZ11,
2
C
8
1
13
4 Hz, 1H); C NMR (CDCl , 50 MHz) d 12.1, 21.6, 21.7,
BrS Si (M CH) m/z 397.0878, found 397.0878.
3
1
6
32
2
25.7, 32.7, 36.5, 42.9, 65.4, 74.8; HRMS calcd for C H O
m/z 158.1307, found 158.1305.
9 18 2
3
.2.10. 6-Bromo-1-[dimethyl(3-methyl-3-butenyl)silyl]-
hexan-1-one (9d). According to the procedure for the
synthesis of 8c, 0.24 g (0.61 mmol) of 7d was hydrolyzed
with 0.99 g (1.8 mmol) of ceric ammonium nitrate to give
3.3.2. Cyclization of 8b followed by oxidation: 1-(4-
hydroxybutyl)cyclopentanol (24) and 1-(3-hydroxy-1-
methylpropyl)cyclopentanol (25). According to the gen-
eral procedure for cyclization and oxidation, the reaction of
250 mg (0.90 mmol) of 8b afforded 4 mg (3%) of 25 as a
1
1
19 mg (64%) of 9d as a pale yellow liquid: IR (neat)
645 cm ; H NMR (CDCl , 400 MHz) d 0.19 (s, 6H,
K1
1
3
SiCH ), 0.81–0.87 (m, 2H, SiCH ), 1.38 (quintet, JZ7 Hz,
3
2
1
2
2
1
2
H), 1.53 (quintet, JZ7 Hz, 2H), 1.70 (s, 3H, ]CCH3),
.83 (quintet, JZ7 Hz, 2H), 1.95–2.01 (m, 2H, ]CCH2),
colorless oil, and 96 mg (67%) of the more polar 24. 24:
1
3
C NMR (CDCl
62.7, 82.5. 25: IR (neat) 3370 (br) cm ; H NMR (CDCl
300 MHz) d 0.98 (d, JZ7 Hz, 3H), 1.20–1.95 (m, 13H),
, 75 MHz) d 20.9, 23.8, 33.1, 39.7, 41.0,
3
K1
1
.60 (t, JZ7 Hz, 2H, COCH ), 3.38 (t, JZ7 Hz, 2H,
,
3
2
1
3
CH Br), 4.67 (br s, 2H, ]CH ); C NMR (CDCl3,
1
2
2
1
3
00 MHz) d K4.6 (CH ), 11.7 (CH ), 21.2 (CH ), 22.2
3
3.55–3.70 (m, 1H), 3.73–3.87 (m, 1H); C NMR (CDCl ,
50 MHz) d 14.7, 23.8, 23.9, 35.3, 38.3, 38.8, 39.7, 60.5,
3
2
2
(
(
CH ), 28.0 (CH ), 31.6 (CH ), 32.8 (CH ), 33.7 (CH ), 48.7
3 2 2 2 2
CH ), 108.9 (CH ), 147.3 (C), 247.1 (C); HRMS (FAB)
2
85.2; HRMS calcd for C
found 140.1207.
H16O (MKH O) m/z 140.1201,
9 2
2
7
9
C
calcd for C H BrOSi (MCH) m/z 305.0936, found
3 26
1
3
05.0934.
3.3.3. Cyclization of 9b followed by oxidation: 1-(4-
hydroxybutyl)cyclohexanol (26). According to the general
procedure for cyclization and oxidation, the reaction of
3
.3. General procedure for intramolecular radical
cyclizations and oxidations: cyclization of 8a followed by
oxidation. 1-(2-Hydroxy-1-methyl)ethylcyclopentanol
2
9 13
70 mg (0.24 mmol) of 9b afforded 31 mg (78%) of 26 :
NMR (CDCl , 75 MHz) d 22.2, 25.8, 29.7, 33.0, 37.4, 41.7,
2.7, 71.7.
C
(
17)
3
6
To a refluxing solution of 150 mg (0.57 mmol) of 8a in
.5 mL of benzene was added via syringe pump over 2.5 h a
solution of 0.18 mL (0.68 mmol) of tributyltin hydride and
.0 mg (0.031 mmol) of AIBN in 6 mL of benzene. The
resulting solution was heated for another 2 h and then
2
3.3.4. Cyclization of 8c: 7,7,9-trimethyl-6-oxa-7-sila-spiro-
[4.5]decane (30). According to the general procedure for
cyclization, 181 mg (0.653 mmol) of 8c reacted with
0.24 mL (0.85 mmol) of tributyltin hydride to give 95 mg
5

2044
K.-H. Tang et al. / Tetrahedron 61 (2005) 2037–2045
(
1
3
74%) of 30 as a pale yellow liquid: IR (neat) 1456, 1252,
CH C]), 4.19 (quintet, JZ4.8 Hz, 1H, OCH), 4.64 (br s,
2
K1 1
029, 1004 cm ; H NMR (CDCl , 400 MHz) d 0.08 (s,
13
1H, ]CH ), 4.68 (br s, 1H, ]CH ); C NMR (CDCl3,
3
2
2
H, SiCH ), 0.10 (s, 3H, SiCH ), 0.23 (t, JZ14 Hz, 1H,
100 MHz) d K1.4 (CH ), 15.0 (CH ), 22.3 (CH ), 23.3
3 2 3
3
3
SiCH ), 0.67 (br d, JZ14 Hz, 1H, SiCH ), 0.98 (d, JZ
(CH ), 31.3 (CH ), 35.7 (CH ), 74.3 (CH), 108.3 (CH ),
2 2 2 2
2
2
C
148.3 (C); MS (rel intensity) m/z 212(M , 3), 197 (13), 143
6
1
1
.4 Hz, 3H, CHCH ), 1.29 (t, JZ13 Hz, 1H, CHCH ), 1.41–
3
2
.59 (m, 5H, CHCH and others), 1.62–1.79 (m, 4H), 1.81–
(97), 111 (39), 101 (21), 85 (11), 75 (100), 67 (8), 59 (38);
HRMS calcd for C H OSi 212.1591, found 212.1595.
2
1
3
.95 (m, 1H, CHCH3); C NMR (CDCl , 100 MHz) d 1.20
3
12 24
(
(
(
(
CH ), 22.8 (CH ), 23.2 (CH ), 24.3 (CH ), 26.4 (CH), 27.5
3 2 2 2
CH ), 38.5 (CH ), 43.3 (CH ), 47.8 (CH ), 84.8 (C); MS
3
2
2
2
3.3.8. Cyclization of 9d: 8,8,11-trimethyl-7-oxa-8-sila-
spiro[5.6]dodecane (40), (cyclohexyloxy)(dimethyl)(3-
methyl-3-butenyl)silane (41) and 1-[dimethyl(3-methyl-
3-butenyl)silyl]hexan-1-one (42). According to the general
procedure for cyclization, 250 mg (0.82 mmol) of 9d
reacted with 0.29 mL (1.1 mmol) of tributyltin hydride to
C
rel intensity) m/z 198 (M , 10), 183 (43), 169 (80), 156
63), 141 (65), 127(81), 113 (14), 75 (100), 61 (23); HRMS
calcd for C H OSi 198.1434, found 198.1439.
11 22
3
.3.5. Cyclization of 9c: 2,2,4-trimethyl-1-oxa-2-sila-
spiro[5.5]undecane (33). According to the general pro-
cedure for cyclization, 353 mg (1.21 mmol) of 9c reacted
with 0.45 mL (1.7 mmol) of tributyltin hydride to give
give 74 mg (40%) of 40 as a pale yellow liquid: IR (neat)
1449, 1252, 1053, 1029 cm ; H NMR (CDCl , 400 MHz)
K1 1
3
d 0.03 (s, 3H, SiCH ), 0.08 (s, 3H, SiCH ), 0.57–0.63 (m,
3
3
5
1
0
1
6
1
8 mg (23%) of 33 as a pale yellow liquid: IR (neat) 1450,
2H, SiCH ), 0.91 (d, JZ6.4 Hz, 3H, CHCH ), 1.16–1.50
2 3
13
K1 1
252, 1041, 1015 cm ; H NMR (CDCl , 400 MHz) d
3
(m, 10H), 1.54–1.68 (m, 3H), 1.71–1.85 (m, 2H); C NMR
.07 (s, 3H, SiCH ), 0.16 (s, 3H, SiCH ), 0.19 (t, JZ13 Hz,
(CDCl , 100 MHz) d 1.07 (CH ), 1.14 (CH ), 16.0 (CH ),
3
3
3
3
3
2
H, SiCH), 0.66 (dq, JZ13, 2 Hz, 1H, SiCH), 0.95 (d, JZ
.4 Hz, 3H, CHCH ), 1.00 (dd, JZ13, 2 Hz, 1H, CHCH ),
.18–1.40 (m, 6H), 1.42–1.77 (m, 5H), 1.84–1.97 (m, 1H);
22.5 (CH ), 22.8 (CH ), 25.2 (CH ), 26.3 (CH ), 30.0 (CH),
2 2 3 2
3
3
32.4 (CH ), 37.1 (CH ), 41.7 (CH ), 50.2 (CH ), 74.1 (C);
2
2
2
2
C
MS (rel intensity) m/z 226 (M , 56), 211 (14), 183 (100),
1
3
C NMR (CDCl , 100 MHz) d 1.50 (CH ), 1.55 (CH ),
3
170 (33), 157 (72), 142 (28), 127 (37); 75 (81); HRMS calcd
for C H OSi 226.1747, found 226.1753. We also isolated
3
3
2
2
2.2 (CH ), 22.4 (CH ), 23.1 (CH ), 24.1 (CH), 26.3 (CH ),
2
7.6 (CH ), 36.6 (CH ), 42.1 (CH ), 48.4 (CH ), 74.1 (C);
3
2
2
2
13 26
2
2
2
15 mg (8%) of 41 as a pale yellow liquid: IR (neat)
1653 cm ; H NMR (CDCl , 400 MHz) d 0.09 (s, 6H,
C
K1 1
MS (rel intensity) m/z 212 (M , 40), 197 (27), 183 (37), 169
100), 156 (81), 141 (45), 127 (89); 75 (66); HRMS calcd
for C H OSi 212.1591, found 212.1595.
3
(
SiCH ), 0.68–0.75 (m, 2H, SiCH ), 1.05–1.33 (m, 6H),
3
2
1
2
24
1.45–1.54 (m, 2H), 1.65–1.80 (m overlapped with a s at
.71, 5H, ]CCH and others), 1.96–2.04 (m, 2H, CH C]),
3.49–3.57 (m, 1H, OCH), 4.64 (br s, 1H, ]CH ), 4.68 (br s,
1
3
2
3
.3.6. Cyclization of 9c followed by oxidation: 1-(3-
2
3
0
13
hydroxy-2-methylpropyl)cyclohexanol (36). According
to the general procedure for cyclization followed by direct
oxidation, 308 mg (1.05 mmol) of 9c reacted with 0.38 mL
1H, ]CH2); C NMR (CDCl , 100 MHz) d K1.3 (CH ),
3
3
15.2 (CH ), 22.3 (CH ), 24.6 (CH ), 25.7 (CH ), 31.3 (CH ),
2
3
2
2
2
36.2 (CH ), 71.1 (CH), 108.3 (CH ), 148.3 (C); MS (rel
2
2
C
intensity) m/z 226 (M , 3), 211 (12), 157 (100), 143 (9), 127
(
3
1.4 mmol) of tributyltin hydride to give 112 mg (62%) of
K1
6 as a pale yellow liquid: IR (neat) 3306 (br) cm ; H
1
(12), 111 (30), 99 (16), 75 (100), 59 (25); HRMS calcd for
C H OSi 226.1747, found 226.1754. In addition was
NMR (CDCl , 400 MHz) d 0.76 (d, JZ6.8 Hz, 3H, CH ),
3
3
13 26
1
3
3
.06–1.65 (m, 13H), 1.76–1.88 (m, 1H), 2.59 (br s, 1H, OH),
.22 (dd, JZ10.4, 9.2 Hz, 1H, OCH ), 3.46 (dd, JZ10.4,
isolated 13 mg (7%) of 42 as a pale yellow liquid: IR (neat)
1646 cm ; H NMR (CDCl , 400 MHz) d 0.18 (s, 6H,
K1
1
2
3
1
.6 Hz, 1H, OCH2); C NMR (CDCl , 100 MHz) d 19.8
3
3
SiCH ), 0.80–0.89 (m, 5H, SiCH and others), 1.16–1.33
3
2
(
(
CH ), 22.3 (CH ), 22.6 (CH ), 25.9 (CH ), 30.9 (CH), 36.0
2
(m, 4H), 1.49 (quintet, JZ7.6 Hz, 2H), 1.70 (s, 3H,
]CCH ), 1.94–2.02 (m, 2H, ]CCH ), 2.56 (t, JZ7.2 Hz,
3
2
2
CH ), 40.1 (CH ), 48.1 (CH ), 69.2 (CH ), 71.6 (C).
2
2
2
2
3
2
2
4.67, 2H, ]CH2); C NMR (CDCl , 100 MHz) d K4.5
H, COCH ), 4.64–4.68 (two overlapped br s at 4.65 and
2
1
3
3
.3.7. Cyclization of 8d: 7,7,10-trimethyl-6-oxa-7-sila-
3
spiro[4.6]undecane (37) and (cyclopentyloxy)(di-
methyl)(3-methyl-3-butenyl)silane (38). According to the
general procedure for cyclization, 289 mg (0.99 mmol) of
(CH ), 11.8 (CH ), 14.1 (CH ), 21.9 (CH ), 22.2 (CH ), 22.7
3
2
3
2
3
(CH ), 31.6 (CH ), 31.7 (CH ), 49.0 (CH ), 108.9 (CH ),
2
2
2
2
2
147.3 (C), 247.8 (C); HRMS (FAB) calcd for C H OSi
13 27
C
(MCH) m/z 227.1831, found 227.1833.
8
give 144 mg (69%) of 37 as a pale yellow liquid: IR (neat)
d reacted with 0.35 mL (1.3 mmol) of tributyltin hydride to
K1
457, 1251, 1048 cm ; H NMR (CDCl , 400 MHz) d
1
1
0
3
.02 (s, 3H, SiCH ), 0.08 (s, 3H, SiCH ), 0.62–0.67 (m, 2H,
3
3
Acknowledgements
SiCH ), 0.92 (d, JZ6 Hz, 3H, CHCH ), 1.22–1.33 (m, 1H,
2
3
1
3
CHCH ), 1.37–1.58 (m, 5H), 1.64–1.84 (m, 7H); C NMR
3
Financial support by the National Science Council of the
Republic of China is gratefully acknowledged.
(
(
(
CDCl , 100 MHz) d 0.5 (CH ), 1.1 (CH ), 16.4 (CH ), 23.5
3 3 3 2
CH ), 23.8 (CH ), 25.3 (CH ), 32.4 (CH ), 33.1 (CH), 38.7
2
2
3
2
CH ), 43.6 (CH ), 50.2 (CH ), 84.8 (C); MS (rel intensity)
2
2
2
C
m/z 212 (M , 26), 197 (23), 183 (100), 169 (61), 155 (41),
1
2
3
42 (44), 127 (64); 75 (57); HRMS calcd for C H OSi
12 24
12.1591, found 212.1597. We also isolated 15 mg (7%) of
8 as a pale yellow liquid: IR (neat) 1653 cm ; H NMR
References and notes
K1
1
(
SiCH ), 1.41–1.56 (m, 4H), 1.66–1.78 (m overlapped with a
s at 1.71, 7H, CCH3 and others), 1.96–2.03 (m, 2H,
CDCl , 400 MHz) d 0.09 (s, 6H, SiCH ), 0.68–0.75 (m, 2H,
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