Synthesis and reaction of bromoallylsilane: A short access to [β,γ-disubstituted α-methylene-γ-butyrolactone

Article abstract of DOI:10.3987/COM-03-S52

(Z)-[β-Bromoallylsilanes (1a-c) were prepared by a stereoselective Ni-catalyzed cross-coupling reaction of 1,1-dibromo-4-phenylbutene (4) with silylmethylmagnesium halide. Sakurai-Hosomi reaction of 1a with aldehyde gave syn-3-alkyl-2-bromo-4-hydroxyalkene (2a, 2c, and 2e) and that with acetal gave syn-4-alkoxy-3-alkyl-2-bromoalkene (2b and 2d) stereoselectively. The products with formyl function reacted with a Ni-carbonyl complex to give [β,γ-disubstituted α-methylene-γ-butyrolactones (3) in good yields. Pd-catalyzed cross-coupling reaction of 1a-c or 4 with silylmethylmagnesium halide gave 1,1-bis(silylmethyl)-1-alkenes (1d-i), which reacted with dimethyl acetal to generate more functionalized allylsilane (6).

Full text of DOI:10.3987/COM-03-S52

HETEROCYCLES, Vol. 61, 2003
365
HETEROCYCLES, Vol. 61, 2003, pp. 365 - 376
Received, 16th July, 2003, Accepted, 28th August, 2003, Published online, 2nd October, 2003
ACCESS TO b,g-DISUBSTITUTED a-METHYLENE-
g-BUTYROLACTONE
Jun'ichi Uenishi* and Masashi Ohmi
Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8412, Japan
E-mail: juenishi@mb.kyoto-phu.ac.jp
Abstract — (Z)-b-Bromoallylsilanes (1a-c) were prepared by a stereoselective
Ni-catalyzed cross-coupling reaction of 1,1-dibromo-4-phenylbutene (4) with
silylmethylmagnesium halide. Sakurai-Hosomi reaction of 1a with aldehyde gave
syn-3-alkyl-2-bromo-4-hydroxyalkene (2a, 2c, and 2e) and that with acetal gave
syn-4-alkoxy-3-alkyl-2-bromoalkene (2b and 2d) stereoselectively. The products
with formyl function reacted with a Ni-carbonyl complex to give b,g-disubstituted
a-methylene-g-butyrolactones (3) in good yields. Pd-catalyzed cross-coupling
reaction of 1a-c or 4 with silylmethylmagnesium halide gave 1,1-bis(silylmethyl)-1-
alkenes (1d-i), which reacted with dimethyl acetal to generate more
functionalized allylsilane (6).
Introduction
Sakurai-Hosomi reaction of substituted allylsilane with aldehyde is an important carbon-carbon bond-
forming reaction for creating a branched homoallyl functional unit (Scheme 1). The reaction has been
widely used in organic synthesis, and various allylsilanes have been prepared.1 However, b-
2
bromoallylsilane has not been prepared except the simple one, and it has therefore rarely been used in
organic synthesis.3 The reaction of haloalkene with a Grignard reagent in the presence of a transition metal
catalyst,known as Kumada-Tamao-Corriu coupling, is used for the preparation of alkyl substituted alkene,4
and this reaction has been employed as a convenient method for the preparation of allylsilanes (Scheme 2).5
R
R
Lewis acid
R'
R
SiMe
R'
R'
3
CHO
OH
OH
major isomer
minor isomer
Scheme 1

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HETEROCYCLES, Vol. 61, 2003
ClMgCH SiMe
2
3
X
SiMe
R
3
R
Cat. NiCl (dppp)
2
Scheme 2
R
R
R''
R''
SiMe R'
2
R
X
O
X
OH
(OR')
O
1
2
3
X = Br, CH SiR"
2
X = Br
3
i
R = PhCH CH
2
2
R = PhCH CH
2
R = PhCH CH
2
2
i
2
R" = Ph, Pr
i
R" = Ph, Pr , C H
8
R' = Me, Ph, OPr
17
Figure 1
We have reported stereoselective Pd-catalyzed hydrogenolysis and cross-coupling reactions of 1,1-
dibromo-1-alkene.6 Since these reactions prefer to occur at the trans carbon-bromine bond of 1,1-dibromo-
1-alkene, (Z)-bromoalkene is obtained stereoselectively.7 During the course of this study, we have thought
that the reaction of 1,1-dibromo-1-alkene with a trimethylsilylmethyl Grignard reagent by Kumada-Tamao-
Corriu coupling would give b-bromoallylsilane (1a) stereoselectively. If that is the case, the Sakurai-
Hosomi reaction of 1 with aldehyde will be able to give homoallylic alcohol having a vinyl bromide unit like
compound (2). In this paper, we report the first general preparation of (Z)-b-bromoallylsilane and its
synthetic application to b,g-disubstituted a-methylene-g-butyrolactone (3) via bromo-substituted
homoallylic alcohol (2).
Preparation of Allylsilane from 1,1-Dibromo-1-alkene
(Z)-Bromoallylsilane (1a) was prepared by a NiCl2(dppp) catalyzed cross-coupling reaction of 1,1-
dibromo-4-phenylbutene (4) with trimethylsilylmethylmagnesium chloride in ether at room temperature.
Under this condition, the cross-coupling took place at the trans position stereoselectively to give a (Z)-
isomer (1a) exclusively in 89% yield, and a bistrimethylsilylmethylated product (1d) was not formed. The
stereochemistry of 1a was confirmed by the result of nOe experiments of 1H NMR spectrum, in which 5.7%
enhancement of the vinyl proton appeared at 5.43 ppm was observed upon irradiation of silylmethylene
(CH2Si) protons appeared at 2.09 ppm. In the same manner, a (dimethyl)phenylsilyl derivative (1b) was
obtained in 83% yield. The reaction with (dimethyl)isopropoxy-silylmethylmaganesium chloride did not
proceed in ether but proceeded in THF to give 1c in 32% yield along with a bissilylmethylated product (1f)
in 6% yield. On the other hand, 1,1-bis(silylmethyl)-1-alkenes (1d-f) were formed by a Pd-catalyzed cross-
coupling reaction of 4 with an excess of silylmethylmagnesium chloride in refluxing THF. The compounds
(1d-f) were obtained in 93, 73 and 67% yields, respectively, as shown in Scheme 3. If the second coupling
of 1a took place stereospecifically with a different silylmethyl Grignard reagent, 1,1-bis(silylmethyl)-1-

HETEROCYCLES, Vol. 61, 2003
367
alkenes having different silylmethyl groups could be obtained. In fact, the reaction of 1a with
(dimethyl)phenylsilylmethylmagnesium chloride in the presence of a Pd catalyst in refluxing THF gave a
(Z)-isomer (1g) preferentially over an (E)-isomer (1h) in a 10:1 ratio in 71% combined yield. On the other
hand, when 1b was used instead of 1a with trimethylsilylmethylmagnesium chloride, 1h was produced as a
major product over 1g in 77% yield with a 10:1 ratio. Therefore, stereocontrolled synthesis of 1,1-
bis(silylmethyl)-1-alkenes having different silyl groups was possible. In a similar manner, 1i was obtained
by the reaction of 1b with (dimethyl)isopropoxysilylmethylmaganesium chloride in 68% combined yield
along with (Z)-isomer in a 10:1 ratio.
Br
ClMgCH SiRMe
2 2
Ph
SiRMe
2
a ; R = Me
b ; R = Ph
c ; R = OPr
Ph
Cat. NiCl (dppp)
2
ether, rt
Br
Br
1a - c
4
i
ClMgCH SiR'Me
2
ClMgCH SiRMe
2
2
2
Cat. Pd(OAc) , PPh
3
Cat. Pd(OAc) , PPh
2
2
3
THF, reflux
THF, reflux
Ph
SiRMe
Ph
SiRMe
2
2
g ; R = Me, R' = Ph
h ; R = Ph, R' = Me
SiRMe
SiR'Me
2
d ; R = Me
e ; R = Ph
f ; R = OPr
2
i
i ; R = Ph, R' = OPr
1g - i
1d - f
i
Scheme 3
Reaction of Allylsilanes with Aldehyde and Acetal
First, we examined the reaction of 1a with benzaldehyde. The reaction was conducted in CH2Cl2 at –78 °C
in the presence of TiCl4. A mixture of syn isomer (2a) and anti isomer (2a’) was obtained selectively in a
10:1 ratio in 79% yield. These homoallylic alcohols were separable by HPLC. TiCl4 was found to be the
Ph
Ph
Ph
SiMe
3
RCHO or RCH(OR')
2
R
R
Br
1a
TiCl , CH Cl
2
4
2
OH
(OR')
Br
OH
(OR')
Br
- 78 °C, 5 min
syn
anti
2a-e
Scheme 4
2a'-e'
best among Lewis acids, such as SnCl4, BF3 etherate, ZnBr2 and TMSOTf. The stereochemistry was
rationally explained by the mechanism of Sakurai-Hosomi reaction, and eventually confirmed by the result
of nOe experiments after leading to lactones (3) at a later stage. When benzaldehyde dimethyl acetal was
used, the diastereoselectivity of 2b and 2b’decreased slightly to 5.3:1. The reaction with isobutanal gave a
syn isomer (2c) exclusively in 78% yield, and the reaction with isobutanal diethyl acetal gave a mixture of

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HETEROCYCLES, Vol. 61, 2003
2d and 2d’ in 97% yield in an 8.7:1 ratio. The reaction with nonyl aldehyde gave 2e in 80% yield as a
single isomer. These results are summarized in Table 1 and they indicate that aliphatic aldehyde or its acetal
tends to give a higher diastereoselectivity than does aromatic aldehyde or its acetal.
Table 1. Reactions of (Z)-b-Bromoallylsilane (1a) with RCHO and RCH(OR')2
entry aldehyde or acetal
R
Ph
R'
H
Product
2a+2a'
Yield (%)
syn : antia)
10 : 1
1
2
3
4
5
PhCHO
79
74
78
97
80
PhCH(OMe)2
5.3 : 1
Ph
Me
H
2b+2b'
2c+2c'
2d+2d'
2e+2e'
PriCHO
Pri
>10 : 1
8.7 : 1
PriCH(OEt)2
C8H17CHO
Pri
Et
H
C8H17
>10 : 1
a, The isomeric ratio was determined by proton nmr of crude products
An anti isomer (2c’) was obtained as a major isomer in two steps from 2c through the corresponding
ketone (5c). Thus, oxidation of 2c with a Dess-Martin oxidant followed by reduction with NaBH4 in
ethanol gave a mixture of syn : anti alcohols (2c and 2c’) with a 1:6 ratio in 60% yield. Similarly, 2e’ was
predominantly obtained with a 1:3 ratio in 61% yield. They were separable by HPLC.
Ph
Dess-Martin
periodinane
R
NaBH
EtOH
2c or 2e
4
2c or 2e
2c' or 2e'
O
CH Cl
2
2
Br
i
5c ; R = Pr
; R = C H
Scheme 5
5e
8
17
Ph
Ph
Ph
SiRMe
2
PhCH(OMe)
2
Ph
Ph
SiMe
3
SiPhMe
SiR'Me
2
2
BF ·Et O
3
2
OMe
OMe
CH Cl , - 78 °C
2
2
1g ; R = Me, R' = Ph
1h ; R = Ph, R' = Me
1d ; R = Me, R' = Me
6a
6b
Scheme 6

HETEROCYCLES, Vol. 61, 2003
369
Although the reaction of 1,1-bis(silylmethyl)-1-alkenes (1g) or (1h) with aldehyde gave complex mixtures
including protodesilylated compound, the reaction of a 10:1 mixture of 1g and 1h with benzaldehyde
dimethyl acetal was promoted by BF3 etherate in CH2Cl2 to give a mixture of 6a and 6b in 42% yield non-
selectively. Characteristic chemoselectivity by trimethylsilylallylsilyl and (diemthyl)phenylsilyl-allylsilyl
functionality could not be observed. Similarly, the reaction of a 1:10 mixture of 1g and 1h also afforded 6a
and 6b in 60% yield with a 1:1 ratio. Under the same reaction conditions, 1d gave 6a along with inseparable
protodesilylated product with a 6:5 ratio.
Synthesis of a-Methylene-g-butyrolactone8
Finally, when 2a was treated with Ni(CO)2(PPh3) 2 in the presence of triethylamine in THF, a-methylene-g-
butyrolactone (cis-3a) was obtained in 71% yield.9 The cis relationships of b,g-substituents were
1
determined by nOe experiments of H NMR spectrometry. Between the two protons located at b,g-
positions, 8.8% enhancement was observed upon irradiation of each b,g-proton. While, trans-3a was
yielded from an anti isomer (2a’) in 71% yield. The relative structure was also determined by nOe
experiments, in which enhancement was observed between g-proton and methylene protons of the
phenethyl group. Similarly, a syn isomer (2c) afforded cis-3c in 68% yield stereospecifically. Since this
reaction sequence leading to b,g-disubsituted a-methylene-g-butyrolactone is extremely short and
stereoselective, (Z)-b-bromoallylsilane will be a general synthetic unit for the efficient preparation of a-
methylenelactones, particularly those possessing anti-cancer activity.
Ph
Ph
Br
Ph
Ni(CO) (PPh )
2
3 2
R
R
R
or
Et N, THF
3
O
O
OH
reflux
O
O
2a ; R = Ph (syn)
2a' ; R = Ph (anti)
cis-3a ; R = Ph (cis only)
trans-3a ; R = Ph (trans only)
i
cis-3c ; R = Pr (cis only)
i
2c ; R = Pr (syn)
Scheme 7
In conclusion, (Z)-b-bromoallylsilanes were prepared from 1,1-dibromo-1-alkene stereoselectively by
Kumada-Tamao-Corriu coupling. The Sakurai-Hosomi reaction with aldehyde followed by
carbolactonization with Ni(CO)2(PPh3)2 gave b,g-disubstituted a-methylene-g-butyrolactones in two steps
in excellent yields. 1,1-Bis(silylmethyl)-1-alkenes were obtained by Pd-catalyzed cross-coupling reaction
of either 1,1-dibromo-1-alkene or (Z)-b-bromoallylsilane with silylmethylmagnesium halide, of which
reaction with dimethyl acetal gave functionalized allylsilane (6).
EXPERIMENTAL
1
All melting points were taken with Yanagimoto micro hot-stage apparatus and were uncorrected. H NMR
spectra were recorded on a JEOL JNM-AL-300 (300 MHz) spectrometer in CDCl3 with tetramethylsilane

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HETEROCYCLES, Vol. 61, 2003
as an internal standard. MS spectra were obtained on JMS-GC mate, and JMS-SX 102A QQ instruments.
IR spectra were recorded on JASCO FT/IR-410 instrument. All air- or moisture-sensitive reactions were
carried out in flame-dried glassware under Ar or N2 atmosphere. THF and ether were distilled freshly over
sodium/benzophenone ketyl under nitrogen atmosphere, and CH2Cl2 was dried over P2O5, and they were
distilled before the use. Thin layer chromatography (TLC) was performed with Merck 60F254 precoated
silica gel plates. Column chromatography was carried out using Merck silica gel 60 (70-230 mesh) for
gravity column.
Preparation of Bromoallylsilane (1a-1c). To a mixture of 4 (2.04 g, 6.9 mmol) and NiCl2(dppp) (374
mg, 0.69 mmol) in ether (120 mL) was dropped ethereal solution of silylmagnesium chloride (1M solution,
13.8 mL) was added at rt. The mixture was stirred overnight. Then, the mixture was poured into sat. NH4Cl
and extracted with hexane. The organic extract was washed with water, dried over MgSO4, and evaporated.
The residual oil was purified by column chromatography on silica gel eluted with hexane to give 1a-c. For
the reaction of 1c, THF was used instead of ether.
1
Rf = 0.81 (3% t-BuOMe in hexane); H NMR
=
6.8 Hz), 7.18-7.35 (5H, m); 13C NMR (75 MHz) d -1.4 (3C), 32.8, 33.3, 34.9, 124.8, 125.3, 125.8, 128.3
(2C), 128.4 (2C), 141.6; MS (EI) m/z 296 (M+); HRMS (EI) m/z Calcd for C14H21BrSi: 296.0596 (M+).
Found: 296.0592.
1
(Z)-2-Bromo-1-(dimethyl)phenylsilyl-5-phenyl-2-pentene (1b). Rf = 0.39 (1% ether in hexane); H
13
td, J = 7.0, 1.1 Hz), 7.19-7.42 (8H, m), 7.52-7.55 (2H, m); C NMR (75 MHz) d -2.9 (2C), 32.1, 33.3,
m/z 358 (M+); HRMS (EI) m/z Calcd for C19H23BrSi: 358.0752 (M+). Found: 358.0758.
(2C), 128.4 (2C), 141.5; MS (EI) m/z 340 (M+); HRMS (EI) m/z Calcd for C16H25OBrSi: 340.0858 (M+).
Found: 340.0856.
Preparation of 1d, 1e, and 1f. To a mixture of 4 (2.8 g, 9.65 mmol) and Pd(OAc)2 (216 mg, 0.97
mmol) in THF (90 mL) was added PPh3 (498 mg, 1.9 mmol), and ethereal or THF solution of
silylmagnesium chloride (1M solution, 20 mL) was added at rt. The mixture was refluxed for 2.5 h. After
cooling, the mixture was poured into sat. NH4Cl and extracted with hexane. The organic extract was
washed with water, dried over MgSO4, and evaporated. The residual oil was purified by column
chromatography on silica gel to give 1,1-bis(silylmethyl)-1-alkenes.
1
was used. Eluent for column chromatography; hexane. Yield 93%. Rf = 0.83 (3% t-BuOMe in hexane); H

HETEROCYCLES, Vol. 61, 2003
371
13
m), 4.90 (1H, t, J = 7.0 Hz), 7.20-7.36 (5H, m); C NMR (75 MHz) d -1.2 (3C), -0.6 (3C), 23.8, 29.4,
30.7, 36.6, 118.8, 125.6, 128.2 (2C), 128.4 (2C), 134.8, 142.7; MS (EI) m/z 304 (M+); HRMS (EI) m/z
Calcd for C18H32Si2: 304.2043 (M+). Found: 304.2040.
1,1-Bis{[(dimethyl)phenylsilyl]methyl}-4-phenyl-1-pentene(1e).
[(Dimethyl)phenylsilyl]-
methylmagnesium chloride was used. Eluent for column chromatography; 1% t-BuOMe in hexane. Yield
1
73%. Rf = 0.58 (3% t-BuOMe in hexane); H NMR (300 MHz) d 0.25 (6H, s), 0.26 (6H, s), 1.58 (2H, s),
13
1.62 (2H, s), 2.13-2.18 (2H, m), 2.52-2.58 (2H, m), 4.89 (1H, d, J = 6.8 Hz), 7.14-7.50 (15H, m); C
HRMS (EI) m/z Calcd for C28H36Si2: 428.2356 (M+). Found: 428.2344.
1,1-Bis{[(dimethyl)isopropoxysilyl]methyl}-4-phenyl-1-pentene
(1f).
[(Dimethyl)isopro-
poxysilyl]methylmagnesium chloride in THF solution was used. Eluent for column chromatography; 3% t-
1
BuOMe in hexane. Yield 67%. Rf = 0.21 (3% t-BuOMe in hexane); H NMR (300 MHz) d 0.11 (6H s),
128.3
(2C), 132.8, 142.5; MS (EI) m/z 392 (M+); HRMS (EI) m/z Calcd for C22H40O2Si2: 392.2567 (M+).
Found: 392.2561.
mmol) in THF (6.7 mL) was added PPh3 (38 mg, 0.134 mmol) and ethereal or THF solution of
silylmagnesium chloride (1M solution, 2-4 mL) was added at rt. The mixture was stirred at rt for 7 h and
refluxed for an additional half hour. After cooling, the mixture was poured into sat. NH4Cl and extracted
with hexane. The organic extract was washed with water, dried over MgSO4, and evaporated. The residual
oil was purified by column chromatography on silica gel eluted with hexane to give 1g-1i.
(Z)-1-(Dimethyl)phenylsilyl-5-phenyl-2-(trimethylsilyl)methyl-2-pentene
(1g).
[(Di-
methyl)phenylsilyl]methylmagnesium chloride in ether solution was used. After GPC chromatography
purification, a mixture of 1g and 1h was obtained in 71% yield as a 10:1 mixture. 1g; Rf = 0.55 (3% t-
1
BuOMe in hexane); H NMR (300 MHz) d -0.05 (9H, s), 0.31 (6H, s), 1.32 (2H, s), 1.69 (2H, s), 2.11-
(2C), 128.4 (2C), 128.9, 133.5 (2C), 134.1, 139.6, 142.5; MS (EI) m/z 366 (M+); HRMS (EI) m/z Calcd
for C23H34Si2: 366.2199 (M+). Found: 366.2198.
(E)-1-(Dimethyl)phenylsilyl-5-phenyl-2-(trimethylsilyl)methyl-2-pentene
(1h).
Trimethyl-
silylmethylmagnesium chloride in ether solution was used. After GPC chromatography purification, a
mixture of 1g and 1h was obtained in 77% yield as a 1:10 mixture of E:Z isomers. 1h; Rf = 0.55 (3% t-

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HETEROCYCLES, Vol. 61, 2003
366.2199 (M+). Found: 366.2203.
[(Dimethyl)isopropoxysilyl]methylmagnesium chloride in THF solution was used. After GPC
chromatography purification, a mixture of 1i and its E-isomer was obtained in 68% yield as a 10:1 mixture.
1
Only the data for the major isomer was described. 1i; Rf = 0.36 (6% t-BuOMe in hexane); H NMR (300
MHz) d 0.14 (6H, s), 0.31 (6H, s), 1.15 (6H, d, J = 6.4 Hz), 1.49 (2H, s), 1.74 (2H, s), 2.25-2.32 (2H,
m/z Calcd for C25H38OSi2: 410.2461 (M+). Found: 410.2456.
A Typical Reaction of Bromoallylsilane with Aldehyde and Acetal
To a mixture of bromoallylsilane (0.34 mmol) in CH2Cl2 (3.4 mL) and aldehyde or acetal (0.4 mmol) was
added TiCl4 (1M solution in CH2Cl2, 0.37 mL) at –78 °C, and the mixture was stirred for 5 min. Then sat.
NaHCO3 was added to the mixture and extracted with EtOAc. Organic phase was washed with brine and
dried over MgSO4. Solvent was removed and the residue was purified by column chromatography on silica
gel to give the product. As an eluent for chromatography, 20% EtOAc in hexane was used for 2a and 2a’,
2c and 2c’, and 2e and 2e’, and 5% EtOAc in hexane for 2b and 2b’, and 2d and 2d’.
3-Bromo-2-phenethyl-1-phenyl-3-buten-1-ol (2a and 2a’). Yield 79% (syn : anti = 10 : 1) as an
1
colorless oil. The diasteteoisomers were separated by HPLC. 2a; Rf = 0.46 (20% EtOAc in hexane); H
(2C), 128.4 (2C), 135.0, 141.8, 142.6; IR (neat) 3398 cm-1; MS (EI) m/z 330 (M+); HRMS (EI) m/z Calcd
1
for C18H19OBr: 330.0619 (M+). Found: 330.0611. 2a’; Rf = 0.42 (20% EtOAc in hexane); H NMR (300
d,
13
J = 1.5 Hz), 5.86 (1H, d, J = 1.5 Hz), 6.98 (2H, d, J = 7.0 Hz), 7.13-7.38 (8H, m); C NMR (75 MHz)
141.3; IR (neat) 3437 cm-1; MS (FAB) m/z 353 (M++Na); HRMS (FAB) m/z Calcd for C18H19OBrNa:
353.0517 (M++Na). Found: 353.0516.
1
an colorless oil. 2b; Rf = 0.46 (6% t-BuOMe in hexane); H NMR (300 MHz) d 1.79-1.94 (1H, m), 2.27-

HETEROCYCLES, Vol. 61, 2003
373
128.5 (2C), 135.0, 140.1, 142.1; MS (CI) m/z 313 (M+-OMe); HRMS (CI) m/z Calcd for C18H18Br:
1
313.0591 (M+-OMe). Found: 313.0599. 2b’; Rf = 0.40 (6% t-BuOMe in hexane); H NMR (300 MHz) d
3.7 Hz), 2.57 (1H, ddd, J = 13.9, 9.9, 4.4 Hz), 3.15 (3H, s), 4.05 (1H, d, J = 9.2 Hz), 5.65 (1H, d, J = 1.5 Hz),
5.73 (1H, d, J = 1.5 Hz), 6.96 (2H, d, J = 7.3 Hz), 7.17-7.39 (8H, m) ; 13C NMR (75 MHz)
d 30.1, 32.8, 55.5, 56.9, 85.0, 119.6, 125.8, 128.0 (2C), 128.1 (2C), 128.2, 128.4 (2C), 128.4 (2C),
136.5, 139.4, 141.4; MS (CI) m/z 313 (M+-OMe); HRMS (CI) m/z Calcd for C18H18Br: 313.0591 (M+-
OMe). Found: 313.0586.
= 11.4, 8.1, 3.3 Hz), 2.43 (1H, ddd, J = 13.6, 9.9, 7.0 Hz), 2.65-2.78 (1H, m), 3.41-3.50 (1H, m), 5.58 (1H,
33.2, 52.7, 77.4, 119.2, 125.8, 128.3 (2C), 128.5 (2C), 136.1, 142.0; IR (neat) 3436 cm-1; MS (FAB) m/z
319 (M++Na); HRMS (FAB) m/z Calcd for C15H21OBrNa: 319.0673 (M++Na). Found: 319.0676.
Spectroscopic data for 2c’ is described in the next experimental section.
1
colorless oil. 2d; Rf = 0.39 (3% t-BuOMe in hexane); H NMR (300 MHz) d 0.78 (3H, d, J = 6.6 Hz),
33.5, 53.1, 69.7, 85.7, 119.0, 125.7, 128.3 (2C), 128.5 (2C), 136.8, 142.3; MS (CI) m/z 325 (M++H);
HRMS (CI) m/z Calcd for C17H26OBr: 325.1167 (M++H). Found: 325.1168.
1
2e; syn; Rf = 0.46 (10% EtOAc in hexane); H NMR (300 MHz) d 0.88 (3H, t, J = 6.6 Hz), 1.19-1.60
(2C), 128.5 (2C), 135.9, 141.9; IR (neat) 3389 cm-1; MS (FAB) m/z 389 (M++Na); HRMS (FAB) m/z
Calcd for C20H31OBrNa: 389.1456 (M++Na). Found: 389.1454. Spectroscopic data for 2e’ is described in
the next experimental section.
Preparation of 2c’ and 2e’
A mixture of alcohol (2c or 2e, 0.2 mmol) and Dess-Martin periodinane (214 mg, 0.3 mmol) was stirred in
CH2Cl2 (2 ml) for 1 h at rt. An excess of oxidant was decomposed by the addition of sat. Na2S2O3. The
reaction mixture was extracted with ether and the extract was washed with sat. NaHCO3, water and brine.
The crude product was dissolved in ethanol (2 mL) and an excess of NaBH4 was added at rt. The mixture

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was diluted with water, and extracted with EtOAc. The extract was dried over MgSO4 and evaporated. The
residue was purified by silica gel column chromatography eluted with 5% EtOAc in hexane to give alcohol.
1
5-Bromo-2-methyl-4-phenyl-5-hxene-3-ol (2c’). Rf = 0.26 (10% EtOAc in hexane); H NMR (300
MHz) d 0.81 (3H, d, J = 7.0 Hz), 1.00 (3H, d, J = 7.0 Hz), 1.53 (1H, br s), 1.62-1.89 (3H, m), 2.23-2.34
13
d, J = 1.1 Hz), 5.76 (1H, d, J = 1.1 Hz), 7.15-7.33 (5H, m); C NMR (75 MHz) d 14.7, 20.4, 29.1, 30.6,
297 (M++H); HRMS (FAB) m/z Calcd for C15H22OBr: 297.0854 (M++H). Found: 297.0861.
1
2-Bromo-3-phenethyl-1-dodecen-4-ol (2e’). Rf = 0.46 (10% EtOAc in hexane); H NMR (300 MHz) d
0.88 (3H, t, J = 7.0 Hz), 1.26-1.85 (17H, m), 2.21 (1H, ddd, J = 12.5, 8.1, 4.8 Hz), 2.37-2.51 (1H, m), 2.71
(1H, ddd, J = 14.3, 9.6, 5.5 Hz), 3.53-3.64 (1H, m), 5.69 (1H, d, J = 1.5 Hz), 5.75 (1H, d, J = 1.5 Hz), 7.15-
13
7.30 (5H, m); C NMR (75 MHz) d 14.1, 22.7, 25.4, 29.2, 29.5, 29.7, 30.9, 31.9, 33.2, 33.8, 55.4, 72.0,
121.0, 125.9, 128.4 (2C), 128.4 (2C), 135.9, 141.7; IR (neat) 3435 cm-1; MS (FAB) m/z 389 (M++Na);
HRMS (FAB) m/z Calcd for C20H31OBrNa: 389.1456 (M++Na). Found: 389.1448.
Reaction of 1,1-Bis(silylmethyl)-1-alkene with Acetal. To a mixture of 1g or 1h (1 mmol) and
benzaldehyde dimethyl acetal (1 mmol) in CH2Cl2 (10 mL) was added dropwise BF3 etherate (1M CH2Cl2
solution, 10 mL) at –78 °C slowly, and the mixture was stirred for 5 min at the same temperature. The
reaction mixture was quenched with sat. NaHCO3, and extracted with EtOAc. The organic extract was
washed with brine, dried over MgSO4 and evaporated. The residue was purified by silica gel column
chromatography eluted with 5% EtOAc in hexane to give 6a and 6b.
1
Compound (6a) Rf = 0.71 (10% EtOAc in hexane); H NMR (300 MHz) d -0.02 (9H, s), 1.17 (1H, d, J =
14.7 Hz), 1.35 (1H, d, J = 14.7 Hz), 1.73-1.90 (1H, m), 2.06-2.21 (1H, m), 2.30 (1H, ddd, J = 10.3, 7.4, 3.7
Hz), 2.49 (1H, ddd, J = 13.6, 11.7, 5.5 Hz), 2.69 (1H, ddd, J = 13.6, 11.7, 4.8 Hz), 3.20 (3H, s), 4.06 (1H, d,
13
J = 7.4 Hz), 4.72 (1H, s), 4.73 (1H, s), 7.13-7.36 (10H, m); C NMR (75 MHz) d -0.9 (3C), 26.2, 31.5,
34.1, 54.2, 57.0, 87.1, 110.5, 125.5, 127.2, 127.6 (2C), 127.9 (2C), 128.2 (2C), 128.4 (2C), 141.1, 143.1,
146.7; MS (EI) m/z 352 (M+); HRMS (EI) m/z Calcd for C23H32OSi: 352.222 (M+). Found: 352.2218.
1
Compound (6b) Rf = 0.57 (6% t-BuOMe in hexane); H NMR (300 MHz) d 0.22 (3H, s), 0.23 (3H, s),
1.43 (1H, d, J = 15.0 Hz), 1.57 (1H, d, J = 15.0 Hz), 1.65-1.82 (1H, m), 1.94-2.11 (1H, m), 2.16-2.38 (2H,
m), 2.54 (1H, ddd, J = 12.3, 12.1, 4.8 Hz), 3.15 (3H, s), 4.00 (1H, d, J = 7.0 Hz), 4.69 (1H, d, J = 1.1 Hz),
4.72 (1H, d, J = 1.1 Hz), 7.05-7.46 (15H, m); 13C NMR (75 MHz) d -2.5, -2.4, 25.1, 31.3, 33.9, 54.0, 57.0,
87.0, 111.5, 125.5, 127.2, 127.5 (2C), 127.7 (2C), 127.9 (2C), 128.2 (2C), 128.3 (2C), 128.9 (2C), 133.6,
139.2, 141.0, 143.0, 146.1; MS (EI) m/z 414 (M+); HRMS (EI) m/z Calcd for C28H34OSi: 414.2379 (M+).
Found: 414.2372.

HETEROCYCLES, Vol. 61, 2003
375
Carbolactonization Reaction
A mixture of homoallylic alcohol (0.3 mmol), Ni(CO)2(PPh3)2 (290 mg, 0.46 mmol) and triethylamine
(0.08 ml, 0.6 mmol) in THF (3 mL) was refluxed for 30 min. After cooling, 10% HCl was added to the
reaction mixture, and the mixture was extracted with ether. The ethereal extract was washed with brine and
dried over MgSO4. Solvent was evaporated and the residue was purified by silica gel column
chromatography eluted with 20% EtOAc in hexane to give lactone.
3-Methylene-4-phenethyl-5-phenyldihydrofuran-2-one (cis-3a). Yield 71% as an colorless crystals,
1
mp 52-53 ℃ (hexane); Rf = 0.16 (6% t-BuOMe in hexane); H NMR (300 MHz) d 1.31-1.44 (1H, m),
1.52-1.65 (1H, m), 2.38-2.58 (2H, m), 3.29 (1H, qdd, J = 7.4, 2.6, 2.4 Hz), 5.62 (1H, d, J = 7.7 Hz), 5.64
13
(1H, d, J = 2.4 Hz), 6.37 (1H, d, J = 2.4 Hz), 6.92 (2H, d, J = 7.4 Hz), 7.11-7.42 (8H, m); C NMR (75
MHz) d 30.8, 32.4, 43.7, 82.0, 122.1, 126.1, 126.4 (2C), 128.2 (2C), 128.5 (2C), 128.6 (3C), 135.8, 139.0,
140.7, 170.4; IR (neat) 1766 cm-1; MS (EI) m/z 278 (M+); HRMS (EI) m/z Calcd for C19H18O2: 278.1307
(M+). Found: 278.1311; Anal. Calcd for C19H18O2: C, 81.99; H, 6.52: Found: C, 82.03; H, 6.72.
3-Methylene-4-phenethyl-5-phenyldihydrofuran-2-one (trans-3a). Yield 71% as an colorless crystals,
1
mp 93-94 ℃ (hexane); Rf = 0.45 (20% EtOAc in hexane); H NMR (300 MHz) d 2.02-2.12 (2H, m),
2.60-2.78 (2H, m), 3.00-3.09 (1H, m), 5.19 (1H, d, J = 5.2 Hz), 5.66 (1H, d, J = 2.0 Hz), 6.37 (1H, d, J = 2.0
Hz), 7.06 (2H, d, J = 8.4 Hz), 7.13-7.41 (8H, m); 13C NMR (75 MHz) d 32.5, 35.3, 47.1, 84.2, 122.6, 126.0
(2C), 126.3, 128.2 (2C), 128.6 (2C), 128.8, 128.9 (2C), 138.7, 139.3, 140.6, 170.1; IR (neat) 1766 cm-1; MS
(EI) m/z 278 (M+); HRMS (EI) m/z Calcd for C19H18O2: 278.1307 (M+). Found: 278.1311; Anal. Calcd
for C19H18O2: C, 81.99; H, 6.72: Found: C, 81.85; H, 6.75.
5-Isopropyl-3-methylene-4-phenyldihydrofuran-2-one (cis-3c). Yield 68% as an colorless crystals,
mp 48-49 ℃ (hexane); Rf = 0.14 (10% EtOAc in hexane); 1H NMR (300 MHz) d 0.92 (3H, d, J =7.0
Hz), 1.02 (3H, d, J = 6.6 Hz), 1.61-1.75 (1H, m), 1.88-2.05 (2H, m), 2.55 (1H, ddd, J = 13.9, 9.6, 6.6 Hz),
2.77 (1H, ddd, J = 13.9, 9.9, 5.5 Hz), 2.90-2.99 (1H, m), 4.03 (1H, dd, J = 8.8, 5.9 Hz), 5.58 (1H, d, J = 1.6
Hz), 6.24 (1H, d, J = 1.6 Hz), 7.15-7.33 (5H, m); 13C NMR (75 MHz) d 18.5, 18.9, 28.1, 28.3, 32.3, 42.1,
86.1, 121.0, 126.2, 128.3 (2C), 128.6 (2C), 140.1, 140.8, 170.6; IR (neat) 1766 cm- 1; MS (EI) m/z 244 (M+);
HRMS (EI) m/z Calcd for C16H20O2: 244.1463 (M+). Found: 244.1468; Anal. Calcd for C16H20O2: C,
78.65; H, 8.25: Found: C, 78.56; H, 8.42.
ACKNOWLEDGMENTS
This work was supported by a Special Grant for Cooperative Research administered by the Japan Private
School Promotion Foundation.
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