Can relief of ring-strain in a cyclopropylmethyllithium drive the Brook rearrangement?

Article abstract of DOI:10.1016/j.tet.2004.10.099

α-Cyclopropyl-α-trialkylsilyl alkoxides were formed either by addition of cyclopropyllithiums to acylsilanes or by addition of organolithiums to a cyclopropylformylsilane. [1,2]-Brook rearrangement led to α-silyloxy organolithiums which on warming underwent cyclopropane ring opening and [1,5]-retro-Brook rearrangement to yield γ-silyl ketones. Despite the favourability of the cyclopropane ring opening, the Brook rearrangement still required the presence of an anion stabilising group to proceed. β-Silylketones were similarly formed by Brook-retro-Brook rearrangement on warming acylsilanes with a vinyllithium.

Full text of DOI:10.1016/j.tet.2004.10.099

Tetrahedron 61 (2005) 3195–3203
Can relief of ring-strain in a cyclopropylmethyllithium drive the
Brook rearrangement?
a,*
a
Jonathan Clayden, David W. Watson and Mark Chambers
b
a
Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK
b
Received 28 July 2004; revised 11 October 2004; accepted 15 October 2004
Available online 21 November 2004
Abstract—a-Cyclopropyl-a-trialkylsilyl alkoxides were formed either by addition of cyclopropyllithiums to acylsilanes or by addition of
organolithiums to a cyclopropylformylsilane. [1,2]-Brook rearrangement led to a-silyloxy organolithiums which on warming underwent
cyclopropane ring opening and [1,5]-retro-Brook rearrangement to yield g-silyl ketones. Despite the favourability of the cyclopropane ring
opening, the Brook rearrangement still required the presence of an anion stabilising group to proceed. b-Silylketones were similarly formed
by Brook–retro-Brook rearrangement on warming acylsilanes with a vinyllithium.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
valuable synthesis of a-oxygen substituted organo-
1
2
lithiums. Stabilisation of the “carbanion” by electron-
withdrawing (PhS etc.) or conjugating (vinyl, or phenyl)
groups favours Brook rearrangement: formation of con-
jugated or a-phenylthio organolithiums by Brook rearrange-
ment in the presence of THF or TMEDA has been widely
1
The 1,2-Brook rearrangement of a-silyl oxyanions to
1
–7
a-silyloxy anions (Scheme 1) has been studied in detail
and is typically a reversible process proceeding via a
8
–11
pentacoordinate silicon intermediate.
With catalytic
1
3–28
base, the reaction can be considered an equilibrium between
neutral, protonated species, and the strength of the Si–O
bond (about 500–520 kJ mol ) compared with the Si–C
used.
K1
2
9
Lansbury showed that cyclopropylmethyllithium 3 is
unstable, and rearranges to homoallyllithium 4 in a matter
of hours at K70 8C or minutes at K20 8C (Scheme 2). Ring
opening reactions of cyclopropylmethyllithiums have more
recently been employed in the study of the stereospecificity
–
1
bond (about 310–350 kJ mol ) means that, provided the
anion 2 forms reasonably rapidly (some degree of
stabilisation is required), Brook rearrangement (carbanion
formation) is favoured over retro-Brook rearrangement
(
alkoxide formation). Organolithiums 2 may be present as
30
of the reverse reaction and in the synthesis of homo-
allylically functionalised compounds from cyclopro-
intermediates in the catalytic Brook rearrangement, but their
reactivity cannot be exploited under these conditions.
31,32
panes.
With the aim of developing new methods for
1
2
the synthesis of functionalised organolithiums, we set out
to investigate whether an equilibrium Brook rearrangement
could be driven to completion by exploiting a similar loss of
With stoichiometric organolithium bases, the reaction is an
equilibrium between the alkoxide 1 and the organolithium
2; the organolithium 2 may be formed quantitatively, and
the rearrangement therefore provides a potentially very
†
cyclopropyl ring strain. Scheme 3 illustrates the proposed
strategy. The oxy-anion 5 and silyl ether 6 should be in
equilibrium, but the collapse of the strained cyclopropyl
ring to form lithiated species 7 removes 6 from the
equilibrium, forcing the reaction to completion and giving
†
8
Lindermann and Ghannam carried out a retro-Brook rearrangement of a
Scheme 1. The 1,2-Brook rearrangement.
cyclopropyl-substituted anion without cyclopropyl ring-opening. How-
ever, the anion was kept at K15 8C for only 15 min: we hoped to use
control of temperature or cyclopropane substitution to promote the ring
opening. After submission of this manuscript, Takeda et al. reported a
cascade Brook rearrangement–cyclopropane ring opening: see Okugawqa
and Tekeda Org. Lett. 2004, 6, 2973].
Keywords: Organolithium; Cyclopropane; Silicon; Anion; Rearrrangement.
*
Corresponding author. Tel.: C44 1612754612; fax: C44 1612754939;
e-mail: j.p.clayden@man.ac.uk
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.10.099

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J. Clayden et al. / Tetrahedron 61 (2005) 3195–3203
Scheme 2. Ring opening of a cyclopropylmethyllithium.
Scheme 5. Synthesis of acylsilanes.
non-enolisable 9f was made by acylation of phenyldi-
methylsilyllithium with N,N-dimethylpivalamide 14.
3
5
Scheme 3. Driving a Brook rearrangement.
useful organolithium products whatever the favourability or
otherwise of the Brook rearrangement itself. The expected
products of the reaction will be the homoallyllithium 7, an
unusual d Cd (bishomoenolate) synthon of which
electrophilic quench of firstly the organolithium and
secondly the silyl enol ether should yield the products 8.
Bromocyclopropane precursors 19 of the cyclopropyl-
lithiums 10 were prepared from styrene or allylbenzene
17a or 17b by cyclopropanation with dibromocarbene
followed by mono-bromine-lithium exchange of the dibro-
mocyclopropane 18a or 18b and protonation to yield 19a
2
4
33
3
6
and 19b as single diastereoisomers (Scheme 6).
The key intermediate in the route is the a-silyl oxyanion 5.
Two connective routes to 5 present themselves, represented
in Scheme 4 by disconnections a (to acyl silanes 9 and
cyclopropyllithiums 10) and b (to cyclopropylformylsilane
11 and a more general family of organolithiums 12). Each
has its advantages, and we tried both, starting with
disconnection a.
‡
Scheme 6. Synthesis of bromocyclopropanes.
2
. Synthesis of the starting materials
3. Brook rearrangements
Acylsilanes 9 were prepared by three published methods
Scheme 5). Benzoylsilane 9a was made from methyl
(
The bromocyclopropanes 19a and 19b were transmetallated
with t-BuLi in ether at K78 8C to afford the cyclopropyl-
lithiums 10a and 10b, and acylsilanes 9a–c were added. The
reaction mixtures were allowed to warm to room
3
4
benzoate by the method of Prakash et al., while 9b–9e
were made by silylation of the appropriate dithianes 15
followed by oxidative hydrolysis of the products 16. The
2
8
Scheme 4. Routes to the rearrangement precursor.
‡
28 19–27
Reich and Takeda have demonstrated the utility of Brook
rearrangements initiated by nucleophilic attack on acylsilanes.

J. Clayden et al. / Tetrahedron 61 (2005) 3195–3203
3197
temperature over 30 min and quenched with ammonium
chloride to give the ketones 20 and 21 as shown in
Scheme 7.
acylsilane was synthesised from cyclopropylmethanol 25 by
oxidation to the aldehyde 26, dithiane formation, silylation
and hydrolysis (Scheme 9).
Scheme 9. Synthesis of a cyclopropylformylsilane.
The reactions of 29 were extremely revealing with regard to
the structural features and conditions required for Brook
rearrangement-ring opening to succeed, and in fact showed
that our original proposition—that even an unfavourable
Brook rearrangement would be pushed to completion by
relief of ring-strain—was flawed. Acylsilane 29 was treated
with either phenyllithium or n-butyllithium and the reaction
mixture was allowed to warm to either K30, 0. C25 or
C45 8C, as shown in Table 1 and Scheme 10. In each case,
one of three products 30, 31 or 32 was obtained.
Scheme 7. g-Silyl ketones from acylsilanes.
The formation of 20 and 21 is clearly the result of a Brook
rearrangement and cyclopropane opening as anticipated,
with the regioselectivity of cyclopropane opening governed
1
by the anion-stabilising ability of R . Scheme 8 shows a
proposed mechanism via an intermediate represented as
1
Table 1. Products of addition-rearrangement reactions of 29
organolithium 6. R ZPh generates benzylic organolithium
1
2
7
organolithium 23. However, these organolithiums are
and R ZBn generates in preference the primary
Entry
R Z
Temperature of
quench (8C)
Product
Yield (%)
a
unstable with respect to a second, 1,5-retro-Brook,
1,37
1
2
3
4
5
6
7
Ph
Ph
Ph
n-Bu
n-Bu
n-Bu
n-Bu
K30
0
C25
K30
0
31
31
37
b
3
31
32
30
30
30
30
rearrangement,
mation of the C-silylated enolates 22 and 24 and thence 20
which presumably results in the for-
b
48
70
a
3
b
and 21. Only with R Zi-Pr was the retro-Brook rearrange-
71
70
a
ment prevented, but in this case no identifiable product was
obtained from the reaction. For the retro-Brook rearrange-
ment to occur, it is necessary for the rearranging silyl enol
ethers 7 and 23 to have E geometry: it may be that the Z silyl
enol ethers are also formed but decompose.
C25
C45
a
50
a
By NMR.
Isolated yield.
b
With phenyllithium, the product 31 of addition and 1,2-
Brook rearrangement was formed at both K30 and 0 8C
(entries 1 and 2), indicating that the Ph group alone is
sufficient to favour the Brook rearrangement and that the
release of cyclopropyl ring strain plays only the minor role
in this reaction. Only on warming to room temperature was
the silane 32 resulting from cyclopropyl ring opening and
Further studies of the scope and mechanism of the reaction
were hindered by the need for structural variation in both
acylsilane and bromocyclopropane components. We there-
fore decided to continue work on the rearrangement by
synthesising the key intermediate 5 via disconnection b,
studying the reactions of cyclopropylformylsilane 29. This
3
8
Scheme 8. Mechanism of the Brook–ring-opening–retro-Brook sequence.

3198
J. Clayden et al. / Tetrahedron 61 (2005) 3195–3203
Scheme 10. Addition–rearrangement reactions of 29.
1
,5-retro-Brook rearrangement observed (entry 3), showing
Acylsilane 9a, which should generate a pentadienyllithium,
gave no identifiable products, possibly because of the
instability of the pentadienyllithium intermediate. However,
the non-aromatic acylsilanes 9e and 9f did lead to formation
of low to moderate yields of b-silylketones, with successful
rearrangement from 9e possibly compromised by its
enolisable proton.
that cyclopropane ring opening is relatively slow. With
n-butyllithium the only product observed, even after
warming the reaction mixture to 45 8C, was the alcohol 30
simply resulting from addition to the acylsilane (entries
4
–7). Cyclopropyl ring opening is apparently unable to
promote the Brook rearrangement when there is no anion
stabilising group adjacent to the forming organolithium
centre. We conclude therefore that while cyclopropyl ring-
opening can provide means of transforming the products of
Brook rearrangement into g-silylated ketones, it can only do
so when the Brook rearrangement is itself inherently
favourable.
5. Conclusion
Brook rearrangement of a-silyl-a-cyclopropyl alkoxides
can generate cyclopropylmethyllithiums which, on warm-
ing, undergo ring opening and 1,5-retro-Brook rearrange-
ment to yield g-silyl ketones. The Brook rearrangement
requires the presence of an anion-stabilising group (Ph,
vinyl) at the forming anionic centre to proceed: release of
cyclopropyl ring strain alone is insufficient to drive the
rearrangement.
4
. Synthesis of b-silylketones
Aiming to extend the range of substrates and products
participating in the Brook rearrangement-ring opening
sequence, we treated 29 with phenylvinyllithium (generated
from b-bromostyrene) and allowed the mixture to warm to
room temperature. We hoped to observe ring opening,
followed perhaps by readdition to the alkene to complete a
new annelation procedure. However, the product 36a
isolated from this reaction, in 42% yield, still contained an
intact cyclopropane, and was evidently the result of 1,2-
Brook rearrangement followed by 1,4-retro-Brook
rearrangement, a reaction now made possible by the allylic
system generated on Brook rearrangement (Scheme 11).
By-products resulting from 1,4-retro-Brook rearrangement
6. Experimental
6.1. General methods
3
9
These have been published previously.
3
6.1.1. Phenyltrimethylsilylmethanone 9a. By the pro-
4
3
4
cedure of Prakash et al., magnesium powder (1.20 g,
50.0 mmol), iodine (0.20 g, 0.8 mmol), NMP (60 mL) and
excess chlorotrimethylsilane (21.7 g, 0.20 mmol) were
mixed and stirred for 5 min. Methyl benzoate (3.40 g,
25.0 mmol) was added drop-wise. The reaction was stirred
for 18 h at room temperature and quenched with saturated
aqueous ammonium chloride solution. Dilute aqueous
2
8
have been observed in related reactions.
This reaction struck us as a potentially valuable synthesis of
b-silylketones, and we therefore treated the acylsilanes 9a,
9
e and 9f with phenylvinyllithium under similar conditions.
Scheme 11. Synthesis of b-silylketones.

J. Clayden et al. / Tetrahedron 61 (2005) 3195–3203
3199
K3
hydrochloric acid (2.0 mol dm , 50 mL) was cautiously
added and the mixture was left to stir for 1 h. The layers
were separated and the aqueous portion was extracted with
pentane (3!100 mL). The combined organic layers were
16.6 mmol) and THF (20 mL) gave the silane 16e as a
colourless oil (4.46 g, 93%); R (petrol–ethyl acetate, 49:1)
f
K1
0.83; nmax (film)/cm 2954, 2910, 2867 (C–H), 1249 and
844 (Si–C); d (300 MHz; CDCl ) 3.07 (2H, tq, JZ12.0,
H
3
dried (MgSO ), filtered and concentrated under reduced
4
1.5 Hz, SCH CH), 2.52 (2H, double septuplet, JZ14.5,
2A
pressure to afford a crude product. Purification by flash
column chromatography (SiO ) eluting with petrol–ethyl
1.5 Hz, SCH CH ), 2.18 (2H, td, JZ5.0, 1.5 Hz, CH K2),
2
B
2
2
2.12–1.84 (3H, m, SCH CH and CHCH -2), 1.08 (6H, td,
JZ6.5, 1.0 Hz, (CH ) CHCH K2) and 0.25 (9H, s,
3 2 2
2
2 2 2
acetate 49:1 yielded the acylsilane 9a as a bright yellow oil
(
3
4
1.78 g, 40%), with spectroscopic data as reported.
Si(CH ) ); d (75 MHz; CDCl ) 45.7, 39.3, 27.4, 25.3,
3 3 C 3
C C
5.1, 24.0 and K2.0; m/z 249 (100%, MCH ); Found M ,
2
249.1167. C11 Si requires MH 249.1162.
6.1.2. Dimethylphenyl-(2-phenyl-[1,3]dithian-2-yl)-
silane 16b. By a modification of the procedure of Reich
H S
24 2
4
0
2
8
41
6.1.6. (Dimethylphenylsilyl)phenylmethanone 9b. By a
et al., 2-phenyl-1,3-dithiane (5.04 g, 25.7 mmol) was
dissolved in THF (50 mL) and cooled to 0 8C. n-Butyl-
lithium (13.8 mL, 2.13 M solution in pentane, 28.1 mmol)
was added drop-wise over 45 min. The solution turned deep
yellow-orange. After 2 h chlorodimethylphenylsilane
2
8
modification of the method of Reich et al., a stirred
solution of 16b (8.00 g, 24.2 mmol) in methanol (84 mL)
and water (23 mL) at 0 8C was treated with chloramine-T
hydrate (33.87 g, 0.12 mol) in portions over 45 min. After
an additional 30 min the mixture was allowed to warm to
room temperature and allowed to stir at this temperature for
45 min. Water (10 mL) was added, and the mixture was
extracted with pentane (7!30 mL). The combined organic
layers were washed with water (30 mL), brine (30 mL),
(
5.00 g, 29.3 mmol) was added. Water (75 mL) was added
and the layers were separated. The aqueous phase was
extracted with ether (3!50 mL). The combined organic
layers were washed with brine (50 mL), dried (MgSO4),
filtered and concentrated to yield the silane 16b as white
needles (8.20 g, 97%), mp 74–76 8C; spectroscopic data as
dried (MgSO ) and concentrated under reduced pressure.
4
Purification by flash column chromatography (SiO ) eluting
2
4
0
reported.
with petrol–ethyl acetate 29:1 yielded the acylsilane 9b as a
yellow oil (1.63 g, 28%); spectroscopic data as reported.
4
1
6
1
2
.1.3. Triisopropyl-(1-phenyl-[1,3]dithian-2-yl)-silane
6c. In a similar way, 2-phenyl-1,3-dithiane (4.47 g,
2.8 mmol), chlorotriisopropylsilane (5.00 g, 25.93 mmol),
4
2
6.1.7. Phenyltriisopropylsilylmethanone 9c. In a similar
manner, 15c (7.16 g, 20.33 mmol), chloramine-T hydrate
(29.6 g, 0.11 mol), methanol (84 mL) and water (20 mL)
gave, after purification by flash column chromatography
n-butyllithium (11.53 mL, 2.13 M solution in pentane,
4.6 mmol) and THF (50 mL) gave the silane 16c as a
white crystalline solid (7.30 g, 91%), mp 34–36 8C; Rf
2
K1
(
2
petrol–ethyl acetate, 49:1) 0.75; nmax (film)/cm
904, 2867 (C–H), 1273 and 883 (C–Si); dH (300 MHz;
CDCl ) 8.12–7.18 (5H, m, ArH), 2.81 (2H, dt, JZ13.5,
2946,
(SiO ) eluting with petrol–ethyl acetate 99:1, the acylsilane
2
9c as a yellow oil (1.28 g, 24%); R (petrol–ethyl acetate,
f
K1
49:1) 0.58; nmax (film)/cm 2945, 2890, 2867 (C–H), 1611
3
2
CH ), 2.12–1.84 (2H, m, SCH CH ), 1.42–1.31 (3H, m,
.5 Hz, SCH CH ), 2.39 (2H, td, JZ14.0, 4.0 Hz, SCH -
(C]O), 1204 and 882 (Si–C); d (300 MHz; CDCl ) 7.84–
H 3
2
A
2
2B
7.48 (5H, m, ArH), 1.54 (3H, septuplet, JZ7.5 Hz,
CH(CH ) !3) and 1.17 (18H, d, JZ7.5 Hz, CH(CH ) !
2
2
2
CH(CH ) !3) and 1.16 (18H, d, JZ7.0 Hz, CH(CH ) !
3
2
3 2
3 2
3 2
3
); dC (75 MHz; CDCl ) 141.6, 130.9, 128.5, 125.5
3); d (75 MHz; CDCl ) 236.4 (C]O), 143.7, 132.6, 128.8,
127.3 (Aromatic), 19.1 and 12.6.
3
C 3
(
Aromatic), 25.9, 25.7, 25.5, 20.0 and 12.2; m/z 353
C
C
(100%, MCH ); Found M , 352.1708. C H S Si
19 32 2
requires M 352.1715.
4
3
6.1.8. 3-Methyltrimethylsilylbutan-1-one 9d. In a simi-
lar way, 16d (6.50 g, 26.20 mmol), chloramine-T hydrate
(37.3 g, 0.16 mol), methanol (100 mL) and water (25 mL)
gave, after distillation [100–105 8C (2 mmHg)], the acyl-
silane 9d as colourless oil (1.5 g, 36%); spectroscopic data
6
.1.4. (2-Isobutyl-[1,3]dithian-2-yl)-trimethylsilane 16d.
In a similar way, 2-isobutyl-1,3-dithiane (5.00 g, 30.7 mmol),
chlorophenyldimethylsilane (5.97 g, 35.04 mmol), n-butyl-
lithium (14.6 mL, 2.27 M solution in pentane, 33.2 mmol)
and THF (50 mL) gave the silane 16d as a colourless oil
4
3
as reported.
4
4
(
(
6.94 g, 91%); R (petrol–ethyl acetate, 49:1) 0.79; n
f max
6.1.9. 1-(Dimethylphenylsilyl)-3-methylbutan-1-one 9e.
K1
film)/cm 2952, 2910, 2865 (C–H), 1251 and 818 (Si–C);
In a similar way, 16e (4.00 g, 12.90 mmol), chloramine-T
hydrate (18.28 g, 80.29 mmol), methanol (50 mL) and water
(13 mL) gave, after purification by flash column chromato-
d (300 MHz; CDCl ) 7.78–7.37 (5H, m, ArH), 3.00 (2H,
H
ddd, JZ14.5, 11, 3.5 Hz, SCH CH ), 2.51 (2H, ddd, JZ
3
2
A
2
1
4.5, 5.5, 3.5 Hz, SCH CH ), 2.06 (2H, d, JZ7.0 Hz,
graphy (SiO ) eluting with petrol–ethyl acetate 49:1, the
2
2
B
2
CH K2), 2.04–1.82 (3H, m, SCH CH ), 0.97 (6H, d, JZ
acylsilane 9e as a colourless oil (0.85 g, 30%); spectro-
scopic data as reported.
2
2
2
4
4
6
.5 Hz, (CH ) CHCH -2) and 0.60 (6H, s, Si(CH ) ); d
3
2
2
3 2
C
(
75 MHz; CDCl ) 136.5, 135.3, 129.9, 127.9 (Aromatic),
3
4
5
4
MCH ); Found M , 310.1239. C H S Si requires M
3
6.1, 39.8, 27.4, 25.3, 24.6, 1.3 and K3.1; m/z 311 (15%,
6.1.10. 2,2,N,N-Tetramethylpropionamide 14. To a
stirred solution of N,N-dimethylamine hydrochloride
(10.83 g, 132.7 mmol) in toluene (50 mL) were added
triethylamine (16.78, 165.8 mmol) and pivaloyl chloride
(4.00 g, 33.17 mmol) at 0 8C. The reaction mixture was
C
C
1
6 26 2
10.1245.
6
.1.5. (2-Isobutyl-[1,3]dithian-2-yl)-dimethylphenylsi-
lane 16e. In a similar way, 2-isobutyl-1,3-dithiane (2.51 g,
5.46 mmol), chlorotrimethylsilane (1.84 g, 17.0 mmol),
n-butyllithium (7.34 mL, 2.27 M solution in pentane,
stirred at 25 8C for 4 h, cooled to 0 8C, quenched by the
K3
1
addition of dilute aqueous hydrochloric acid (1.0 mol dm
4 mL) at the same temperature. Water (50 mL) was then
,

3200
J. Clayden et al. / Tetrahedron 61 (2005) 3195–3203
added and the mixture was extracted with ethyl acetate (3!
0 mL). The combined organic extracts were washed with a
saturated solution of sodium bicarbonate (50 mL) and brine
50 mL), dried (MgSO ), filtered and concentrated under
2.10–1.95 (1H, m, PhCH CH), 1.91 (1H, dd, JZ10.5,
2
5
6.0 Hz, CBr CH CH ) and 1.45 (1H, dd, JZ6.0, 6.0 Hz,
2
A
B
CBr CH CH ); d (75 MHz; CDCl ) 139.5, 128.9, 128.6,
126.8 (Aroamtic), 38.5, 32.2, 29.3 and 28.7.
2
A
B
C
3
(
4
reduced pressure. Purification by flash column chromato-
graphy eluting with petrol–ethyl acetate 3:1 yielded the
amide 14 as a colourless oil (292 mg, 45%); R (petrol–ethyl
3
6.1.14. (2-Bromocyclopropyl)benzene 19a. By the
6
3
6
f
method of de Lang et al. , a three-necked, round-bottomed
flask was charged with lithium bromide (5.12 g, 59.0 mmol)
in THF (40 mL) and ether (40 mL). The air in the flask was
replaced by nitrogen and n-butyllithium (30.0 mL of 2.0 M
solution in hexane, 60.0 mmol) was added with cooling
below 0 8C. Subsequently a solution of (2,2-dibromo-
cyclopropyl)-benzene (18a) (15.0 g, 54.0 mmol) in THF
(16 mL) was added over a period of 1 h while the temper-
ature of the reaction mixture was kept carefully between
K100 and K110 8C. The thick white suspension was stirred
for 1 h at K100 8C, after which, under continuous cooling,
it was cautiously quenched with ethanol (10 mL). After the
exothermic reaction had subsided, water (20 mL) was added
and the mixture was extracted with hexane (3!30 mL). The
K1
acetate, 8:2) 0.41; nmax (film)/cm
2963, 2931, 2876
(
(
C–H), 1630 (C]O), 1398 and 1364 (C(CH ) ); d
3 3 H
300 MHz; CDCl ) 3.03 (6H, s, N(CH ) ) and 1.21 (9H, s,
3
3 2
C(CH ) ); d (75 MHz; CDCl ) 177.9 (C]O), 38.9, 38.5
3
3
3
C
and 28.4.
6.1.11. 1-(Dimethylphenylsilyl)-2,2-dimethylpropan-1-
one 9f. Dimethylphenylsilyl chloride (1.19 g, 7.00 mmol)
3
5
was stirred with lithium (147 mg, 21.0 mmol) in THF
19 mL) at K8 8C for 36 h. The solution turned red. For
(
calibration, an aliquot (1 mL) was injected into water and
the alkaline solution was titrated against dilute aqueous
hydrochloric acid (2.0 mol dm ). Dimethylphenylsilyl-
K3
lithium (17.99 mL, 0.32 M solution in THF, 5.76 mmol)
was added drop-wise to a stirred solution of 2,2,N,N-
tetramethylpropionamide 14 (619.0 mg, 4.80 mmol), in dry
THF (20 mL) under nitrogen, at K78 8C, and the mixture
was kept for 1.5 h at K78 8C. Saturated aqueous ammonium
chloride (25 mL) was added to the mixture followed by
water (25 mL). The mixture was extracted with ether (3!
combined organic fractions were dried (MgSO ), filtered
4
and the solvent removed under reduced pressure. The crude
product was distilled [105 8C (12 mmHg)] to yield the
bromide 19a as a colourless oil (7.94 g, 75%); spectroscopic
3
5
data as reported.
4
7
6.1.15. (2-Bromocyclopropylmethyl)-benzene 19b. In a
similar way, 18b (2.98 g, 10.3 mmol), lithium bromide
(0.98 g, 11.3 mmol), n-butyllithium (4.52 mL of 2.5 M
solution in hexane, 11.3 mmol), THF (32 mL) and ether
(14 mL) gave, after purification by kugelrohr distillation
5
(
0 mL). The combined extracts were washed with brine
50 mL), dried (MgSO ) and evaporated under reduced
4
pressure. Purification by flash column chromatography
SiO ) eluting with petrol–ether 95:5 yielded the acylsilane
(
2
9f as a pale yellow oil (792.5 mg, 75%); spectroscopic data
as reported.
[200 8C (1 mmHg)], the bromide 19b as a pale yellow oil
(film)/cm
max
3
5
K1
(1.5 g, 70%); R (petrol–ether, 49:1) 0.91; n
f
3
061, 3027, 2919 (C–H) and 736 (C–Br); dH (300 MHz;
4
.1.12. (2,2-Dibromocyclopropyl)-benzene 18a. By the
6
6
CDCl ) 7.37–7.21 (5H, m, ArH), 2.78 (1H, dd, JZ15.0,
5.5 Hz, PhCH H ), 2.74 (1H, dd, JZ6.5, 4.0 Hz, CHBr),
2.63 (1H, dd, JZ15.0, 7.0 Hz, PhCH H ), 1.62–1.51 (1H,
m, CHCHBr), 1.24–1.12 (1H, m, CHBrCH H ) and 0.98–
0.87 (1H, m, CHBrCH H ); d (75 MHz; CDCl ) 140.0,
3
3
6
method of de Land et al., styrene (13.88 g, 0.13 mol),
bromoform (50.0 g, 0.20 mol) and triethylbenzylammonium
chloride (0.4 g, 1.76 mmol) were stirred vigorously. A
solution of sodium hydroxide (20.8 g, 0.52 mol) in water
A
B
A
B
A
B
A
B
C
3
(
21 mL) was then added in small portions, at such a rate that
128.7, 128.6, 126.6 (Aromatic), 38.4, 23.2, 19.9 and 15.9.
the temperature of the mixture remained below 50 8C. When
all the sodium hydroxide had been added and the
exothermic reaction had subsided, the reaction mixture
was stirred for an additional 2 h at 60 8C after which time
water (80 mL) was added. After extraction with dichloro-
methane (3!100 mL), the combined organic fractions were
6.1.16. 1,4-Diphenyl-4-trimethylsilylbutan-1-one 20a. To
a stirred solution of 19a (196.2 mg, 0.84 mmol) in ether
(10 mL) was added t-butyllithium (1.01 mL of 1.66 M
solution in hexane, 1.68 mmol) drop-wise at 0 8C, and the
mixture was left to stir at this temperature for 1 h. The
reaction was cooled to K80 8C and a solution of 9a
(150 mg, 0.84 mmol) in THF (15 mL) was added drop-wise
over 10 min. After the addition was complete the reaction
was allowed to warm to K30 8C over 30 min. The reaction
mixture was quenched by the addition of saturated aqueous
ammonium chloride solution (5 mL). The solvents were
removed under reduced pressure and water (15 mL) was
added. The aqueous phase was extracted with ether (3!
20 mL) and the combined organic layers were dried
washed with water (100 mL), dried (MgSO ) and the
4
solvents were removed under reduced pressure. Distillation
[
120 8C (12 mmHg)] of the residue afforded the dibromide
18a as a colourless oil (24.0 g, 67%); spectroscopic data as
reported.
3
5
4
6
6
.1.13. (2,2-Dibromocyclopropylmethyl)-benzene 18b.
In similar way, allylbenzene (6.31 g, 53.4 mmol), bromo-
form (20.26 g, 80.16 mmol), triethylbenzylammonium
chloride (200 mg, 0.88 mmol), sodium hydroxide (20.0 g,
(MgSO ), filtered and concentrated under reduced pressure.
4
0
distillation of the crude product [120 8C (1 mmHg)], the
.5 mol), water (20 mL) and ethanol (0.32 mL) gave, after
Purification by flash column chromatography (SiO ) eluting
2
with petrol–ethyl acetate 19:1 yielded the title compound
20a as a pale yellow oil (99.1 mg, 40%); R (petrol–ethyl
dibromide 18b as a pale brown oil (3.10 g, 20%); R (petrol–
f
f
K1
K1
ethyl acetate, 49:1) 0.83; nmax (film)/cm
2
3062, 3028,
915 (C–H) and 735 (C–Br); d (300 MHz; CDCl ) 7.43–
acetate, 49:1) 0.33; nmax (film)/cm
2953, 2895 (C–H),
1685 (C]O), 1248 an 838 (Si–C); d (300 MHz; CDCl )
H 3
H
3
7
.28 (5H, m, ArH), 3.09 (1H, dd, JZ15.5, 4.0 Hz,
7.87–7.05 (10H, m, ArH), 3.01–2.80 (2H, m, CH -2), 2.28–
2
PhCH H ), 2.83 (1H, dd, JZ15.5, 6.5 Hz, PhCH CH ),
2.16 (2H, m, CH K3), 2.10 (1H, dd, JZ10.0, 5.0 Hz, CH-4)
A
B
A
B
2

J. Clayden et al. / Tetrahedron 61 (2005) 3195–3203
3201
and K0.01 (9H, s, Si(CH ) ); d (75 MHz; CDCl ) 200.9
3
(75 MHz; CDCl ) 200.3, 140.8, 139.5, 137.4, 133.8, 132.9,
3
3
C
3
(
1
C]O), 142.9, 137.1, 133.0, 128.6, 128.4, 128.1, 127.8,
24.7 (Aromatic), 38.3, 36.7, 24.0 and K2.9; m/z 297 (80%,
MCH ), 314 (50%, MCNH ); Found MH , 297.1670.
129.5, 129.1, 128.6, 128.5, 128.2, 128.1, 126.2 (Aromatic),
45.5, 43.7, 27.1, 21.4, K1.8 and K2.0; m/z 390 (30%, MC
C
C
4
C
C
4
C
NH ); Found M , 372.1900. C H OSi requires M
25 28
C H OSi requires M 297.1674).
19 24
372.1909.
4
6.1.20. Cyclopropanecarbaldehyde 26. By the procedure
8
6
.1.17. 4-(Dimethylphenylsilanyl)-1,4-diphenylbutan-1-
one 20b. In a similar way, 9b (150 mg, 0.63 mmol), 19a
147 mg, 0.75 mmol), t-butyllithium (0.98 mL, 1.25 M solu-
4
9
of Heck et al., cyclopropylmethanol (22.1 g, 0.31 mol)
dissolved in dichloromethane (20 mL) was added rapidly to
a stirred solution of pyridinium chlorochromate (100.0 g,
0.46 mol) in dichloromethane (100 mL) at room tempera-
ture. After stirring for 3 h the mixture was passed through a
short column of silica. The black residue was rinsed with
ether and the washings were also put through the column.
The combined eluates were concentrated under reduced
pressure to afford the aldehyde 26 as a green oil (10.5 g,
(
tion in ether, 1.23 mmol), ether (15 mL), THF (15 mL) and
saturated ammonium chloride solution (3 mL) gave, after
purification by flash column chromatography (SiO ) eluting
with petrol–ethyl acetate 99:1, the title compound 20b as a
pale yellow oil (80 mg, 35%); R (petrol–ethyl acetate, 24:1)
2
f
K1
.20; nmax (film)/cm 3064, 3023, 2955, 2894 (C–H), 1684
0
(
C]O), 1251 and 832 (Si–C); d (300 MHz; CDCl ) 7.84–
H 3
4
8
6
.86 (15H, m, ArH), 2.92 (1H, ddd, JZ17.5, 8.5, 6.0 Hz,
49%); spectroscopic data as reported.
CH H K2), 2.81 (1H, ddd, JZ17.5, 8.0, 6.5 Hz, CH H -2),
A
B
A B
2
CH H -3 and CH H -3), 0.33 (3H, s, SiCH ) and 0.26
.36 (1H, dd, JZ12.0, 4.0 Hz, CHK4), 2.31–2.18 (2H, m,
6.1.21. 2-Cyclopropyl-[1,3]dithiane 27. By a modification
5
0
A
B
A
B
3A
of the procedure of Moran et al., boron trifluoride diethyl
etherate (85.2 g, 0.60 mol) was added slowly to a stirred
solution of aldehyde 26 (10.5 g, 0.15 mol), 1,3-propane-
dithiol (16.7 g, 0.15 mol) in dichloromethane (300 mL) and
(
3H, SiCH ); d (75 MHz; CDCl ) 200.9 (C]O), 142.4,
3B C 3
1
1
42.2, 137.2, 134.4, 133.1, 129.4, 128.7, 128.5, 128.3,
28.2, 127.9, 125.1 (Aromatic), 38.4, 36.5, 24.3, K3.7 and
C
˚
K5.9; m/z 281 (100%, M-Ph), 376 (10%, MCNH ); Found
MNH , 376.2089. C H OSi requires MNH 376.2097.
24 26
molecular sieves (4 A) (150 g) at 0 8C. The solution was
4
C
4
4
stirred for 2 h at 0 8C and warmed to room temperature and
was stirred for another 15 h. A saturated aqueous solution of
sodium bicarbonate (200 mL) was then cautiously added
and the aqueous phase was extracted with chloroform (3!
200 mL). The combined organic phases were dried
6
2
.1.18. 1,4-Diphenyl-3-trimethylsilylmethylbutan-1-one
1a. In a similar way, 19b (177 mg, 0.84 mmol), 9a
(
150 mg, 0.84 mmol), t-butyllithium (0.91 mL, 1.85 M
solution in ether, 1.68 mmol), ether (15 mL), THF (15 mL)
and saturated aqueous ammonium chloride solution (3 mL)
gave, after purification by flash column chromatography
(MgSO
The crude product was distilled [80 8C (1 mmHg)] to yield
the dithiane 27 as a colourless oil (9.8 g, 41%); R (petrol–
4
), filtered and concentrated under reduced pressure.
f
K1
(
compound 21a as a pale yellow oil (115 mg, 44%); Rf
SiO ) eluting with petrol–ethyl acetate 19:1, the title
ethyl acetate, 49:1) 0.25; nmax (film)/cm
2897 and 2826 (C–H); d (300 MHz; CDCl
JZ10.0 Hz, CHS
2.16–2.06 (1H, m, SCH
SCH CH ), 1.12–1.00 (1H, m, CHCS
(2H, m, CHCH2A) and 0.49–0.43 (2H, m, CHCH2B); d
(75 MHz; CDCl ) 52.5 (CS ), 31.0, 26.2, 16.1 and 5.9; m/z
3003, 2935,
2
) 3.41 (1H, d,
H
3
K1
(
2
(
petrol–ethyl acetate, 49:1) 0.85; nmax (film)/cm
952, 2896 (C–H), 1684 (C]O), 1248 and 839 (Si–C); dH
300 MHz; CDCl ) 7.85–7.18 (10H, m, ArH), 2.99 (1H, dd,
3026,
2
), 2.90–2.78 (4H, m, SCH2A and SCH2B),
CH ), 1.93–1.78 (1H, m,
), 0.72–0.60
H
A B
2
H
3
2
A
B
2
JZ16.5, 5.0 Hz, CH H -2), 2.84–2.72 (2H, m, CH H -2
C
A
B
A B
and CH H -4), 2.61–2.51 (2H, m, CH H K4 and CH-3),
0
3
2
A
B
A B
C
C
.75 (1H, dd, JZ15.0, 5.5 Hz, CH H CH-3), 0.67 (1H, dd,
161 (90%, MCH ); Found M , 160.0369. C
requires M 160.0380.
H S
7 12 2
A
B
JZ15.0, 7.0 Hz, CH H CH-3) and 0.02 (9H, s, Si(CH ) );
A
B
3 3
d (75 MHz; CDCl ) 200.4 (C]O), 140.9, 137.6, 133.0,
C
3
1
4
29.5, 128.7, 128.5, 128.2, 126.3, 126.3 (Aromatic), 45.6,
3.8, 33.4, 22.4 and K0.4; m/z 311 (80%, MCH ), 328
6.1.22. (2-Cyclopropyl-[1,3]dithian-2-yl)-trimethylsilane
28. By the method used for 16b, 27 (9.80 g, 66.2 mmol),
chlorotrimethylsilane (8.24 g, 75.9 mmol), n-butyllithium
(29.9 mL, 2.4 M solution in pentane, 71.8 mmol) and THF
C
C
C
(30%, MCNH ); Found MH , 311.1830. C H OSi
4 20 26
requires MH 311.1831.
(
100 mL) gave the silane 28 as a colourless oil (14.4 g,
K1
6
.1.19. 3-[(Dimethylphenylsilyl)methyl]-1,4-diphenyl-
butan-1-one 21b. In a similar way, 19b (186 mg,
.88 mmol), 9b (176 mg, 0.73 mmol), t-butyllithium
94%); R
3002, 2954, 2913 (C–H), 1247 and 845 (Si–C); d
(300 MHz; CDCl ) 2.83 (2H, t, JZ13.0 Hz, SCH2ACH ),
2.30–2.25 (2H, m, SCH2BCH ), 1.90–1.85 (1H, m, SCH
CH ), 1.73–1.61 (1H, m, SCH CH ), 1.16–1.12 (1H,
m, CHCH ), 0.39–0.32 (4H, m, CHCH2A and CHCH2B) and
0.00 (9H, s, Si(CH ); d (75 MHz; CDCl ) 67.8 (CS Si),
25.0, 24.5, 20.4, 2.8, K3.1; m/z 233 (90%, MCH ); Found
f
(petrol–ethyl acetate, 49:1) 0.68; nmax (film)/cm
H
0
3
2
(
(
1.07 mL, 1.37 M solution in ether, 1.47 mmol), ether
15 mL), THF (15 mL) and saturated aqueous ammonium
2
-
2
H
H
A B
A
B
2
chloride solution (3 mL) gave, after purification by flash
column chromatography (SiO ) eluting with petrol–ethyl
acetate, the title compound 21b as colourless plates (79 mg,
2
)
3
2
3
C
3
2
C
C
2
0
9%), mp 32–33 8C 99:1; R (petrol–ethyl acetate, 49:1)
f
M , 232.0769. C10H S Si requires M 232.0776.
20 2
K1
.23; nmax (film)/cm
3064, 3025, 2955 (C–H), 1683
(
7
C]O), 1250 and 832 (Si–C); d (300 MHz; CDCl ) 7.75–
3
.08 (15H, m, ArH), 2.91 (1H, dd, JZ16.0, 5.5 Hz,
6.1.23. Cyclopropyltrimethylsilylmethanone 29. By the
method used for 9b, 28 (13.1 g, 60.0 mmol), chloramine-T
hydrate (87.5 g, 0.31 mol), methanol (150 mL), water
(38 mL) gave a crude product. During work-up, the solvent
from the combined organic fractions was removed by
distillation through a vigreux column at atmospheric
H
CH H K2), 2.75 (1H, dd, JZ16.0, 6.5 Hz, CH H -2),
2
A
B
A B
.71–2.51 (3H, m, CH H -4, CH H -4 and CHK3), 1.01
A B A B
(
1H, dd, JZ15.0, 6.0 Hz, SiCH H C-3), 0.99 (1H, dd, JZ
A B
1
5.0, 7.0 Hz, SiCH H C-3) and 0.32 (6H, s, Si(CH ) ); d
A B 3 2 C

3202
J. Clayden et al. / Tetrahedron 61 (2005) 3195–3203
pressure (Care! Product has a low boiling point) to afford the
title compound 29 as pale yellow oil (3.69 g, 47%); Rf
Si(CH ) ); d (75 MHz; CDCl ) 200.7 (C]O), 137.2,
3 3 C 3
132.9, 128.6, 128.1 (Aromatic), 42.4, 19.2, 16.7 and K1.7.
K1
(
2
petrol–ethyl acetate, 49:1) 0.28; nmax (film)/cm
3005,
959, 2901 (C–H), 1625 (C]O), 1249 and 864 (Si–C); dH
6.1.27. 1-Cyclopropyl-3-phenyl-3-trimethylsilylpropan-
1-one 36a. By the method used for 20a, cyclopropyltri-
methylsilylmethanone (29) (150.0 mg, 1.06 mmol), b-
bromostyrene (252.2 mg, 1.34 mmol), t-butyllithium
(1.66 mL, 1.28 M solution in ether, 2.12 mmol), ether
(
300 MHz; CDCl ) 2.49 (1H, tt, JZ8.0, 4.5 Hz, CHCO),
3
1
.05–1.01 (2H, m, CH ), 0.84–0.79 (2H, m, CH ), 0.23
2A 2B
(
9H, s, Si(CH ) ; d (75 MHz; CDCl ) 142.2 (C]O), 25.3,
3 3 C 3
1
1.4 and K2.99.
(15 mL), THF (15 mL) and saturated aqueous ammonium
chloride solution (3 mL) gave, after purification by flash
column chromatography (SiO ) eluting with petrol–ethyl
2
6
.1.24. 1-Cyclopropyl-1-trimethylsilylpentan-1-ol 30. n-
Butyllithium (0.43 mL, 2.45 M solution in pentane,
.05 mmol) was added drop-wise to THF (15 mL) at
acetate 49:1, the title compound 36a as a colourless oil
1
(
(
110 mg, 42%); R (petrol–ethyl acetate, 49:1) 0.18; n
f max
K78 8C with stirring. A solution of 29 (150 mg, 1.06 mmol)
in THF (15 mL) was added drop-wise. The reaction mixture
was allowed to warm to 0 8C over 40 min, and was
quenched by the addition of saturated aqueous solution
ammonium chloride (3 mL). The solvents were removed
using a rotary evaporator and water (15 mL) was added. The
mixture was extracted with ether (3!15 mL). The com-
bined organic layers were then dried (MgSO ) and
4
concentrated to afford a crude oil. Purification by flash
column chromatography (SiO ) eluting with petrol–ethyl
K1
film)/cm 3024, 2955, 2897 (C–H), 1698 (C]O), 1249
and 840 (Si–C); d (300 MHz; CDCl ) 7.29–7.40 (5H, m,
3
H
ArH), 3.10 (1H, dd, JZ16.5, 10.5 Hz, CH H K2), 2.91
A
B
(
1H, dd, JZ16.5, 5.0 Hz, CH H -2), 2.75 (1H, dd, JZ10.5,
A B
5
CH ), 0.89–0.84 (2H, m, CHCH CH ), 0.79–0.73 (2H,
.0 Hz, CHK3), 1.92 (1H, tt, JZ7.5, 4.5 Hz, CHCH -
2A
2
B
2A
2B
m, CHCH2ACH ) and K0.01 (9H, s, Si(CH ) ); d
C
2B
3 3
(
75 MHz; CDCl ) 210.4 (C]O), 143.3, 128.3, 127.6,
3
1
m/z 247 (90%, MCH ), 264 (30%, MCNH ); Found
24.8 (Aromatic), 44.2, 31.8, 20.7, 11.0, 10.7 and K2.8;
2
C
C
4
acetate 29:1 yielded the title compound 30 as a colourless
oil (151 mg, 71%); R (petrol–ethyl acetate, 29:1) 0.24; n
C
MH , 247.1509. C H OSi requires MH 247.1518.
1
5 22
f
max
K1
(
film)/cm
3494 (O–H), 3002, 2933, 2903 (C–H), 1248
6
.1.28. 1-(Dimethylphenylsilyl)-5-methyl-1-phenyl-
hexan-3-one 36b. Similarly, b-bromostyrene (324.5 mg,
.78 mmol), 9e (300.0 mg, 1.36 mmol), t-butyllithium
and 837 (Si–C); dH (300 MHz; CDCl ) 1.55 (2H, t, JZ
7
0
3
.5 Hz, CH -2), 1.42–1.30 (4H, m, CH K3 and CH -4),
2 2 2
1
.93 (3H, t, JZ7.0 Hz, CH K5), 0.85 (1H, m, CHC-1), 0.53
3
(
(
2.13 mL, 1.28 M solution in ether, 2.72 mmol), ether
15 mL), THF (15 mL) and water (3 mL) gave, after puri-
(
0
1H, s, OH), 0.42–0.27 (4H, m, CHCH2A and CHCH ) and
.09 (9H, s, Si(CH ) ); d (75 MHz; CDCl ) 65.7 (COH),
3 3 C 3
2B
fication by flash column chromatography (SiO ) eluting
2
3
9.8, 26.2, 23.9, 16.9, 14.4, 0.5, K1.6 and K2.8; m/z 200
C
C
with petrol–ethyl acetate 49:1, the title compound 36b as a
yellow oil (40 mg, 9%); R (petrol–ethyl acetate, 49:1) 0.75;
(45%, MCH ); Found M , 199.1505. C H OSi requires
11 23
M 199.1513.
f
K1
nmax (film)/cm
1
3066, 3023, 2956 (C–H), 1602 (C]O),
251 and 832 (Si–C); dH (300 MHz; CDCl ) 7.48–6.94
3
6
3
.1.25. (Cyclopropylphenylmethoxy)trimethylsilane
1. In a similar way, 29 (150 mg, 1.06 mmol), phenyl-
(
10H, m ArH), 2.95 (1H, dd, JZ11, 23.5 Hz, CH H -2),
51
A B
2
2
.92 (1H, dd, JZ11, 11 Hz, CHK1), 2.63 (1H, dd, JZ11,
3.5 Hz, CH H -2), 2.14 (2H, d, JZ6.5 Hz, CH K4), 2.01
lithium (0.75 mL, 1.41 M solution in ether) and THF
15 mL) gave, after purification by flash column chroma-
tography (SiO ) eluting with petrol–ethyl acetate 49:1, the
A
B
2
(
(1H, t quintet, JZ6.5, 6.5 Hz, CH-5), 0.80 (3H, d, JZ
2
6
CH CH-5), 0.29 (3H, s, SiCH ) and 0.26 (3H, s, SiCH );
.5 Hz, CH CH CH-5), 0.76 (3H, d, JZ6.5 Hz, CH -
3
A
3B
3A
title compound 31 as a colourless oil (86 mg, 37%); Rf
(
K1
petrol–ethyl acetate, 49:1) 0.81; nmax (film)/cm 3006,
957, 2861 (C–H), 1250 and 840 (Si–C); dH (300 MHz;
3B
3A
3B
d (75 MHz; CDCl ) 210.1, (C]O), 142.5, 137.0, 134.4,
C
3
2
1
3
29.6, 128.4, 128.0, 127.9, 125.1 (Aromatic), 52.2, 43.9,
1.4, 24.5, 22.8, 22.6, K3.7 and K5.0; m/z 247 (100%, MK
CDCl ) 7.41–7.27 (5H, m, ArH), 4.12 (1H, d, JZ7.0 Hz,
CHPh), 1.23–1.12 (1H, m, CHCPh), 0.61–0.32 (4H, m,
PhCHCHCH2A and PhCHCHCH ) and 0.08 (9H, s,
3
C
C
Ph), 342 (10%, MCNH ); Found MNH , 342.2252.
C H OSi requires MNH 342.2253.
4
4
2B
2
1
28
4
Si(CH ) ); d (75 MHz; CDCl ) 145.4, 128.3, 127.2,
3
3
C
3
1
26.2 (Aromatic), 78.4, 20.2, 3.9, 3.1 and 0.5.
6
.1.29. 1-(Dimethylphenylsilyl)-4,4-dimethyl-1-phenyl-
5
3
pentan-3-one 36c. Similarly, 1-(dimethylphenylsilyl)-
2,2-dimethylpropan-1-one 9f (150 mg, 0.68 mmol), b-
bromostyrene (162.29 mg, 0.89 mmol), t-butyllithium
(1.01 mL, 1.35 M solution in ether, 1.36 mmol), THF
(15 mL), ether (15 mL) and saturated aqueous ammonium
chloride solution (3 mL) gave, after purification by flash
5
.1.26. Trimethylsilylbutan-1-one 32. In a similar way,
2
6
after stirring at K78 8C for 5 min the reaction mixture was
warmed to room temperature over 40 min, and quenched
by the addition of saturated aqueous ammonium chloride
solution at this temperature. Quantities used were 29
(
solution in ether, 1.06 mmol), THF (15 mL). Purification
by flash column chromatography (SiO ) eluting with petrol–
2
150 mg, 1.06 mmol), phenyllithium (0.75 mL, 1.41 M
column chromatography (SiO ), eluting with petrol–ethyl
2
acetate 49:1, the title compound 36c as colourless plates
(130 mg, 59%), mp 42–44 8C; R (petrol–ethyl acetate,
f
K1
ethyl acetate 49:1 yielded the title compound 32 as a
colourless oil (182 mg, 78%); R (petrol–ethyl acetate, 49:1)
49:1) 0.29; nmax (film)/cm
2963 (C–H), 1705 (C]O),
1250 and 816 (Si–C); d (300 MHz; CDCl ) 7.51–7.00 (5H,
H 3
f
K1
0
1
.37; nmax (film)/cm
2952, 2892 (C–H), 1687 (C]O),
248 and 838 (Si–C); d (300 MHz; CDCl ) 7.99–7.36 (5H,
m, ArH), 3.17(1H, dd, JZ17.0, 9.5 Hz, CH H K2), 3.07
A B
(1H, dd, JZ9.5, 3.0 Hz, CH-1), 2.73 (1H, dd, JZ17.0,
3.0 Hz, CH H K2), 1.06 (9H, s, C(CH ) ), 0.32 (3H, s,
H
3
m, ArH), 3.01 (3H, t, JZ7.5 Hz, CH -2), 1.83–1.72 (2H, m,
2
A
B
3 3
CH K3), 0.60 (2H, t, JZ8.5 Hz, CH -4) and 0.02 (9H, s,
Si(CH ) ) and 0.28 (3H, s, Si(CH ) ); d (75 MHz; CDCl )
3 A 3 B C 3
2
2

J. Clayden et al. / Tetrahedron 61 (2005) 3195–3203
3203
2
14.3 (C]O), 143.2, 137.3, 134.4, 129.5, 128.3, 128.1,
24. Takeda, K.; Nakajima, A.; Yoshii, E. Synlett 1996, 753.
1
K4.7; m/z 247 (100%, MKPh), 342 (30%, MCNH );
28.0, 124.9 (Aromatic), 44.2, 37.4, 30.3, 26.6, K3.4 and
25. Takeda, K.; Nakajima, A.; Takeda, M.; Yasushi, O.; Sato, T.;
Yoshii, E.; Koizume, T.; Shiro, M. J. Am. Chem. Soc. 1998,
120, 4947.
C
4
C
Found M , 342.2248. C H OSi requires MNH
4
2
1
28
3
24.1909.
26. Takeda, K.; Nakajima, A.; Takeda, M.; Yoshii, E. Org. Synth.
1
999, 76, 199.
2
7. Takeda, K.; Nakane, D.; Takeda, M. Org. Lett. 2000, 2, 1903.
8. Reich, H. J.; Eisenart, E. K.; Olson, R. E.; kelly, M. J. J. Am.
Chem. Soc. 1986, 108, 7791.
Acknowledgements
2
We are grateful to the EPSRC and Merck Sharp and Dohme
Ltd for a CASE award (to D.W.W.).
2
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