A convenient allylic functionalization of bis(prop-2-enyl)methanol by direct trimetalation

Article abstract of DOI:10.1055/s-0028-1083196

A practical synthesis of functionalized symmetrical dialkenylcarbinols has been developed. Key feature is a direct trilithiation of readily available bis(prop-2-enyl)methanol followed by trapping of the trianion with various electrophiles. This simple protocol allows rapid derivatization and preparation of compounds inaccessible by currently existing methods. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0028-1083196

3692
PAPER
A Convenient Allylic Functionalization of Bis(prop-2-enyl)methanol by Direct
Trimetalation
A
llylic Functional
u
r
é
enyl)metha
l
nol ien Bigot, Bernhard Breit*
Institut für Organische Chemie und Biochemie, Freiburg Institute for Advanced Studies (FRIAS), Albert-Ludwigs-Universität Freiburg,
Albertstr. 21, 79104 Freiburg, Germany
Fax +49(761)2038715; E-mail: bernhard.breit@chemie.uni-freiburg.de
Received 29 July 2008
have developed an efficient access to this class of com-
Abstract: A practical synthesis of functionalized symmetrical
pounds through the addition of 2 equivalents of an alke-
dialkenylcarbinols has been developed. Key feature is a direct
trilithiation of readily available bis(prop-2-enyl)methanol followed
by trapping of the trianion with various electrophiles. This simple
nylmetal species to ethyl formate.7b The alkenylmetal
intermediate is generated through Grignard synthesis,
protocol allows rapid derivatization and preparation of compounds halogen/lithium exchange with t-BuLi or, alternatively,
inaccessible by currently existing methods.
through a Shapiro reaction of the trisylhydrazone
(trisyl = 2,4,6-triisopropylphenyl).
Key words: alkenes, alcohols, lithiation, metalations, organometal-
lic reagent
Mg (2 equiv), THF, ∆
Br
R
R
or t-BuLi (1.7 equiv)
THF, –78 °C
OH
Mirror symmetrical dialkenylcarbinol moieties of type 1
are important building blocks particularly appealing for
desymmetrizing processes.1 A growing number of useful
enantioselective transformations have appeared in these
past years such as asymmetric epoxidation,2 hydrosilyla-
tion,3 carbonyl ene addition,4 cyclopropanation,5 ring-
closing metathesis,6 and hydroformylation7 (Scheme 1).
R
[M]
R
R
HCO2Et
(0.4–0.5 equiv)
0 °C
2
M = Li, MgX
n-BuLi (2 equiv)
NHSO2Ar
R = Me, Et, i-Pr,
t-Bu, CH2TMS
N
THF, –78 °C to 0 °C
63–87% yield
Me
Scheme 2 Synthetic route to dialkenylcarbinols bearing alkyl sub-
stituents
OR'
R
CO2Me
OH
Unfortunately, this approach failed as we tried to prepare
dialkenylcarbinols having electron-withdrawing groups at
the allylic position. This is mainly due to the propensity of
the alkenylmetal to undergo 1,2-elimination, even at low
temperatures, to furnish the allene (Scheme 3).8
R''
Si
O
R''
O
O
H
ref. 4
R
R
ref. 5
ref. 3
R
R
OR'
R
R
OH
HCO2Et
[M]
ref. 6
ref. 2
1
+
R
R
R
RM
•
O
OR'
R
2
R
R
O
R = OR', SR', NR'SO2R'', F
ref. 7
R
Scheme 3 Competitive 1,2-elimination of the alkenylmetal species
OR'
R
R = alkyl, alkylFG
R', R'' = see
corresponding ref.
To circumvent this problem we wondered whether such
functionalized dialkenylcarbinol derivatives could be ac-
cessed through a direct functionalization of bis(prop-2-
enyl)methanol (3) by deprotonation of both allylic posi-
tions and subsequent trapping of the trianion with an ap-
propriate electrophile. This would additionally offer the
opportunity for rapid derivatization from a common and
readily available precursor.9
The deprotonation of methallylic alcohols is known.10
Trost et al. have optimized and extensively used a lithia-
tion protocol using an excess of n-BuLi/TMEDA complex
in a Et2O–THF mixture for silylation and stannylation of
the formed dianions.11 However, this method suffers from
moderate yields mainly due to the formation of side prod-
R
O
Scheme 1 Enantioselective desymmetrizing processes of dialkenyl-
carbinol ethers and esters 1
Nevertheless the scope of these methodologies is limited
by the scarcity of efficient synthetic procedures to access
dialkenylcarbinols 2 bearing diversely functionalized sub-
stituents R (Scheme 2). In the course of our investigation
towards a desymmetrizing hydroformylation reaction, we
SYNTHESIS 2008, No. 22, pp 3692–3696
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x.
x
x
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2
0
0
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Advanced online publication: 23.10.2008
DOI: 10.1055/s-0028-1083196; Art ID: 17408SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Allylic Functionalization of Bis(prop-2-enyl)methanol
3693
ucts resulting from undesired vinylic deprotonation. We fair to good yields, demonstrating the utility of this meth-
report herein a general and efficient extension of this od since the corresponding products could not be obtained
method allowing for the direct functionalization of by our previous route. A range of allylsilane carbinols
bis(prop-2-enyl)methanol (3) through trimetalation.
could be prepared (entries 6–8) as well. In this case, in situ
deprotection of the silylated hydoxyl function occurred
upon acidic workup.13
We started our investigations by adapting the Trost proto-
col to our system,11a using Me3SnCl as the electrophile as
we were particularly interested in the rapid generation of
carbinols bearing various trialkylstannane moieties
(Table 1). Treatment of 3 with 5 equivalents of n-BuLi in
a mixture of Et2O–hexane–THF in the presence of
TMEDA (6 equiv) at 0 °C, further stirring for 4 hours at
25 °C, and subsequent quenching with Me3SnCl led to the
detection of only traces of desired product 4 (entry 1).
However, the reaction proved to proceed very cleanly
with only unreacted starting material present, which left
us optimistic for possible improvement. Indeed, switching
to slightly more basic s-BuLi under otherwise identical
conditions afforded smoothly the desired product in 44%
isolated yield together with recovered 3 and only traces of
monostannylated product (entry 2). While an increased re-
action time led mostly to degradation (entry 3), the modi-
fication of the solvent polarity (without THF)12 furnished
after standard workup the desired product in 64% yield
(entry 4). Finally, treatment of 3 with 2 additional equiv-
alents of s-BuLi and TMEDA allowed the complete con-
version to the trianion. Trapping with the tin electrophile
gave 4 in 80% isolated yield (entry 5).
Table 2 Scope of the Transformation of 3
OH
OH
i) s-BuLi (7 equiv)
TMEDA (8 equiv)
Me
Me
R
R
0–25 °C, 4 h
ii) electrophile
4–11
3
Entry
Electrophile (equiv)
Me3SnCl (3)
Product (R)
4 (Me3Sn)
5 (Bu3Sn)
6 (OH)
Yield (%)
80
1
2
3
4
5
6
7
8
Bu3SnCl (3)
73
Davis oxaziridine (5)
PhSSPh (3)
31
7 (PhS)
38
MeSSMe (5)
8 (MeS)
60
Me3SiCl (5)
9 (Me3Si)
75a
Me2PhSiCl (5)
Et3SiCl (5)
10 (Me2PhSi)
72a
11 (Et3Si)
79a
a Overall yields after desilylation of the hydroxy group (see experi-
mental section).
Table 1 Optimization of the Trimetalation Protocol of 3
OH
OH
For further synthetic use, we could selectively protect the
primary hydroxy functions of triol 6 to provide carbinol
12 in good yield (Scheme 4), which is a particularly inter-
esting building block for polypropionate synthesis. While
our attempts of trapping the trianion with various fluorine
electrophiles were unsuccessful, we envisoned to get ac-
cess to this interesting compound by functionalization of
the diallylsilane 9 via an electrophilic fluorodesilylation
reaction. Indeed, treatment of diallylsilane 9 with Select-
fluorTM in acetonitrile overnight at room temperature fur-
nished smoothly the difluoride 13 in high yield.14
i) base, TMEDA
0–25 °C, time
Me
Me
Me3Sn
SnMe3
3
4
ii) Me3SnCl (3 equiv)
Entry Base
(equiv)
TMEDA Solvent
(equiv)
(ratio)a
Time Yield
(h)
(%)b
n.d.c
1
2
3
n-BuLi (5)
s-BuLi (5)
s-BuLi (5)
6
6
6
Et2O–hexane–THF
(2:1:1)
4
Et2O–Cy–THF
(2:1:1)
4
44
In summary, we have developed a practical and efficient
complementary access to functionalized symmetrical di-
alkenylcarbinols involving a direct trimetalation of readi-
ly available bis(prop-2-enyl)methanol (3). This method
Et2O–Cy–THF
(2:1:1)
20
n.d.d
4
5
s-BuLi (5)
s-BuLi (7)
6
8
Et2O–Cy (3:1)
Et2O–Cy (3:2)
4
4
64
80
TBDPSCl
(2 equiv)
imidazole
(3 equiv)
a Cy = cyclohexane.
OH
OH
b Isolated yields of pure 4.
c Trace of product is detected according to TLC.
d Complex mixture.
TBDPSO
OTBDPS
HO
OH
4 Å MS
CH2Cl2
–20 °C, 2 h
12
6
66%
With these optimized conditions in hand, we next turned
our attention to investigate the reaction scope (Table 2).
The method proved to tolerate even bulky electrophiles al-
lowing a clean introduction of a Bu3Sn substituent in good
yields (entry 2). Trapping the trianion with an oxygen
electrophile (Davis oxaziridine, entry 3) or with sulfur
electrophiles (entries 4, 5) led to the desired products in
SelectfluorTM
(2 equiv)
OH
OH
Me3Si
SiMe3
F
F
MeCN, r.t., 12 h
86%
9
13
Scheme 4 Further functionalization of the products
Synthesis 2008, No. 22, 3692–3696 © Thieme Stuttgart · New York

3694
A. Bigot, B. Breit
PAPER
1.77 (dd, J = 11.7, 0.9 Hz, 2 H), 4.31 (pq, J = 3.4, 3.3 Hz, 1 H), 4.68
(td, J = 9.3, 1.0 Hz, 2 H), 4.83 (tt, J = 9.9 Hz, 1.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 9.9 (6 C), 13.8 (6 C), 14.1 (2 C),
27.4 (6 C), 29.2 (6 C,), 80.3, 106.5 (2 C), 150.2 (2 C).
allows rapid derivatization and preparation of compounds
otherwise inaccessible by previously developed strate-
gies.
HRMS: m/z calcd for C27H55OSn2 [M – Bu]+: 633.2290; found:
633.2299.
Reactions were performed in flame-dried glassware under argon
(purity >99.998%). The solvents were dried by standard procedures,
distilled, and stored under argon. Petroleum ether (PE) refers to the
fraction with bp 40–60 °C. All temperatures quoted are uncorrect-
ed. 1H, 13C NMR spectra: Varian Mercury 300 HFCP, Bruker AM
400 with CHCl3 as internal standard. 19F NMR spectra: Bruker AM
400 with CCl3F as external standard. Melting points: apparatus by
Dr. Tottoli (Büchi). Elemental analyses: VarioEL (Elementaranaly-
sen GmbH). Mass spectrometry: Thermo Finnigan MAT 8200 and
TSQ 7000. Flash chromatography: Silica gel 40–63 mm (230–400
mesh, Macherey-Nagel). Organolithium reagents were titrated with
2-(phenylhydrazonomethyl)phenol.15 The following compounds
were prepared according to literature procedure: 2,4-dimethylpen-
ta-1,4-dien-3-ol (3)9 and 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziri-
dine (Davis oxaziridine).16
2,4-Bis[(tert-butyldiphenylsilyloxy)methyl]penta-1,4-dien-3-ol
(12)
According to the general procedure (except for the workup), depro-
tonation of 3 (500 mg, 4.4 mmol) with s-BuLi (23.0 mL, 31.2 mmol,
7 equiv, 1.36 M) in the presence of TMEDA (5.3 mL, 35.6 mmol, 8
equiv) in Et2O (44.5 mL) and subsequent quenching with Davis ox-
aziridine (5.82 g, 22.2 mmol, 5 equiv) dissolved in THF (18 mL) af-
forded, after workup (few drops of aq sat. NH4Cl were added at
25 °C, 2 g of silica gel was poured into the mixture, and all volatile
materials were removed in vacuo) and chromatography [EtOAc–
MeOH, 95:5, Rf = 0.21 (EtOAc–MeOH, 95:5)] the triol 6 (199 mg,
1.3 mmol, 31%) as a light yellow oil, which was directly converted
into 12, as follows. Triol 6 (199 mg, 1.3 mmol) was suspended in
CH2Cl2 (13 mL) in the presence of 4 Å MS and the mixture was
stirred 1 h at 25 °C and then cooled to –20 °C. TBDPSCl (0.7 mL,
2.7 mmol, 2 equiv) was added to the mixture and a solution of imi-
dazole (282 mg, 4.1 mmol, 3 equiv) in CH2Cl2 (5 mL) was slowly
dropped into the mixture and the whole stirred for 2 h at this tem-
perature. After warming to 25 °C, H2O (5 mL) was added, the aque-
ous phase extracted with CH2Cl2 (3 × 8 mL), the combined organic
phases were dried (MgSO4) and the solvents removed in vacuo.
Chromatography on silica gel (PE–CH2Cl2–EtOAc, 10:10:1, Rf =
0.24 (PE–EtOAc, 9:1)] furnished the title compound 12 (565 mg,
0.9 mmol, 66%) as a colorless oil.
1H NMR (400 MHz, CDCl3): d = 1.04 (s, 18 H), 3.08 (d, J = 5.8 Hz,
1 H), 4.06 (dt, J = 13.3, 1.0 Hz, 2 H), 4.15 (d, J = 13.4 Hz, 2 H), 4.76
(d, J = 5.6 Hz, 1 H), 5.21 (m, 2 H), 5.24 (m, 2 H), 7.31–7.43 (m, 12
H), 7.62–7.67 (m, 8 H).
13C NMR (100 MHz, CDCl3): d = 19.5 (2 C), 26.8 (6 C), 64.9 (2 C),
75.1, 112.5 (2 C), 127.7 (4 C), 129.8 (4 C), 133.2 (2 C), 135.6 (2 C),
147.1 (2 C, 2).
MS (CI, NH3): m/z (%) = 621 ([M + H]+, 16), 620 (36), 619 (72),
381 (29), 364 (27), 255 (100).
HRMS: m/z calcd for C35H39O3Si2 [M – t-Bu]+: 563.2437; found:
563.2429.
Functionalized Carbinols from 2,4-Dimethylpenta-1,4-dien-3-
ol (3); General Procedure
To a stirred solution of 3 and freshly distilled TMEDA (8 equiv) in
anhyd Et2O (concd of 3 = 0.1 M) was added dropwise s-BuLi (7
equiv, 1.15–1.36 M in cyclohexane) at 0 °C, then the ice bath was
removed and the resulting yellow mixture was stirred for 4 h at
25 °C. After cooling to 0 °C, the electrophile (3–5 equiv) was added
(pure or dissolved in anhyd Et2O or THF) in one portion and the
mixture was allowed to warm to 25 °C and further stirred for 30
min. The mixture was diluted with Et2O (5 mL/mmol of 3), washed
with an aq sat. CuSO4 (10 mL/mmol of 3), back extracted once with
Et2O (10 mL/mmol of 3) and the combined organic layers were
washed with H2O (10 mL/mmol of 3) and brine (10 mL/mmol of 3),
dried (K2CO3), and the solvents were removed in vacuo. Flash chro-
matography on silica gel furnished the corresponding carbinol
(Table 2).
2,4-Bis[(trimethylstannyl)methyl]penta-1,4-dien-3-ol (4)
According to the general procedure, deprotonation of 3 (500 mg, 4.4
mmol) with s-BuLi (27.1 mL, 31.2 mmol, 7 equiv, 1.15 M) in the
presence of TMEDA (5.3 mL, 35.6 mmol, 8 equiv) in Et2O (44.5
mL) and subsequent quenching with Me3SnCl (13.3 mL, 13.3
mmol, 3 equiv, 1 M in Et2O) furnished after workup and chroma-
tography [PE–Et2O, 25:1 with 1% Et3N, Rf = 0.50 (PE–EtOAc, 9:1)]
the title compound 4 (1.55 g, 3.5 mmol, 80%) as a colorless oil.
2,4-Bis[(phenylsulfanyl)methyl]penta-1,4-dien-3-ol (7)
1H NMR (400 MHz, CDCl3): d = 0.09 (t, J = 26 Hz, 18 H), 1.54 (d,
J = 3.8 Hz, 1 H), 1.63 (dd, J = 11.7, 0.9 Hz, 2 H), 1.77 (dd, J = 11.7,
0.9 Hz, 2 H), 4.31 (pq, J = 3.9, 3.4 Hz, 1 H), 4.68 (pt, J = 10.6 Hz,
2 H), 4.82 (ptt, J = 10.5 Hz, 1.35 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = –8.9 (6 C), 16.4 (2 C), 80.1, 106.6
(2 C), 149.6 (2 C).
According to the general procedure, deprotonation of 3 (100 mg, 0.8
mmol) with s-BuLi (5.4 mL, 6.2 mmol, 7 equiv, 1.15 M) in the pres-
ence of TMEDA (1.0 mL, 7.1 mmol, 8 equiv) in Et2O (8.9 mL) and
subsequent quenching with PhSSPh (584 mg, 2.6 mmol, 3 equiv)
dissolved in THF (3 mL) furnished after workup and chromatogra-
phy [PE–EtOAc, 95:5, Rf = 0.14 (PE–EtOAc, 9:1)] the title com-
pound 7 (99 mg, 0.3 mmol, 38%) as a light yellow oil.
1H NMR (400 MHz, CDCl3): d = 2.21 (br s, 1 H), 3.42 (dd, J = 14.2,
1.2 Hz, 2 H), 3.59 (dd, J = 14.1, 1.1 Hz, 2 H), 5.03 (br s, 1 H), 5.13
(m, 2 H), 5.25 (pt, J = 1.1 Hz, 2 H), 7.17–7.21 (m, 2 H), 7.24–7.29
(m, 4 H), 7.31–7.35 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 36.4 (2 C), 75.6, 115.7 (2 C),
126.6 (2 C), 128.9 (4 C), 130.3 (4 C), 135.9 (2 C), 143.8 (2 C).
MS (CI, NH3): m/z (%) = 329 ([M + H]+, 8), 311 (100), 219 (51),
201 (14).
Anal. Calcd for C13H28OSn2 (437.78): C, 35.67; H, 6.45. Found: C,
35.86; H, 6.37.
2,4-Bis[(tributylstannyl)methyl]penta-1,4-dien-3-ol (5)
According to the general procedure, deprotonation of 3 (400 mg, 3.5
mmol) with s-BuLi (19.2 mL, 24.9 mmol, 7 equiv, 1.30 M) in the
presence of TMEDA (4.2 mL, 28.4 mmol, 8 equiv) in Et2O (35.6
mL) and subsequent quenching with pure Bu3SnCl (2.8 mL, 10.6
mmol, 3 equiv) furnished after workup and chromatography (PE–
Et2O, 25:1 with 1% Et3N, Rf = 0.74 (PE–EtOAc, 9:1)] the title com-
pound 5 (1.7 g, 2.5 mmol, 73%) as a colorless oil.
Anal. Calcd for C19H20OS2 (328.49): C, 69.47; H, 6.14; S, 19.52.
Found: C, 69.29; H, 5.97; S, 19.60.
1H NMR (400 MHz, CDCl3): d = 0.83–0.93 (m, 30 H), 1.25–1.35
(m, 12 H), 1.43–1.53 (m, 12 H), 1.61 (dd, J = 11.8, 0.9 Hz, 2 H),
Synthesis 2008, No. 22, 3692–3696 © Thieme Stuttgart · New York

PAPER
Allylic Functionalization of Bis(prop-2-enyl)methanol
3695
2,4-Bis[(methylsulfanyl)methyl]penta-1,4-dien-3-ol (8)
According to the general procedure, deprotonation of 3 (500 mg, 4.4
mmol) with s-BuLi (24.0 mL, 31.2 mmol, 7 equiv, 1.30 M) in the
presence of TMEDA (5.3 mL, 35.6 mmol, 8 equiv) in Et2O (44.5
mL) and subsequent quenching with pure MeSSMe (1.9 mL, 22.2
mmol, 5 equiv) afforded after workup and chromatography (PE–
EtOAc, 95:5, Rf = 0.14 (PE–EtOAc, 9:1)] the title compound 8 (552
mg, 2.7 mmol, 60%) as a light yellow oil.
1H NMR (400 MHz, CDCl3): d = 2.03 (s, 6 H), 2.92 (d, J = 5.7 Hz,
1 H), 3.02 (dd, J = 13.9, 1.1 Hz, 2 H), 3.18 (dd, J = 13.9, 1.0 Hz, 2
H), 4.98 (d, J = 5.1 Hz, 1 H), 5.11 (m, 2 H), 5.33 (t, J = 1.3 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 14.9 (2 C), 36.2 (2 C), 75.8, 115.3
(2 C), 143.5 (2 C).
MS (CI, NH3): m/z (%) = 205 ([M + H]+, 4), 186 (100), 157 (20),
139 (32), 109 (11).
presence of TMEDA (5.3 mL, 35.6 mmol, 8 equiv) in Et2O (45 mL)
and subsequent quenching with Et3SiCl (3.8 mL, 22.2 mmol, 5
equiv) furnished after workup the crude trisilylated compound,
which was hydrolyzed as follows. The crude mixture was dissolved
in THF (23 mL), H2SO4 (12 mL, 3 M) was slowly added, and the
mixture was stirred overnight at 25 °C. Subsequent workup as de-
scribed for 9, flash chromatography (PE–Et2O, 95:5, Rf = 0.50 (PE–
Et2O, 9:1)] and final bulb-to-bulb distillation (200–210 °C/0.1
mbar) afforded the title compound 11 (1.19 g, 3.5 mmol, 79%) as a
colorless oil.
1H NMR (400 MHz, CDCl3): d = 0.57 (q, J = 8.1 Hz, 12 H), 0.94 (t,
J = 8.0 Hz, 18 H), 1.37 (dd, J = 14.3, 1.0 Hz, 2 H), 1.52 (d, J = 4.0
Hz, 1 H), 1.58 (dd, J = 14.3, 1.0 Hz, 2 H), 4.31 (d, J = 3.2 Hz, 1 H),
4.79 (m, 2 H), 4.99 (t, J = 1.3 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 3.6 (6 C), 7.4 (6 C), 16.4 (2 C),
80.2, 109.6 (2 C), 147.4 (2 C).
MS (CI, NH3): m/z (%) = 341 ([M + H]+, 21), 323 (47), 311 (55),
209 (100), 131 (97), 115 (36), 103 (33).
Anal. Calcd for C9H16OS2 (204.35): C, 52.90; H, 7.89; S, 31.38.
Found: C, 52.86; H, 7.77; S, 31.23.
2,4-Bis[(trimethylsilyl)methyl]penta-1,4-dien-3-ol (9)
Anal. Calcd for C19H40OSi2 (340.69): C, 66.98; H, 11.83. Found: C,
67.29; H, 11.82.
According to the general procedure, deprotonation of 3 (1.0 g, 8.9
mmol) with s-BuLi (45.8 mL, 62.4 mmol, 7 equiv, 1.36 M) in the
presence of TMEDA (10.6 mL, 71.3 mmol, 8 equiv) in Et2O (90
mL) and subsequent quenching with pure Me3SiCl (5.7 mL, 44.5
mmol, 5 equiv) furnished after workup the crude trisilylated com-
pound, which was hydrolyzed as follows. The crude mixture was
dissolved in THF (72 mL), H2SO4 (18 mL, 1 M) was slowly added,
and the mixture was stirred 30 min at 25 °C. Subsequently, Et2O (70
mL) was added, the phases were separated, and the aqueous phase
was extracted with additional Et2O (3 × 40 mL). The combined or-
ganic phases were washed with aq sat. Na2CO3 (150 mL), dried
(K2CO3), and the solvents were removed in vacuo. Flash chroma-
tography [PE–Et2O, 9:1, Rf = 0.32 (PE–Et2O, 9:1)] and final bulb-
to-bulb distillation (120–130 °C/0.1 mbar) afforded the title com-
pound 9 (1.71 g, 6.6 mmol, 75%) as a colorless oil.
2,4-Bis(fluoromethyl)penta-1,4-dien-3-ol (13)
To a solution of 9 (1.0 g, 3.9 mmol) in MeCN (30 mL) was added
SelectfluorTM (2.7 g, 7.7 mmol, 2 equiv) under argon and the mix-
ture was stirred overnight. Then silica gel (2 g) was added, and the
mixture was evaporated to dryness. Flash chromatography of the
residue (PE–Et2O, 8:2, Rf = 0.11 (PE–EtOAc, 9:1)] furnished the ti-
tle compound 13 (513 mg, 3.4 mmol, 86%) as a light yellow oil.
1H NMR (400 MHz, CDCl3): d = 1.96 (d, J = 4.5 Hz, 1 H), 4.82 (dd,
J = 19.2, 11.6 Hz, 2 H), 4.90 (br s, 1 H), 4.94 (dd, J = 19.5, 11.6 Hz,
2 H), 5.39 (dq, J = 2.1, 1.1 Hz, 1 H), 5.42 (br s, 2 H).
13C NMR (100.620 MHz, CDCl3): d = 73.2, 82.8 (2 C, JC,F = 163.0
Hz), 116.1 (2 C, JC,F = 10.2 Hz), 143.8 (2 C, JC,F = 13.6 Hz).
19F NMR (235 MHz, CDCl3): d = –217.3 (td, JH,F = 47.2, 4.0 Hz, 2
F).
Analytical data are identical with the literature values.7b
MS (CI, NH3): m/z (%) = 166 ([M + NH4]+, 100), 86 (8).
HRMS: m/z calcd for C6H8FO [M – CH2F]+: 115.0559; found:
2,4-Bis[(dimethylphenylsilyl)methyl]penta-1,4-dien-3-ol (10)
According to the general procedure, deprotonation of 3 (500 mg, 4.4
mmol) with s-BuLi (22.9 mL, 31.2 mmol, 7 equiv, 1.36 M) in the
presence of TMEDA (5.3 mL, 35.6 mmol, 8 equiv) in Et2O (45 mL)
and subsequent quenching with pure PhMe2SiCl (3.7 mL, 22.2
mmol, 5 equiv) afforded after workup the crude trisilylated com-
pound, which was hydrolyzed as follows. The crude was dissolved
in THF (28 mL) and H2SO4 (10 mL, 1 M) was slowly added and the
whole stirred for 1 h at 25 °C. Subsequent workup as for 9 and flash
chromatography (PE–Et2O, 9:1, Rf = 0.28 (PE–Et2O 95:5)] fur-
nished the title compound 10 (1.22 g, 3.1 mmol, 72%) as a colorless
oil.
115.0559.
Acknowledgment
This work was supported by the Fonds der Chemischen Industrie
and the DFG International Research Training group ‘Catalysts and
Catalytic Reactions for Organic Synthesis’ (GRK 1038). We thank
M. Lutterbeck and C. Giesin for technical assistance as well as
Wacker Chemie AG for generous gift of chemicals.
1H NMR (400 MHz, CDCl3): d = 0.291 (s, 6 H), 0.296 (s, 6 H), 1.55
(dd, J = 14.2, 1.0 Hz, 2 H), 1.73 (dd, J = 14.2, 1.0 Hz, 2 H), 4.02 (d,
J = 3.0 Hz, 1 H), 4.70 (d, J = 0.8 Hz, 2 H), 4.86 (pt, J = 1.26 Hz, 2
H), 7.33–7.35 (m, 6 H), 7.48–7.50 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = –2.7 (s, 4 C), 21.0 (2 C), 79.7,
110.3 (2 C), 127.8 (4 C), 129.1 (2 C), 133.7 (4 C), 139.0 (2 C), 146.4
(2 C).
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3696
A. Bigot, B. Breit
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Synthesis 2008, No. 22, 3692–3696 © Thieme Stuttgart · New York