Facial-selective allylation of methyl ketones for the asymmetric synthesis of α-substituted tertiary homoallylic ethers

Article abstract of DOI:10.1002/1521-3765(20010316)7:6<1304::AID-CHEM1304>3.0.CO;2-9

The asymmetric synthesis of enantiomerically pure α-substituted tertiary homoallylic ethers 4a, 11 and 12a-c by the allylation of ethyl methyl ketone (1a) with γ-substituted allylsilanes 9 a-h is described. The allylsilanes were obtained by a nickel-catal

Full text of DOI:10.1002/1521-3765(20010316)7:6<1304::AID-CHEM1304>3.0.CO;2-9

FULL PAPER
Facial-Selective Allylation of Methyl Ketones for the Asymmetric Synthesis
of a-Substituted Tertiary Homoallylic Ethers
[
a]
[a]
[a]
[a]
Lutz F Tietze,* Ludwig Völkel, Christian Wulff, Berthold Weigand,
[a]
[a]
[b]
[b]
Christian Bittner, Paul McGrath, Keyji Johnson, and Martina Schäfer
Dedicated to Professor Jean Franco Î i s Normant on the occasion of his 65th birthday
Abstract: The asymmetric synthesis of
enantiomerically pure a-substituted ter-
tiary homoallylic ethers 4a, 11 and
in the presence of the trimethylsilyl
ether of N-trifluoroacetylnorpseudo-
ephedrine (3), and catalytic amounts of
a mixture of trimethylsilyl triflate and
trifluoromethanesulfonic acid led to the
homoallylic ethers 4a, 11 and 12a ± c
with two new stereogenic centres, with a
selectivity of 1:9 to >20:1 for the
homoallylic and of 1:99 to >60:1 for
the allylic centre. The facial selectivity
does not depend on the configuration of
the allylsilane, and in all reactions the
anti product is preferentially formed.
Interestingly, a pronounced switch of
facial selectivity takes place with in-
creasing length of the alkyl group of the
allylsilane.
1
2a ± c by the allylation of ethyl methyl
ketone (1a) with g-substituted allylsi-
lanes 9a ± h is described. The allylsilanes
were obtained by a nickel-catalysed
Grignard cross-coupling reaction of
(
E)- and (Z)-(3-iodoallyl)trimethylsi-
Keywords: allylation ´ amino alco-
hols ´ homoallylic alcohols ´ silanes
lane with various Grignard reagents.
The reaction of the allylsilanes with 1a
Introduction
Ph COCF3
TfOH
O
+
TMS
NH
+
TMSO
A large number of natural products such as hydroxymyopor-
Me
R
–78°C
Me
one,[ cembranoids, cineromycins and erythrolids con-
1]
[2]
[3]
[4]
3
1
2
tain an aliphatic tertiary alcohol moiety with a methyl group
as one of the substituents. In Nature, this functionality is
usually formed by an oxidative process of a methyl-substi-
tuted alkene. The chemical synthesis can easily be achieved by
the allylation of an alkyl methyl ketone using allylsilanes, for
1a: R = Et
1
b: R = (CH2)2OTBDPS
Ph COCF3
NH
O
Li / NH3(l)
OH
R
[
5]
example. However, this transformation leads to a racemic
mixture. In contrast, a facially selective allylation of alkyl
methyl ketones is possible by the reaction of methyl ketone 1
with allyltrimethylsilane 2 in the presence of the norpseudo-
Me
R
or Li,
4
5
Scheme 1. Allylation of alkyl methyl ketones 1a and 1b with allyltrime-
thylsilane 2 in the presence of 3.
[
6]
ephedrine derivative 3 and a catalytic amount of trifluoro-
methanesulfonic acid (TfOH) (Scheme 1). The homoallylic
ethers 4 are the only products that are formed from the
reaction of 1a, with a diastereomeric ratio (d.r.) of 9:1 when
the reaction is carried out at � 788C, and with a d.r. of 24:1 at
[
a] Prof. Dr. DR. h.c. L. F Tietze, Dipl.-Chem. L. Völkel, Dr. C. Wulff,
Dipl.-Chem. B. Weigand, Dipl.-Chem. C. Bittner, Dr. P. McGrath
Institut für Organische Chemie
�
1048 C. Even more selective is the reaction of 1b, which
der Georg-August-Universität Göttingen
Tammannstrasse 2, 37077 Göttingen (Germany)
Fax : (‡49)551399476
proceeds with a d.r. of 99:1 at � 788C. The corresponding
tertiary alcohols 5 can easily be obtained from 4 by reductive
cleavage of the benzyl ether moiety either using lithium in
liquid ammonia, or lithium in the presence of 4,4'-di-tert-
butylbiphenyl. The described procedure is the only general
method currently known for the facially selective addition to
alkyl methyl ketones. All allylation methods employing either
equimolar amounts of a chiral allyl reagent (such as allylbor-
E-mail: ltietze@gwdg.de
[
b] Dr. K. Johnson, Dr. M. Schäfer
Institut für Anorganische Chemie
der Georg-August-Universität Göttingen
Tammannstrasse 4, 37077 Göttingen (Germany)
Supporting information for this article is available on the WWW under
http://www.wiley-vch.de/home/chemistry/ or from the author.
1304
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Chem. Eur. J. 2001, 7, No. 6

1304±1308
anes and allyltitanium compounds) or chiral catalysts (which
gave excellent selectivities with aldehydes) failed when
DIBAL-H, MeLi,
Me
TMS
DME, reflux
(11%)
[
7±10]
9a
applied to alkyl methyl ketones.
Herein we describe the
TMS
facially selective allylation of 1a with g-substituted allylsi-
lanes to generate a-substituted tertiary homoallylic ethers
with two new stereogenic centres.
10
Ni(OAc)2, NaBH4
H2, EtOH
TMS
Me
9b
(74%)
Scheme 3. Synthesis of g-substituted allylsilanes 9a and 9b.
Results and Discussion
first case, (E)-9a was obtained as a pure compound, albeit in a
low yield. The second procedure led to the formation of the
(Z)-configured crotylsilane 9b in 74% yield.
Synthesis of g-substituted allylsilanes: Several procedures are
known for the selective synthesis of (E)- and (Z)-configured
[
11]
allylsilanes.
However, the Grignard cross-coupling of
trimethylsilyl(TMS)-alkenyl halides, such as (E)-7 and (Z)-7,
with various alkyl Grignard reagents 8a ± d provided the most
suitable access to a large number of substituted allylsilanes
Allylation of 1a: 2-Butanone is the methyl ketone that
experiences the poorest facial differentiation, and was there-
fore chosen as the substrate for the allylation with different
allyltrimethylsilanes 9. The reaction was performed in a
domino-type fashion[ by adding catalytic amounts of a
mixture of TfOH/TMSOTf (1:1) to a mixture of ketone 1a,
the g-substituted allylsilane 9, and the TMS ether 3 in
dichloromethane at � 788C, to give the homoallylic ethers 4a,
[
12]
(Scheme 2). Allylsilane (Z)-7 was obtained as described by
17]
DIBAL-H, hexane;
I
TMS
TMS
I2, THF
40%)
(
E)-7
(
TMS
1
1 and 12 (Scheme 4). Although allyltrimethylsilane 2 gave 4a
6
1.) EtMgBr; I2
as the main product in 95% yield after 1 h, the g-substituted
allylsilanes 9a ± h are less reactive (Table 2). The reactivity of
the allylsilanes 9, and the diastereomeric ratios found for the
2
.) (KO2C)2N2/ HOAc
I
(
Z)-7
(46%)
TMS
RMgX (8), Et O
TMS
2
Ph COCF3
NH
TMSOTf /
TfOH,
O
I
cat. Cl2Ni(PPh3)2
R
TMS
+
+
TMSO
CH2Cl2,
(
(
E)-7
Z)-7
9c: R = Et, E 9g: R = Bu, E
9d: R = Et, Z 9h: R = Bu, Z
9e: R = Pr, E 9i: R = Bn, E
9f: R = Pr, Z 9j: R = Bn, Z
8
8
8
8
a: R = Et
b: R = Pr
c: R = Bu
d: R = Bn
Me
–78 °C
R
2
, 9a–j
1a
3
(35-95%)
Scheme 2. Synthesis of g-substituted allylsilanes 9c ± j.
Ph COCF3
NH
Ph COCF3
NH
O
O
3
+
3
Schinzer et al.,[13] and (E)-7 was synthesized in 40% overall
yield by hydroalumination of propargyl trimethylsilane with
diisobutylaluminum hydride (DIBAL-H) followed by treat-
ment with iodine. Coupling of (E)-7 and (Z)-7 with the alkyl
Grignard reagents 8 in the presence of a catalytic amount of
Me
Me
4
4
R
R
4
1
a: R = H
1: R = Me
12a: R = Et
12b: R = Pr
12c: R = Bu
Cl Ni(PPh ) proceeded stereoselectively, and led to the
2
3
2
Scheme 4. Allylation of ethyl methyl ketone 1a with g-substituted
allylsilanes 9a ± j in the presence of 3.
formation of the isomerically pure allylsilanes 9c ± j in 58 to
7% yield (Table 1). Allylsilanes 9a and 9b were prepared
8
starting with the methylation of propargyl trimethylsilane to
give 10, followed by reduction, using either DIBAL-H/MeLi
Table 2. Allylations of ethyl methyl ketone (1a) with g-substituted
allylsilanes 2 and 9a ± h in the presence of 3.
[
14±16]
or Ni-P2 (nickel boride catalyst)/H (Scheme 3).
In the
2
Allylsilane/
config.
R
Main
product
t
Yield [%][b] R:S (C-3)[c] S:R (C-4)[d]
[
a]
Table 1. Cross-coupling of the vinylic halides 7 with various Grignard
reagents.
2
9
9
H
4a
2 h 95
3 d 79
5 d 73
6 d 64
5 d 46
9 d 70
8 d 35
10 d 67
10 d 47
±
1:9
1:9
1:3
a/E
b/Z
Me 11
Me 11
1:16
1: > 99
23:1
> 40:1
23:1
> 50:1
> 25:1
> 60:1
R
Vinylic halide
Product[a]
t [h]
Yield [%]
Et
Et
Pr
(E)-7
(Z)-7
(E)-7
(Z)-7
(E)-7
(Z)-7
(E)-7
(Z)-7
9c
9d
9e
9 f
9g
9h
9i
4
4.5
2.5
6
20
3.5
3.5
24
70
68
69
69
59
58
74
87
9c/E
9d/Z
9e/E
9 f/Z
9g/E
9h/Z
Et 12a
Et 12a
Pr 12b
Pr 12b
Bu 12c
Bu 12c
2.2:1
6.4:1
4.5:1
14:1
5.6:1
> 20:1
Pr
Bu
Bu
Bn
Bn
[
[
a] In the case of 9i,j no products were obtained. [b] Mixture of isomers.
c] Allylic centre by GC analysis. [d] Homoallylic centre by 13C NMR
9j
[
a] E/Z-selectivity ꢀ99% in all cases.
analysis.
Chem. Eur. J. 2001, 7, No. 6
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1305

L. F. Tietze et al.
FULL PAPER
products 4a and 11 strongly depend on the length of R and, to
some extent, also on their double-bond configuration. Most
surprising, however, was the finding, that a change in the
facial selectivity was observed with an increasing length of the
alkyl chain of the allylsilane. The facial selectivities ranged
from 1: > 99 to >60:1 for the allylic centre at C-3 and from 1:9
to >20:1 for the homoallylic centre C-4. Thus, reaction of 1a
with 2, and 9a and 9b gave the homoallylic ethers 4a and 11,
respectively, as the main products, with the R configuration at
C-4 and the S configuration at C-3. On the contrary, the
reaction of 1a with 9e ± h led to 12a ± c as the main products,
with the S configuration at C-4 and the R configuration at C-3.
The change in facial selectivity at C-4 using the methyl- and
the ethyl-substituted allylsilane (E)-9a and (E)-9c, as well as
with J ˆ 8.0 Hz. The methyl group at the homoallylic centre
gives rise to a singlet at d ˆ 0.98, while the two other methyl
groups both appear as triplets with J ˆ 7.3 Hz at d ˆ 0.63 and
0.88. The signals for the diastereotopic hydrogen atoms of the
methylene groups are found as multiplets centred at d ˆ 1.15
and 1.48 (CH of the side chain) and d ˆ 1.62 (C -CH CH ).
2
q
2
3
The secondary vinylic proton resonates as a doublet of
doublets of doublets with J ˆ 9.9, 10.0 and 16.7 Hz at d ˆ 5.61.
The signals for the vinylic CH group appear as doublets of
2
doublets at d ˆ 4.97 (J ˆ 2.2 and 16.7 Hz) for H
and at d ˆ
trans
5.11 (J ˆ 2.2 and 9.9 Hz) for H . The allylic CH group
cis
resonates as a doublet of doublets of doublets at d ˆ 1.87 with
J ˆ 2.0, 10.0, and 10.0 Hz.
(
Z)-9b and (Z)-9d, proceeded gradually from 1:9 to 2.2:1, and
Mechanistic considerations: It is well known that the allyla-
tion of aldehydes and ketones using either (E)- or (Z)-
allylsilanes lead to the same stereochemistry of the main
from 1:3 to 6.4:1, respectively. However, the total opposite is
found for C-3 in which the facial selectivity went from 1:16 to
2
[
18]
[20]
3:1, and from 1: > 99 to >60:1.
In the reactions, the
product in both cases. However, the Lewis acid catalysed
selectivity for C-4 is usually higher when using (Z)-allylsi-
lanes. The yields range from 35 ± 95%, depending on the
substituent and on the configuration of the allylsilane. There-
fore the yields are always slightly better for the (E)-
allylsilanes. In all cases, no by-products were formed, except
for small amounts of the desilylated norpseudoephedrine
derivative 3, which could be recovered by chromatography.
All products were crystalline, and therefore the diastereo-
merically pure homoallylic ethers were obtained by recrystal-
lisation from pentane. The benzyl-substituted allylsilanes 9i
and 9j did not give the corresponding homoallylic ethers
when reacted with ethyl methyl ketone (1a) under the
described conditions, probably for steric reasons. Similarly, a
reaction did not take place when alkenyl iodide (E)-7 was
used. In both cases, starting material was recovered.
crotylations give mainly the syn products, whereas in the
described reactions, the products with an anti orientation of
the relevant substituents at the stereogenic centres were
formed nearly exclusively. Recently, we were able to give a
clear mechanistic explanation for the highly selective allyla-
tion of aldehydes, which pro-
ceeds with a d.r. >99:1, by using
Ph
our procedure based on on-line
O
NMR spectroscopy.[
21]
It was
N
H
H
shown that an oxazolidinium
ion 13a is formed as an inter-
mediate, which then reacts in a
stereoselective way with allyl-
trimethylsilane. In contrast, the
surprisingly high facial selectiv-
H5C2
O CF3
H
R
CH3
1
1
3 a : R = H
3 b : R = CH3
To shorten the reaction time, the allylation was carried out
at higher temperatures (e.g. � 408C). However, the resulting
yields and selectivities were significantly lower in all cases. An
important point to take into consideration is the quality of the
catalyst. During the optimisation of the allylation reaction, it
was shown that the catalytically active species in the allylation
of ketones is TfOH. The reproducibility of the allylation and
of the yield strongly depends on the purity of the acid. We
therefore produced the acid for these investigations by partial
hydrolysis of TMSOTf. Under these conditions, constant and
reproducible results were obtained. In the meantime, we also
use high-quality TfOH, which is available in glass ampoules
from Fluka and Aldrich.
ity found in the allylation of ketones, and especially the
change in facial selectivity with an increase in the bulkiness of
the substituent R of the allylsilane, cannot as yet be
rationalised consistently. Contrary to what was found in the
allylation of aldehydes, an oxazolidinium ion 13b is not an
intermediate. However, as is the case in the reaction of
aldehydes, the NHCOCF moiety in 3 is necessary for a high
3
selectivity. Thus, the reaction of 1a and allylsilane 2 in the
presence of TfOH and the TMS ether of 1-phenylethanol
proceeds with a low diastereoselectivity (d.r. ˆ 1:1.8).
Conclusion
Structure elucidation: The structures of the homoallylic ethers
were determined by X-ray analysis (for 11, 12a and 12c) as
The allylation of ethyl methyl ketone 1a with g-substituted E-
and Z-allylsilanes was studied, and was found to give a-
substituted homoallylic ethers with two new stereogenic
centres. In the presence of the norpseudoephedrine derivative
3, homoallylic ethers 11, 12a, 12b, and 12c were obtained with
excellent selectivities of 1: > 99 for C-3 and >20:1 for C-4.
The resulting functionality was not accessible either by other
allylation procedures, or by an aldol-type reaction. In contrast
to the Lewis acid induced allylation of aldehydes and ketones,
the anti products were formed nearly exclusively in this case.
The most surprising feature of this reaction, however, is the
reversal of facial selectivity with increasing bulkiness of the
1
13
[19]
well as by H and C NMR spectroscopy. As an example,
1
the characteristic signals in the H NMR spectrum of 12a are
discussed in detail. The signals for the norpseudoephedrine
moiety are quite similar for all homoallylic ethers. The
aromatic hydrogen atoms resonate as a multiplet at d ˆ
7
4
.17 ± 7.38. The signal of the benzylic proton is found at d ˆ
.54 as a doublet with J ˆ 4.0 Hz, and the neighbouring proton
gives rise to multiplet centred at d ˆ 4.06. The methyl group
resonates as a doublet at d ˆ 1.20 with J ˆ 6.8 Hz. The signal
for the amide proton is found at d ˆ 6.40 as a broad doublet
1306
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Chem. Eur. J. 2001, 7, No. 6

Facial-Selective Allylation
1304±1308
substituent of the allylsilane. The high facial selectivity, and
the change in the selectivity when bulkier allylsilanes were
used, is explained by an enzyme-like model in which the
formation of a pocket is assumed, due to hydrogen bonding of
Allylation with substituted allylsilanes: general procedure: The catalyst
(
30 mL, TfOH/TMSOTf 1:1) was added dropwise to a mixture of auxiliary 3
(
0.50 mmol, 1.0 equiv), ethyl methyl ketone (1.00 mmol, 2.0 equiv), and
allylsilane (1.00 mmol, 2.0 equiv) in CH
2
Cl
2
(2.5 mL) at � 788C. The
mixture was stirred at this temperature for 5 ± 10 days, and triethylamine
1
and 3.
(0.15 mL) was then added at � 788C. The reaction mixture was washed with
4
water (2 mL) and dried over MgSO . tert-Butylammonium fluoride
(
TBAF; 0.50 mmol) was added, and the solution was stirred for 1 h at
room temperature. The solvent was evaporated, and the crude product was
purified by chromatography (silica gel, petroleum ether/tert-butyl methyl
ether 10:1 ± 20:1). The crystals for X-ray analysis were obtained by
recrystallisation from pentane at � 208C.
Experimental Section
(
E)-(3-Iodoallyl)trimethylsilane ((E)-7): DIBAL-H (200 mmol, 20% sol-
ution in hexane) was added to a solution of propargyl trimethylsilane
200 mmol) in hexane (80 mL) at 258C. The reaction mixture was stirred at
08C for 3.5 h, and was then concentrated in vacuum. The residue was
dissolved in THF (100 mL) and iodine (200 mmol, solution in THF
100 mL)) was added at � 508C. The mixture was warmed up to 258C,
hydrolysed by adding water (100 mL), and treated with saturated aqueous
Na solution to remove the remaining iodine. The organic layer was
separated, the aqueous layer was extracted with CH Cl
(4 Â 25 mL), and
the combined organic layer was dried over MgSO and concentrated in
vacuum. Distillation (Vigreux, 10 cm, ꢁ5 mbar) gave (E)-7 (21.2 g, 40%)
Formation of the catalyst: Trimethylsilyl trifluormethanesulfonate
(
5
(
(
TMSOTf, 1 mL, 7.48 mmol) was poured into a Schlenk flask. Water
33.6 mL, 1.87 mmol) was then added to the TMSOTf. After three days, the
hydrolysis was complete and a catalytically active mixture of (TMS)
TfOH and TMSOTf (1:2:2) was formed.
2
O,
(
(
3S,4R,1'S,2'S)-3,4-Dimethyl-4-(1'-phenyl-2'-trifluoracetamido-1'-pro-
2 2 3
S O
20
1
poxy)-hex-1-ene (11): M.p. 678C; [a]
D
ˆ � 36.0 (c ˆ 1, CHCl
3
); H NMR
2
2
(
CDCl
3
, 200 MHz): d ˆ 0.62 (t, J ˆ 7.5 Hz, 3H), 1.06 (d, J ˆ 7.0 Hz, 3H),
4
1
.13 (s, 3H), 1.21 (d, J ˆ 7.0 Hz, 3H), 1.28 (q, J ˆ 7.5 Hz, 2H), 2.44 (dq, J ˆ
1
7.0 Hz, 1H), 4.08 (m
5
c
, 1H), 4.55 (d, J ˆ 3.5 Hz, 1H), 5.03 ± 5.10 (m, 2H),
as a colorless, light-sensitive liquid. H NMR (CDCl
3
, 200 MHz): d ˆ 0.02
.96 (ddd, J ˆ 18.0, 9.5, and 8.0 Hz, 1H), 6.42 (d, J ˆ 8.0 Hz, 1H), 7.17 ± 7.38
(
6
2
s, 9H), 1.54 (dd, J ˆ 1.2 and 8.5 Hz, 2H), 5.69 (dt, J ˆ 1.2 and 14.2 Hz, 1H),
1
3
(m, 5H); minor diastereomer (distinguishable signals): d ˆ 0.89 (t, J ˆ
.45 (dt, J ˆ 8.5 and 14.2 Hz, 1H); C NMR (CDCl
3
, 50 MHz): d ˆ � 2.03,
13
7
.5 Hz, 3H), 0.97 (d, J ˆ 7.0 Hz, 3H), 2.33 (dq, J ˆ 7.0 Hz, 1H); C NMR
7.50, 69.98, 143.0; HR-MS: calcd for C 13ISi 239.9831, found 239.9831.
6
H
(
CDCl
3
, 50 MHz): d ˆ 8.08, 14.89, 16.90, 20.31, 30.26, 44.71, 51.95, 73.87,
Cross-coupling: general procedure: Alkylmagnesium bromide (ꢁ2m
diethyl ether solution, 30 mmol) was added to a mixture of bis(triphenyl-
phosphane)nickel dichloride (15.0 ± 45.0 mmol) and (3-iodo-2-propenyl)tri-
methylsilane ((E)-7 or (Z)-7, 15.0 mmol) in diethyl ether (50 mL) at
1
8
1
C
1.14, 114.79, 115.89 (q,
J
C,F ˆ 288 Hz), 126.69, 127.72, 128.19, 140.78,
2
41.42, 156.41 (q,
J
C,F ˆ 37 Hz); elemental analysis calcd (%) for
19
H
26
F
3
NO : C 63.85, H 7.33; found: C 64.02, H 7.45.
2
�
358C. The mixture was stirred at this temperature for 3 ± 24 h (see
Table 1), and then hydrolysed with saturated aqueous NH Cl. The organic
layer was washed with saturated NH Cl solution, and combined with the
pentane extracts (2 Â 20 mL) of the aqueous layer. The combined organic
layer was washed with saturated aqueous NaHCO and brine, and dried
over anhydrous MgSO . The solvent was evaporated, and the products
(3R,4S,1'S,2'S)-3-Ethyl-4-methyl-4-(1'-phenyl-2'-trifluoracetamido-pro-
poxy)-hex-1-ene (12a): M.p. 90.18C; [a]2
0
ˆ � 21.4 (c ˆ 0.5, CHCl
3
);
4
D
1
H NMR (CDCl
7.3 Hz, 3H), 0.98 (s, 3H), 1.15 (m
(m , 1H), 1.62 (m
3
, 300 MHz): d ˆ 0.63 (t, J ˆ 7.3 Hz, 3H), 0.88 (t, J ˆ
4
c
, 1H), 1.20 (d, J ˆ 6.8 Hz, 3H), 1.48
, 2H), 1.87 (ddd, J ˆ 2.0, 10.0, 10.0 Hz, 1H), 4.06 (m
c
,
3
c
c
1H), 4.54 (d, J ˆ 4.0 Hz, 1H), 4.97 (dd, J ˆ 2.2, 16.7 Hz, 1H), 5.11 (dd, J ˆ
2.2, 9.9 Hz, 1H), 5.61 (ddd, J ˆ 9.9, 10.0, 16.7 Hz, 1H), 6.40 (dbr, J ˆ 8.0 Hz,
1H), 7.17 ± 7.38 (m, 5H); minor diastereomer (distinguishable signals): d ˆ
4
were obtained as colourless liquids (purification by distillation or chroma-
tography). The isomeric purities were analysed by GC.
0
2
9
7
1
1
6
.90 (t, J ˆ 7.3 Hz, 3H), 1.10 (s, 3H), 1.22 (d, J ˆ 6.8 Hz, 3H), 2.06 (ddd, J ˆ
2
-Butynyltrimethylsilane (10): Methyllithium (133 mmol, 1.6m solution in
diethyl ether) was added dropwise to a mixture of propargylsilane
.0, 10.0, and 10.0 Hz, 1H), 4.05 (dd, J ˆ 2.2, 16.7 Hz, 1H), 5.13 (dd, J ˆ 2.2,
13
.9 Hz, 1H), 5.70 (ddd, J ˆ 9.9, 10.0, 16.7 Hz, 1H); C NMR (CDCl
3
,
(
111 mmol) in THF (150 mL) at � 788C. The solution was stirred for 3 h,
5 MHz): d ˆ 8.08, 12.13, 16.86, 21.00, 21.58, 28.90, 51.89, 53.89, 73.90, 80.93,
and then iodomethane (222 mmol) was added at � 788C. After warming up
to 258C over a period of 3 h, the reaction mixture was stirred for 5 h at this
temperature. Water (100 mL) and pentane (100 mL) were then added. The
1
15.84 (q,
J
C,F ˆ 288.4 Hz), 116.73, 126.80, 127.69, 128.17, 138.78, 141.36,
2
56.39 (q, JC,F ˆ 37 Hz); elemental analysis calcd (%) for C20
28 3 2
H F NO : C
4.67, H 7.60; found: C 64.45, H 7.67.
organic layer was washed with water (10 Â 250 mL) and dried over Na
2 4
SO .
Distillation (30 cm Vigreux) led to the alkyne 10 (11.9 g, 85%, 86%
(3R,4S,1'S,2'S)-3-Propyl-4-methyl-4-(1'-phenyl-2'-trifluoracetamido-pro-
1
20
solution in THF) as a colourless liquid. V.p. 1108C; H NMR (CDCl
3
,
poxy)-hex-1-ene (12b): M.p. 65.98C; [Ga] ˆ � 27.0 (c ˆ 0.5, CHCl );
D
3
1
3
3
00 MHz): d ˆ � 0.06 (s, 9H), 1.24 (q, J ˆ 3.0 Hz, 2H), 1.62 (t, J ˆ 3.0 Hz,
H NMR (CDCl , 300 MHz): d ˆ 0.60 ± 0.67 (m, 4H, 6-H ), 0.89 (t, J ˆ
3
3
H); 13C NMR (CDCl
, 75 MHz): d ˆ � 2.18, 3.45, 6.82, 73.68, 76.23.
3
7.3 Hz, 3H), 0.90 (s, 3H), 1.08 ± 1.38 (m, 5H), 1.21 (d, J ˆ 1.5, 10.0 Hz, 3H),
.06 (m
, 1H), 4.53 (d, J ˆ 5.0 Hz, 1H), 4.96 (dd, J ˆ 2.0, 17.0 Hz, 1H), 5.09
dd, J ˆ 2.0, 10.0 Hz, 1H), 5.62 (ddd, J ˆ 10, 10, 17 Hz, 1H), 6.42 (dbr, J ˆ
.0 Hz, 1H), 7.20 ± 7.36 (m, 5H); minor diastereomer (distinguishable
4
c
(
1
E)-2-Butenyltrimethylsilane (9a): Methyllithium (1.6m in diethyl ether,
00 mmol) was added to a solution of DIBAL-H (1m in hexane, 100 mmol)
(
8
in DME (30 mL) at 258C. The mixture was stirred for 1 h. Hexane and
diethyl ether were then removed under vacuum at 258C (DME remained),
and the alkyne 10 (50.0 mmol) was added. The mixture was heated at reflux
for 24 h, and then water (100 mL) and pentane (100 mL) were added. The
organic layer was washed with water (7 Â 100 mL), and the alkene 9a
signals): d ˆ 0.62 (t, J ˆ 7.5 Hz, 3H), 1.11 (s, 3H), 2.18 (dt, J ˆ 1.5 and
1
3
1
7
8
1
0.0 Hz, 1H), 5.72 (ddd, J ˆ 10.0, 10.0, and 17.0 Hz, 1H); C NMR (CDCl
3
,
5 MHz): d ˆ 7.95, 13.88, 16.58, 20.58, 21.50, 28.70, 30.33, 51.70, 51.79, 73.90,
0.81, 115.81 (q, 1
J
C,F ˆ 288 Hz), 116.24, 126.80, 127.69, 128.17, 138.78,
41.36, 156.39 (q, 2JC,F ˆ 36 Hz); elemental analysis calcd (%) for
(
5.50 mmol, 11%) was isolated by distillation as a colourless 50% solution
1
21 30 3 2
C H F NO : C 65.43, H 7.84; found: C 65.24, H 7.85.
in pentane. H NMR (CDCl
3
, 300 MHz): d ˆ � 0.02 (s, 9H), 1.14 (d, J ˆ
1
3
7
7
.5 Hz, 2H), 1.66 (d, J ˆ 6.0 Hz, 3H), 5.15 ± 5.50 (m, 2H); C NMR (CDCl
3
,
(
3R,4S,1'S,2'S)-3-Butyl-4-methyl-4-(1'-phenyl-2'-trifluoracetamido-pro-
5 MHz): d ˆ � 2.01, 18.03, 22.59, 123.08, 127.02.
20
D
1
poxy)-hex-1-ene (12c): M.p.66.48C; [a]
ˆ � 24.0 (c 0.5, CHCl
3
); H NMR
(
1
Z)-2-Butenyltrimethylsilane (9b): A solution of NaBH
59 mg) in EtOH (10 mL), ethylenediamine (8.40 mmol, 505 mg), and
the alkyne 10 (42.0 mmol) were added to a suspension of Ni(OAc) ´ 4H
4.20 mmol, 1.05 g) in EtOH (20 mL). The mixture was stirred vigorously
4
(4.20 mmol,
(CDCl
J ˆ 7.0 Hz, 3H), 0.91 (s, 3H), 1.08 ± 1.43 (m, 5H), 1.20 (d, J ˆ 6.8 Hz, 3H),
1.62 (m
3
, 500 MHz), d ˆ 0.64 ± 0.74 (m, 1H), 0.79 (t, J ˆ 7.5 Hz, 3H), 0.89 (t,
2
2
O
c
, 2H), 1.96 (dt, J ˆ 1.6, 10.0 Hz, 1H), 4.54 (d, J ˆ 4.0 Hz, 1H), 4.96
(
(dd, J ˆ 2.0, 17.0 Hz, 1H), 5.08 (dd, J ˆ 2.0, 10.0 Hz, 1H), 5.61 (ddd, J ˆ
10.0, 10.0, 17.0 Hz, 1H), 6.42 (dbr, J ˆ 8.0 Hz, 1H), 7.24 ± 7.35 (m, 5H);
minor diastereomer (distinguishable signals): d ˆ 0.62 (t, J ˆ 7.5 Hz, 3H),
under a hydrogen atmosphere for 24 h (1 atm, 258C) and filtered through
silica gel (pentane). The organic layer was then washed with water (5 Â
13
1
00 mL), and dried over Na
2
SO
4
. Distillation (20 cm Vigreux) led to the
1.12 (s, 3H), 5.73 (ddd, J ˆ 10.0, 10.0, and 17.0 Hz, 1H); C NMR (CDCl
3
,
alkene 9b (3.98 g, 31.0 mmol, 74%) as a colourless liquid. V.p. 1208C;
75 MHz): d ˆ 8.03, 14.00, 16.75, 21.57, 22.71, 27.98, 28.76, 29.86, 51.85, 52.01,
1
1
H NMR (CDCl
.55 (d, J ˆ 6.0 Hz, 3H), 5.26 ± 5.50 (m, 2H); C NMR (CDCl
d ˆ � 1.78, 12.59, 18.06, 121.16, 126.42.
3
, 300 MHz): d ˆ � 0.08 (s, 9H), 1.48 (d, J ˆ 7.5 Hz, 2H),
73.89, 80.96, 115.84 (q, JC,F ˆ 288 Hz), 116.43, 126.85, 127.67, 128.15, 139.29,
1
3
2
1
3
, 75 MHz):
141.30, 156.39 (q,
J
C,F ˆ 37 Hz); elemental analysis calcd (%) for
22 32 3 2
C H F NO : C 66.14, H 8.07; found: C 66.17, H 7.99.
Chem. Eur. J. 2001, 7, No. 6
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0706-1307 $ 17.50+.50/0
1307

L. F. Tietze et al.
FULL PAPER
1
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Chemie GmbH for supplying chlorotrimethylsilane.
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Received: September 29, 2000 [F2765]
1308
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0947-6539/01/0706-1308 $ 17.50+.50/0
Chem. Eur. J. 2001, 7, No. 6