Synthesis of allylsilanes by reductive lithiation of thioethers

Article abstract of DOI:10.1021/jo049237u

Although much work in reductive lithiation has been done, the utilization of allylthioethers bearing various substituents to prepare allylsilanes has not been explored. The main reason clearly stems from the anticipated lack of regioselectivity. We describe herein the first study on the regioselectivity of the reductive silylation involving dissymmetric allylthioethers. We surveyed a broad spectrum of parameters and showed that this process displays a great dependence of the reaction conditions. We also discovered that an electron transporter, DBB or naphthalene, can cleave THF at room temperature by sonication, to generate a strong base, 4-lithiobutoxide. This feature was successfully exploited to the straightforward synthesis of bis-silanes in one pot. Examples are provided for maximizing both the chemical yield and the regioselectivity of the reductive silylation through the tuning of the reaction conditions. By changing these conditions, several allylsilanes can be selectively synthesized from one thioether.

Full text of DOI:10.1021/jo049237u

Syn th esis of Allylsila n es by Red u ctive Lith ia tion of Th ioeth er s
Ste´phane Streiff,‡ Nigel Ribeiro,‡ and Laurent De´saubry*
UMR 7509, Centre de Neurochimie, 67084 Strasbourg Cedex, France
desaubry@chimie.u-strasbg.fr
Received May 5, 2004
Although much work in reductive lithiation has been done, the utilization of allylthioethers bearing
various substituents to prepare allylsilanes has not been explored. The main reason clearly stems
from the anticipated lack of regioselectivity. We describe herein the first study on the regioselectivity
of the reductive silylation involving dissymmetric allylthioethers. We surveyed a broad spectrum
of parameters and showed that this process displays a great dependence of the reaction conditions.
We also discovered that an electron transporter, DBB or naphthalene, can cleave THF at room
temperature by sonication, to generate a strong base, 4-lithiobutoxide. This feature was successfully
exploited to the straightforward synthesis of bis-silanes in one pot. Examples are provided for
maximizing both the chemical yield and the regioselectivity of the reductive silylation through the
tuning of the reaction conditions. By changing these conditions, several allylsilanes can be selectively
synthesized from one thioether.
SCHEME 1. Syn th esis of Silyla ted Ter p en es
In tr od u ction
The biological importance of polyprenoids has led to
numerous methods for their preparation.1 During the
course of our synthesis of tricyclopolyprenols, we needed
to develop a convenient method to introduce regiospe-
cifically a trimethylsilyl group in the middle of a poly-
prenyl chain. Toward this end, we modified Biellmann
and Ducep’s method to construct the polyprenyl chain
and to transform the allylthioether intermediate into a
silane.2 This approach involves the deprotonation and
subsequent alkylation of allylic thioethers (Scheme 1).
The thioether removal originally described by Biellmann
and Ducep was performed with lithium in ethylamine.2
Thus, this procedure is not suitable for the introduction
of a silyl group, since both the intermediate carbanion
and the chlorosilane would react with the solvent. In
1978, Screttas et al. have shown that the use of naph-
thalene (Np) allows this lithiation to be run in THF.3
Generating organolithium from phenylthioethers has
found many useful applications. The laboratories of
Cohen, Yus, and others have clearly established this
approach as one of the most general and versatile
methods of organolithium production (Scheme 1).4 Arenes
other than naphthalene have been developed as electron
transporters, such as 4,4′-di-tert-butyldiphenyl (DBB) and
1-(dimethylamino)naphthalene (DMAN).5 A major im-
provement was the demonstration that a catalytic amount
of electron transporter was sufficient to perform the
reductive lithiation of phenylthioethers.6 The reaction of
allyllithiums, generated by this method, with carbonyl
electrophiles can be stereocontrolled by the use of ti-
tanium isopropoxide or cerium chloride.7 Unfortunately,
this approach is limited to reactions with aldehydes and
ketones. Thus, although much work in reductive lithia-
tion has been done, the utilization of allylthioethers
bearing various substituents to prepare allylsilanes has
not been explored deeply: most of the described reductive
silylations concerned symmetrically substituted allyl-
thioethers, to avoid getting a mixture of regioisomers.4,8
‡ These two authors contributed equally to this work.
(1) For some recent reviews, see: (a) Hanson, J . R. Nat. Prod. Rep.
2003, 70-78. (b) Connolly, J . D.; Hill, R. A. Nat. Prod. Rep. 2003, 640-
659. (c) Fraga, B. M. Nat. Prod. Rep. 2003, 392-413 and previous
articles of these series.
(2) (a) Biellmann, J . F.; Ducep, J . B. Tetrahedron Lett. 1969, 10,
3707-3710. (b) Altman, L. J .; Ash, L.; Kowerski, R. C.; Epstein, W.
W.; Larsen, B. R.; Rilling, H. C.; Muscio, F.; Gregonis, D. E. J . Am.
Chem. Soc. 1972, 94, 3257-3259. (c) Altman, L. J .; Ash, L.; Marson,
S. Synthesis 1974, 129-135.
(3) Screttas, C. G.; Micha-Screttas, M. J . Org. Chem. 1978, 43,
1064-1071.
(4) For some reviews, see: (a) Cohen, T.; Bhupathy, M. Acc. Chem.
Res. 1989, 22, 152-161. (b) Ramon, D. J .; Yus, M. Eur. J . Org. Chem.
2000, 225-237.
(5) (a) Cohen, T.; Matz, J . R. Synth. Commun. 1980, 10, 311-317.
(b) Freeman, P. K.; Hutchinson, L. L. J . Org. Chem. 1980, 22, 1924-
1930.
(6) Yus, M.; Ramon, D. J . Chem. Soc., Chem. Commun. 1991, 398-
400.
10.1021/jo049237u CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/28/2004
7592
J . Org. Chem. 2004, 69, 7592-7598

Synthesis of Allylsilanes
TABLE 2. Red u ctive Silyla tion Accor d in g to
Ba r bier -Typ e Con d ition s of Th ioeth er 1a
SCHEME 2. Red u ctive Silyla tion of Th ioeth er 1
electron
transporter (equiv)
reaction
time, h
entry
yield, %
ratio 2:3
1
2
3
4
5
DMAN (1)
DMAN (0.1)
DMAN (0.5)
DBB (1)
1.5
12
5
1.5
12
81
84
78
79
65
59:41
66:34
56:44
58:42
59:41
DBB (0.1)
a
All reactions were performed in THF at -78 °C.
TABLE 1. Tw o-Step Red u ctive Silyla tion of Th ioeth er 1
Accor d in g to Sch em e 2a
SCHEME 3. P u ta tive Equ ilibr iu m of Lith ia ted
In ter m ed ia tes
electron
transporter (equiv)
isolated
yield, %
entry
ratio 2:3
1
2
3
4
5
6
7
8
DMAN (1)
DMAN (0.1)
DMAN (0.5)
DBB (1)
DBB (0.1)
DBB (0.2)
DBB (0.5)
Np (0.05)
82
76
81
87
76
79
84
74
8:92
12:88
10:90
14:86
8:92
15:85
11:89
17:83
a
All reactions were performed in THF at -78 °C.
Our need to develop a straightforward access to syn-
thons substituted by a TMS in the middle of a polyprenyl
chain prompted us to explore the potential of the reduc-
tive silylation. We describe herein the first study on the
regioselectivity of the reductive silylation involving dis-
symmetric allylthioethers. We surveyed a broad spectrum
of parameters such as the nature of the allylthioether,
the nature and the quantity of the electron transporter,
the temperature, and the time of reactions. The goal of
this study was to establish procedures to control the
selectivity of the reductive silylation.
any major impact on the yield or the regioselectivity of
the reaction. Interestingly, the yields remained similar,
while the regioselectivity changed: 2 became the major
product. This reaction took more time to be completed
than the corresponding two-step process. In analogy with
a hypothesis proposed by Yus and colleagues for a similar
case, an equilibration of intermediate 4a to 4b that would
be too slow to occur under Barbier-type conditions could
be invoked to account for our observation (Scheme 3).9
Another explanation could involve a different aggregation
state (probably dimeric) of the lithiated intermediates.10
As experience was gained with the previous example,
we applied the silylation reaction to 5 (Scheme 4).
Surprisingly, the products changed dramatically accord-
ing to reaction conditions (Table 3). At -78 °C, when
TMSCl was added after the reduction by LiDBB, the
adduct 6 was formed as a sole product in 71% yield (entry
1). Only the Z isomer of 6 was produced. In that case,
this thiother had not been reduced, but deprotonated.
Although the reductive lithiation of phenylthioethers had
been known for over 20 years, this observation was in
apparent contradiction with previous reports.4,11
Raising the temperature to -42 °C gave only the
expected adduct 7 as a 85:15 mixture of E:Z isomers in
78% yield (entry 2). We did not detect any trace of the
isomeric allylsilane 10. Increasing the temperature to
-11 °C changed dramatically the outcome of the reac-
tion: only the product of rearrangement 8 was obtained
with a good E:Z selectivity (entry 3). However, the yield
was considerably lowered, probably due to degradation
and polymerization of the radical intermediates at that
temperature, as evidenced by the formation of some tarr.
The regioisomer 9 was not detected. The same regiose-
lectivity with another hard nucleophile (tert-butyl bro-
Resu lts a n d Discu ssion
Syn t h esis of Allylsila n es a n d Du a l F u n ct ion of
DBB. First, we choose thioether 1 as a substrate to exam-
ine the effects of several parameters on the yield and the
regioselectivity of the reaction depicted in Scheme 2.
When the mixture of allythioether 1, lithium, and an
electron transporter (DMAN, DBB, or naphthalene) re-
covered its original dark-green color, indicating that the
lithiation was completed, it was quenched with TMSCl.
The corresponding allylsilanes 2 and 3 were obtained in
fairly good yields in a roughly 10:90 ratio (Table 1).The
trimethylsilyl group was introduced at the least con-
gested position. Neither the nature of the electron shuttle
nor its concentration affected dramatically the outcome
of this reaction. A quantity of electron transporter as low
as 0.05 equiv was sufficient to efficiently catalyze the
reductive lithiation (entry 8).
Next, we performed this reductive lithiation under
Barbier-type conditions (i.e., performing this reduction
in the presence of the chlorosilane) (Table 2). J ust as
before the nature of the electron transporter did not have
(7) (a) Guo, B. S.; Doubleday, W.; Cohen, T. J . Am. Chem. Soc. 1987,
109, 4710-4711. (b) Abraham, W. D.; Cohen, T. J . Am. Chem. Soc.
1991, 113, 2313-2314. (c) McCullough, D. W.; Bhupathy, M.; Piccolino,
E.; Cohen, T. Tetrahedron 1991, 47, 9727-9736.
(8) Regio- and stereoselective reductive silylation by a siloxy or
hydroxyl group has been reported: Marumoto, S.; Kuwajima, I. J . Am.
Chem. Soc. 1993, 115, 9021-9024.
(9) Guijarro, D.; Yus, M. J . Organomet. Chem. 2001, 624, 53-57.
(10) Clayden, J . Organolithiums: Selectivity for Synthesis; Perga-
mon Press: New York, 2002; Chapter 1, pp 1-8.
J . Org. Chem, Vol. 69, No. 22, 2004 7593

Streiff et al.
SCHEME 4. Red u ctive Silyla tion of Th ioeth er 5 Accor d in g to Con d ition s Disp la yed in Ta ble 3
TABLE 3. Red u ctive Silyla tion of Th ioeth er 5
a
Isolated products.
mide) has been reported by Nojima and colleagues.12
Running this silylation under Barbier-type conditions at
-78 or -42 °C produced the expected adduct 7 as a sole
product (entries 4 and 5). At -11 °C, the Barbier-type
conditions diminished the stereoselectivity, since the
product of rearrangement 8 was formed with a lower E:Z
selectivity (compare entries 6 and 3). This study is the
first one to establish that by tuning the reaction condi-
tions, three different allylsilanes (6, 7, and 8) can be
obtained from the very same substrate with a high
selectivity.
TABLE 4. Red u ctive Silyla tion of Th ioeth er 11
Accor d in g to Sch em e 5
ratio
14
Barbier-type
conditions
yield,a
%
entry
T, °C
12
13
16
1
2
3
4
5
6
no
no
no
yes
yes
yes
-78
-42
-11
-78
-42
-11
77
81
21
72
84
11
31
28
5
64
72
100
100
12
8
88
92
a
Isolated products.
To gain more information on the reactivity of trisub-
stituted thioethers, we studied the behavior of 11, which
carries two methyls at the extremity of the olefin (Table
4, Scheme 5).
At -78 °C, when TMSCl was added after the reduction
by LiDBB, the expected allylsilanes 12 and 14 were the
major products, in a 31:64 ratio (Table 4, entry 1). Traces
of bis-silylated adduct 13 were isolated. This compound
(11) For a preliminary communication of the results describing THF
cleavage, see: Streiff, S.; Ribeiro, N.; De´saubry, L. Chem. Commun.
2004, 346-347.
(12) Tanaka, J .; Nojima, M.; Kusabayashi, S. J . Am. Chem. Soc.
1987, 109, 3391-3397.
7594 J . Org. Chem., Vol. 69, No. 22, 2004

Synthesis of Allylsilanes
SCHEME 5. Red u ctive Silyla tion of Th ioeth er 11
probably comes from the anomalous deprotonation of
12.13 For comparison, the same reaction conditions per-
formed on thioether 5 led exclusively to an adduct sub-
stituted by both a thioether and a TMS moiety, indicating
that the introduction of the methyl groups decreases
dramatically the anomalous deprotonation of allylthio-
ethers.
benzyl group of compound 23 was removed during the
course of this reaction.
Effective Activa tion Meth od a n d Sp ecificity of
DBB a s a n Electr on Tr a n sp or ter . Next, we studied a
parameter that had not been examined yet: the condi-
tions of formation of the reducing agent LiDBB (Table
6). To prepare this reagent, an excess of lithium and a
catalytic amount of DBB were sonicated for less than 5
min at room temperature to afford a dark-green solution.
This was then immediately cooled to the desired tem-
perature (conditions A). In the second procedure (condi-
tions B) the time of LiDBB preparation was extended to
1 h. In conditions C, the medium was sonicated for 5 min
and stirred at room temperature for 1 h. When LiDBB
was prepared within 5 min (conditions A), the silyl
thioether 32 was never formed (entries 1-4 and 10). On
the other hand, when it was prepared according to
conditions B, we observed a substantial amount of adduct
32 at -42 °C in non-Barbier-type conditions (entry 7).
This reaction was exclusive at -78 °C (entry 6).
One possible reason for these observations which came
to mind is that THF might be cleaved into 4-lithiobutox-
ide, which would deprotonate the thioethers. Such a
reductive cleavage of THF has been reported, albeit
under more drastic conditions. Eisch was the first to note
that THF could be cleaved by lithium in the presence of
an arene.15 This author showed that refluxing a mixture
of biphenyl and lithium in THF affords some butanol
after hydrolysis of the reaction system. At that temper-
ature, 4-lithiobutoxide decomposed, and its formation was
not quantified. Later, Cohen showed that, in the presence
of boron trifluoride etherate, LiDBB cleaves THF instan-
taneously at a temperature as low as -78 °C.16 This reac-
tivity stems from the complexation of the oxygen atom
by this strong Lewis acid. More recently, Yus and col-
leagues reported that the dilithium naphthalene dianion
reacts slowly with THF at room temperature for 24 h,
affording after hydrolysis small amounts of butanol as
well as products of condensation of naphthalene with
THF.17
As previously, increasing the temperature to -42 °C
totally suppressed this deprotonation: the expected
allylsilanes 12 and 14 were the sole ones to be observed
(entry 2). At -11 °C, the overall yield was again dimin-
ished (to 21%) (entry 3). Only the silyl thioether 16 and
some bibenzyl were isolated, suggesting a homolytic
cleavage of the radical anion as outlined in Scheme 5.
Under Barbier-type conditions at -78 and -42 °C, we
observed uniquely the formation of the expected allylsi-
lanes 12 and 14, with, in particular, an improved
regioselectivity at -42 °C (compare entries 4 and 5 to
entries 1 and 2). In this latter case (entry 5), a 84% yield
of a 8:92 ratio of regioisomers 12 and 14 was observed.
At -11 °C, we isolated again only the debenzylated
adduct 16. These examples provide a second demonstra-
tion of the possibility to orientate selectively the reductive
silylation to different major products (14 and 16) depend-
ing on reaction conditions.
Comparing the regioselectivity of the reductive silyla-
tion of 1, 5, and 11, we can conclude that the structure
of the substrate, the temperature, and the presence or
the absence of chlorosilane during the reductive lithiation
step are three critical factors that cannot be considered
independently from one another, probably because each
of these three factors will affect the aggregation state of
the lithiated intermediates and its reactivity. Another
effect that may intervene is the intramolecular π-com-
plexation of the lithium cation to an alcene moiety. Such
an interaction has been reported by Ro¨lle and Hoff-
mann.14
The main common point that came out of this study is
that Barbier-type conditions at -42 °C prevent the
anomalous deprotonation and give the best yield and
selectivity. We settled therefore on this condition to
examine the reactivity of several allylthioethers (Table
5). We observed that the trimethylsilyl group was pref-
erentially introduced at the least substituted position
with a regioselectivity ranging from 100:0 (in the case of
26, entry 4) to 56:44 (in the case of 23, entry 3). The low
selectivity of this latter case is due to a similar level of
substitution of allylsilanes 24 and 25. As expected, the
When we analyzed a solution of LiDBB prepared
according to conditions B, we were pleased to notice the
(14) Ro¨lle, T.; Hoffmann, R. W. J . Chem. Soc., Perkin Trans. 2 1995,
1953-1954.
(15) Eisch, J . J . J . Org. Chem. 1963, 28, 707-710.
(16) (a) Mudryk, B.; Cohen, T. J . Am. Chem. Soc. 1991, 113, 1866-
1867. THF cleavage can also be achieved with a catalytic amount of
DBB or naphthalene, see: (b) Ramon, D. J .; Yus, M. Tetrahedron 1992,
48, 3585-3588. For other synthetic applications of THF cleavage,
see: (c) Oikawa, M.; Oikawa, H.; Ichihara, A. Tetrahedron 1995, 51,
11457-11464. (d) Dvorak, C. A.; Rawal, V. H. J . Chem. Soc., Chem.
Commun. 1997, 2381-2382.
(13) Similar deprotonation by strong bases has been reported, see
for example: (a) Marr, F.; Fro¨hlich, R.; Hoppe, D. Tetrahedron:
Asymmetry 2000, 13, 2587-2592. (b) Schlosser, M.; Zellner, A.; Leroux,
F. Synthesis 2001, 1830-1836.
(17) Yus, M.; Herrera, R. P.; Guijarro, A. Chem. Eur. J . 2002, 8,
2574-2584.
J . Org. Chem, Vol. 69, No. 22, 2004 7595

Streiff et al.
TABLE 5. Red u ctive Silyla tion of Th ioeth er s u n d er Ba r bier -Typ e Con d ition sa
a
Reactions performed with 0.1 equiv of DBB, 50 equiv of Li, and 1.5 equiv of TMSCl with 0.5 M substrate in THF at -42 °C.
TABLE 6. Con d ition s of F or m a tion of th e Red u cin g Agen t “LiDBB”: Effects on th e Red u ctive Silyla tion of Th ioeth er s
29 a n d 30
Barbier-type
entry
thioether
conditionsa
conditionsa
T, °C
yield, %
31:32
1
2
3
4
6
7
8
9
10
11
12
13
29
29
29
29
29
29
29
29
30
30
30
29
A
A
A
A
B
B
B
B
A
B
B
C
no
no
yes
yes
no
-78
-42
-78
-42
-78
-42
-78
-42
-78
-78
-78
-78
71
72
83
86
69
59
71
83
88
92
79
54
100:0
100:0
100:0
100:0
0:100
88:12
100:0
100:0
100:0
100:0
100:0
77:33
no
yes
yes
no
no
yes
no
a
Conditions A: a mixture of Li and DBB in THF was sonicated for less than 5 min at rt. Conditions B: sonication for 1 h at rt.
Conditions C: a mixture of Li and DBB in THF was sonicated for less than 5 min and stirred at rt for 1 h. 29 or 30 was then added at
the indicated temperature. For Barbier-type conditions TMSCl was added at the same time as 29 or 30, otherwise it was added when the
medium recovered its dark-green color.
formation of a substantial amount of n-butanol (0.27 M).
We quantitatively monitored, after hydrolysis, the forma-
tion of n-butanol by GC (Figure 1). The efficiency of this
process accounts well for the deprotonation of 29, as
depicted in Scheme 6. Naphthalene is also able to cleave
THF in the same conditions with a slightly lower efficacy.
Surprisingly biphenyl, whose reduction potential is in-
termediate between that of DBB and naphthalene, could
not cleave THF significantly.18
Whatever the reaction conditions, the reductive lithia-
tion of pyridylthioether 30 is much faster than its de-
(18) (a) Evans, A. G.; J erome, B.; Rees, N. H. J . Chem. Soc., Perkin
Trans. 2 1973, 447-453. (b) Curtis, M. E.; Allred, A. L. J . Am. Chem.
Soc. 1965, 87, 2554-2563.
7596 J . Org. Chem., Vol. 69, No. 22, 2004

Synthesis of Allylsilanes
SCHEME 8. Syn th esis of Bis-sila n e 35
chlorosilane may be added. When this color reappears
again, the reductive lithiation is completed and the
second portion of TMSCl is added.
We also synthesized 33 in 61% under Barbier-type con-
ditions using an excess of TMSCl (5 equiv) (method B).
Gratifyingly, we were able to apply the same strategy
to allylthioether 34 (Scheme 8). TMSCl was replaced by
TBDMSCl to get a less volatile product. The bis-silylated
adduct 35 was obtained in 67% yield. This synthesis
represents therefore an improvement of the published
procedures that involved two steps.20 This class of dinu-
cleophilic reagents is useful in organic synthesis.21
F IGURE 1. Formation of n-butanol after hydrolysis of 0.1 M
solutions of electron transporter sonicated at room tempera-
ture.
SCHEME 6. THF Clea va ge a n d in Situ
Dep r oton a tion of Th ioeh er 29
Con clu sion
The reductive lithiation enables the synthesis of allyl-
silanes from readily available starting materials in one
operation. This process displays a great dependence of
the reaction course not only from the reaction conditions,
but also from the structure of the allylthioether. However,
we demonstrated that it is possible to tune the reaction
conditions to synthesize various allylsilanes selectively
from the same thioether. We also provided the first
evidence that an electron transporter can cleave THF at
room temperature by sonication. This feature was suc-
cessfully exploited to the straightforward synthesis of bis-
silanes. Due to their usefulness in organic synthesis, the
reductive lithiation reactions are still the subject of
intensive development. These reactions are performed in
THF. The only alternative solvent that has been used
successfully is dimethyl ether.22 Therefore, our finding
that THF can be cleaved in mild conditions should be
taken into account in the design of new reductive
lithiations.
SCHEME 7. Syn th esis of Bis-sila n e 33a
a
Method A: (1) Li, cat. DBB, -78 °C, 4-lithiobutoxide, 30 min;
(2) TMSCl (1 equiv), -78 °C; (3) 12 h, -78 °C; (4) TMSCl, -78 °C.
Method B: (1) Li, cat. DBB, -78 °C, 4-lithiobutoxide, 30 min; (2)
TMSCl (5 equiv), -78 °C, 4 h.
protonation by 4-lithiobutoxide: only allysilane 31 was
observed (entries 10-12 of Table 6). Regarding phenyl-
thioether 29, deprotonation is faster than reduction at
-78 °C (entry 6). At -42 °C, it is the opposite (entry
7). Interestingly, entry 13 (conditions C) shows that
DBB can induce some THF cleavage at room tempera-
ture without sonication over 1 h (compare entry 13
with 6).
With few exceptions DDB-catalyzed lithiations do not
involve extended sonication at room temperature, which
may be why our observation has not been reported.19
Syn th esis of F u n ction a lized Allylsila n es. We took
advantage of the property of DBB to catalyze the reduc-
tive lithiation of both THF and thioethers to synthesize
the bis-silane 33 (Scheme 7).11 Thioether 29 was first
treated as in entry 6 in Table 6, to afford the intermedi-
ary adduct 32, which underwent a subsequent reductive
lithiation overnight before it was quenched by TMSCl.
The bis-silane 33 was obtained in 68% yield. This
procedure is particularly convenient. Compared to other
methods, it does not require any preliminary titration
and manipulation of a sensitive reagent. The reappear-
ance of the original dark-green color indicates that the
deprotonation of the thioether is completed and the
Exp er im en ta l Section
P r oced u r es for th e Red u ctive Silyla tion of Th ioeth er
1: Non -Ba r bier -Typ e Con d ition (Rea ction Cor r esp on d -
in g to En tr y 5 of Ta ble 1). To a two-necked round-bottom
flask equipped with an argon inlet were added THF (1.4 mL)
and DBB (18 mg, 0.07 mmol, 0.1 equiv). Small lithium pieces
(233 mg, 33.5 mmol, 50 equiv) were prepared as previously
and quickly added to the solution of DBB while the flask was
(19) THF derivatives substituted by a vinyl moiety undergo a smooth
reductive lithiation under mild condition, see ref 12a. For reviews on
the reductive cleavage of small ring heterocycles, see ref 4b, and: Yus,
M.; Foubelo, F. Rev. Heteroatom Chem. 1997, 17, 73-107.
(20) (a) Morita, T.; Okamoto, Y.; Sakurai, H. Tetrahedron Lett. 1980,
21, 835-838; (b) Hithcok, P. B.; Lappert, M. F.; Leung, W. P.; Liu, D.
S.; Mak, T. C. W.; Wang, Z. X. J . Chem. Soc., Dalton Trans. 1999,
1257-1262.
(21) (a) House, H. O.; Gaa, P. C.; VanDerveer, D. J . Org. Chem. 1983,
48, 1661-1670; (b) Narjes, F.; Bolte, O.; Icheln, D.; Konig, W. A.;
Schaumann, E. J . Org. Chem. 1993, 58, 626-632. (c) Tubul, A.;
Santelli, M. Tetrahedron 1988, 44, 3975-3982.
(22) Cohen, T.; Kreethadumrongdat, T.; Liu, X.; Kulkarni, V. J . Am.
Chem. Soc. 2001, 123, 3478-3483.
J . Org. Chem, Vol. 69, No. 22, 2004 7597

Streiff et al.
rapidly being purged with argon. The mixture was sonicated
for 5 min, then cooled to -78 °C. A solution of allylthioether
1 (200 mg, 0.67 mmol, 1 equiv) in THF (1 mL) was added to
the preformed solution of LiDBB under argon and the mixture
was stirred until the original dark-green color reappeared,
then TMSCl (146 mg, 1.34 mmol, 2 equiv) was added. The
reaction was maintained at -78 °C for an additional 5 min
and the resulting solution was filtered to remove the lithium
excess. The mixture was extracted three times with Et2O. The
combined organic layer was washed with water and brine,
dried over MgSO4, and concentrated to dryness. Purification
of the resulting yellow oily residue by chromatography (hex-
ane) yielded 135 mg (76%) of a mixture of 2 and 3 in a 8:92
ratio as a colorless oil: Rf 0.78 (hexane).
Ba r bier -Typ e Con d ition (Rea ction Cor r esp on d in g to
En tr y 5 of Ta ble 2). Lithium 4,4′-di-tert-butylbiphenyl was
prepared as follows. To a two-necked round-bottom flask
equipped with an argon inlet were added THF (1.4 mL) and
DBB (18 mg, 0.07 mmol, 0.1 equiv). Small lithium pieces (233
mg, 33.5 mmol, 50 equiv) were prepared as previously and
quickly added to the solution of DBB while the flask was
rapidly being purged with argon. The mixture was sonicated
for 5 min, then cooled to -78 °C. A solution of allylthioether
1 (200 mg, 0.67 mmol, 1 equiv) in THF (1 mL) and TMSCl
(109 mg, 1.0 mmol, 1.5 equiv) were added to the preformed
solution of LiDBB under argon and the mixture was stirred
until the original dark-green color reappeared. The resulting
solution was filtered to remove the lithium excess. The mixture
was extracted three times with Et2O. The combined organic
layer was washed with water and brine, dried over MgSO4,
and concentrated to dryness. Purification of the resulting
yellow oily residue by chromatography (hexane) yielded 115
mg (65%) of a mixture of 2 and 3 in a 59:41 ratio as a colorless
oil.
Tr im eth yl[(E)-2,6,10-tr im eth ylu n d eca -1,5,9-tr ien e-3-yl]-
sila n e (2). H NMR (300 MHz, CDCl3) δ 0.00 (s, 9H), 1.46 (d,
J ) 9.9 Hz, 1H), 1.60 (s, 3H), 1.62 (s, 6H), 1.68 (s, 3H), 1.97-
2.16 (m, 6H), 4.87-5.02 (m, 2H), 5.07-5.13 (m, 2H). 13C NMR
(75 MHz, CDCl3) δ -0.6, 16.7, 19.3, 23.2, 27.4, 27.7, 27.8, 30.5,
38.5, 110.4, 124.1, 125.9, 131.0, 136.7, 146.3.
1
Tr im eth yl[(2ê,5E)-2,6,10-tr im eth ylu n deca-2,5,9-tr ien yl]-
1
sila n e (3). H NMR (300 MHz, CDCl3) δ 0.04 (s, 9H), 1,25 (s,
2H), 1.54 (m, 3H), 1.60 (s, 6H), 1.61 (s, 3H), 1.67 (s, 4H), 1.93-
2.14 (m, 2H), 4.87-5.02 (m, 1H), 5.07-5.13 (m, 2H). 13C NMR
(75 MHz, CDCl3) δ 0.0, 16.6, 18.3, 23.8, 26.4, 26.9, 27.3, 27.8,
40.4, 121.6, 124.2, 131.9, 133.8, 136.4.
Compounds 2 and 3 could not be separated. The following
data concern the mixture of these two isomers: IR (KBr) 2960
(s), 2925 (s), 2855 (s), 1653 (w), 1444 (m), 1376 (m), 1248 (s),
1161 (m), 1108 (w), 933 (w), 910 (m), 854 (s), 736 (m), 694 (m)
cm-1. MS (IE, 70 eV) 264 (M+, 27), 195 (4), 181 (4), 122 (4),
107 (7), 93 (5), 73,1 (100), 59 (4). Anal. Calcd for C17H32Si: C,
77.19; H, 12.19. Found: C, 77.31; H, 12.21.
Ack n ow led gm en t. We are indebted to Prof. Y.
Nakatani and G. Ourisson for their invaluable support.
We are also grateful to Prof. D. Uguen for having
suggested to us that opening of THF may account for
our observations. S.S. and N.R. have been funded by a
doctoral fellowship from the Ministry of Research and
Technology (MRT, France).
Su p p or tin g In for m a tion Ava ila ble: Synthesis and char-
acterization of thioethers and allysilanes. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O049237U
7598 J . Org. Chem., Vol. 69, No. 22, 2004