Tandem epoxysilane rearrangement/Wittig-type reactions using γ-phosphinoyl- and γ-phosphonio-α,β-epoxysilane

Article abstract of DOI:10.1016/j.tetlet.2006.10.121

Reaction of γ-phosphinoyl- and γ-phosphonio-α,β-epoxysilane with a base followed by addition of a ketone or an aldehyde afforded dienol silyl ether derivatives via a tandem process that involves base-induced ring opening of the epoxide, Brook rearrangemen

Full text of DOI:10.1016/j.tetlet.2006.10.121

Tetrahedron Letters 47 (2006) 9271–9273
Tandem epoxysilane rearrangement/Wittig-type reactions using
c-phosphinoyl- and c-phosphonio-a,b-epoxysilane
Michiko Sasaki, Mai Horai and Kei Takeda*
Department of Synthetic Organic Chemistry, Graduate School of Medical Sciences, Hiroshima University, 1-2-3 Kasumi,
Minami-Ku, Hiroshima 734-8553, Japan
Received 19 September 2006; revised 23 October 2006; accepted 24 October 2006
Available online 9 November 2006
Abstract—Reaction of c-phosphinoyl- and c-phosphonio-a,b-epoxysilane with a base followed by addition of a ketone or an
aldehyde afforded dienol silyl ether derivatives via a tandem process that involves base-induced ring opening of the epoxide, Brook
rearrangement, and Wittig-type reaction.
Ó 2006 Elsevier Ltd. All rights reserved.
Recently we have developed the epoxysilane rearrange-
ment that converts c-metalated a,b-epoxysilanes into
b-siloxyallylic carbanion derivatives, which are often
difficult to generate in other ways.1 During the explora-
tion of the possibility of cascade reactions initiated by
the rearrangement, we became interested in its use in
Wittig-type reactions2 (Scheme 1) by the introduction
of a heteroatom substituent such as a phosphonoyl
group as an a-carbanion-stabilizing group, allowing a
direct access to dienol silyl ethers. Dienol silyl ethers
have been used as versatile building blocks in a variety
of synthetic transformations, including Diels–Alder
reaction,3 c-selective reaction with electrophiles in dien-
olates,4 and modular synthesis of a polyenic backbone.5
Although this has led to considerable efforts toward
developing methods for synthesizing such conjugated
systems,6 most of which use a,b-unsaturated aldehydes
as a starting material, only a few methods of synthesis
have so far been reported.
First, we prepared c-phosphoryl derivative 6 from the
known epoxy silane 5 and examined the tandem epoxy-
silane
rearrangement/Horner–Wadsworth–Emmons
reaction. Treatment of 6 with LDA followed by the
addition of hexanal afforded adduct 8 (single diastereo-
mer) and the protonated product 9 in 19% and 38%
yields, respectively, no desired product 7 being obtained
(Scheme 2).
The result can be understood by considering that
cycloelimination from betaine intermediates does not
readily occur when electron-withdrawing groups in the
O
H
base
O
O
R
R'
R3SiO
X
R3Si
X
R3Si
X
H
1
2
R'
R
O-
X
4a X = P(O)(OR)2
4b X = P(O)Ph2
4c X = PPh3+X-
Wittig-Type Reaction
R
R3SiO
R3SiO
H
R'
H
3
4
Scheme 1. Epoxysilane 1 as a precursor of dienol silyl ethers.
*
Corresponding author. Tel./fax: +81 82 257 5184; e-mail: takedak@hiroshima-u.ac.jp
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.10.121

9272
M. Sasaki et al. / Tetrahedron Letters 47 (2006) 9271–9273
P(OMe)3
O
O
O
1. n-BuLi, THF
-80 ˚C, 5 min
2. cyclohexanone
-80 ° to -50 °C
ButMe2Si
I
ButMe2Si
P(OMe)2
O
O
reflux
30 min
5
6
t BuMe2Si
PPh2
LiO
H
O
(80%)
t BuMe2SiO
PPh2
11
HO
C5H11
1. LDA
O
2. hexanal
C5H11
12'
6
R3SiO
R3SiO
P(OMe)2
THF
-80 ° to 10 °C
tBuMe2SiO
7
(0%)
8
base
-80 ° to -10 °C
(19%)
H
H
O
13
R3SiO
P(OMe)2
yield (%)
9
entry base (equiv)
13 (E/Z)
38 (1.0)
58 (1.3)
77 (1.0)
12 (E/Z)
17 (1.3)
19 (1.0)
-
(38%)
Scheme 2. Preparation of 6 and its reaction with hexanal.
1
2
3
KHMDS (2.0)
NaHMDS (2.0)
NaHMDS (3.0)
phosphonate reagents are absent.2b Next we focused on
a phosphine oxide-based approach, which can afford
condensation products directly in the presence of potas-
sium ion without isolation of the adducts. When phos-
phine oxide 11, prepared from 10 via the reaction with
lithium diphenylphosphide followed by H2O2 oxidation
and then epoxidation, was treated with KHMDS
followed by cyclohexanone, dienol silyl ether 13 and
protonated products 14 were obtained in a low yield
together with decomposition products (Scheme 3). In
contrast, the use of n-BuLi produced adducts of ketone
12 in a 64% yield, which were converted into 13 by expo-
sure to KHMDS. These results prompted us to change a
counter cation from lithium to potassium or sodium
in situ after the formation of the lithium salt of 12.7
Scheme 4. One-pot synthesis of 13.
in Scheme 5, to be suitable for our purposes. When 16
was treated with n-BuLi at ꢀ80 °C over a period of
15 min followed by the addition of cyclohexanone and
then warmed to room temperature, dienol silyl ethers
13 were obtained in a 40% yield in a ratio of 1.6 (Z/E)
(Scheme 5).
The reactions with aldehydes gave somewhat better
results in terms of yield and Z/E selectivity of the enol silyl
ether moiety. Thus, when 16 was reacted with n-BuLi
and then benzaldehyde at ꢀ80 °C, 17 was obtained in
a 47% yield in a ratio of 3.4 (Z/E) (Table 1, entry 1).
The yield was improved to a 75% yield when the reac-
tion was conducted at 15 °C (entry 2). The reactivity
and selectivity of the reaction were affected by a change
in the solvent from THF to CH2Cl2. Although the reac-
tion in CH2Cl2 under the same reaction conditions led to
recovery of the starting material (entry 3), lowering the
reaction temperature to ꢀ40 °C gave 17 in the Z selec-
tivity (entry 4).
Lithium salt 120, generated from 11 with n-BuLi and
cyclohexanone, was treated with KHMDS or NaHMDS
in situ (Scheme 4). The best result was obtained by
3 equiv of NaHMDS to afford 13 (Scheme 4) in a 77%
yield. Reactions with aldehydes resulted in low yields.
We next turned our attention to Wittig reaction using c-
phosphonio derivative 4c, the synthesis of which using
the corresponding halides we had attempted at the ini-
tial stage of the project but had given up on because
of unavailability of isolable and purifiable material.
Encouraged by the above result with the phosphine
oxide, we decided to reexamine the preparation of 4c.
After an extensive experimentation, we found triflate
derivative 16,8 readily prepared by the sequence shown
A similar trend was observed with the reactions with
other aldehydes (Table 2).
In conclusion, we have demonstrated further possibili-
ties of the epoxysilane rearrangement as an initiator in
cascade reactions. A unique feature of this method is
that, in addition to the tandem nature of the process,
the starting phosphonium salt is a stable crystalline solid
that is readily derived from propargyl alcohol and can
be stored for several months without significant
decomposition.
1. LiPPh2
O
O
But Me2Si
Br
But Me2Si
PPh2
2. H2O2 (78%)
3. CPBA (85%)
n-BuLi, -80 ˚C, 10 min
10
11
m
1.
O
1.
mCPBA (100%)
2. cyclohexanone
tBuMe2Si
OH
t BuMe2Si
PPh3
OTf
-80 ° to -10 °C, 1 hr
2. Tf2O, pyridine
3. PPh3, Et2O (86%)
HO
O
11
15
16
THF
R3SiO
PPh2
O
(64%)
H
R3SiO
PPh2
tBuMe2SiO
12 (
E/Z
= 1.7)
KHMDS
H
1. n-BuLi. THF, -80 °C, 15 min
2. cyclohexanone,
R3SiO
THF
14
16
H
-80 ° to -70 °C
H
13
15 min
-80 °C to rt, 1 hr
13 (
E/Z
= 1.7)
40% (
Z:E
= 1.6:1.0)
(95%)
Scheme 3. Preparation of 11 and its reaction with cyclohexanone.
Scheme 5. Preparation of 16 and its reaction with cyclohexanone.

M. Sasaki et al. / Tetrahedron Letters 47 (2006) 9271–9273
9273
Table 1. Reaction of 16 with benzaldehyde
shima University, and N-BARD, Hiroshima University
for the use of their facilities.
OSiMe2But
3
O
Ph
OTf
1.
n-BuLi
t
Ph
4
Bu Me2SiO
tBuMe2Si
PPh3
+
H
2.PhCHO
H
16
References and notes
(Z)-17
(E)-17
Entry Conditions
1
Solvent Yield (%) Z/Ea
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Yamaguchi, K. Org. Lett. 2002, 4, 1511–1514; (b) Sasaki,
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Okugawa, S.; Takeda, K. Org. Lett. 2004, 6, 2973–2975; (d)
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Org. Lett. 2004, 6, 4367–4369; (e) Tanaka, K.; Takeda, K.
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THF
47
75
0
3.4
3.4
—
1. ꢀ80 °C, 15 min
2. ꢀ80 °C, 30 min
2
3
4
THF
1. 15–20 °C, 3 min
2. 15–20 °C, 5 min
CH2Cl2
1. 15–20 °C, 3 min
2. 15–20 °C, 10 min
CH2Cl2 65
9.4
1. ꢀ40 °C to ꢀ35 °C, 3 min
2. ꢀ40 °C to ꢀ30 °C, 25 min
a The ratios of 3E/3Z were almost 1.0.
Table 2. Reaction of 16 with aldehydes
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E.; Reitz, A. B. Chem. Rev. 1989, 89, 863–927; (b)
Wadsworth, W. S., Jr. Org. React. 1977, 25, 73–253.
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OSiMe2But
3
4
O
R
OTf
1.
n-BuLi
But Me2SiO
R
t BuMe2Si
PPh3
+
H
2. RCHO
H
(Z)-17
16
(
E)-17
Entry
R
Conditionsa
Yield (%)
Z/Eb
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¨
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1
2
3
4
5
6
7
8
n-C5H11
n-C5H11
(CH3)2CH
(CH3)2CH
c-C6H11
c-C6H11
(CH3)3C
(CH3)3C
A
B
A
B
A
B
A
B
77
60
68
58
69
48
50
42
4.4
8.0
10.6
8.0
6.6
9.1
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Chem. 1996, 60, 3236–3242; (b) Paolobelli, A. B.; Latini,
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Soc. 1990, 112, 4906–4911; (b) Iqbal, J.; Khan, M. A.
Synth. Commun. 1989, 19, 515–521; (c) Cazeau, P.;
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Tetrahedron 1987, 43, 2089–2092; (d) Kozikowski, A. P.;
Jung, S. H. Tetrahedron Lett. 1986, 27, 3227–3230; (e)
Kozikowski, A. P.; Jung, S. H. J. Org. Chem. 1986, 51,
3400–3402; (f) Fleming, I.; Goldhill, J.; Paterson, I.
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Z onlyc
Z onlyc
a Condition A: 1. 15–20 °C, 3 min, 2. 15–20 °C, 5 min in THF; con-
dition B: 1. ꢀ40 °C to ꢀ35 °C, 3 min, 2. ꢀ40 °C to ꢀ30 °C, 25 min in
CH2Cl2.
b The ratios of 3E/3Z were almost 1.0.
c 3Z isomer was formed exclusively.
Acknowledgments
7. We have reported that the exchanging cation in enolate can
be realized by the addition of NaHMDS to a solution of
lithium enolate Takeda, K.; Sawada, Y.; Sumi, K. Org.
Lett. 2002, 4, 1031–1033.
8. We found that 16 is a stable crystalline compound (mp
126 °C) when stored at room temperature.
This research was partially supported by a Grant-in-Aid
for Scientific Research on Priority Areas 17035054 from
the Ministry of Education, Culture, Sports, Science and
Technology (MEXT). We thank the Research Center
for Molecular Medicine, Faculty of Medicine, Hiro-