Preparation of silyl polyenol ethers by carbonyl olefination of silyl esters

Article abstract of DOI:10.1016/j.tetlet.2014.01.040

Silyl enol ethers were produced by the carbonyl olefination of silyl esters with titanium carbene complexes generated by the desulfurizative titanation of thioacetals. The regioselective preparation of silyl dienol and trienol ethers has been achieved by

Full text of DOI:10.1016/j.tetlet.2014.01.040

Tetrahedron Letters 55 (2014) 1434–1436
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Preparation of silyl polyenol ethers by carbonyl olefination of silyl
esters
⇑
Takeshi Takeda , Tatsuya Fukada, Akira Tsubouchi
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Silyl enol ethers were produced by the carbonyl olefination of silyl esters with titanium carbene com-
plexes generated by the desulfurizative titanation of thioacetals. The regioselective preparation of silyl
dienol and trienol ethers has been achieved by using unsaturated silyl esters and thioacetals.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 4 December 2013
Revised 7 January 2014
Accepted 10 January 2014
Available online 18 January 2014
Keywords:
Silyl enol ethers
Polyenes
Carbonyl olefination
Titanium carbene complexes
Silyl esters
Silyl enol ethers are useful synthetic intermediates as enolate
equivalents and electron-rich olefins.1 Their vinylogues, silyl dienol
and trienol ethers, are versatile building blocks2 and have been em-
ployed for various cyclization reactions,3 which include the Diels–
Alder4 and hetero Diels–Alder5 reactions. The use of silyl dienol
ethers in the Mukaiyama aldol type reaction as dienolate equiva-
lents has also been investigated.6 Several methods for the prepara-
tion of silyl polyenol ethers,2 such as transformation of enones
through the Wittig-type carbonyl olefination,7 the reaction of allyl-
lithiums generated from 3-trialkylsiloxy-1,4-pentadienes with
electrophiles,8 isomerization of 1-(siloxylmethyl)butadienes,9 and
the tandem epoxysilane rearrangement/Wittig reaction of phos-
phorus-containing epoxy silanes,10 have been investigated. Despite
these extensive studies, base-induced deprotonation of unsatu-
rated carbonyl compounds followed by exposure to a silylating
agent is still the major approach to silyl polyenol ethers.8,11 The
preparation of silyl enol ethers by silylation of enolates, however,
suffers a serious drawback in that it generally lacks regioselectivi-
ty. In contrast, no ambiguity as to the location of the double bond
exists in their preparation by the carbonyl olefination of silyl
esters. Although the organometallic species generated by the
treatment of gem-dibromides with TiCl4–Zn–TMEDA12 and
We have studied the carbonyl olefination using titanium car-
bene complexes generated by the desulfurizative titanation of
2 Cp2Ti[P(OEt)3]2
5
SR
R2
TiCp2
n
R2
n
SR
- Cp2Ti(SR)2
3
4
O
R1
OSi
OSi
2
n'
R2
n
R1
1
n'
- Cp2Ti=O
n, n' = 0, 1
O
O
O
Ph
OTIPS
Ph
OTIPS Ph
OTBS
2a
2b
2c
O
O
O
OTIPS
OTIPS
OTIPS
MeO
Ph
2d
2e
3a
2f
O
SPh
SPh
SPh
SPh
TMS
Ph
OTIPS
Ph
a
-elimination of dimethyltitanocene13 are employed for the
2g
3b
transformation of silyl esters into silyl enol ethers, their application
to the preparation of silyl polyenol ethers is largely restricted due
to unavailability of appropriate starting materials.
SPh
SPh
S
S
S
S
MeO
3c
3d
3e
⇑
Corresponding author. Tel./fax: +81 42 388 7034.
E-mail address: takeda-t@cc.tuat.ac.jp (T. Takeda).
Scheme 1. Preparation of silyl polyenol ethers 1 by carbonyl olefination of silyl
esters 2.
0040-4039/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2014.01.040

T. Takeda et al. / Tetrahedron Letters 55 (2014) 1434–1436
1435
thioacetals and related compounds.14 Since our carbonyl olefin-
ation works well for carboxylic acid derivatives such as esters,14a
thioesters,14d and amides,14i we envisioned the preparation of silyl
enol ethers by the carbonyl olefination of silyl esters. Here we de-
scribe a versatile method for the preparation of silyl polyenol
ethers 1 using saturated as well as unsaturated silyl esters 2 and
thioacetals 3 as starting materials (Scheme 1).
with unsaturated thioacetal 3d was examined under various condi-
tions (Table 1). The treatment of 2b with the carbene complex 4d,
generated by the desulfurizative titanation of unsaturated thioac-
etal 3d with titanocene(II) 5, in THF at 25 °C for 2 h produced 1d
in moderate yield (entry 1). The reaction carried out at reflux gave
1d in better yield (entry 2). The use of several mixed solvent sys-
tems was examined, and cyclopentyl methyl ether (CPME) was
found to be an efficient co-solvent (entry 5). The best result was
obtained when the reaction was performed at 50 °C using a pro-
longed reaction time (entry 6). Satisfactory results were also ob-
tained under similar reaction conditions in the preparation of
silyl dienol ether 1i using the unsaturated silyl ester 2g (entries 7
and 8).
First, the preparation of dienol ether 1d bearing a siloxy group
at the terminus of diene system by the reaction of silyl ester 2b
Table 1
Formation of the silyl dienol ethers 1d and ia
With optimized reaction conditions in hand, we next examined
the reactions of various types of carbene complexes 4 with silyl es-
ters 2 (Table 2). The silyl enol ethers 1a and b were obtained by the
reaction of alkylidene complex generated from 3b with the silyl es-
ters 2b and d (entries 1 and 2). The reaction of unsaturated carbene
complex derived from 3d with saturated and aromatic silyl esters
2a–d resulted in the regioselective formation of dienol ethers
1c–f with a siloxy group at the terminal sp2 carbon (entries 3–6).
The silyl dienol ethers 1g–j bearing a siloxy group at the inner
sp2 carbon in the conjugated system were also regioselectively ob-
tained by the reaction of saturated carbene complexes generated
Entry
2
3
Temp/°C, time/h
Solvent
1 (Yield/%)b
1
2
3
4
5
6
7
8
2b
2b
2b
2b
2b
2b
2g
2g
3d
3d
3d
3d
3d
3d
3a
3a
25, 2
THF
THF
1d (19)
1d (46)
1d (49)
1d (50)
1d (59)
1d (64)
1i (64)
1i (64)
Reflux, 4
Reflux, 4
Reflux, 4
Reflux, 4
50, 14
THF/toluene = 1:3
THF/diglyme = 1:3
THF/CPME = 1:3
THF/CPME = 1:3
THF/CPME = 1:3
THF/CPME = 1:3
Reflux, 1
50, 14
a
Cp2Ti[P(OEt)3]2 5 (5 equiv) and 3 (2 equiv) were used.
Isolated yield based on 2 used.
b
from 3a–c with
a,b-unsaturated silyl esters 2e–g (entries 7–10).
Likewise, the carbonyl olefination of unsaturated ester 2e with
unsaturated thioacetal 3d produced the trienol ether 1k (entry
11). In these reactions, the stereochemistry of the silyl esters was
completely retained. As for the geometry of the double bond
formed by the carbonyl olefination, the Z-isomers generally pre-
dominated, and higher Z-stereoselectivity was observed in the
reactions using unsaturated thioacetals. It is noteworthy that the
carbonyl olefination of 2 carried out in a larger scale produced
the silyl dienol ethers 1 in better yields (see entries 3 and 4).
The synthetic utility of the present method is further demon-
strated in Scheme 2. The selective formation of silyl trienol ethers,
6-methyl-1-phenyl-1,3,5-heptatrienes 1l and m bearing a siloxy
group at a different position, was achieved by selection of appro-
priate silyl esters and thioacetals.
The preferential formation of (Z)-silyl enol ethers 1 is rational-
ized by the transition states for the formation of oxatitanacyclobu-
tane intermediates depicted in Scheme 3. The transition states A
and B would be relatively stable because the transition states C
and D suffer an additional gauche-like steric interaction between
the substituents of carbene complex 4 and silyl ester 3 indicated
by a hashed double headed arrow. The reaction preferentially pro-
ceeds via the transition state A to produce the titanacyclobutane 6
because the transition state B is rather destabilized by steric inter-
action between the quasi-axial Cp group and trialkylsiloxy group
which is more bulky than R2. The titanacycle 6 affords (Z)-silyl enol
ether Z-1 through the extrusion of titanocene oxide with retention
of configuration. The better Z selectivity observed in the reaction of
Table 2
Preparation of silyl enol ethers 1a
Entry
2
3
1
Yield/%b
(E:Z ratio)c
OTIPS
OTIPS
42
(56:44)
1a
1
2
2b
2d
3b
3b
TMS
TMS
Ph
63
(40:60)
1b
OMe
1c
65, 72d
(28:72)
3
4
5
2a
2b
2c
3d
3d
3d
Ph
OTIPS
64, 75e
(17:83)
Ph
1d
1e
OTIPS
OTBS
Ph
66
(22:78)
OMe
83d
(22:78)
1f
6
2d
3d
OTIPS
OTIPS
76d
(40:60)
7f
8f
2e
2f
3b
3c
1g
TMS
83
(66:34)
1h
OTIPS
OTIPS
MeO
Ph
64
(45:55)
9f
2g
2g
3a
3b
1i
Ph
O
OTIPS
S
5
Ph
78
(38:62)
10f
1j
+
TIPSO
OTIPS
TMS
Ph
Ph
S
3e
2f
1l
1k
70%, 3E:3Z = 20:80a
74
(25:75)
11f
2e
3d
OTIPS
OTIPS
Ph
O
5
S
a
+
All reactions were performed at 50 °C for 14 h using 0.3 mmol of 2, unless
otherwise noted.
Ph
OTIPS
S
b
c
1m
Isolated yields based on 2 used.
2g
aCarried out at reflux for 1 h.
3d
76%, 3E:3Z = 21:79a
Determined by NMR spectroscopies. The stereochemistry of products was
confirmed by NOE or NOESY experiment.
Carried out in 0.5 mmol scale.
d
e
f
Carried out in 1 mmol scale.
Carried out at reflux for 1 h.
Scheme 2. Preparation of 6-methyl-1-phenyl-1,3,5-heptatrienes 1l and m bearing
a siloxy group at a different position.

1436
T. Takeda et al. / Tetrahedron Letters 55 (2014) 1434–1436
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R1
A
B
R2
Cp
Cp
Ti
SiO
R1
Ti
O
R1
Cp
Cp
R2
SiO
O
D
C
Cp2Ti
R1
O
A
-1
Z
R2
OSi
- Cp2Ti=O
6
Scheme 3. Transition states for the formation of oxatitanacyclobutanes.
alkenylcarbene complexes is rationalized by a planar transoid con-
formation of alkenylcarbene complex, which partially alleviates
steric repulsion between R1 and the trialkylsiloxy group in the
transition state A.
In conclusion, we have developed a new and efficient method
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Supplementary data
Supplementary data (experimental procedures and full charac-
terization of all products) associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.
01.040.
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