Novel sequential 1,4-Brook rearrangement-Wittig reaction: New one-pot approach for silyl dienol ethers

Article abstract of DOI:10.1016/j.tetlet.2012.08.114

A novel one-pot synthetic method of silyl dienol ethers via 1,4-Brook rearrangement-Wittig reaction sequence has been developed. This tandem reaction proceeded via the intramolecular silyl migration step, which enabled stereoselective formation of phosphorane intermediates. The reaction is operationally simple and high yielding, thus providing a new useful formula for silyl dienol ether synthesis.

Full text of DOI:10.1016/j.tetlet.2012.08.114

Tetrahedron Letters 53 (2012) 5955–5957
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Novel sequential 1,4-Brook rearrangement–Wittig reaction: new one-pot
approach for silyl dienol ethers
Yuji Matsuya a, , Azusa Koiwai a, Daishiro Minato a, Kenji Sugimoto a, Naoki Toyooka b
⇑
a Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
b Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel one-pot synthetic method of silyl dienol ethers via 1,4-Brook rearrangement–Wittig reaction
sequence has been developed. This tandem reaction proceeded via the intramolecular silyl migration
step, which enabled stereoselective formation of phosphorane intermediates. The reaction is operation-
ally simple and high yielding, thus providing a new useful formula for silyl dienol ether synthesis.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 20 July 2012
Revised 22 August 2012
Accepted 27 August 2012
Available online 3 September 2012
Keywords:
Silyl dienol ether
1,4-Brook rearrangement
Wittig reaction
Tandem reaction
Silyl dienol ethers are significantly versatile compounds in the
field of organic synthesis, because their broad utility has spread
to various types of reactions such as Diels–Alder cyclization1 and
conjugated Mukaiyama–Aldol-type reactions.2 Therefore, they
have been widely utilized as useful synthetic blocks and key inter-
mediates in a large number of synthetic studies.3 These electron-
rich dienes can be commonly prepared from
a,b-unsaturated
carbonyl compounds by base-induced deprotonation followed by
exposure to a silylating agent.4 In general, however, these methods
often have difficulties in the regulation of geometric isomers of the
diene.5 On the other hand, another approach for the preparation of
silyl dienol ethers, involving Wittig-type reactions, has been re-
ported,6 in which the Wittig intermediates (silyl enol phosphorane,
4) are generated from a,b-unsaturated carbonyl compounds 1, tri-
Scheme 1. Outline of one-pot synthesis of silyl dienol ethers 5.
alkylphosphine, and silylating agents (Scheme 1). These reaction
systems have been demonstrated to involve 1,4-addition of phos-
phine then silylation (silyl chloride)7 or carbonyl activation then
phosphine addition (silyl triflate),6a,6b and it has been stated that
a suitable choice of silylating agents would make the selective for-
mation of E/Z isomers of 4 possible. However, the substrate 1 re-
ported in the literatures seems to be limited to a few simple
structures and several cyclic enones, and the scope and generality
of the reaction have not been disclosed sufficiently.8 In addition,
these procedures must include an isolation process of phospho-
nium salts 2 and/or 20 and usage of a strong base for deprotonation
of them to generate phosphorane 4 which is then reacted with
aldehydes in a step by step manner, thus maybe making the oper-
ation rather complicated.
Recently, we have explored novel tandem reaction systems
based on an intramolecular silyl migration process, and have re-
ported versatile reactions of silylated alkynes with aldehydes med-
iated by a tertiary amine to produce useful synthetic blocks.9 These
continuous studies, combining with aforementioned sily dienol
ether-forming reactions,6,7 inspired us to develop a new tandem
process for the efficient preparation of silyl dienol ethers via silyl
migration as a key step. As shown in Scheme 1, we envisaged that
silylated enone 3 would be directly transformed into phosphorane
4 through 1,4-addition of strongly nucleophilic phosphine and sub-
sequent 1,4-Brook rearrangement (silyl migration), which would
⇑
Corresponding author.
E-mail address: matsuya@pha.u-toyama.ac.jp (Y. Matsuya).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.08.114

5956
Y. Matsuya et al. / Tetrahedron Letters 53 (2012) 5955–5957
Table 2
be followed by the Wittig reaction with various aldehydes to pro-
vide silyl dienol ethers in the same reaction medium. Herein, we
wish to report an efficient one-pot synthesis of silyl dienol ethers
via a stereoselective formation of silyl enol phosphorane as a tran-
sient intermediate.
Reaction of silylated enone 3 with tributylphosphine in the presence of 4-nitrobenz-
aldehyde
We initiated the investigation of the working hypothesis using
enone 3a possessing a trimethylsilyl (TMS) group as a substrate,10
upon treatment with tertiary phosphine and benzaldehyde in ben-
zene at room temperature (Table 1). While triphenylphosphine did
not cause any reactions (entry 1), the substrate 3a was consumed
by exposure to more nucleophilic tri-n-butylphosphine to give a
rather complex mixture, in which we could find compounds 6
and 60 as a mixture of several isomers after chromatographic sep-
aration in 8% yield (entry 2).11 Because these products were pre-
sumed to originate from trimethylsilyl dienol ether 5a as a result
of hydrolytic decomposition during a work-up process, this finding
prompted us to explore more suitable reaction conditions to our
purpose. Thus, we examined several solvents for this reaction sys-
tem to reach the finding that dichloromethane and chloroform
brought about comparatively satisfactory yields after simple stir-
ring at room temperature for 1 h (entries 3–6), although reasons
for these solvent effects remained unclear.
To avoid the hydrolysis of the silyl ether observed in Table 1,
sterically congested silyl groups such as tert-butyldimethylsilyl
(TBS), triisopropylsilyl (TIPS), and tert-butyldiphenylsilyl (TBDPS)
were employed for the reaction instead of the labile TMS group,10
and efficient one-pot synthesis of silyl dienol ethers could be
achieved using various silylated enone substrates (Table 2). When
tributylphosphine was added to a solution of TBS-enone 3b and 4-
nitrobenzaldehyde in CH2Cl2 or CHCl3 and allowed to react at room
temperature with stirring, the reaction mixture immediately
turned to a deep yellow solution, and the enone and the aldehyde
cleanly disappeared and instead a new yellow product was de-
tected on TLC. This product could be easily isolated only by passing
through a short silica gel column for removal of tributylphosphine
oxide as a sole by-product, and the yield of silyl dienol ether 5b
was almost quantitative (entry 1). Because all reagents were used
in a one-to-one manner, the products in the reaction medium were
actually only 5b and phosphine oxide. As concerns the geometric
isomers of 5b, we observed the presence of three isomers on the
1H NMR spectra, and it was found that two of them were 3,4-E
(1,2-E and 1,2-Z) and another was 3,4-Z (1,2-geometry not deter-
mined) from the coupling constants data. However, a gradual alter-
ation of the ratio due to interconversion of these isomers was
markedly observed both in the reaction conditions and even in a
solution state after the isolation, and therefore, accurate analyses
of the geometric stereoselectivity of 5 seemed to be impossible
at this stage. Thus, we present only the isolation yields of 5 in Ta-
Entry
X
R
Yield (%) of 5a
1
TBS
TBS
TBS
TIPS
TIPS
TBDPS
Ph
3b
3c
3d
3e
3f
Quant. (96)
96
60 (32)
66
58
2b
3
4-Me-C6H4
Me
Ph
4-Cl-C6H4
Ph
4
5c
6
3g
80
a
Isolation yields. The yields in parentheses were obtained from the reaction in
CHCl3 as a solvent; otherwise in CH2Cl2.
b
Reaction time was 5 h.
Reaction time was 6 h.
c
ble 2. The other TBS-enones 3c and 3d also produced the corre-
sponding silyl dienol ethers 5c and 5d, respectively, in
satisfactory yields (entries 2 and 3). When using methyl ketone
substrate 3d, the yield was somewhat low probably due to suscep-
tibility of the resulting silyl dienol ether 5d toward hydrolysis. The
reaction successfully proceeded in the case of TIPS-enones 3e and
3f as a substrate to give the products in moderate yields (entries 4
and 5). In addition, TBDPS-enone 3g was also proved to be a prom-
ising substrate for the silyl dienol ether forming reaction (entry 6).
With these results in hand, we further investigated the general-
ity of the reaction using TBS-enone 3b and various aldehydes (Ta-
ble 3). It was confirmed that all the aldehydes used in this study,
other than 4-nitrobenzaldehyde, did not cause the olefin isomeri-
zation of the product, implying that the presence of a strongly elec-
tron-withdrawing group (4-NO2-C6H4–) on the dienol ethers
happened to cause such isomerization as exemplified in 5b (entry
Table 3
Reaction of TBS-enone 3b with various aldehydesa
Entry
R
Product
Yieldb (%)
Ratio (E:Z)c
1
2
Ph
7
8
9
Quant.
92
98
96
89
97
39
66
82
69:31
71:29
71:29
4-Cl-C6H4
4-CF3-C6H4
4-NO2-C6H4
4-MeO-C6H4
2-MeO-C6H4
2,6-Me2-C6H3
2-Naphthyl
PhCH=CH
n-Pr
3
4d
5
5b
10
11
12
13
14
15
16
17
—
e
67:33
62:38
82:18f
78:22
Table 1
6
7
8
9
10
11
12i
Reaction of TMS-enone 3a with phosphine in the presence of benzaldehydea
g
—
87
Quant.
84
74:26
72:21h
71:29
PhCH2CH2
Me
a
All reactions were carried out using 1 equiv of aldehyde and 1 equiv of phos-
Entry
Phosphine
Solvent
Yield (%, 6+60)
phine, unless otherwise stated.
b
Isolation yields.
1
2
3
4
5
6
Ph3P
Benzene
Benzene
THF
DMF
CH2Cl2
CHCl3
0
8
11
0
43
69
c
The ratio was estimated by 1H NMR spectra.
(n-Bu)3P
(n-Bu)3P
(n-Bu)3P
(n-Bu)3P
(n-Bu)3P
d
The reaction was carried out at room temperature.
The ratio was inconstant due to rapid isomerization under the reaction
e
conditions.
f
A small amount of another isomer was detected on 1H NMR.
Not determined.
Another geometric isomer (7%) was observed.
Excess amount of acetaldehyde (3 equiv) was used.
g
h
a
All reactions were carried out using 1 equiv of benzaldehyde and 1 equiv of
phosphine.
i

Y. Matsuya et al. / Tetrahedron Letters 53 (2012) 5955–5957
5957
In summary, we have developed a novel one-pot synthetic
method of silyl dienol ethers via a 1,4-Brook rearrangement–Wittig
reaction sequence. The phosphorane intermediates were success-
fully generated in a stereoselective manner taking advantage of a
stereochemical demand of the intramolecular silyl migration step.
The reaction is operationally simple and high yielding, thus provid-
ing a new useful formula for silyl dienol ether synthesis. Further
applications of the reaction, including improvement of stereocon-
trol of the Wittig step, are currently under investigation in our
laboratory.
Acknowledgement
Scheme 2. Plausible reaction mechanism.
This work was supported in part by a Grant-in-Aid (No.
24790008) for Scientific Research by the Ministry of Education,
Culture, Sports, Science, and Technology of the Japanese
Government.
4). Thus, in the other cases, the ratio of geometric isomers could be
unambiguously determined, which should reflect a true stereose-
lectivity of the reaction. Aromatic aldehydes with various substit-
uents were conducted to the reaction, and in every case the
desired silyl dienol ether 7–11 were cleanly obtained without
any side reactions (entries 1–6). More sterically hindered 2,6-
dimethylbenzaldehyde gave a relatively poor result (entry 7), but
2-naphthaldehyde afforded 13 in a moderate yield (entry 8). Sev-
eral aliphatic aldehydes were also examined, and the reactions
proceeded smoothly to produce silyl dienol ethers 14–17 in high
yields (entries 9–12). In most of the cases, the silyl dienol ethers
were obtained as a mixture of two geometric isomers, 3,4-E and
3,4-Z, with predominant formation of the 3,4-E isomer,12 under
ꢀ20 °C reaction temperature, as indicated in Table 3. It is notewor-
thy that 1,2-geometry of the products was exclusively of Z-form,13
which suggests that geometry of the transient intermediate, phos-
phorane 4, was completely regulated to Z-form in this reaction
system.
A plausible reaction mechanism is shown in Scheme 2. Addition
of tributylphosphine to the enone 3 in a 1,4-fashion potentially
produces two adducts 18 and 180. Subsequent 1,4-Brook rearrange-
ment can occur only in 18, because liability to the intramolecular
silyl migration should be restricted from the distances between
the oxide group and the silyl group, which are dictated by the ole-
fin geometry. Because the adducts 18 and 180 can be under equilib-
rium through 3, this would be a definitive reason for the Z-selective
formation of the intermediate phosphorane 4. To exclude the pos-
sibility of involving an intermolecular silyl migration in the reaction
conditions, we performed a crossover experiment using 3c and 3f
as enone substrates containing different silyl (X) and R groups.
Namely, equimolar amounts of each enone were reacted with trib-
utylphosphine and aldehyde simultaneously in the same flask (the
same concentration as the experiments in Table 3), and it was con-
firmed that scramble of the substituents X and R did not occur and
only dienol ethers that originated from an intramolecular silyl
migration were detected in the reaction. These results gave a posi-
tive proof that 1,4-Brook rearrangement would control the stereo-
chemistry of phosphorane 4.14 We are considering that these
transformations are under equilibrium, because a slow Wittig reac-
tion between 4 and ketone 3 was observed in the absence of alde-
hyde. Once the phosphorane 4 was formed, the aldehydes rapidly
participated in a standard Wittig reaction with 4 irreversibly to
furnish silyl dienol ethers 5 with a predominant E-selectivity. Thus,
the presence of the aldehyde is likely to support the progress of
this sequential reaction process.15 Although the TMS ethers
(X = TMS) were unstable to give rise to the formation of 6 and 60,
the bulkier TBS dienol ethers, as well as TIPS and TBDPS ethers,
were sufficiently stable to purify with easy handling.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.
08.114.
References and notes
1. (a) Danishefsky, S.; Yan, C. F. Synth. Commun. 1978, 8, 211; (b) Danishefsky, S.;
Zambone, R.; Kahn, M.; Etheridge, S. J. J. Am. Chem. Soc. 1980, 102, 2097; (c)
Danishefsky, S.; Prisbylla, M. P.; Hiner, S. J. Am. Chem. Soc. 1978, 100, 2918; (d)
Trost, B. M.; Chupak, L. S.; Lubbers, T. J. Org. Chem. 1997, 62, 736; (e) White, J.
D.; Choi, Y. Helv. Chim. Acta 2002, 85, 4306; (f) Kusama, H.; Karibe, Y.; Onizawa,
Y.; Iwasawa, N. Angew. Chem., Int. Ed. 2010, 49, 4269; (g) Iaroshenko, V. O.;
Bunescu, A.; Spannenberg, A.; Langer, P. Chem. Eur. J. 2011, 17, 7188.
2. (a) Mukaiyama, T.; Ishida, A. Chem. Lett. 1975, 319; (b) Mukaiyama, T.; Ishida, A.
Chem. Lett. 1977, 467; (c) Chan, T. H.; Brownbridge, P. J. Am. Chem. Soc. 1980,
102, 3534; (d) Paolobelli, A. B.; Latini, D.; Ruzziconi, R. Tetrahedron Lett. 1993,
34, 721; (e) Denmark, S. E.; Beutner, G. L. J. Am. Chem. Soc. 2003, 125, 7800.
3. For reviews on preparation and utility of silyl dienol ethers, see: (a) Petrzilka,
M.; Grayson, J. I. Synthesis 1981, 753; (b) Brownbridge, P. Synthesis 1983, 85.
4. (a) Iqbal, J.; Khan, M. A. Synth. Commun. 1989, 19, 515; (b) Cazeau, P.; Duboudin,
F.; Moulines, F.; Babot, O.; Dunogues, J. Tetrahedron 1987, 43, 2089; (c) Fleming,
I.; Goldhill, J.; Paterson, I. Tetrahedron Lett. 1979, 20, 3209; (d) Suzuki, H.;
Koyama, Y.; Morooka, Y.; Ikawa, T. Tetrahedron Lett. 1979, 20, 1415.
5. For a report on stereocontrolled synthesis of silyl dienol ethers, see: Sodeoka,
M.; Yamada, H.; Shibasaki, M. J. Am. Chem. Soc. 1990, 112, 4906.
6. (a) Kozikowski, A. P.; Jung, S. H. Tetrahedron Lett. 1986, 27, 3227; (b)
Kozikowski, A. P.; Jung, S. H. J. Org. Chem. 1986, 51, 3400; For a recent report
on use of epoxysilane rearrangement, see: (c) Sasaki, M.; Horai, M.; Takeda, K.
Tetrahedron Lett. 2006, 47, 9271.
7. Evans, D. A.; Hurst, K. M.; Takacs, J. M. J. Am. Chem. Soc. 1978, 100, 3467.
8. In addition to Refs. 6,7, for the other relating reactions, see: (a) Evans, D. A.;
Takacs, J. M.; Hurst, K. M. J. Am. Chem. Soc. 1979, 101, 371; (b) Ricci, A.;
Degl’Innocenti, A.; Borselli, G.; Reginato, G. Tetrahedron Lett. 1987, 28, 4093; (c)
Martin, S. F.; Garrison, P. J. Tetrahedron Lett. 1977, 18, 3875.
9. (a) Matsuya, Y.; Hayashi, K.; Nemoto, H. J. Am. Chem. Soc. 2003, 125, 646; (b)
Matsuya, Y.; Hayashi, K.; Nemoto, H. Chem. Eur. J. 2005, 11, 5408; (c) Matsuya,
Y.; Hayashi, K.; Wada, A.; Nemoto, H. J. Org. Chem. 2008, 73, 1987.
10. Silylated enones 3 could be readily prepared via trans-selective reduction of
silylated propargyl alcohols. See, Supplementary data.
11. The compounds 6 and 60 as a mixture of isomers have already been reported,
see: Galli, C.; Gentili, P.; Rappoport, Z. J. Org. Chem. 1994, 59, 6786.
12. These 3,4-geometries were unambiguously determined by the coupling
constants of 3- and 4-olefin protons.
13. The 1,2-geometry (Z) was determined by NOE observation experiments (1-
aromatic and 2-olefin protons) for 3,4-E and 3,4-Z silyl dienol ethers produced
by the reaction of 3c with 4-chlorobenzaldehyde, which were separated by
column chromatography and isolated as a pure form. See, Supplementary data.
14. It was confirmed that
a kind of cyclic enone (5,6-dihydro-6-phenyl-4-
trimethylsilyl-2-pyrone), which should be impossible to cause the
intramolecular silyl migration, did not give any products under the same
reaction conditions (the cyclic enone completely recovered).
15. The reaction utilizing some ketones, instead of aldehydes, did not bring
practical results due to considerably slow reaction rate.