Facile isomerization of silyl enol ethers catalyzed by triflic imide and its application to one-pot isomerization-(2 + 2) cycloaddition

Article abstract of DOI:10.3762/bjoc.8.73

A triflic imide (Tf₂NH) catalyzed isomerization of kinetically favourable silyl enol ethers into thermodynamically stable ones was developed. We also demonstrated a one-pot catalytic reaction consisting of (2 + 2) cycloaddition and isomerization. In the reaction sequence, Tf₂NH catalyzes both of the reactions.

Full text of DOI:10.3762/bjoc.8.73

Facile isomerization of silyl enol ethers catalyzed by
triflic imide and its application to one-pot
isomerization–(2 + 2) cycloaddition
Kazato Inanaga1, Yu Ogawa2, Yuuki Nagamoto2, Akihiro Daigaku1,
Hidetoshi Tokuyama1, Yoshiji Takemoto2 and Kiyosei Takasu*2
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2012, 8, 658–661.
1Graduate School of Pharmaceutical Sciences, Tohoku University,
Aobayama, Sendai 980-8578, Japan and 2Graduate School of
Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo, Kyoto
606-8501, Japan
doi:10.3762/bjoc.8.73
Received: 29 February 2012
Accepted: 05 April 2012
Published: 27 April 2012
Email:
Kiyosei Takasu* - kay-t@pharm.kyoto-u.ac.jp
This article is part of the Thematic Series "Organocatalysis".
Guest Editor: B. List
* Corresponding author
Keywords:
© 2012 Inanaga et al; licensee Beilstein-Institut.
License and terms: see end of document.
isomerization; one-pot reaction; organocatalysis; silyl enol ethers;
triflic imide
Abstract
A triflic imide (Tf2NH) catalyzed isomerization of kinetically favourable silyl enol ethers into thermodynamically stable ones was
developed. We also demonstrated a one-pot catalytic reaction consisting of (2 + 2) cycloaddition and isomerization. In the reaction
sequence, Tf2NH catalyzes both of the reactions.
Introduction
Silyl enol ethers, which are isolable equivalents of metal cally stable ones can be predominantly obtained by the reaction
enolates, are useful and important intermediates in synthetic with a silylating agent in the presence of a weak base, such as
chemistry [1-3]. They react as a good nucleophile for the intro- triethylamine, under equilibration conditions. Although the
duction of a carbon skeleton or a functional group at the α-pos- preparation of silyl enol ethers has been extensively studied,
ition of a carbonyl group under appropriate conditions. there have only been a limited number of studies on their
Although silyl enol ethers are easily prepared from the corres- isomerization [4-7]. Deyine reported that a catalytic amount of
ponding ketones, the regiochemical issue would arise in the triethylammonium chloride promotes the isomerization to give
case of asymmetric ketones. Treatment with a strong base such thermodynamically favourable ones in moderate yield [5].
as lithium diisopropylamide (LDA), followed by silyl chloride, However, harsh conditions (reaction temperature: ca. 100 to
under cryogenic conditions selectively affords kinetically 200 °C) were required for the complete equilibration.
favourable silyl enol ethers. On the other hand, thermodynami- Yamamoto and co-workers reported that a SnCl4–(BINOL
658

Beilstein J. Org. Chem. 2012, 8, 658–661.
monomethyl ether) complex (5–10 mol %) catalyzes the (entry 6). When 10-camphorsulfonic acid (5 mol %) was used
isomerization of silyl enol ethers at −78 °C [6]. By using this as a catalyst for 1 h, the isomerization was incomplete (entry 7).
catalyst, they remarkably achieved the kinetic resolution of Enol ethers bearing typical silyl groups were also isomerized
racemic silyl enol ethers. To make this isomerization syntheti- (entries 8–12). The decomposition of TMS enol ether 1b into
cally useful and valuable, the development of more-reactive 3b slightly increased at ambient temperature compared to that at
catalysts and a facile procedure would be required. In this com- −10 °C (entries 8 and 9). In the reaction of TIPS enol ether 1d,
munication, we describe isomerization of silyl enol ethers by an the reaction rate decreased and more catalyst (5 mol %) was
organocatalyst under mild conditions and its application to a necessary to achieve equilibrium within 5 min (entry 12).
one-pot catalytic reaction involving isomerization of silyl enol
ethers and (2 + 2) cycloaddition.
Several silyl enol ethers were explored for catalytic isomeriza-
tion under the optimized conditions (1 mol % of Tf2NH,
−10 °C, CH2Cl2). The results are summarized in Table 2. All
Results and Discussion
During our research on triflic imide (Tf2NH)-catalyzed reac- the kinetically favourable silyl enol ethers 1 were smoothly
tions [8], we accidentally found that the isomerization of kineti- isomerized to the thermodynamically stable 2 in the presence of
cally favourable silyl enol ethers into thermodynamically stable Tf2NH.
ones occurs smoothly in the presence of Tf2NH. When the TBS
enol ether 1a was treated with a catalytic amount of Tf2NH A plausible mechanism for the catalytic isomerization is shown
(1.0 mol %) in CH2Cl2 at ambient temperature, isomerization in Scheme 1. Silyl enol ether 1 is rapidly protonated by a
resulted in the thermodynamically stable 2a in 92% yield along catalytic amount of Tf2NH to give the corresponding siloxo-
with the recovered 1a and ketone 3 (Table 1, entry 1). Equilib- nium cation 4, and, then, another molecule of silyl enol ether 1
rium was reached within 5 min. The reaction using 20 mol % of deprotonates the α-position of 4. Equilibration results in the
Tf2NH resulted in an increase of decomposition into 3 (entry 2). selective production of the thermodynamically more stable 2.
When the reaction was performed at −10 °C, the chemical yield As a side reaction, the counter anion, Tf2N−, could attack the
of 2 was slightly improved (entry 3). In contrast, no isomeriza- silicon atom of 2 to produce silyl triflic imide (R3SiNTf2)
tion was observed at −78 °C even after 1 h (entry 4). The [8-12] and the corresponding ketone 3. Therefore, the use of a
catalytic isomerization reaction also proceeded in toluene (entry large amount of Tf2NH causes decomposition into 3 (Table 1,
5), but no (or almost no) isomerization occurred in CH3CN entry 2).
Table 1: Tf2NH-catalyzed isomerization of silyl enol ethers.a,b
entry
1 (SiR3)
solvent
temp. (°C)
% yield
2
1 (recovd.)
3
1
1a (TBS)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
toluene
CH3CN
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
rt
92
71
93
1
6
2
2c
3
1a
rt
4
25
3
1a
−10
−78
−10
−10
−10
rt
4
4d
5
1a
97
5
2
1a
92
2
2
6
1a
96
64
6
2
7d,e,f
8
1a
25
85
91
0
11
9
1b (TMS)
1b
9
−10
−78
−10
−10
4
5
10
11
12e
1b
95
5
5
1c (TES)
1d (TIPS)
78
92
17
5
3
aYields were determined by GC–MS. bRegioisomer 1 (>99% purity) was used as a substrate. c20 mol % of catalyst was used. dReactions were
carried out for 1 h. e5 mol % of catalyst was used. f10-Camphorsulfonic acid was used as a catalyst.
659

Beilstein J. Org. Chem. 2012, 8, 658–661.
Table 2: Substrate scope for Tf2NH-catalyzed isomerization.a,b
entry
substrate
product
% yield recovd. 1
of 2
(%)
1c
83
7
1e
2e
2d
3e
89
95
99
11
3
1f
2f
Scheme 1: Plausible mechanism for Tf2NH-catalyzed isomerization of
silyl enol ethers.
1g
2g
(Scheme 2a). No formation of their regioisomers was observed.
The obtained compound 6 is identical to the product in the reac-
tion of 2a with 5 [10,13]. It is noteworthy that two different
reactions, isomerization and (2 + 2) cycloaddition, are catalyzed
by Tf2NH [14-18]. By contrast, when 1a reacted with 5 in the
presence of Tf2NH at −78 °C, (2 + 2) cycloaddition directly
proceeded to give 2-methylbicyclo[4.2.0]octane 7 in 66% yield
along with the formation of two diastereomers (Scheme 2b).
Obviously, at this temperature, no isomerization of 1a occurred.
4f,g
1
1h
2h
aReactions were performed under the same conditions as given in Ta-
ble 1, entry 3. bYields were determined by GC–MS. cPurity of 1e is
99% (including isomer 2e (1%)). dPurity of 1f is 100% (no isomer 2f).
ePurity of 1g is 95% (including isomer 2g (5%)). fPurity of 1h is 93%
(including isomer 2h (7%)). g5 mol % of Tf2NH was used.
We have previously reported the Tf2NH catalyzed (2 + 2) The above finding can be applied to (2 + 2) cycloaddition, even
cycloaddition of silyl enol ethers with acrylates generating if a mixture of regioisomeric silyl enol ethers is used as a sub-
substituted cyclobutanes [10]. We are intrigued that the isomer- strate (Scheme 3). Thus, the reaction of ketone 3h with TBSOTf
ization of silyl enol ethers and successive (2 + 2) cycloaddition in the presence of NEt3 afforded a regioisomeric mixture of
could be promoted by Tf2NH in a one-pot reaction. When 1a silyl enol ethers 1h and 2h (ca. 7:3). After extraction to remove
was treated with Tf2NH (1 mol %) under the isomerization the amine reagent, the crude regioisomeric mixture was
conditions (−10 °C), followed by the addition of methyl acry- subjected to Tf2NH at −10 °C and subsequently reacted with
late (5) at −78 °C, 6-methylbicyclo[4.2.0]octane 6 and its acrylate 5 to afford (2 + 2) cycloadduct 8 in 70% yield. This
diastereomer were obtained in 86% and 6%, respectively result indicates that the Tf2NH catalyzed reaction can save not
Scheme 2: Regioselective formation of bicyclo[4.2.0]octanes from the same substrates by the isomerization–(2 + 2) cycloaddition procedure.
660

Beilstein J. Org. Chem. 2012, 8, 658–661.
Scheme 3: Formation of bicyclo[5.2.0]octane from the regioisomeric mixture of silyl enol ethers.
10.Inanaga, K.; Takasu, K.; Ihara, M. J. Am. Chem. Soc. 2005, 127,
3668–3669. doi:10.1021/ja042661s
only the separation to remove the corresponding kinetically
favourable regioisomer, but also loss of the undesired regio-
isomer.
11.Boxer, M. B.; Yamamoto, H. J. Am. Chem. Soc. 2006, 128, 48–49.
doi:10.1021/ja054725k
12.Takasu, K.; Miyakawa, Y.; Ihara, M.; Tokuyama, H. Chem. Pharm. Bull.
2008, 56, 1205–1206. doi:10.1248/cpb.56.1205
Conclusion
13.Kurahashi, K.; Takemoto, Y.; Takasu, K. ChemSusChem 2012, 5,
270–273. doi:10.1002/cssc.201100373
In summary, we have developed a new catalytic isomerization
reaction of silyl enol ethers. Kinetically favourable silyl enol
ethers were smoothly converted into thermodynamically stable
ones by treatment with a catalytic amount of Tf2NH under mild
conditions. Moreover, we demonstrated that the one-pot reac-
tion involves two different catalytic reactions, an isomerization
and a (2 + 2) cycloaddition.
14.Fogg, D. E.; dos Santos, E. N. Coord. Chem. Rev. 2004, 248,
2365–2379. doi:10.1016/j.ccr.2004.05.012
15.Shindoh, N.; Takemoto, Y.; Takasu, K. Chem.–Eur. J. 2009, 15,
12168–12179. doi:10.1002/chem.200901486
16.Shindoh, N.; Tokuyama, H.; Takemoto, Y.; Takasu, K. J. Org. Chem.
2008, 73, 7451–7456. doi:10.1021/jo8009243
17.Takasu, K.; Tanaka, T.; Azuma, T.; Takemoto, Y. Chem. Commun.
2010, 46, 8246–8248. doi:10.1039/c0cc03336g
18.Azuma, T.; Takemoto, Y.; Takasu, K. Chem. Pharm. Bull. 2011, 59,
1190–1193. doi:10.1248/cpb.59.1190
Supporting Information
Supporting Information File 1
Experimental details and spectral data.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-8-73-S1.pdf]
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Creative Commons Attribution License
Acknowledgements
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
This work was supported by Grants-in-Aid for Scientific
Research on Innovative Areas “Reaction Integration” (2105)
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan and the Naito Foundation.
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