Tetrakis(trifluoromethanesulfonyl)propane: Highly effective Bronsted acid catalyst for vinylogous Mukaiyama-Michael reaction of α,β- enones with silyloxyfurans

Article abstract of DOI:10.1039/b800815a

1,1,3,3-Tetrakis(trifluoromethanesulfonyl)propane was found as an excellent Bronsted acid catalyst for the Mukaiyama-Michael reaction of α,β-enones with 2-silyloxyfurans; using β,β-disubstituted enones as a Michael acceptor, an excellent yield construction of quaternary carbon centers could be achieved; in addition, very low catalyst loading of Bronsted acid was used in a range from 0.05 to 1.0 mol%. The Royal Society of Chemistry.

Full text of DOI:10.1039/b800815a

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Tetrakis(trifluoromethanesulfonyl)propane: highly effective Brønsted acid
catalyst for vinylogous Mukaiyama–Michael reaction of a,b-enones with
silyloxyfuransw
Arata Takahashi, Hikaru Yanai and Takeo Taguchi*
Received (in Cambridge, UK) 21st January 2008, Accepted 7th March 2008
First published as an Advance Article on the web 8th April 2008
DOI: 10.1039/b800815a
1,1,3,3-Tetrakis(trifluoromethanesulfonyl)propane was found as
an excellent Brønsted acid catalyst for the Mukaiyama–Michael
reaction of a,b-enones with 2-silyloxyfurans; using b,b-disubsti-
tuted enones as a Michael acceptor, an excellent yield construc-
tion of quaternary carbon centers could be achieved; in addition,
very low catalyst loading of Brønsted acid was used in a range
from 0.05 to 1.0 mol%.
fonyl)methane (Tf2CH2).7 Since the Tf2CH-structure acts as a
good proton donor due to gem-disubstitution by two triflyl
groups, highly acidic Tf2CHC6F5 was reported as a ‘super
Brønsted acid’ catalyst.8 In addition, Yamamoto, Ishihara and
co-workers reported a chiral organocatalyst equipped with a
Tf2CH-structure.9 We have examined the catalyst activity of
various carbon acids having a Tf2CH-unit in the molecule. In
this paper, we report on the vinylogous Mukaiyama–Michael
reaction catalyzed by 1,1,3,3-tetrakis(trifluoromethanesulfo-
nyl)propane 1 (Tf2CHCH2CHTf2) having two acidic protons
attached on the 1,3-carbons.10,11 This is the first example of
synthetic reactions catalyzed by carbon acid 1.12
Organic Brønsted acids such as carboxylic acids, phosphonic
acid and urea are useful and popular catalysts in modern
organic synthesis.1 These organic acids are essentially green
due to avoiding the use of metal salts, although the catalyst
loading of Brønsted acids is generally higher than those of
transition metal catalysts or Lewis acids. In addition, the low
catalyst activity of organic catalysts severely limits their
application to synthetic reactions. For these reasons, the
development of highly active Brønsted acid catalysts is an
important task.
At first, to survey the activity of acid catalysts, the reaction
of 4-methyl-3-penten-2-one 2a with TBSO-furan (1.1 molar
equivalent) as a model reaction was carried out (Table 1).13 In
the presence of 0.25 mol% of propane diacid 1, the reaction
for 2 h at À78 1C provided Michael adduct 3a in 88% yield
(entry 1). The catalyst loading of 1 could be reduced to 0.05
mol% without significant decrease in the product yield (entry
2). Interestingly, Tf2CH2 did not catalyze this reaction (entry
3), while a weak catalyst activity was observed by replacing a
hydrogen of Tf2CH2 with a methyl or C6F5 group. That is,
Tf2CHMe (1.0 mol%) and Tf2CHC6F5 (0.05 mol%) catalyzed
the 1,4-addition reaction to give 3a in 7% and 36% yield,
respectively (entries 4, 5). Compared to the high catalyst
Recently, to realize low catalyst loading of Brønsted acid
catalysts, Yamamoto and Boxer proposed the generation of
silylated bis(triflyl)imide, which is known as a highly active
silicon Lewis acid, featuring its ‘self repairing’ by in situ
reaction of a catalytic amount of Tf2NH (Tf = CF3SO2)
and silyl enol ethers.2 For instance, the Mukaiyama-aldol
reaction of aldehydes with tris(trimethylsilyl)silyl (TTMS) enol
ethers was nicely catalyzed by only 0.05 mol% of Tf2NH.
Efficient low catalyst loading was achieved only in the cases
using bulky TTMS enol ethers as silylated nucleophiles, while
the use of widely used tert-butyldimethylsilyl (TBS) enol ethers
instead of TTMS enol ethers resulted in a significant decrease
in the yield of aldol products. On the other hand, Jung and co-
workers reported that the Mukaiyama–Michael reaction of
cyclic enones with 2-TBSO-1,3-diene is catalyzed by Tf2NH.3,4
However, high catalyst loading, typically 1–5 mol%, remained
a problem in this reaction.
Table 1 Survey of effective acid catalysts for the reaction of 2a with
TBSO-furane
As one of our ongoing researches on acid catalysis,5,6 we
reported the aluminium methide complex Me2AlCHTf2 pre-
pared by the reaction of Me3Al and bis(trifluoromethanesul-
Entry Acid catalyst (mol%)
T/1C
t/h Yielda (%)
1
2
3
4
5
6
7
8
9
a
Tf2CHCH2CHTf2 1 (0.25) À78
2
3
3
3
5
6
6
3
5
88
87
0
7
36
7
7
64
NRb
Tf2CHCH2CHTf2 1 (0.05) À78 to À24
Tf2CH2 (1.0)
Tf2CHMe (1.0)
Tf2CHC6F5 (0.05)
TfOH (0.25)
Tf2NH (0.25)
Me3Al (40)
À78
À78
À78 to rt
À78
À78
À78
rt
School of Pharmacy, Tokyo University of Pharmacy and Life
Sciences, 1423-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
E-mail: taguchi@ps.toyaku.ac.jp; Fax: +81 42 676 3257;
Tel: +81 42 676 3257
w Electronic supplementary information (ESI) available: Details of
experiments, NMR data of 1 and all new compounds, and crystal
structure of 1. CCDC 674990. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/b800815a
None
b
Isolated yield. No reaction.
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Chem. Commun., 2008, 2385–2387 | 2385

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Table 2 Vinylogous Mukaiyama–Michael reaction of a,b-enones 2a
catalyst 1 required a notable increase in catalyst loading, but
resulted in a low yield of 3a (40 mol%, 64% yield) (entry 8).13
The reaction in the absence of acid catalysts at room tempera-
ture also resulted in no change of 2a and silyloxyfuran
(entry 9).
Despite a number of reports demonstrating that Lewis acids
can promote 1,4-addition of silicon enolate to sterically
crowded b,b-disubstituted enones via a single-electron transfer
mechanism,14 the construction of
a quaternary carbon
Entry
2
R1
R2
1 (mol%)
3
Yieldb (%)
through Brønsted acid-catalyzed Michael type addition to
b,b-disubstituted enones has been limited.3,15
1c
2c
3d
4d
2b –(CH2)5– Me
0.25
0.05
0.10
3b 90
3c 82
3d 89
3e 88
2c
2d
2e
H
H
H
Me
Ph
Next, in the presence of catalytic amount of propane diacid
1, the vinylogous Mukaiyama–Michael reaction of various
a,b-enones was conducted. The results are shown in Table 2.
The reaction of cyclohexylideneacetone 2b with silyloxyfuran
was nicely catalyzed by 0.25 mol% of 1 to give 1,4-adduct 3b
in 90% yield (entry 1). Methyl vinyl ketone 2c and aryl vinyl
ketone derivatives 2d, 2e were also found as good substrates
for the present reaction (3c 82% yield, 3d 89% yield and 3e
88% yield). Since effective catalyst loading was varied in a
range from 0.05 to 0.25 mol% in these cases, excellent catalyst
activity of propane diacid 1 was clearly demonstrated.
To reveal the substituent effect on the furan ring, we
examined the reaction of 2a with various methylated
4-BrC6H4 0.10
a
Reaction temperature, À78 to À24 1C; reaction time, 1–3 h.
b
c
Isolated yield. Acidic workup by aq. HCl in THF. Acidic workup
d
by CF3SO3H in CH2Cl2.
activity of 1, the efficiency of other Brønsted acids such as
TfOH and Tf2NH was remarkably lower. For instance, in the
presence of 0.25 mol% of TfOH, Michael adduct 3a was
obtained in only 7% yield (entry 6). The use of Tf2NH also
gave essentially the same result as the case of TfOH (entry 7).
Additionally, the use of Me3Al instead of Brønsted acid
Table 3 Vinylogous Mukaiyama–Michael reaction of 2a with methylated 2-silyloxyfurans
Entry 2-Silyloxyfuran
1
1 (mol%) T/1C t/h Products
Yielda (%) Ratiob (1,4 : 1,2)
0.25
À78
2
86
42 : 1
2c
0.25
À78
4
86
10 : 1
3c
4c
1.00
0.25
À78
À24
2
2
72d
55e
1,4-only
1,4-only
a
b
Isolated yield. Based on isolated yield. 1.5 molar equivalent of 2-silyloxyfuran was used. 25% of 5 was obtained. 29% of 5 was obtained.
c
d
e
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silyloxyfuran derivatives (Table 3). In the presence of 0.25
mol% of 1, the reaction of 2a with 3-methyl-2-tert-butyldi-
methylsilyloxyfuran smoothly proceeded at À78 1C to give
1,4-adduct 3f in 84% yield along with a small amount of 1,2-
adduct 4f (2% yield) after acidic work-up (entry 1). As shown
in entry 2, in the case of 4-methyl-2-silyloxyfuran, the 1,4- :
1,2-selectivity was decreased to 10 : 1, although an excellent
combined yield of 3g and 4g was observed (86% yield).
Surprisingly, in the presence of 1 mol% of 1, the reaction with
5-methyl-2-silyloxyfuran gave 1,4-adduct 3h, which has con-
secutive quaternary carbons, in 72% yield without the forma-
tion of any 1,2-adducts. In this reaction, isomer 5 was also
formed as a major byproduct (B25% yield) (entry 3). Since, as
shown in entry 4, lower catalyst loading of 1 (0.25 mol%)
resulted in a significant decrease of the reaction rate and poor
yield of 3h, 41 mol% of 1 was necessary to obtain a smooth
reaction.
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263.
Regarding the reaction mechanism of the present reaction,
we believe that Brønsted acid 1 initially reacts with silylox-
yfurans to give a silane methide intermediate.16 Since the
silylation activity of this silane methide would be expected to
be high due to I-strain between the silyl group and sterically
bulky methide part,17 the observed efficient activation of a,b-
enones as a Michael accepter would involve a simultaneous
coordination of this silane methide to the carbonyl oxygen and
the following facile O-silylation of the enone carbonyl during
the C–C bond formation (Michael addition step).
In conclusion, we found that tetrakis(trifluoromethanesul-
fonyl)propane 1 operates as an excellent catalyst for the
vinylogous Mukaiyama–Michael reaction of a,b-enones with
silyloxyfurans. Under the present catalyst conditions, an
efficient construction of the quaternary carbons could be
achieved in the reaction of b,b-disubstituted enones. A 1,4-
adduct having consecutive quaternary carbons was also ob-
tained in good yield by this Brønsted acid-catalyzed reaction
of b,b-disubstituted enones with 5-methyl-2-silyloxyfuran. In
addition, very low catalyst loading was realized in a range
from 0.05 to 1.0 mol%. Further study on the synthetic
application of 1 and the mechanistic insight are under progress
in our laboratory.
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reaction: N. Takenaka, J. P. Abell and H. Yamamoto, J. Am.
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Tayama, K. Omoto and K. Maruoka, J. Am. Chem. Soc., 2004,
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and J. Wang, Org. Lett., 2005, 7, 1637; R. Gnaneshwar, P. P.
Wadgaonkar and S. Sivaram, Tetrahedron Lett., 2003, 44, 6047.
16 1H and 13C NMR spectra of a 1 : 1 mixture of propane diacid 1 and
4-methyl-3-penten-2-one 2a in CDCl3 at room temperature did not
show any shifts of signals.
Notes and references
1 Acid Catalysis in Modern Organic Synthesis, ed. H. Yamamoto and
K. Ishihara, Wiley-VCH, Weinheim, 2008; Asymmetric Organoca-
17 B. Mathieu and L. Ghosez, Tetrahedron, 2002, 58, 8219.
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Chem. Commun., 2008, 2385–2387 | 2387