1,4-Addition of silicon dienoates to α,β-unsaturated aldehydes catalyzed by in situ-generated silicon Lewis acid

Article abstract of DOI:10.1039/c0cc02438d

In situ-generated silyl methide species (R₃Si-CTf ₂R′) effectively catalyzed the reaction of β-substituted α,β-unsaturated aldehydes with silicon dienoates such as 3-bromo-2-TESO-furan to give the corresponding γ-adducts with excelle

Full text of DOI:10.1039/c0cc02438d

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1,4-Addition of silicon dienoates to a,b-unsaturated aldehydes catalyzed
by in situ-generated silicon Lewis acidw
Hikaru Yanai, Arata Takahashi and Takeo Taguchi*
Received 8th July 2010, Accepted 28th September 2010
DOI: 10.1039/c0cc02438d
In situ-generated silyl methide species (R3Si–CTf2R0) effectively
catalyzed the reaction of b-substituted a,b-unsaturated alde-
hydes with silicon dienoates such as 3-bromo-2-TESO-furan to
give the corresponding c-adducts with excellent 1,4-selectivity
and good anti selectivity.
The 1,4-addition of silicon enolates to a,b-unsaturated
carbonyl systems, namely the Mukaiyama–Michael reaction,
is one of the most important C–C bond forming reactions
with high stereoselectivity.1 A number of works show that
a,b-unsaturated ketones, esters and imides perform as suitable
Fig. 1 In situ-generation of silyl methide species A and electrophilic
substrates for this chemistry. On the other hand, the reaction
activation of carbonyl substrates.
of silicon enolates with a,b-unsaturated aldehydes under the
classical Lewis acid-mediated conditions generally proceeds in
B. Furthermore, it would be also a considerable factor for the 1,4-
selectivity that steric bulkiness of counterion [Tf2CCH2CHTf2]ꢀ
1,2-selective manner to give the corresponding allylic alcohol
or its silyl ether.2 Similar 1,2-selectivity in the Lewis acid-
brings about effective shielding of aldehyde functionality to avoid
competitive 1,2-addition. In this communication, we would like to
version using silicon dienoates such as 2-silyloxyfurans.3 In
describe that, in the presence of carbon acids (C–H acids) such
mediated reactions was also observed in the vinylogous
as 1a, the reaction of a,b-unsaturated aldehydes with 2-silyloxy-
furans gives the 1,4-adducts with excellent regio- and diastereo-
contrast, MacMillan reported an elegant work of 1,4-selective
reaction. That is, by using a combined catalyst of chiral imida-
selectivities. These results clearly show that the use of carbon acid
zolidinone and 2,4-dinitrobenzoic acid, the 1,4-addition reaction of
results in a remarkable difference compared to the classical Lewis
2-TMSO-furans to b-substituted a,b-unsaturated aldehydes
proceeds with excellent enantioselectivity.4,5 Maruoka also demon-
acid-mediated conditions.
It has been reported that, in the presence of equimolar
strated that the chiral ammonium bifluoride selectively catalyzes
1,4-addition of silicon nitronate to a,b-unsaturated aldehydes.6
Recently, we reported that 1,1,3,3-tetrakis(trifluoromethane-
sulfonyl)propane 1a (Tf2CHCH2CHTf2)7 is one of the most
effective Brønsted acid pre-catalysts for the 1,4-addition reaction
of 2-silyloxyfurans to a,b-unsaturated ketones.8–10 In this reaction
system, the in situ-generation of silicon Lewis acid (silyl methide
species A) from 2-silyloxyfuran and 1a initially occurs and the
resultant silyl methide A strongly activates the carbonyl substrates
via carbonyl silylation reaction (Fig. 1).11 According to Childs’s
acidity index Dd exemplified by 1H NMR shift differences of
crotonaldehyde CH3CHQCHCHO caused by its co-ordination
to the acids,12 the use of modern silicon Lewis acids such as
Me3SiNTf2 and Me3SiCTf2C6F5 realizes significantly high level of
down-field shift of b-proton.13 This result would suggest that
O-silylation of a,b-unsaturated aldehydes (R2 = H) results in the
strong LUMO activation as in the case of MacMillan’s catalyst
and the following attack of soft nucleophiles such as silicon
enolates proceeds at b-carbon of highly polarized intermediates
amount of BF3ꢁOEt2, the reaction of crotonaldehyde 2a with
3-bromo-2-TMSO-furan gave the 1,2-adduct in 68% yield
with low anti/syn selectivity (eqn (1)).3b
ð1Þ
Keeping the above reported result in our mind, we examined the
reaction of 2a with 3-bromo-2-TESO-furan in the presence of a
catalytic amount of Tf2CHCH2CHTf2 1a.14,15 Selected results are
shown in Table 1. In contrast to the BF3ꢁOEt2-mediated reaction,
the reaction in the presence of 0.5 mol% of 1a smoothly proceeded
at ꢀ78 1C for 2 h to give 1,4-adduct 3a–Br and 1,2-adduct 4a–Br
in 91% and 4.5% yield, respectively, after acidic aqueous work-up
(entry 1). In this case, the anti/syn ratio of 1,4-adduct 3a–Br was
11 : 1. The loading of 1a could be reduced to 0.25 mol% without
lowering of both regio- and diastereoselectivities, and the
1,4-adduct 3a–Br was obtained in excellent yield (entry 2).
Interestingly, by increasing the loading of 1a to 2.0 mol%, the
1,4-selectivity was reduced to 7.8 : 1 (entry 3). These results
suggest that the 1,4-selectivity depends on the amount of carbon
acid pre-catalyst and its significantly low loading is crucial to
obtain 1,4-adduct in good regioselectivity. Yamamoto’s super
School of Pharmacy, Tokyo University of Pharmacy and Life
Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
E-mail: taguchi@toyaku.ac.jp; Fax: +81 42 676 3257;
Tel: +81 42 676 3257
w Electronic supplementary information (ESI) available: Details of experi-
ments, NMR data of all new compounds, and crystal structure of anti-6d
and anti-6e. CCDC 783222 and 783223. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c0cc02438d
c
8728 Chem. Commun., 2010, 46, 8728–8730
This journal is The Royal Society of Chemistry 2010

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Table 1 Effects of acids on the 1,4-selectivity in the reaction of 2a with 2-silyloxyfurans
Anti/syn
ratio of 3ab
Entry
X
Acid/mol%
Yielda (%)
1,4-/1,2-
1
2b
3
4
5
6
7
8
Br
Br
Br
Br
Br
Br
Br
H
Tf2CHCH2CHTf2 1a (0.5)
Tf2CHCH2CHTf2 1a (0.25)
Tf2CHCH2CHTf2 1a (2.0)
Tf2CHC6F5 1b (0.5)
TfOH (2.0)
Tf2NH (2.0)
TESOTf (4.0)
Tf2CHCH2CHTf2 1a (0.5)
96
94
97
92
91
95
88
99
20 : 1
20 : 1
7.8 : 1
19 : 1
4.9 : 1
5.1 : 1
4.9 : 1
4.5 : 1
11 : 1
11 : 1
10 : 1
12 : 1
9.5 : 1
9.4 : 1
9.1 : 1
5.5 : 1
a
b
Combined yield of isolated 3a and 4a. On the basis of H NMR of crude mixture.
1
Brønsted acid Tf2CHC6F5 1b10a also showed comparable high
level of catalytic activity and the reaction using 0.25 mol% of 1b
yielded the corresponding adducts 3a–Br and 4a–Br in 92% yield
without the loss of both 1,4- and diastereoselectivities (entry 4).
In the case of the other type of Tf-substituted Brønsted acids
such as triflic acid and bis(triflic) imide, at least 2.0 mol% of the
loading was required to complete the reaction and the moderate
1,4-selectivity was observed (entries 5 and 6). These results
suggest that, by decreasing the nucleophilicity of the conju-
gated base of Brønsted acids, 1,4-selectivity was improved
([Tf2CR]ꢀ > Tf2Nꢀ > TfOꢀ). In addition, the TESOTf-
catalyzed reaction gave an essentially similar result to the
TfOH-induced reaction (entries 7 vs. 5). The introduction of
bromo group at furan ring plays an important role to realize the
high 1,4-selectivity, that is, the reaction of 2a with non-
brominated 2-TESO-furan gave 1,4-adduct 3a–H and 1,2-adduct
4a–H in 81% and 18% yield, respectively (entry 8).
the 1,4-adduct 3b in 84% yield without the formation of
1,2-adducts (entry 1). In the reaction of hex-2-enal 2c under
similar conditions, a 10 : 1 mixture of g-butenolide products 3c
and 4c was obtained in 94% yield and a high anti/syn selectivity
of 3c (17 : 1) was observed (entry 2). Notably, the reaction of
a,b-unsaturated aldehydes equipped with a sterically bulky
substituent on b position remained a high level of 1,4-selectivity.
For example, the reaction of b-isopropylated aldehyde 2d with
silyloxyfuran proceeded in the presence of 1.0 mol% of carbon
acid 1a to give a mixture of anti-1,4-adduct 3d and 1,2-adduct 4d
in a ratio of 8.0 : 1 (entry 3; 77% yield). Likewise, 3-cyclohexyl-
propenal 2e (E/Z = 10 : 1) was converted to the corresponding
1,4-adduct 3e in good yield with both excellent regio-
and diastereoselectivities (entry 4; 85% yield). In addition,
methacrolein 2f was found to be a nice substrate for the present
1,4-selective reaction. That is, the treatment of 2f by 1.5 equiv. of
3-bromo-2-TESO-furan in the presence of 0.5 mol% of carbon
acid 1a gave the 1,4-adduct 3f in 90% yield as a 1.1 : 1 mixture of
diastereomers and the formation of 1,2-adduct was not observed
(Scheme 1).16 On the other hand, the reactions of b-aryl-
substituted aldehydes such as cinnamaldehyde did not show
the high level of 1,4-selectivity.17
Next, to reveal the scope and limitation of the present
vinylogous Mukaiyama–Michael (VMM) chemistry of
a,b-unsaturated aldehyde system, we examined the reaction of
several a,b-unsaturated aldehydes with 3-bromo-2-TESO-furan
in the presence of Tf2CHCH2CHTf2 1a (Table 2). By using
0.5 mol% of 1a, the reaction of acrolein 2b with 3-bromo-2-
TESO-furan smoothly completed at ꢀ78 1C within 2 h to give
Furthermore, we examined the reaction of acrolein 2b
with some silicon dienoates (Table 3). As shown in entry 1,
4-bromo-2-TESO-furan reacted with 2b in the presence of
0.5 mol% of carbon acid 1a at ꢀ78 1C to give g-1,4-adduct
3g in 80% yield. Likewise, g-substituted a-fluoro-g-butenolide
3h was obtained in 82% yield by the reaction with 3-fluoro-2-
TIPSO-furan (entry 2). 2-TESO-thiophen was also found to be
an effective nucleophile. That is, in the presence of 1.0 mol%
of 1a, the reaction of 2b with 2-TESO-thiophen smoothly
proceeded to give g-1,4-adduct 3i in 76% along with the
formation of small amount of a-1,4-adduct 5 (entry 3).
Table 2 Regio- and diastereoselective VMM reaction of a,b-unsaturated
aldehyde 2
Entry
2
R
1a/mol% Yielda (%) 1,4-/1,2- Drb
1c
2
3
4
2b
2c
2d
H
n-Pr
i-Pr
0.5
0.5
1.0
84
94
77
85
1,4-only
10 : 1
8.0 : 1
11 : 1
—
17 : 1
anti only
10 : 1
2ed c-Hex 1.0
a
b
Combined yield of isolated 3 and 4. Anti/syn ratio of 3. Based on
1H NMR. 1.5 equiv. of 3-bromo-2-TESO-furan was used. E/Z =
10 : 1.
c
d
Scheme 1
c
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Chem. Commun., 2010, 46, 8728–8730 8729

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Table 3 VMM reaction of acrolein with silicon dienoates
In conclusion, we found that the use of in situ-generated silyl
methide species R3Si–CTf2R0 results in the 1,4-selective C–C
bond forming reaction of a,b-unsaturated aldehydes with silicon
dienoates. In this external carbon acid catalyzed reaction, the
1,4-/1,2-selectivity was effected by the loading of carbon acids
and notable low loading (in a range from 0.25–1.0 mol%) of the
carbon acids to complete this reaction was found to be an
important factor to realize the high 1,4-selectivity.
Entry
1
Silicon dienoate
1a/mol%
3
Yielda (%)
0.5
3g
80
Notes and references
1 K. Narasaka, K. Soai and T. Mukaiyama, Chem. Lett., 1974, 1223.
2 To the best of our knowledge, there is only one example for Lewis
acid-mediated 1,4-addition chemistry toward a,b-unsaturated
aldehyde system, see: K. Maruoka, H. Imoto, S. Saito and
H. Yamamoto, J. Am. Chem. Soc., 1994, 116, 4131.
3 (a) F. von der Ohe and R. Bruckner, Tetrahedron Lett., 1998, 39,
1909; (b) C. S. Lopez, R. Alvarez, B. Vaz, O. N. Faza and A. R. de
Lera, J. Org. Chem., 2005, 70, 3654.
4 (a) S. P. Brown, N. C. Goodwin and D. W. C. MacMillan, J. Am.
Chem. Soc., 2003, 125, 1192; (b) B. Simmons, A. M. Walji and D. W. C.
MacMillan, Angew. Chem., Int. Ed., 2009, 48, 4349; (c) C. J. Borths,
D. E. Carrera and D. W. C. MacMillan, Tetrahedron, 2009, 65,
6746.
2
1.0
1.0
3h
3i
82
76
3b
a
b
Isolated yield. a-1,4-Adduct 5 was obtained in 6% yield.
5 W. Wang, H. Li and J. Wang, Org. Lett., 2005, 7, 1637.
6 T. Ooi, K. Doda and K. Maruoka, J. Am. Chem. Soc., 2003, 125, 9022.
7 R. J. Koshar and L. L. Barber, Jr., US Patent, 4 053 519, 1977.
8 Carbon acid induced C–C bond forming reactions, see:
(a) A. Takahashi, H. Yanai and T. Taguchi, Chem. Commun., 2008,
2385; (b) A. Takahashi, H. Yanai, M. Zhang, T. Sonoda, M. Mishima
and T. Taguchi, J. Org. Chem., 2010, 75, 1259; (c) H. Yanai,
Y. Yoshino, A. Takahashi and T. Taguchi, J. Org. Chem., 2010, 75,
5375.
9 Our papers in relation to carbon acid-based Lewis acid catalyst,
see: (a) H. Yanai, A. Takahashi and T. Taguchi, Tetrahedron,
2007, 63, 12149; (b) H. Yanai, A. Takahashi and T. Taguchi,
Tetrahedron Lett., 2007, 48, 2993.
10 Other examples for the carbon acid mediated reactions, see:
(a) K. Ishihara, A. Hasegawa and H. Yamamoto, Angew. Chem.,
Int. Ed., 2001, 40, 4077; (b) K. Ishihara, A. Hasegawa and
H. Yamamoto, Synlett, 2002, 1299; (c) A. Hasegawa, Y. Naganawa,
M. Fushimi, K. Ishihara and H. Yamamoto, Org. Lett., 2006, 8, 3175.
11 Selected examples for in situ-generation of silicon Lewis acids,
see: (a) K. Takasu, Synlett, 2009, 1905; (b) M. B. Boxer and
H. Yamamoto, J. Am. Chem. Soc., 2006, 128, 48; (c) M. E. Jung
and D. G. Ho, Org. Lett., 2007, 9, 375.
Scheme 2
Finally, we examined the acetalization reaction of the enol
silyl ether intermediates in a one-pot manner (Scheme 2). For
example, after the VMM reaction of crotonaldehyde 2a, the
resultant mixture was treated by acetyl chloride at 0 1C in
ethylene glycol to give the acetal 6a as the 1,4-adduct and free
allylic alcohol 4a as the 1,2-adduct in 85% and 4% yield,
respectively. Likewise, acetal 6d was obtained from 2d in good
yield. During this acetalization process, we did not observe
any loss of both 1,4- and anti/syn-selectivities (see ESIw).
Regarding these results, we propose the reaction pathway of the
present 1,4-addition chemistry. In the first step, I-strain induced
silyl transfer from silyl methide species to aldehyde substrates
results in the strong electrophilic activation (see Fig. 1).12b Since
the electrophilic activation of a,b-unsaturated aldehydes by silicon
Lewis acids significantly decreases in the LUMO level, the
following addition of silicon dienoates proceeds at highly cationic
b-carbon.18 Furthermore, the steric bulkiness of methide anion
[Tf2CR]ꢀ would avoid the competitive 1,2-addition, hence
resulting in the high 1,4-selectivity. The observed correlation
between 1,4-selectivity and the loading of carbon acid can be also
explained by both the concentration of intermediate B in the
medium and the activation of silicon dienoates by [Tf2CR]ꢀ. That
is, in the reaction using a small amount of carbon acid, the strongly
activated intermediates thus generated smoothly converted to the
corresponding 1,4- and 1,2-adducts by simple kinetic control. In
contrast, the relatively large loading of carbon acid would result in
a high concentration level of B to degrade the 1,4-selectivity by the
competitive 1,2-addition reaction. In addition, despite the low
nucleophilicity of [Tf2CR]ꢀ, the high loading of carbon acid
would accelerate this 1,2-addition through the activation of silicon
dienoates via the formation of penta-co-ordinated silicate species.
12 (a) R. F. Childs, D. L. Mulholland and A. Nixon, Can. J. Chem.,
1982, 60(6), 801; (b) B. Mathieu and L. Ghosez, Tetrahedron, 2002,
58, 8219; (c) A. Hasegawa, K. Ishihara and H. Yamamoto, Angew.
Chem., Int. Ed., 2003, 42, 5731.
13 Selected Dd values (ppm) are as follows: BF3 (1.17),12a Me3SiNTf2
(1.74),12b and Me3SiCTf2C6F5 (1.99)12c
.
14 In the previous work, we found that 3-bromo-2-TESO-furan is
useful nucleophile for the anti-selective VMM reaction of
b-monosubstituted a,b-unsaturated ketones, see: ref. 8b.
15 Synthetic applications of a-bromo-g-butenolides, see: (a) H. Takei,
Y. Fukuda, T. Taguchi, T. Kawahara, H. Mizutani and T. Mukuta,
Chem. Lett., 1980, 1311; (b) T. Olpp and R. Bruckner, Angew.
Chem., Int. Ed., 2005, 44, 1553; (c) B. Vaz, M. Domınguez,
R. Alvarez and A. R. de Lera, Chem.–Eur. J., 2007, 13, 1273.
16 In the reaction of 2f with 3-bromo-2-TBSO-furan, (E)-enol silyl
ether and its desilylated derivative 3f were obtained in 80% and
10% yields, respectively, by extractive work-up under neutral
conditions. This result would suggest that the desilylation step is
the diastereoselectivity-determining step.
17 In the reaction of cinnamaldehyde 2g with 3-bromo-2-TESO-
furan, a 1.5 : 1 mixture of the 1,4-adduct and the 1,2-adduct was
obtained in excellent yield after acetalization (see ESIw).
18 An NMR study of triethylsilylated carboxonium ion prepared from
a,b-unsaturated ketone clearly showed the extensive charge delocali-
zation among CCQO, Cb and Si atoms, see: G. K. S. Prakash,
C. Bae, G. Rasul and G. A. Olah, J. Org. Chem., 2002, 67, 1297.
c
8730 Chem. Commun., 2010, 46, 8728–8730
This journal is The Royal Society of Chemistry 2010