Carbon acid induced mukaiyama aldol type reaction of sterically hindered ketones

Article abstract of DOI:10.1021/jo100915e

(Figure presented) 1,1,3,3-Tetrakis(trifluoromethanesulfonyl)propane (Tf₂CHCH₂CHTf₂) is one of the most effective Bronsted acid precatalysts for the Mukaiyama aldol type reactions of sterically hindered ketones. By using Tf₂CHCH₂CHTf ₂ in a range from 0.5 to 2.0 mol %, the vinylogous Mukaiyama aldol reaction of α-substituted cyclohexanones with 2-silyloxyfurans smoothly proceeded to give the aldol products in excellent yield without the loss of diastereoselectivity. Under similar conditions, acyclic ketene silyl acetals also performed as nice nucleophiles toward sterically hindered ketones. These findings suggest that Tf₂CHCH₂CHTf₂ induced Mukaiyama aldol type reactions can overcome the steric hindrance between reaction sites.

Full text of DOI:10.1021/jo100915e

pubs.acs.org/joc
carbonyl substrates by silicon Lewis acids such as Me3-
Carbon Acid Induced Mukaiyama Aldol Type
Reaction of Sterically Hindered Ketones
SiNTf2 and Me3SiC(C6F5)Tf2 is significantly stronger than
that by conventionally used Lewis acids such as BF3, AlCl3,
and TiCl4.5 This fact supports the idea that strong electro-
philic activation of carbonyl substrates by silicon Lewis acids
makes the effective nucleophilic addition to sterically hinde-
red carbonyl electrophiles possible. Since the reactivity of
ketones is lower than that of aldehydes due to steric and
electronic reasons, the Mukaiyama aldol reaction of ketones
often required the use of stoichiometric or substoichiometric
amounts of suitable Lewis acids such as TiCl4 and BF3 to
obtain the corresponding aldol products in good to excellent
yield.6,7 Meanwhile, the required catalyst loading of highly
active silicon Lewis acids to complete the reaction is rela-
tively low.8 As an elegant example according to this concept,
Sawamura and co-workers reported that the Mukaiyama
aldol reaction of acetophenone and dimethylketene silyl
acetal smoothly proceeds in the presence of only 1 mol % of
toluene-coordinated silylium borate [Et3Si(toluene)]B(C6F5)4,
which shows a strong cationic silicon character.9 Furthermore,
Yamamoto and co-workers demonstrated that 1 mol % of
R3SiNTf2, generated in situ from Tf2NH and enol silyl ethers, is
enough to complete the Mukaiyama aldol reaction with simple
ketone substrates.10 However, the extension to stereoselective
reactions was not examined in these studies.
Hikaru Yanai, Yasuhiro Yoshino, Arata Takahashi, and
Takeo Taguchi*
School of Pharmacy, Tokyo University of Pharmacy and Life
Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
taguchi@toyaku.ac.jp
Received May 10, 2010
1,1,3,3-Tetrakis(trifluoromethanesulfonyl)propane (Tf2-
CHCH2CHTf2) is one of the most effective Brønsted acid
precatalysts for the Mukaiyama aldol type reactions of
sterically hindered ketones. By using Tf2CHCH2CHTf2
in a range from 0.5 to 2.0 mol %, the vinylogous Mukaiyama
aldol reaction of R-substituted cyclohexanones with 2-silyl-
oxyfurans smoothly proceeded to give the aldol products
in excellent yield without the loss of diastereoselectivity.
Under similar conditions, acyclic ketene silyl acetals also
performed as nice nucleophiles toward sterically hindered
ketones. These findings suggest that Tf2CHCH2CHTf2
induced Mukaiyama aldol type reactions can overcome
the steric hindrance between reaction sites.
As our achievement in this field, we reported that 1,1,3,3-
tetrakis(trifluoromethanesulfonyl)propane 1 (Tf2CHCH2-
CHTf2)11 performs as an excellent Brønsted acid precatalyst for
the diastereoselective vinylogous Mukaiyama-Michael (VMM)
reaction of R,β-unsaturated ketones with 2-silyloxyfurans. It
was also reported that its activity is significantly higher than
that of TfOH, Tf2NH, or Tf2CHC6F5.12-14 In this reaction
(5) Acidities were expressed as chemical shift difference Δδ of
MeCHdCHCHO. Selected Δδ values (ppm) are as follows: BBr3 (1.49),4
BCl3 (1.39),4 BF3 (1.17),4 AlCl3 (1.23),4 TiCl4 (1.03),4 Me3SiNTf2 (1.74),1 and
Me3SiCTf2C6F5 (1.99).2
(6) For a systematic study on the steric limitation of TiCl4 promoted
Mukaiyama aldol reaction, see: Wenke, G.; Jacobsen, E. N.; Totten, G. E.;
Karydas, A. C.; Rhodes, Y. E. Synth. Commun. 1983, 13, 449–458.
(7) For selected papers on catalytic Mukaiyama aldol reactions of
ketones, see: (a) Hollis, T. K.; Robinson, N. P.; Bosnich, B. Tetrahedron
Lett. 1992, 33, 6423–6426. (b) Oishi, M.; Aratake, S.; Yamamoto, H. J. Am.
Chem. Soc. 1998, 120, 8271–8272. (c) Marx, A.; Yamamoto, H. Angew.
Chem., Int. Ed. 2000, 39, 178–181. (d) Denmark, S. E.; Fan, Y. J. Am. Chem.
Soc. 2002, 124, 4233–4235. (e) Oisaki, K.; Zhao, D.; Kanai, M.; Shibasaki,
M. J. Am. Chem. Soc. 2006, 128, 7164–7165. (f) Hatano, M.; Takagi, E.;
Ishihara, K. Org. Lett. 2007, 9, 4527–4530.
(8) (a) Murata, S.; Suzuki, M.; Noyori, R. J. Am. Chem. Soc. 1980, 102,
3248–3249. (b) Mukai, C.; Hashizume, S.; Nagami, K.; Hanaoka, M. Chem.
Pharm. Bull. 1990, 38, 1509–1512. (c) Kawai, M.; Onaka, M.; Izumi, Y. Bull.
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Plunkett, S. J. Tetrahedron Lett. 1996, 37, 9401–9402. (g) Oishi, M.; Aratake,
S.; Yamamoto, H. J. Am. Chem. Soc. 1998, 120, 8271–8272.
The construction of quaternary carbon in functionalized
molecules remains as a formidable task in the field of organic
synthesis. Especially, the construction of consecutive qua-
ternary carbons by polar reactions, such as the aldol type
reaction, is a great challenge. To overcome steric repulsion
around reaction sites in the bond-forming step, the use of
1
modern silicon Lewis acids such as Me3SiNTf2 (Tf =
2
CF3SO2) and Me3SiC(C6F5)Tf2 should be a promising
approach.3 According to Childs’ acidity index exemplified
by 1H NMR shift differences of crotonaldehyde caused by its
coordination to the acids,4 the electrophilic activation of
(1) (a) Mathieu, B.; de Fays, L.; Ghosez, L. Tetrahedron Lett. 2000, 41,
9561–9564. (b) Mathieu, B.; Ghosez, L. Tetrahedron 2002, 58, 8219–8226.
(2) Hasegawa, A.; Ishihara, K.; Yamamoto, H. Angew. Chem., Int. Ed.
2003, 42, 5731–5733.
(9) Hara, K.; Akiyama, R.; Sawamura, M. Org. Lett. 2005, 7, 5621–5623.
(10) Ishihara, K.; Hiraiwa, Y.; Yamamoto, H. Synlett 2001, 12, 1851–
1854.
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Synthesis; Yamamoto, H., Ed.; Wiley-VCH: Weinheim, Germany, 2000; Vol. 1,
pp 355-393. (b) Dilman, A. D.; Ioffe, S. L. Chem. Rev. 2003, 103, 733–772.
(c) Hosomi, A.; Miura, K. Si(IV) Lewis Acids. In Acid Catalysis in Modern
Organic Synthesis; Yamamoto, H., Ishihara, K., Eds.; Wiley-VCH: Weinheim,
Germany, 2008; Vol. 1, pp 469-516.
(11) Koshar, R. J.; Barber, L. L. US Patent 4053519, 1977.
(12) (a) Takahashi, A.; Yanai, H.; Zhang, M.; Sonoda, T.; Mishima, M.;
Taguchi, T. J. Org. Chem. 2010, 75, 1259–1265. (b) Takahashi, A.; Yanai, H.;
Taguchi, T. Chem. Commun. 2008, 2385–2387.
(13) For our papers in relation to carbon acid mediated reactions, see:
(a) Yanai, H.; Takahashi, A.; Taguchi, T. Tetrahedron 2007, 63, 12149–
12159. (b) Yanai, H.; Takahashi, A.; Taguchi, T. Tetrahedron Lett. 2007, 48,
2993–2997.
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801–808.
DOI: 10.1021/jo100915e
r
Published on Web 06/28/2010
J. Org. Chem. 2010, 75, 5375–5378 5375
2010 American Chemical Society

Yanai et al.
JOCNote
TABLE 1. Survey of Effective Brønsted Acid Precatalyst for the VMA
Reaction
Brønsted
acid (mol %)
time
(h)
yielda
(3a-Si þ 3a-H, %)
ratiob
(3a-Si/3a-H)
FIGURE 1. Electrophilic activation of carbonyl substrates in the
Tf2CHCH2CHTf2/2-silyloxyfuran system.
entry
1c
2
1 (1.0)
1 (0.5)
1 (0.5)
Tf2NH (0.5)
TfOH (0.5)
1
2
2.5
2.5
2.5
92
49
82
63
25
2.7:1
2.3:1
4.1:1
2.9:1
1:3.1
system, silyl methide species R3Si-CTf2CH2CHTf2 A in situ
generated by the reaction of 1 with 2-silyloxyfurans activates
R,β-unsaturated ketone substrates,15 and the following C-C
bond formation between the resultant oxocarbenium B (R1 =
CHdCHR0) with 2-silyloxyfuran results in the formation of the
VMM product with excellent anti-selectivity (Figure 1). Due to
the high silylating activity (Lewis acidity) of silyl methide A
through notably large I-strain1 and its “self-repairing”
pathway,16 the required loading of 1 was significantly low
(typically, in a range from 0.05 to 1.0 mol %). As a next
challenge, we became interested in the application of carbon
acid (C-H acid) 1 to the stereoselective Mukaiyama aldol type
reaction of sterically hindered ketones because the 1,2-addition
is more sensitive toward the steric crowding around the reaction
site, compared to the 1,4-addition.17 In this paper, we demon-
strate that 1 performs as an excellent Brønsted acid precatalyst
for not only previously reported 1,4-addition chemistry12 but
also the Mukaiyama aldol type 1,2-addition reaction of steri-
cally hindered ketones proceeding in an excellent diastereo-
selective manner.
At first, to examine the efficiency of Brønsted acids, we
carried out the reaction of cyclohexanone 2a with 2-TBSO-
furan as a model reaction (Table 1). In the presence of 1.0
mol % of 1, the vinylogous Mukaiyama aldol (VMA)
reaction of 2a with 2-TBSO-furan smoothly completed with-
in 1 h at -78 °C to give the aldol adduct 3a-Si and its
desilylated derivative 3a-H in 67 and 25% yield, respectively
(entry 1; combined yield of 3a-Si and 3a-H, 92%). We also
found that the slow addition of 2-TBSO-furan was notably
effective for obtaining aldol product 3a in good yield. That is,
when 2-TBSO-furan was added to the solution of 2a and
carbon acid 1 in CH2Cl2 at -24 °C over 1.5 h, the resultant
mixture was stirred at the same temperature for an additional
1 h and the VMA product 3a was obtained in 82% yield
(entry 3 vs 2). In contrast, by using 0.5 mol % of nitrogen acid
Tf2NH or oxygen acid TfOH instead of 1 under the same
3d
4d
5d
aIsolated yield. bBased on isolated yield. cReaction was carried out at
-78 °C. d2-TBSO-furan was slowly added over 1.5 h.
TABLE 2. Diastereoselective VMA Reaction of R-Substituted Cyclic
Ketones
acid
(mol %)
yielda
(%)
entry
2
R1
R2
3
drb
11:1
10:1
12:1:1:0.5
13:1
1
2b Me
2b Me
2b Me
2c allyl
2d Me
2e Me
H
H
H
H
1 (0.5)
TiCl4 (40)
Bi(OTf)3 (5) 3b
3b
3b
78
70
65
78
53
70
2c
3d
4
1 (1.0)
3c
3d
3e
5e
6
Me 1 (2.0)
1 (0.5)
single
12:1
H
aCombined yield of isolated 3-Si and 3-H. bBased on 1H NMR of the
crude mixture. cFrom ref 18. dFrom ref 19. 2-TMSO-furan was also used
as a nucleophile. eReaction was carried out at -24 °C.
conditions, the product yield was significantly reduced
(entries 4 and 5).
On the basis of the above finding of high efficiency of the
carbon acid for the VMA reaction of 2a, we examined the
diastereoselective VMA reaction of R-substituted cyclohexa-
nones with 2-TBSO-furan (Table 2). Recently, Romo re-
ported that, in the presence of 40 mol % of TiCl4, the VMA
reaction of 2-methylcyclohexanone 2b with 2-TBSO-furan
proceeds with an excellent diastereoselectivity to give a
mixture of 3b-Si and 3b-H in 70% yield (entry 2; TON =
1.75).18 Furthermore, from a viewpoint of catalyst loading,
Bi(OTf)3 was found to be a more effective Lewis acid catalyst
for the similar reaction (entry 3; TON = 13).19 On the other
hand, under the optimized conditions, only 0.5 mol % of 1
was enough to complete the VMA reaction of 2b with
2-TBSO-furan, giving rise to 3b in 78% yield without the
decrease in the diastereoselectivity (entry 1, dr = 11:1; TON
= 156). Synthetically more useful 2-allylcyclohexanone 2c
also reacted with 2-TBSO-furan in the presence of 1.0 mol %
(14) Other examples of the carbon acid catalyzed reactions: (a) Ishihara,
K.; Hasegawa, A.; Yamamoto, H. Angew. Chem., Int. Ed. 2001, 40, 4077–
4079. (b) Ishihara, K.; Hasegawa, A.; Yamamoto, H. Synlett 2002, 1296–
1298. (c) Ishihara, K.; Hasegawa, A.; Yamamoto, H. Synlett 2002, 1299–
1301. (d) Kokubo, Y.; Hasegawa, A.; Kuwata, S.; Ishihara, K.; Yamamoto,
H.; Ikariya, T. Adv. Synth. Catal. 2005, 347, 220–224. (e) Hasegawa, A.;
Naganawa, Y.; Fushimi, M.; Ishihara, K.; Yamamoto, H. Org. Lett. 2006, 8,
3175–3178.
(15) Selected examples for in situ generation of silicon Lewis acid:
(a) Takasu, K. Synlett 2009, 1905–1914. (b) Inanaga, K.; Takasu, K.; Ihara,
M. J. Am. Chem. Soc. 2005, 127, 3668–3669. (c) Jung, M. E.; Ho, D. G. Org.
Lett. 2007, 9, 375–378.
(16) Boxer, M. B.; Yamamoto, H. J. Am. Chem. Soc. 2006, 128, 48–49.
(17) It has been known that Lewis acid mediated 1,4-addition of silicon
enolates often proceeds via single electron transfer mechanism. See: Otera,
J.; Fujita, Y.; Sakuta, N.; Fujita, M.; Fukuzumi, S. J. Org. Chem. 1996, 61,
2951–2962.
(18) Kong, K.; Romo, D. Org. Lett. 2006, 8, 2909–2912.
(19) Ollevier, T.; Bouchard, J.-E.; Desyroy, V. J. Org. Chem. 2008, 73,
331–334.
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Yanai et al.
JOCNote
SCHEME 1. VMA Reaction of 2b with 4-Substituted 2-TBSO-
Furans
SCHEME 2. Mukaiyama Aldol Reaction of 2b in Gram Scale
SCHEME 3. Mukaiyama Aldol Reaction of 2g with Dimethyl-
ketene Silyl Acetal
TABLE 3. Diastereoselective Mukaiyama Aldol Reaction with Acyclic
Ketene Silyl Acetals
equatorial adducts 4b, 4c, and 4d were obtained in excellent
yields without the formation of diastereomers (entries
2-4).20-22 Relatively less reactive 2d was also found to be
a nice substrate (entry 5, 96% yield). In addition, although it
has been known that the treatment of ketones with dimethyl-
ketene silyl acetal (R3 = Me) frequently results in the forma-
tion of enol silyl ether of ketones through silyl transfer reac-
tion without the aldol type C-C bond formation,23 the carbon
acid induced Mukaiyama aldol chemistry realized the clean
C-C bond formation between consecutive quaternary carbons
with the perfect equatorial selectivity. That is, in the presence of
1.0 mol % of carbon acid 1, the Mukaiyama aldol reaction of 2b
with dimethylketene silyl acetal smoothly proceeded to give the
desired equatorial adduct 4f in 90% yield (entry 6).24 Likewise,
the aldol product 4g was obtained in 81% yield by the reaction
of 2-allylcyclohexanone with dimethylketene silyl acetal under
the same conditions (entry 7).
entry
2
R1
R2
R3
1 (mol %)
4
yielda (%)
1
2
3
4
5
6
7
2a
2b
2c
2f
2d
2b
2c
H
H
H
H
H
Me
H
H
H
H
H
H
H
Me
Me
0.05
0.05
0.05
0.05
0.5
4a
4b
4c
4d
4e
4f
98
94
90
96
96
90
81
Me
allyl
Bn
Me
Me
allyl
1.0
1.5
4g
aIsolated yield.
of carbon acid 1 to give the corresponding VMA product 3c
in 78% yield as a mixture of two diastereomers in a ratio of
13:1 (entry 4). While the reactivity of 2,2-dimethylcyclohexa-
none 2d is significantly reduced by the steric and electronic
effects around the carbonyl group, the reaction of 2d with
2-TBSO-furan in the presence of 2.0 mol % of carbon acid 1
gave the VMA product 3d-Si in moderate yield as a sole
diastereomer without the formation of desilylated product
(entry 5). Likewise, in the presence of 0.5 mol % of 1,
R-methylated dihydrothiopyran-4-one 2e was also converted to
the VMA product 3e-Si in 70% with an excellent diastereo-
selectivity (entry 6).
This diastereoselective Mukaiyama aldol reaction can be
carried out in gram scale. For instance, by using 2.9 mg of
carbon acid 1, 1.1 g of 2b smoothly converted to the desired
aldol product 4b in excellent yield without loss of diastereo-
selectivity (Scheme 2).
The present conditions using carbon acid 1 was also effective
in the C-C bond formation between acyclic ketone with
dimethylketene silyl acetal. It is known that, in the presence
of 1 molar equiv of TiCl4, the reaction of highly hindered
undecan-6-one 2g with dimethylketene silyl acetal does not give
the desired aldol product.6 In contrast, the use of 1 realized the
clean formation of aldol adduct 5a (Scheme 3, also see Support-
ing Information). This result strongly supports the idea that the
present conditions are highly useful for the formation of the
C-C bond between sterically hindered substrates.
In this carbon acid induced VMA reaction, 4-substituted
2-TBSO-furans can be used (Scheme 1). For example, the
reaction of 2b with 4-methyl-2-TBSO-furan was promoted
by 1.0 mol % of 1 at -78 °C to give the corresponding VMA
adduct 3f-Si in 83% as a mixture of two diastereomers in a
ratio of >50:1 without the formation of the desilylated
alcohol product. Under similar conditions, β-bromolactone
3g-Si was also obtained in 87% yield with an excellent
diastereoselectivity.
Next, we examined the efficiency of 1 in the Mukaiyama
aldol reaction using acyclic ketene silyl acetals (Table 3). In
this case, in the presence of only 0.05 mol % of 1, the reaction
of cyclohexanone 2a with ketene silyl acetal derived from
ethyl acetate (R3 = H) rapidly completed at -78 °C to give
the desired adduct 4a in 98% yield (entry 1; TON = 1960).
Remarkably, in all reactions of R-monosubstituted cyclo-
hexanones 2b, 2c, and 2f with simple ketene silyl acetal, the
As an initiation step of this Mukaiyama aldol type reac-
tion, we propose the generation of silyl methide species A by
(21) For the hetero-Diels-Alder reaction of R-substituted cyclohexanone
with Rawal’s diene, see: Huang, Y.; Rawal, V. H. J. Am. Chem. Soc. 2002,
124, 9662–9663.
(22) The Mukaiyama aldol reaction of 2b with ketene trimethylsilyl acetal
required at least 1.0 mol % of Tf2CHCH2CHTf2 to complete the reaction
(see Supporting Information).
(23) (a) Hydrio, J.; Van de Weghe, P.; Collin, J. Synthesis 1997, 68–72.
(b) Song, J. J.; Tan, Z.; Reeves, J. T.; Fandrick, D. R.; Yee, N. K.;
Senanayake, C. H. Org. Lett. 2008, 10, 877–880.
(24) By the reaction of highly hindered R,R-dimethylcyclohexanone with
dimethylketene silyl acetal in the presence of 1.0 mol % of carbon acid 1, the
corresponding enol silyl ether was obtained in 76% yield without the
formation of the desired aldol product (see Supporting Information).
(20) Similar equatorial selectivity has been known in some Lewis acid
mediated reactions of R-substituted cyclohexanones with silicon enolates.
See: (a) Nakamura, E.; Horiguchi, Y.; Shimada, J.; Kuwajima, I. J. Chem.
Soc., Chem. Commun. 1983, 796–797. (b) Chen, J.; Sakamoto, K.; Orita, A.;
Otera, J. J. Org. Chem. 1998, 63, 9739–9745. (c) Bandini, E.; Martelli, G.;
Spunta, G.; Bongini, A.; Panunzio, M. Synlett 1999, 1735–1738.
J. Org. Chem. Vol. 75, No. 15, 2010 5377

Yanai et al.
JOCNote
required loading of carbon acid 1 can be reduced to 0.05-
1.0 mol %. Tf2CHCH2CHTf2 induced Mukaiyama aldol type
reactions are remarkably useful for the C-C bond formation
between sterically hindered substrates.
Experimental Section
General Procedure: Preparation of 5-(1-(tert-Butyldimethyl-
silyloxy)cyclohexyl)furan-2(5H)-one (3a-Si) and 5-(1-Hydroxy-
cyclohexyl)furan-2(5H)-one (3a-H). To a solution of cyclohexa-
none 2a (103.5 μL, 1.0 mmol) and Tf2CHCH2CHTf2 1 (2.86 mg,
5 μmol) in CH2Cl2 (1.0 mL) was added a solution of tert-
butyl(furan-2-yloxy)dimethylsilane (218.1 mg, 1.1 mmol) in
CH2Cl2 (1.0 mL) at -24 °C over 90 min via a syringe pump. After
being stirred at the same temperature for 1 h, the reaction mixture
was quenched with saturated NaHCO3 solution (20 mL) and
extracted with EtOAc (20 mL ꢀ 3). The organic layer was dried
over anhydrous MgSO4 and evaporated. The obtained residue
was purified by column chromatography on silica gel (hexane/
EtOAc = 10:1-1:1) to give the VMA product 3a-Si in 66% yield
(194.9 mg, 0.66 mmol) and its desilyated product 3a-H in 16%
yield (27.7 mg, 0.16 mmol). The structure of 3a-H was confirmed
by comparison of spectrum data with those reported in the litera-
ture.19 For 3a-Si: colorless crystals; mp 53.3-54.6 °C; IR (KBr)
FIGURE 2. Catalyst cycle of the present aldol reaction.
the reaction of 1 with ketene silyl acetals and the following
electrophilic activation of ketone substrate 2 through carbo-
nyl silylation by silyl methide A (Figure 2).12,25 Since this
electrophilic activation by silyl methide would be signifi-
cantly strong, the nucleophilic attack of ketene silyl acetal to
intermediate B smoothly proceeds to give intermediate C.
The resultant intermediate C would also show an excellent
silylating activity; therefore, the aldol product is formed by
the silylation of carbonyl substrate 2 by intermediate C along
with the regeneration of intermediate B.26
In summary, we found that 1 performs as one of the most
effective Brønsted acid precatalysts for the diastereoselective
Mukaiyama aldol type reactions with low reactive ketones.
By using carbon acid 1 in a range from 0.5 to 2.0 mol %, the
VMA reaction of R-substituted cyclohexanones with 2-TBSO-
furans smoothly proceeded to give the highly substituted
γ-butenolides in excellent yield without any loss of diastereo-
selectivity. Under similar conditions, acyclic ketene silyl acetals
also performed as nice nucleophiles. In the latter case, the
1
ν 3085, 2934, 2856, 1811, 1746, 1600, 1251, 1119, 772 cm-1; H
NMR (400 MHz, CDCl3) δ 0.09 (3H, s), 0.11 (3H, s), 0.83 (9H, s),
1.27-1.53 (5H, m), 1.58-1.72 (5H, m), 4.97-5.02 (1H, br s), 6.10
(1H, dd, J = 5.8, 2.0 Hz), 7.47 (1H, dd, J = 5.8, 1.3 Hz); 13C NMR
(100 MHz, CDCl3) δ -2.3, -1.8, 18.5, 22.0, 22.1, 25.3, 25.8, 34.4,
34.9, 76.2, 87.5, 122.5, 154.0, 173.0; MS (ESI-TOF) m/z 319 [M þ
H]þ; HRMS calcd for C16H28NaO3Si [M þ Na]þ 319.1705, found
319.1688. Anal. Calcd for C16H28O3Si: C, 64.82; H, 9.52. Found:
C, 64.58; H, 9.41.
Supporting Information Available: Detailed experimental
procedure, compound characterization data, 1H and 13C NMR
spectra. This material is available free of charge via the Internet
at http://pubs.acs.org.
(25) Hollis, T. K.; Bosnich, B. J. Am. Chem. Soc. 1995, 117, 4570–4581.
(26) For a mechanistic investigation of R3Si-CTf3 induced Mukaiyama
aldol reaction with enol silyl ethers, see: Hiraiwa, Y.; Ishihara, K.; Yamamoto,
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5378 J. Org. Chem. Vol. 75, No. 15, 2010