Organosilicon Reducing Reagents for Stereoselective Formations of Silyl Enol Ethers from α-Halo Carbonyl Compounds

Article abstract of DOI:10.1021/acs.joc.7b03005

Salt-free stereoselective synthesis of silyl enol ethers was achieved by treating α-halo carbonyl compounds with 2,3,5,6-tetramethyl-1,4-bis(trimethylsilyl)-1,4-dihydropyrazine. In this reaction, easily removable trimethylsilyl halides and 2,3,5,6-tetramethylpyrazine were generated as the reaction byproducts. Due to the inertness of the reaction byproducts, we found a one-pot transformation of the in situ generated silyl enol ethers into various α-functionalized carbonyls by reaction with Togni-II reagent or aldehydes.

Full text of DOI:10.1021/acs.joc.7b03005

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Note
Organosilicon Reducing Reagents for Stereoselective Formations
of Silyl Enol Ethers from #–Halo Carbonyl Compounds
Suman Pramanik, Supriya Rej, Shun Kando, Hayato Tsurugi, and Kazushi Mashima
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 17 Jan 2018
Downloaded from http://pubs.acs.org on January 17, 2018
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Organosilicon Reducing Reagents for Stereoselective Formations of
Silyl Enol Ethers from α–Halo Carbonyl Compounds
Suman Pramanik, Supriya Rej, Shun Kando, Hayato Tsurugi,* and Kazushi Mashima*
Department of Chemistry, Graduate School of Engineering Science, Osaka University, Toyonaka,
Osaka, 560-8531, Japan.
CORRESPONDING AUTHOR:
Kazushi Mashima, mashima@chem.es.osaka-u.ac.jp, Tel/Fax +81-6-6850-6245
Hayato Tsurugi, tsurugi@chem.es.osaka-u.ac.jp, Tel +81-6-6850-6247
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ABSTRACT
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Salt-free stereoselective synthesis of silyl enol ethers was achieved by treating -halo
carbonyl compounds with 2,3,5,6-tetramethyl-1,4-bis(trimethylsilyl)-1,4-dihydropyrazine. In this
reaction, easily removable trimethylsilyl halides and 2,3,5,6-tetramethylpyrazine were generated
as the reaction byproducts. Due to the inertness of the reaction byproducts, we found a one-pot
transformation of the in situ-generated silyl enol ethers into various –functionalized carbonyls
by the reaction with Togni-II reagent or aldehydes.
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Silyl enol ethers are important intermediates in organic chemistry as the synthetic equivalent
of enol ether anions that are often used with Lewis acid catalysts for a variety of C—C bond-
forming reactions with electrophiles.1–3 The versatility of silyl enol ethers thus led to the
development of various synthetic methodologies as exemplified in Figure 1. Figure 1(a) shows
the well-established synthetic route, in which chlorosilanes trap metal enolates in situ-generated
by treating carbonyl compounds with strong base4 or α-halo carbonyl compounds with metal
powder,5 though equimolar amounts of metal salt-waste are coproduced. Other examples include
metal-catalyzed reactions with hydrosilanes such as 1,4-hydrosilylation of conjugated enones
(Figure 1(b))6 and α-C—H bond activation of ketones followed by silylation (Figure 1(c)).7
Metal-catalyzed methods, however, are not widely applied to a variety of carbonyl compounds
because hydrosilanes are highly reactive to various functional groups in the presence of metal
catalysts, resulting in narrow functional group tolerance as well as contamination of silyl ethers
via C=O reduction.6c,7b,7e Accordingly, the development of more convenient synthetic methods
without contamination by salt-waste and side reactions is in high demand.
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Figure 1. General strategies for silyl enol ethers formation: a) metal enolates with chlorosilanes,
b) hydrosilylation of enones, c) dehydrogenative silylation of ketones.
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We recently developed a series of organosilicon compounds 1-3 for their unique ability to
reduce not only transition metal halides, but also organic halides without the formation of any
salt waste (Figure 2).8 These organosilicon reductants are synthesized by treating toluene or N-
heterocyclic compounds with sodium or potassium metal and trimethylsilyl chloride, and are
soluble in common organic solvents to keep the homogeneity during the reaction. Herein, we
developed a new salt-free method for synthesizing silyl enol ethers by treating enolizable α-halo
carbonyl compounds with 1-3 and demonstrated the regio- and stereoselective synthesis of
trisubstituted silyl enol ethers under mild reaction conditions. Furthermore, due to the formation
of silyl enol ethers was achieved in a salt-free manner and the inertness of the reaction
byproducts to keep the reaction mixture in homogeneous, the one-pot protocol was exemplified
by reactions with an electrophilic trifluoromethylation reagent (Togni-II reagent), aldehydes in
the presence of Me3SiOTf as the Lewis acid catalyst, and the Ni-catalyzed Kumada-Tamao
cross-coupling reaction with Grignard reagents.
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Figure 2. Organosilicon reductants 1-3.
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We first searched for the best organosilicon reductant among 1-3 for the salt-free formation of
silyl enol ether 5a by treating 4a-Br in CD3CN at 70 °C, and the results are shown in Table 1.
Although no conversion was observed for 1 (entry 1), reductant 2c afforded 5a in 98% yield
accompanied by trimethylsilylbromide and tetramethylpyrazine, both of which could be easily
separated and removed from the products either by column chromatography or by evaporation as
the volatile (entry 4). When 2a and 2b were used, 5a was obtained in lower yields (entries 2 and
3). Moreover, 3 exhibited the same efficiency as 2c, giving 5a in 97% yield (entry 5). We
selected 2c as the best reductant, and the solvent effects were examined next: a high polar
solvent, DMF, afforded 5a in lower yield (26%) (entry 6), as well as the reaction in an ethereal
solvent, THF, gave 5a in poor yield (entry 7). Silyl enol ether formation was less effective in
non-polar solvents such as benzene and toluene (entries 8 and 9). Acetonitrile was thus selected
as the best solvent for silyl enol ether formation.
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Table 1. Optimization of silyl enol ether synthesis
from α–bromo carbonyl.a
entry
reductant
solvent
CD3CN
CD3CN
CD3CN
CD3CN
CD3CN
DMF
yield (%)b
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4
5
6
7
8
9
0
1
67
34
98
97
26
4
2a
2b
2c
3
2c
2c
2c
2c
THF
C6D6
12
14
toluene-d8
aReaction conditions: 4a-Br (1.0 equiv, 0.10 mmol), reductant (1.0
equiv, 0.10 mmol), in above mentioned solvent at 70 °C for 1 h.
bYields were measured by 1H NMR spectroscopy in the presence of
mesitylene as an internal standard.
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We applied the optimized conditions in Table 1 for the transformation of α-halo carbonyl
compounds 4 into the corresponding silyl enol ethers 5 using 2c, and the results were shown in
Table 2. In the initial attempt, we checked the formation of disubstituted silyl enol ethers from
-bromoketones 4b—e. Reactions of 2c with 4'-methoxyphenacyl bromide (4b) and 4'-
methylphenacyl bromide (4c), in which electron-donating para-substituents attached to the
phenyl ring, gave the corresponding silyl enol ethers 5b in 99% yield and 5c in 97% yield
(entries 1 and 2). Treatment of 2c with 4'-chlorophenacyl bromide (4d) afforded 5d,
quantitatively (entry 3). The reaction with bulky tert-butyl substituted aliphatic substrate 4e was
slow, and a longer reaction time (24 h) was required to give 5e in quantitative yield (entry 4).
We next evaluated the synthesis of tri-substituted silyl enol ethers by controlling the E/Z
stereochemistry, and achieved highly Z-selective formation of the silyl enol ethers, which is
advantageous compared to literature mentioned procedures; in fact, low temperature reaction and
selection of the appropriate bases and solvents are crucial to accomplish the formation of Z-
selective silyl enol ethers.3a,4e,f 2-Bromopropiophenone (4f) afforded trisubstituted silyl enol
ether 5f in 96% yield with 98% Z-selectivity (entry 5). Similarly, geminal dibromo compound
4g was transformed in a perfect Z-selective manner to 5g, in which one synthetically useful
C(sp2)—Br bond remained (entry 6). 2-Bromo-2-methylpropiophenone (4h) and 3-bromo-3-
methyl-2-butanone (4i), both of which contained a tert-carbon—bromide bond, were converted
to the corresponding tetrasubstituted silyl enol ethers 5h in 99% yield and 5i in 97% yield,
respectively (entries 7 and 8). Reduction of ethyl α-bromophenylacetate (4j) and diethyl
bromomalonate (4k) proceeded in excellent yields to give the corresponding ethoxy silyl enol
ethers 5j with a Z-selectivity of 86% and 5k with a Z-selectivity of 99%, respectively (entries 9
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and 10). In fact, the applicability of α-bromothioester 4l—n and α-bromoamide 4o for the
generation of silyl enol ethers was examined by the treatment with reductant 3 due to its high
reactivity, which resulted in the formation of 5l—o in excellent yield (94—97% yield, entries
11—14). In contrast, primary and secondary α-bromoamides produced the corresponding α-
silylated amides under similar conditions, as silyl group migration proceeded from the silyl enol
ether to the α-position of the amides.9,10
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Table 2. Substrate scope for silyl enol ethers
synthesis from α–halo carbonyls.a
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entry product
1
yield [%]b
99 (5b, X = Br,
R3 = 4-MeOC6H4)
97 (5c, X = Br,
2
3
4
R3 = 4-MeC6H4)
99 (5d, X = Br,
R3 = 4-ClC6H4)
95 (5e, X = Br,
R3 = tBu)c
96 (5f, X = Br),
E/Z = 2/98
5
6
97 (5g, X = Br),
E/Z = <1/>99
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99 (5h, X = Br, R3 = Ph)
97 (5i, X = Br, R3 = Me)
98 (5j, X = Br,
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R1 = Ph), E/Z = 14/86
96 (5k, X = Br,
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R1 = CO2Et), E/Z = 1/99
96 (5l, X = Br,
R1 = R2 = H)d
94 (5m, X = Br, R1 = Me,
R2 = H), E/Z = >99/<1d
99 (5n, X = Br,
R1 = R2 = Me)d
14
15
97 (5o, X = Br)d
93 (5p, X = Cl),
E/Z = 2/98
16
95 (5q, X = Cl)
aReaction conditions: 4 (1.0 equiv, 0.40 mmol), 2c (1.0 equiv, 0.40
mmol), in CD3CN at 70 °C for 1 h. bYields and E/Z ratio (for
1
entries 5—8 and 11) were measured by H NMR spectroscopy in
the presence of mesitylene as an internal standard. cReaction was
24 h. dThe reaction was performed at rt for 1 h in the presence of 3
(1 equiv).
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Noteworthy was that one of two C—Cl bonds in 2,2-dichloroacetophenone (4p) selectively
reacted to give trisubstituted silyl enol ether 5p with a high Z-selectivity of 98% (entry 13), and
one of three C—Cl bonds of ethyl 2,2,2-trichloroacetate (4q) was reduced by 2c to produce
tetrasubstituted silyl enol ether 5q (entry 16). Although the activated C—Cl bonds of 4p and 4q
were reducible by 2c, reduction of the C—Cl bond of phenacyl chloride (4a-Cl), giving 5a,
required the use of 3, which has a more negative redox potential, as no reduction was observed
with 2c (eq. 1).
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Because the reactions of 2c with α-bromo carbonyls smoothly generated the corresponding
silyl enol ethers in excellent yields without any metal-derived wastes that sometimes suppress
further transformation in the reaction mixture, a one-pot reaction was conducted with
electrophiles. In fact, successive addition of an electrophilic trifluoromethylation reagent, Togni-
II reagent, to the reaction mixture afforded α-trifluoromethylated compounds 6, although silyl
enol ether trapping by Togni-II reagent was previously reported,11 and the results were
summarized in Table 3. After mixing 2c and 4a-Br in CH3CN at 70 °C for 1 h, Togni-II reagent
(1.5 equiv) was added at room temperature for 2 h to afford trifluoromethylated product 6a in
91% yield (entry 1). Silyl enol ethers 5b—d generated in situ from phenacyl bromides with
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electron–donating and –withdrawing substituents at the para-position of the aromatic ring
readily reacted with Togni–II reagent to give the corresponding trifluoromethylated products
6b—d in excellent yields in all cases (entries 2—4). Formation of silyl enol ether 5e required a
longer reaction time (vide supra), but the one-pot trifluoromethylation proceeded to form 6e in
84% yield (entry 5). In contrast, in situ-generated trisubstituted silyl enol ethers 5f and 5j as well
as tetrasubstituted silyl enol ether 5h resulted relatively in lower yields of trifluoromethylated
products 6f, 6j, and 6h (81%, 67%, and 56%), respectively (entries 6—8).
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Table 3. Substrate scope for one–pot reaction of
silyl enol ether formation followed by
trifluoromethylation of α–bromo carbonyls.a
entry product
yield [%]
1
2
3
4
5
91 (6a, R3 = Ph)
93 (6b, R3 = 4-MeOC6H4)
91 (6c, R3 = 4-MeC6H4)
92 (6d, R3 = 4-ClC6H4)
84 (6e, R3 = tBu)b,c
6
7
81 (6f, R1 = Me, R2 = H)
56 (6h, R1 = R2 = Me)d
8
67 (6j)
aReaction conditions: 4 (1.0 equiv, 0.40 mmol), 2c (1.0 equiv, 0.40
mmol), in CH3CN at 70 °C for 1 h, then Togni-II reagent (1.5
equiv, 0.60 mmol) was added at rt and stirred for 2 h. bSilyl enol
ether formation reaction was performed for 24 h. cYield was
measured by 1H NMR spectroscopy. dSecond step was performed
for 18 h at rt.
The one-pot silyl enol ether formation was applied to the Mukaiyama-Aldol reaction in the
presence of a Lewis acid catalyst, and results are provided in Table 4. The one-pot mixture of
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phenacyl bromide (4a-Br) and its derivatives having methoxy, methyl, and chloro substituents at
the para-position (4b—d) and 2c at 70 °C for 1 h was quenched by adding benzaldehyde (7a) in
the presence of trimethylsilyl triflate (Me3SiOTf, 5 mol%) at room temperature for 2 h to give
the aldol products 8aa—da in excellent yields (entries 1—4). In situ-generated silyl enol ether
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t
5e bearing a bulky Bu group on the carbonyl carbon also reacted with 7a to selectively afford
8ea in 93% yield (entry 5). Sterically hindered tri- and tetrasubstituted silyl enol ethers from 4f,
4h, and 4j produced the corresponding β-silyloxycarbonyl products 8fa, 8ha, and 8ja in 92%,
89%, and 91% yields, respectively (entries 6—8), in which 8fa and 8ja was obtained as
diastereomeric mixtures in 60:40 and 67:33 ratios.27 For the transformation of 4j, in situ-
generated Me3SiBr promoted the reaction. A variety of aryl aldehydes were also applied for the
one-pot reaction with 4j as the -bromoester without TMSOTf (Table 5). Both of electron-rich
and –defficient aldehydes 7c and 7e as well as sterically bulky aldehyde 7f afforded 8jc, 8je ,
and 8jf in excellent yield as a mixture of two diastereomers in approximately 7:3 to 8:2 ratio
(entries 1-3). When heteroaryl substituted aldehydes 7g, 7h, and 7i were used, the corresponding
products 8jg—ji were formed in good to excellent yields (entries 4-6).
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Table 4. Substrate scope for one–pot reaction of
silyl enol ether formation and followed by
Mukaiyama-Aldol reaction of α–bromo carbonyls.a
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entry product
yield (%) [d.r.]b
90 (8aa, R3 = Ph)
94 (8ba, R3 = 4-MeOC6H4)
91 (8ca, R3 = 4-MeC6H4)
92 (8da, R3 = 4-ClC6H4)
93 (8ea, R3 = tBu)c
92 (8fa, R1 = Me, R2 = H)
[60:40]
89 (8ha, R1 = R2 = Me)
1
2
3
4
5
6
7
8
91 (8ja) [67:33]d
aReaction conditions: 4 (1.0 equiv, 0.40 mmol), 2c (0.40 mmol), in
CH3CN at 70 °C for 1 h, then 7a (1.0 equiv, 0.40 mmol) and
Me3SiOTf (0.05 equiv, 0.02 mmol) added at rt and stirred for 2 h.
bDiastereomeric ratios were measured by 1H NMR spectroscopy.
cSilyl enol ether formation reaction was performed for 24 h. dNo
Me3SiOTf was added.
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Table 5. Substrate scope of aldehydes for one–pot
silyl enol ether formation and Mukaiyama–Aldol
reaction.a
7
8
9
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entry product
1
yield (%) [d.r.]b
84 (8jc, R = NMe2)
[68:32]
93 (8je, R = CF3)
[61:39]
2
3
4
5
6
93 (8jf, Ar =
2,4,6-Me3Ph) [81:19]
71 (8jg, Ar =
2-Mepy) [53:47]
89 (8jh, Ar =
thienyl) [65:35]
94 (8ji, Ar =
furyl) [62:38]
aReaction conditions: 4j (1.0 equiv, 0.40 mmol), 2c (1.0 equiv, 0.40
mmol), in CH3CN at 70 °C for 1 h, and then 7 (1.0 equiv, 0.40
mmol) was added at room temperature and stirred for 2 h.
bDiastereomeric ratios were measured by H NMR spectroscopy in
1
the presence of mesitylene as an internal standard.
We performed the derivatization of C(sp2)—X bond containing silyl enol ether 5p, obtained
from vicinal dichloro compound 4p, by a Kumada-Tamao coupling reaction (Scheme 1).12 The
reaction between in situ-generated silyl enol ether 5p and Grignard reagents (p-tolylmagnesium
bromide and ethylmagnesium bromide) in the presence of the Ni catalyst produced the
corresponding C—C coupled products 9pa and 9pb in high yield and maintained the high Z-
selectivity.
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Scheme 1. One-pot silyl enol ether formation and Kumada-Tamao coupling reaction of 2,2-
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dichloroacetophenone.
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In conclusion, we demonstrated the formation of silyl enol ethers by a simple treatment of α–
halo carbonyl compounds with 2c, from which Me3SiX and tetramethylpyrazine were easily
removed. Additionally, a one-pot mixture of halo carbonyls and 2c was successfully applied to
trifluoromethylation and Mukaiyama-Aldol reactions. Application of 1—3 as versatile transition
metal-free reducing reagents are ongoing.
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EXPERIMENTAL SECTION
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General information. All reactions and manipulations involving air- and moisture-sensitive
organometallic compounds were operated using the standard Schlenk or glovebox techniques
under argon atmosphere. Organosilicon reductants 1, 2a—c, and 3 were prepared according to
the modified procedure of the literature by replacing potassium metal by sodium metal except for
the synthesis of 2c that needed the use of potassium.13 Anhydrous solvents were purchased from
Kanto Chemical, and further purified by pass through activated alumina under positive argon
pressure as described by Grubbs et al.14 Deuterated solvents (CD3CN, toluene-d8, THF-d8, C6D6)
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and DMF were distilled over CaH2, degassed, and stored under Ar-filled glovebox.
1-
Trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni-II Reagent) was purchased from Tokyo
Chemical Industry CO. LTD. (TCI) and used without further purification (the substance contains
60% diatomaceous earth). Other chemicals were purchased and used without further purification.
-Halocarbonyl compounds of thioesters 4l,m,n and N,N-diethylamides 4o,r,s were synthesized
according to the literature procedures as described below.15,16 1H NMR (400 MHz), 13C{1H}
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NMR (100 MHz), and F{1H} NMR (376 MHz) spectra were measured on Bruker Avance III-
1
400 spectrometers. All H NMR chemical shifts were recorded in ppm (δ) referenced to the
chemical shifts of residual solvent resonances (CHCl3 was used as internal standard, δ 7.26 or
CH3CN was used as internal standard, δ 1.97). All 13C{1H} NMR chemical shifts were recorded
in ppm (δ) relative to carbon resonances in CDCl3 at δ 77.16 and or CD3CN at δ 118.26. Mass
spectra were obtained on Bruker Daltonics MicroTOF II-HB and JEOL JMS 700. Flash column
chromatography was performed by using silica gel 60 (0.040–0.0663 nm, 230–400 mesh ASTM).
General procedure for the synthesis of -bromo thioesters.15 In an argon filled Schlenk tube
equipped with a magnetic stir bar, 2-bromoacetyl bromide or its mono- and dimethylated
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derivatives (1.0 equiv, 14.86 mmol) was dissolved in CH2Cl2 (10 mL). p-Tolylthiophenol (0.80
equiv, 11.89 mmol) was added at 0°C. NEt3 (1.5 equiv, 22.29 mmol) was added further
dropwise to the reaction mixture in a period of 15 minutes at 0°C. The resulting mixture was
stirred for 1 h at room temperature. The reaction was quenched with 1M HCl, and extracted with
CH2Cl2 (50 mL). The combined organic layer was washed with saturated NaHCO3 and brine
solution, and then dried over anhydrous Na2SO4. The organic layer was evaporated and crude
product was purified by flash column chromatography on silica gel by using hexane as eluent to
give corresponding α-bromo thioesters, S-(p-tolyl) 2-bromoethanethioate (4l), S-(p-tolyl) 2-
bromopropanethioate (4m), and S-(p-tolyl) 2-bromo-2-methylpropanethioate (4n).
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General procedure for the synthesis of -bromo amides.16 In an argon filled Schlenk tube
equipped with a magnetic stir bar, diethylamine (2.0 equiv, 29.72 mmol) and anhydrous diethyl
ether (15 mL) were added and the Schlenk tube was placed in an ice bath at 0°C. 2-bromoacetyl
bromide or its mono- and dimethylated derivatives (1.0 equiv, 14.86 mmol) was added dropwise
to the reaction mixture in a period of 15 minutes, and the mixture was allowed to warm up to
room temperature and stirred for 4 h. The resulting suspension was filtered off and the yellowish
filtrate was washed with saturated ammonium chloride (20 mL), saturated sodium bicarbonate
(20 mL), and a saturated brine solution (20 mL). After drying with magnesium sulfate (MgSO4),
the organic layer was evaporated and crude product was purified by flash column
chromatography on silica gel by using hexane and ethyl acetate as eluent to afford corresponding
α-bromo amides, 2-bromo-N,N-diethylacetamide (4r), 2-bromo-N,N-diethylpropanamide (4s), 2-
bromo-N,N-diethyl-2-methylpropanamide (4o).
General procedure for the formation of silyl enol ethers from α-halo carbonyls. To a
solution of reductant 2c or 3 (1.0 equiv, 0.40 mmol) in acetonitrile (1.2 mL), -halo carbonyl
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compound 4 (1.0 equiv, 0.40 mmol) was added under argon atmosphere. The reaction was
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heated at 70 °C for 1 h. The clean formation of silyl enol ether was observed, and the yield was
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determined by H NMR spectroscopy by using mesitylene as an internal standard. Stable silyl
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enol ethers were isolated either by column chromatography or by evaporation of the volatile for
long time.
-Silylation of -bromo amides by organosilicon reductant 3. To a solution of reductant 3
(1.0 equiv, 0.40 mmol) in acetonitrile (1.2 mL), -bromo amides 4r or 4s (1.0 equiv, 0.40 mmol)
were added under argon atmosphere. The mixture was stirred at room temperature for 1 h. The
clean formations of α-silylated amides, N,N-diethyl-2-(trimethylsilyl)acetamide (10r) and N,N-
diethyl-2-(trimethylsilyl)propanamide (10s), were observed from 1H NMR spectroscopy, and we
did not find any O-silylated products. The reaction mixture was evaporated and was directly
purified by flash column chromatography on silica gel using ethyl acetate and hexane as eluent.
The products contain small amount of 4,4’-bipyridine, even after column chromatography.
General procedure for the trifluoromethylation of α-halo carbonyls. To a solution of
reductant 2c (1.0 equiv, 0.40 mmol) in acetonitrile (1.2 mL), -bromo carbonyl compounds 4
(1.0 equiv, 0.40 mmol) was added under argon atmosphere. The mixture was heated at 70 °C for
1 h followed by addition of Togni-II reagent (474.0 mg, the substance contains 60%
diatomaceous earth, 1.5 equiv, 0.60 mmol), and the reaction was stirred at room temperature for
2 h. The reaction mixture was filtered through a plug of silica to remove insoluble materials and
eluted with ethyl acetate. The solvent was evaporated, and the mixture was purified by flash
column chromatography on silica gel by using dichloromethane, ethyl acetate and hexane as
eluent.
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General procedure for the Mukaiyama-Aldol reaction of α-halo carbonyls. To a solution of
reductant 2c (1.0 equiv, 0.40 mmol) in acetonitrile (1.2 mL), -bromo carbonyl compounds 4
(1.0 equiv, 0.40 mmol) was added under argon atmosphere. The mixture was stirred at 70 °C for
1 h followed by addition of aldehydes (1.0 equiv, 0.40 mmol) and TMSOTf (4.5 mg, 0.05 equiv,
0.02 mmol) if mentioned in Table 4. The resultant reaction mixture was stirred at room
temperature for 2 h. The mixture was directly purified by flash column chromatography on silica
gel using ethyl acetate and hexane as eluent.
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Application for one-pot Kumada-Tamao Coupling. To a solution of reductant 2c (1.0 equiv,
0.40 mmol) in acetonitrile (1.2 mL), 4n (1.0 equiv, 0.40 mmol) was added under argon
atmosphere. The mixture was stirred at 70 °C for 1 h, and then, the solvent was evaporated
under vacuum. Under inert atmosphere NiCl2(dppp) (0.05 equiv, 0.02 mmol) and diethyl ether
(2.0 mL) were added. The reaction mixture was kept in an ice bath with slow addition of the
corresponding Grignard reagent (1.2 equiv, 0.48 mmol) over 15 minutes. The reaction mixture
was turned to brown. After competition of the addition, the mixture was stirred at 0°C for 30
minutes and then warned to room temperature for 20 h. After that, dichloromethane (20 mL)
was added into the reaction mixture and the organic part was evaporated. The crude mixture was
purified by flash column chromatography on silica gel by using hexane as eluent.
Spectral Data for Organic Compounds.
For thioesters:
S-(p-Tolyl) 2-bromoethanethioate15 (4l).
Purified by flash column
chromatography (silica gel, hexane); Yellow oil; IR (neat KBr, /cm-1) 2919, 2851, 1790, 1701,
1655, 1637, 1618, 662; 1H NMR (400 MHz, CDCl3, 30 °C)  7.35 (d, J = 8.0 Hz, 2H), 7.28 (d, J
= 8.0 Hz, 2H), 4.13 (s, 2H), 2.42 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3, 30 °C)  191.4,
140.4, 134.5, 130.3, 123.4, 33.2, 21.4; HRMS (FAB+, m/z): [M+H]+ calculated for C9H10OBrS:
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244.9630, found 244.9636. S-(p-Tolyl) 2-bromopropanethioate (4m). Purified by flash column
chromatography (silica gel, hexane); Yellow oil; IR (neat KBr, /cm-1) 2960, 2921, 2847, 1702,
1685, 1655, 723, 518; 1H NMR (400 MHz, CDCl3, 30 °C)  7.35 (d, J = 8.0 Hz, 2H), 7.27 (d, J =
8.0 Hz, 2H), 4.64 (q, J = 6.8 Hz, 1H), 2.41 (s, 3H), 1.92 (d, J = 6.8 Hz, 3H); 13C{1H} NMR (100
MHz, CDCl3, 30 °C)  195.2, 140.3, 134.6, 130.3, 123.5, 47.7, 22.2, 21.5; HRMS (FAB+, m/z):
[M+H]+ calculated for C10H12OBrS: 258.9787, found 258.9793. S-(p-Tolyl) 2-bromo-2-
methylpropanethioate (4n). Purified by flash column chromatography (silica gel, hexane); Red
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oil; IR (neat KBr, /cm-1) 2987, 2924, 2858, 1815, 1693, 1598, 711, 647, 549; H NMR (400
MHz, CDCl3, 30 °C)  7.35 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 2.42 (s, 3H), 2.05 (s,
13
6H); C{1H} NMR (100 MHz, CDCl3, 30 °C)  198.7, 140.0, 134.9, 130.2, 124.4, 64.2, 31.6,
21.4; HRMS (FAB+, m/z): [M+H]+ calculated for C11H14OBrS: 272.9943, found 272.9940.
For N,N-diethylamides:
2-Bromo-N,N-diethyl-2-methylpropanamide16 (4o). Purified by flash column chromatography
(silica gel, EtOAc/hexane = 1/10); Yellowish oil; IR (neat KBr, /cm-1) 2974, 2925, 2851, 1637,
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1277, 1126, 1107, 793; H NMR (400 MHz, CDCl3, 30 °C)  3.67–3.34 (br, 4H), 1.92 (s, 6H),
1.15 (br, 6H); 13C{1H} NMR (100 MHz, CDCl3, 30 °C)  169.6, 57.4, 32.9; HRMS (FAB+, m/z):
[M+H]+ calculated for C8H17ONBr: 222.0488, found 222.0484.
2-Bromo-N,N-diethylacetamide17 (4r). Purified by flash column chromatography (silica gel,
EtOAc/hexane = 1/10); Yellowish oil; IR (neat KBr, /cm-1) 2977, 2935, 2875, 1646, 1285, 1216,
1097, 705, 610; 1H NMR (400 MHz, CDCl3, 30 °C)  3.81 (s, 2H), 3.35 (q, J = 6.8 Hz, 4H), 1.22
13
(t, J = 6.8 Hz, 3H), 1.10 (t, J = 6.8 Hz, 3H); C{1H} NMR (100 MHz, CDCl3, 30 °C)  166.0,
43.0, 40.6, 26.5, 14.4, 12.6; HRMS (FAB+, m/z): [M+H]+ calculated for C6H13ONBr: 194.0175,
found 194.0183.
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2-Bromo-N,N-diethylpropanamide18 (4s). Purified by flash column chromatography (silica gel,
EtOAc/hexane = 1/10); Yellowish oil; IR (neat KBr, /cm-1) 2976, 2933, 2872, 1649, 1263, 1221,
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1135, 1086, 793, 604; H NMR (400 MHz, CDCl3, 30 °C)  4.50 (qd, J = 6.4 Hz, J = 0.6 Hz,
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1H), 3.52–3.45 (m, 2H), 3.26–3.18 (m, 2H), 1.78 (dd, J = 6.4 Hz, J = 1.0 Hz, 3H), 1.21 (td, J =
7.2 Hz, J = 1.0 Hz, 3H), 1.10 (td, J = 7.2 Hz, J = 1.0 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3,
30 °C)  168.5, 42.3, 40.9, 38.6, 21.9, 14.7, 12.5; HRMS (FAB+, m/z): [M+H]+ calculated for
C7H15ONBr: 208.0332, found 208.0337.
For isolated silyl enol ethers:
Trimethyl((1-(p-tolyl)vinyl)oxy)silane19,20 (5c). The crude reaction mixture was kept into high
vacuum at 30 °C for 2 h to remove the reaction solvent acetonitrile and the byproducts
trimethylsilyl bromide and Me4-pyrazine. Yellow oil (75 mg, 91% yield); IR (neat KBr, /cm-1)
2960, 2922, 2958, 1685, 1617, 1183, 1111, 1012; 1H NMR (400 MHz, CD3CN, 30 °C)  7.53 (d,
J = 8.2 Hz, 2H), 7.18 (d, J = 8.2 Hz, 1H), 4.95 (d, J = 1.2 Hz, 1H), 4.43 (d, J = 1.2 Hz, 1H), 2.35
13
(s, 3H), 0.28 (s, 9H); C{1H} NMR (100 MHz, CD3CN, 30 °C)  156.7, 139.3, 135.7, 129.8,
126.1, 91.2, 21.2, 0.1; HRMS (FAB+, m/z): [M+H]+ calculated for C12H19OSi: 207.1200, found
207.1205.
((1-(4-Chlorophenyl)vinyl)oxy)trimethylsilane20 (5d). The crude reaction mixture was kept into
high vacuum at 30 °C for 2 h to remove the reaction solvent acetonitrile and the byproducts
trimethylsilyl bromide and Me4-pyrazine. Yellow oil (82 mg, 90% yield); IR (neat KBr, /cm-1)
1
2960, 2918, 2847, 1685, 1655, 1637, 1618, 1105, 1012, 753, 553; H NMR (400 MHz, CD3CN,
30 °C)  7.61 (d, J = 8.6 Hz, 2H), 7.36 (d, J = 8.6 Hz, 1H), 5.00 (d, J = 1.8 Hz, 1H), 4.51 (d, J =
1.8 Hz, 1H), 0.28 (s, 9H); 13C{1H} NMR (100 MHz, CD3CN, 30 °C)  155.5, 137.3, 134.6,
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129.2, 127.8, 92.5, 0.1; HRMS (FAB+, m/z): [M+H]+ calculated for C11H16ClOSi: 227.0653,
found 227.0667.
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(Trimethyl((2-methyl-1-phenylprop-1-en-1-yl)oxy)silane22 (5h). Purified by flash column
chromatography (silica gel, CH2Cl2/hexane = 1/5); Colorless oil (81 mg, 92% yield); IR (neat
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KBr, /cm-1) 2918, 2847, 1699, 1685, 1655, 1637, 1094, 1023; H NMR (400 MHz, CDCl3,
30 °C)  7.36–7.24 (m, 5H), 1.82 (s, 3H), 1.71 (s, 3H), 0.01 (s, 9H); C{1H} NMR (100 MHz,
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CDCl3, 30 °C)  143.7, 139.2, 129.3, 127.8, 127.2, 113.0, 19.9, 18.4, 0.5; HRMS (FAB+, m/z):
[M]+ calculated for C13H20OSi: 220.1278, found 220.1282.
(Z)-((1-Ethoxy-2-phenylvinyl)oxy)trimethylsilane21 (5j). The crude reaction mixture was kept
into high vacuum at 30 °C for 2 h to remove the reaction solvent acetonitrile and the byproducts
trimethylsilyl bromide and Me4-pyrazine. Colorless oil (83 mg, 88% yield); IR (neat KBr, /cm-
1) 3028, 2979, 2900, 1699, 1685, 1648, 1599, 1158, 1059; NMR spectroscopic data for the Z-
isomer (major) are as follows: 1H NMR (400 MHz, CD3CN, 30 °C)  7.43 (t, J = 7.6 Hz, 2H),
7.22 (t, J = 7.6 Hz, 2H), 7.01 (t, J = 7.2 Hz, 1H), 4.75 (s, 1H), 4.07 (q, J = 7.0 Hz, 2H), 1.32 (t, J
= 7.0 Hz, 3H), 0.33 (s, 9H); C{1H} NMR (100 MHz, CDCl3, 30 °C)  155.5, 138.2, 129.12,
13
129.09, 127.6, 124.7, 87.2, 63.6, 15.5, -0.05. NMR spectroscopic data for the E-isomer (minor)
are as follows: Selected peak for 1H NMR (400 MHz, CD3CN, 30 °C)  4.67 (s, 1H), 3.92 (q, J =
7.0 Hz, 2H), 1.34 (t, J = 7.0 Hz, 3H), 0.31 (s, 9H); C{1H} NMR (100 MHz, CDCl3, 30 °C) 
13
157.9, 138.7, 130.4, 129.5, 128.0, 127.4, 124.4, 80.2, 64.9, 14.9, 0.7; HRMS (FAB+, m/z): [M]+
calculated for C13H20O2Si: 236.1233, found 236.1232.
For trifluoromethylated products:
3,3,3-Trifluoro-1-phenylpropan-1-one23,24 (6a). Purified by flash column chromatography (silica
gel, CH2Cl2/hexane = 1/5). White solid (69 mg, 91% yield); mp = 33—36°C; IR (neat KBr,
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/cm-1) 1684, 1419, 1373, 1262, 1227, 1098, 854, 758, 624, 592 cm-1; H NMR (400 MHz,
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CDCl3, 30 °C)  7.93 (d, J = 7.4 Hz, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.4 Hz, 2H), 3.80
13
(q, J = 10.0 Hz, 2H); C{1H} NMR (100 MHz, CDCl3, 30 °C)  189.8 (q, J = 2.3 Hz), 136.0,
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134.3, 129.1, 128.5, 124.2 (q, J = 277 Hz), 42.2 (q, J = 28.3 Hz); 19F{1H} NMR (376 MHz,
CDCl3, 30 °C)  –62.04; HRMS (EI, m/z): [M]+ calculated for C9H7F3O: 188.0449, found
188.0448.
3,3,3-Trifluoro-1-(4-methoxyphenyl)propan-1-one23,24 (6b).
Purified by flash column
chromatography (silica gel, CH2Cl2/hexane = 1/4). Yellow solid (81 mg, 93% yield); mp = 41—
42°C; IR (neat KBr, /cm-1) 2974, 2945, 1683, 1600, 1513, 1458, 1370, 1279, 1236, 1114, 996,
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918, 835, 781, 591, 532 cm-1; H NMR (400 MHz, CDCl3, 30 °C)  7.91 (d, J = 8.8 Hz, 2H),
6.96 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 3.73 (q, J = 10.0 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl3, 30 °C)  188.2 (q, J = 2.4 Hz), 164.5, 130.9, 129.1, 124.3 (q, J = 277 Hz), 114.2, 55.7,
41.9 (q, J = 28 Hz); 19F{1H} NMR (376 MHz, CDCl3, 30°C)  –61.97; HRMS (ESI, m/z): [M +
Na]+ calculated for C10H9F3NaO2: 241.0452, found 241.0457.
3,3,3-Trifluoro-1-(p-tolyl)propan-1-one23,24 (6c). Purified by flash column chromatography
(silica gel, CH2Cl2/hexane = 1/4). White solid (74 mg, 91% yield); mp = 54—55°C; IR (neat
KBr, /cm-1) 1686, 1605, 1416, 1370, 1266, 1131, 1100, 809, 657, 590, 529 cm-1; 1H NMR (400
MHz, CDCl3, 30 °C)  7.84 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 3.78 (q, J = 10.0 Hz,
2H), 2.44 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3, 30 °C)  189.4 (q, J = 2.5 Hz), 145.4, 133.6,
129.7, 128.6, 124.2 (q, J = 277 Hz), 42.1 (q, J = 28 Hz), 21.7; 19F{1H} NMR (376 MHz, CDCl3,
30 °C)  –62.04; HRMS (ESI, m/z): [M + Na]+ calculated for C10H9F3NaO: 225.0503, found
225.0516.
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1-(4-Chlorophenyl)-3,3,3-trifluoropropan-1-one24 (6d).
Purified by flash column
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7
8
chromatography (silica gel, CH2Cl2/hexane = 1/4). White solid (82 mg, 92% yield); mp = 55—
56°C; IR (neat KBr, /cm-1) 1695, 1590, 1402, 1371, 1274, 1226, 1135, 1100, 999, 856, 821, 729,
639 cm-1; 1H NMR (400 MHz, CDCl3, 30 °C)  7.87 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H),
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3.77 (q, J = 10.0 Hz, 2H); C{1H} NMR (100 MHz, CDCl3, 30 °C)  188.7 (q, J = 2.5 Hz),
141.0, 134.3, 129.9, 129.5, 124.0 (q, J = 277.1 Hz), 42.3 (q, J = 28.5 Hz); F{1H} NMR (376
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MHz, CDCl3, 30 °C)  –62.01; HRMS (EI, m/z): [M]+ calculated for C9H6ClF3O: 222.0059,
found 222.0053.
1,1,1-Trifluoro-4,4-dimethylpentan-3-one24 (6e). Purified by flash column chromatography
(silica gel, CH2Cl2/hexane = 1/10). (note: due to low boiling point difficult to purify from
reaction solvent); Colorless liquid; IR (neat KBr, /cm-1) 2959, 2924, 2854, 1727, 1463, 1367,
1258, 1058, 833, 797, 700 cm-1; 1H NMR (400 MHz, CDCl3, 30 °C)  3.33 (q, J = 10.0 Hz, 2H),
1.19 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3, 30 °C)  205.1 (q, J = 1.7 Hz), 124.2 (q, J = 277
Hz), 44.9, 40.0 (q, J = 27.9 Hz), 25.9; 19F{1H} NMR (376 MHz, CDCl3, 30 °C)  –61.07.
3,3,3-Trifluoro-2-methyl-1-phenylpropan-1-one23 (6f).
Purified by flash column
chromatography (silica gel, CH2Cl2/hexane = 1/4). Colorless liquid (66 mg, 81% yield); IR (neat
KBr, /cm-1) 1693, 1597, 1462, 1382, 1223, 1170, 1133, 1001, 970, 687, 633 cm-1; H NMR
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(400 MHz, CDCl3, 30 °C)  7.95 (d, J = 7.6 Hz, 2H), 7.63 (t, J = 7.6 Hz, 1H), 7.51 (t, J = 7.6 Hz,
2H), 4.29–4.21 (m, 1H), 1.48 (d, J = 7.2 Hz, 3H); C{1H} NMR (100 MHz, CDCl3, 30 °C) 
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194.5 (q, J = 1.9 Hz), 135.9, 134.1, 129.0, 128.7, 125.5 (q, J = 280 Hz), 44.5 (q, J = 26.5 Hz),
11.8 (q, J = 2.8 Hz); 19F{1H} NMR (376 MHz, CDCl3, 30 °C)  –68.28; HRMS (EI, m/z): [M]+
calculated for C10H9F3O: 202.0605, found 202.0606.
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1-(4-Methoxyphenyl)-2-(trifluoromethyl)pentan-1-one25 (6h).
Purified by flash column
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6
chromatography (silica gel, CH2Cl2/hexane = 1/5); Colorless liquid (48 mg, 56 % yield); IR (neat
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8
9
KBr, /cm-1) 2993, 2953, 1687, 1597, 1474, 1446, 1400, 1312, 1264, 1197, 1128, 961, 705, 641
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60
1
cm-1; H NMR (400 MHz, CDCl3, 30 °C)  7.64 (d, J = 7.6 Hz, 2H), 7.50 (t, J = 7.6 Hz, 1H),
7.42 (t, J = 7.6 Hz, 2H), 1.56 (s, 6H); C{1H} NMR (100 MHz, CDCl3, 30 °C)  200.9, 138.3,
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131.6, 129.2 (q, J = 276 Hz), 128.4, 127.8, 53.5 (q, J = 24.6 Hz), 20.9 (q, J = 2.5 Hz); F{1H}
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NMR (376 MHz, CDCl3, 30 °C)  –72.63; HRMS (EI, m/z): [M]+ calculated for C11H11F3O:
216.0762, found 216.0760.
Ethyl 3,3,3-trifluoro-2-phenylpropanoate25 (6j). Purified by flash column chromatography (silica
gel, EtOAc/hexane = 1/25) (note: PhCH2CO2Et present with the target compound as an impurity
due to the product and PhCH2CO2Et both has same Rf value); Colorless oil (62 mg, 67% yield);
IR (neat KBr, /cm-1) 2964, 2917, 2851, 1735, 1685, 1655, 1637, 1260, 1165, 1111, 1027; H
1
NMR (400 MHz, CDCl3, 30 °C)  7.48–7.28 (m, 5H), 4.35–4.15 (m, 3H), 1.28 (t, J = 7.2 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3, 30 °C)  171.7, 129.6, 129.4, 129.3, 129.0, 128.7, 125.2
(q, J = 278 Hz), 62.2, 55.7 (q, J = 28.6 Hz), 14.0; F{1H} NMR (376 MHz, CDCl3, 30 °C)  –
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67.66.
For Mukaiyama-Aldol products:
1,3-Diphenyl-3-((trimethylsilyl)oxy)propan-1-one26 (8aa).
Purified by flash column
chromatography (silica gel, EtOAc/hexane = 1/25); Colorless oil (108 mg, 90% yield); IR (neat
KBr, /cm-1) 3023, 2957, 2917, 2854, 1686, 1595, 1449, 1251, 1096, 951, 843, 751, 700 cm-1; 1H
NMR (400 MHz, CDCl3, 30 °C)  8.00–7.97 (m, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.49–7.43 (m,
4H), 7.36 (t, J = 7.4 Hz, 2H), 7.30–7.28 (m, 1H), 5.41 (dd, J = 8.8 Hz, J = 4.0 Hz, 1H), 3.59 (dd,
J = 15.5 Hz, J = 8.8 Hz, 1H), 3.06 (dd, J = 15.5 Hz, J = 4.0 Hz, 1H), 0.01 (s, 9H); 13C{1H} NMR
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(100 MHz, CDCl3, 30 °C)  198.6, 144.9, 137.8, 133.1, 128.6, 128.54, 128.47, 127.5, 125.9, 71.8,
49.8, 0.06; HRMS (EI, m/z): [M]+ calculated for C18H22O2Si: 298.1389, found 298.1388.
1-(4-Methoxyphenyl)-3-phenyl-3-((trimethylsilyl)oxy)propan-1-one (8ba). Purified by flash
column chromatography (silica gel, EtOAc/hexane = 1/25); Colorless oil (124 mg, 94% yield);
IR (neat KBr, /cm-1) 3027, 2957, 2900, 2840, 1676, 1601, 1509, 1260, 1169, 1094, 1028, 840,
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700, 571 cm-1; 1H NMR (400 MHz, CDCl3, 30 °C)  7.97 (d, J = 8.8 Hz, 2H), 7.45–7.25 (m, 5H),
6.94 (d, J = 8.8 Hz, 2H), 5.39 (dd, J = 8.8 Hz, J = 4.0 Hz, 1H), 3.89 (s, 3H), 3.53 (dd, J = 15.3
13
Hz, J = 8.8 Hz, 1H), 3.00 (dd, J = 15.3 Hz, J = 4.0 Hz, 1H), 0.01 (s, 9H); C{1H} NMR (100
MHz, CDCl3, 30 °C)  197.1, 163.6, 145.0, 131.0, 130.9, 128.4, 127.4, 125.9, 113.7, 71.9, 55.6,
49.5, 0.07; HRMS (EI, m/z): [M]+ calculated for C19H24O3Si: 328.1495, found 328.1488.
3-Phenyl-1-(p-tolyl)-3-((trimethylsilyl)oxy)propan-1-one (8ca).
Purified by flash column
chromatography (silica gel, EtOAc/hexane = 1/25); Colorless oil (113 mg, 91% yield); IR (neat
KBr, /cm-1) 3030, 2957, 2900, 1683, 1607, 1250, 1095, 942, 842, 750, 700, 570 cm-1; 1H NMR
(400 MHz, CDCl3, 30 °C)  7.89 (d, J = 8.2 Hz, 2H), 7.44 (d, J = 7.2 Hz, 2H), 7.38–7.34 (m, 2H),
7.30–7.24 (m, 3H), 5.41 (dd, J = 8.8 Hz, J = 4.0 Hz, 1H), 3.56 (dd, J = 15.5 Hz, J = 8.8 Hz, 1H),
13
3.03 (dd, J = 15.5 Hz, J = 4.0 Hz, 1H), 2.43 (s, 3H), 0.00 (s, 9H); C{1H} NMR (100 MHz,
CDCl3, 30 °C)  198.2, 145.0, 143.8, 135.3, 129.3, 128.7, 128.4, 127.4, 125.9, 71.8, 49.7, 21.7,
0.07; HRMS (EI, m/z): [M]+ calculated for C19H24O2Si: 312.1546, found 312.1543.
1-(4-Chlorophenyl)-3-phenyl-3-((trimethylsilyl)oxy)propan-1-one (8da).
Purified by flash
column chromatography (silica gel, EtOAc/hexane = 1/25); Colorless oil (122 mg, 92% yield);
IR (neat KBr, /cm-1) 3031, 2957, 2900, 1687, 1590, 1399, 1251, 1092, 842, 757, 700, 557 cm-1;
1H NMR (400 MHz, CDCl3, 30 °C)  7.92 (d, J = 8.4 Hz, 2H), 7.45–7.42 (m, 4H), 7.36 (t, J =
7.2 Hz, 2H), 7.28 (t, J = 7.2 Hz, 1H), 5.37 (dd, J = 8.8 Hz, J = 3.8 Hz, 1H), 3.55 (dd, J = 15.4 Hz,
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J = 8.8 Hz, 1H), 2.99 (dd, J = 15.4 Hz, J = 3.8 Hz, 1H), 0.02 (s, 9H); 13C{1H} NMR (100 MHz,
CDCl3, 30 °C)  197.5, 144.6, 139.6, 136.1, 130.0, 128.9, 128.5, 127.6, 125.8, 71.9, 49.7, 0.04;
HRMS (EI, m/z): [M]+ calculated for C18H21ClO2Si: 332.0999, found 332.0990.
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4,4-Dimethyl-1-phenyl-1-((trimethylsilyl)oxy)pentan-3-one (8ea). Purified by flash column
chromatography (silica gel, EtOAc/hexane = 1/50); Colorless oil (105 mg, 93% yield); IR (neat
KBr, /cm-1) 2964, 2914, 2868, 1707, 1610, 1543, 1477, 1365, 1251, 1070, 843, 751, 700 cm-1;
1H NMR (400 MHz, CDCl3, 30 °C)  7.38–7.31 (m, 5H), 5.30 (dd, J = 8.8 Hz, J = 4.0 Hz, 1H),
3.11 (dd, J = 16.2 Hz, J = 8.8 Hz, 1H), 2.53 (dd, J = 16.2 Hz, J = 4.0 Hz, 1H), 1.09 (s, 9H), 0.03
(s, 9H); 13C{1H} NMR (100 MHz, CDCl3, 30 °C)  213.4, 145.0, 129.0, 128.4, 128.3, 127.3,
125.9, 71.3, 48.0, 44.3, 25.9, 0.15; HRMS (EI, m/z): [M]+ calculated for C16H26O2Si: 278.1702,
found 278.1700.
2-Methyl-1,3-diphenyl-3-((trimethylsilyl)oxy)propan-1-one27 (8fa). Purified by flash column
chromatography (silica gel, EtOAc/hexane = 1/25), syn/anti mixture was obtained in a ratio of
60/40, which was determined by the integration of 5.03 and 4.90 ppm CHOSiMe3 signals
according to the literature; Colorless oil (115 mg, 92% yield); IR (neat KBr, /cm-1) 3060, 3032,
1
2959, 2875, 1774, 1736, 1718, 1685, 1655, 1066; H NMR spectroscopic data for the major
diastereomer are as follows: 1H NMR (400 MHz, CDCl3, 30 °C)  8.09–7.12 (overlap with minor
isomer) (m, 10H), 5.03 (d, J = 7.6 Hz, 1H), 3.88–3.79 (overlap with minor isomer) (m, 1H), 1.33
(d, J = 6.8 Hz, 3H), 0.02 (s, 9H); NMR spectroscopic data for the minor diastereomer are as
follows: 1H NMR (400 MHz, CDCl3, 30 °C)  8.09–7.12 (overlap with major isomer) (m, 10H),
4.90 (d, J = 9.2 Hz, 1H), 3.88-3.79 (overlap with major isomer) (m, 1H), 0.89 (d, J = 6.8 Hz, 3H),
–0.15 (s, 9H); Combined 13C{1H} NMR spectroscopic data for both diastereomers are as
follows: 13C{1H} NMR (100 MHz, CDCl3, 30 °C)  204.5, 203.0, 143.6, 143.1, 142.2, 138.5,
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137.2, 132.7, 131.7, 129.8, 129.6, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 127.8, 127.4,
127.2, 126.7, 78.5, 76.5, 50.2, 49.4, 14.7, 14.4, 0.02, -0.15; HRMS (FAB+, m/z): [M+H]+
calculated for C19H25O2Si: 313.1618, found 313.1623.
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2,2-Dimethyl-1,3-diphenyl-3-((trimethylsilyl)oxy)propan-1-one28 (8ha).
Purified by flash
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column chromatography (silica gel, EtOAc/hexane = 1/20); Colorless oil (116 mg, 89% yield);
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IR (neat KBr, /cm-1) 2918, 2851, 1774, 1736, 1718, 1701, 1685, 1655, 1637, 1161, 1077; H
NMR (400 MHz, CDCl3, 30 °C)  7.58 (d, J = 7.2 Hz, 2H), 7.45–7.28 (m, 8H), 5.23 (s, 1H), 1.22
(s, 3H), 1.11 (s, 3H), –0.08 (s, 9H); C{1H} NMR (100 MHz, CDCl3, 30 °C)  211.4, 141.1,
13
140.7, 130.3, 128.3, 127.9, 127.6, 127.3, 80.1, 53.8, 24.2, 20.9, 0.07; HRMS (FAB+, m/z):
[M+H]+ calculated for C20H27O2Si: 327.1775, found 327.1782.
Ethyl 2,3-diphenyl-3-((trimethylsilyl)oxy)propanoate (8ja).
Purified by flash column
chromatography (silica gel, EtOAc/hexane = 1/20); Colorless oil (125 mg 91% yield); IR (neat
KBr, /cm-1) 3031, 2958, 2901, 1733, 1496, 1455, 1370, 1251, 1157, 1088, 901, 842, 698, 557
cm-1; NMR spectroscopic data for the major diastereomer are as follows: 1H NMR (400 MHz,
CDCl3, 30 °C)  7.49-7.03 (overlap with minor isomer) (m, 10H), 5.18 (d, J = 10.0 Hz, 1H),
4.34–4.26 (m, 1H), 4.19–4.11 (m, 1H), 3.83 (overlap with minor isomer) (d, 1H, J = 10.0 Hz),
1.31 (t, J = 6.8 Hz, 3H), 0.04 (s, 9H); NMR spectroscopic data for the minor diastereomer are as
follows: 1H NMR (400 MHz, CDCl3, 30 °C)  7.49-7.03 (overlap with major isomer) (m, 10H),
5.14 (d, J = 9.0 Hz, 1H), 3.97-3.87 (m, 2H), 3.84 (overlap with major isomer) (d, J = 9.0 Hz, 1H),
0.99 (t, J = 7.2 Hz, 3H), –0.23 (s, 9H); Combined 13C{1H} NMR spectroscopic data for both
diastereomers are as follows: 13C{1H} NMR (100 MHz, CDCl3, 30 °C)  172.8, 171.8, 142.9,
141.8, 136.9, 135.2, 129.4, 129.0, 128.3, 128.2, 128.1, 127.8, 127.5, 127.4, 127.1, 127.0, 78.2,
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77.2, 62.1, 61.5, 60.9, 60.5, 14.4, 14.0, 0.14, –0.27; HRMS (EI, m/z): [M]+ calculated for
C20H26O3Si: 342.1651, found 342.1647.
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Ethyl 3-(4-(dimethylamino)phenyl)-2-phenyl-3-((trimethylsilyl)oxy)propanoate10 (8jc). Purified
by flash column chromatography (silica gel, EtOAc/hexane = 1/25); Colorless oil; IR (neat KBr,
/cm-1) 3031, 2956, 2917, 2850, 2801, 1732, 1615, 1523, 1446, 1350, 1249, 1158, 1071, 842,
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1
698, 562 cm-1; H NMR spectroscopic data for the major diastereomer are as follows: H NMR
(400 MHz, CDCl3, 30 °C)  7.50–7.16 (overlap with minor isomer) (m, 5H), 6.91 (d, J = 8.8 Hz,
2H), 6.50 (d, J = 8.8 Hz, 2H), 5.10 (d, J = 10.2 Hz, 1H), 4.30-4.25 (overlap with minor isomer)
(m, 1H), 4.16–4.12 (m, 1H), 3.84 (overlap with minor isomer) (d, J = 10.2 Hz, 1H), 2.88 (s, 6H),
1.31 (t, J = 7.2 Hz, 3H), 0.02 (s, 9H); 1H NMR spectroscopic data for the minor diastereomer are
as follows: 1H NMR (400 MHz, CDCl3, 30 °C)  7.50-7.16 (overlap with major isomer) (m, 5H),
6.96 (d, J = 8.8 Hz, 2H), 6.69 (d, J = 8.8 Hz, 2H), 5.05 (d, J = 9.2 Hz, 1H), 4.30–4.25 (overlap
with minor isomer) (m, 1H), 3.96-3.88 (m, 1H), 3.84 (overlap with major isomer) (d, J = 9.2 Hz,
1H), 2.95 (s, 6H), 1.01 (t, J = 7.2 Hz, 3H), –0.24 (s, 9H); Combined 13C{1H} NMR spectroscopic
data for both diastereomers are as follows: 13C{1H} NMR (100 MHz, CDCl3, 30 °C)  173.1,
172.0, 150.3, 149.9, 132.6, 129.1, 128.7, 128.2, 128.1, 127.8, 127.4, 127.2, 112.2, 111.9, 111.4,
77.9, 76.9, 62.1, 61.6, 60.7, 60.4, 40.6, 40.1, 14.4, 14.0, 0.21, –0.18; HRMS (EI, m/z): [M]+
calculated for C22H31NO3Si: 385.2073, found 385.2076.
Ethyl 2-phenyl-3-(4-(trifluoromethyl)phenyl)-3-((trimethylsilyl)oxy)propanoate10 (8je). Purified
by flash column chromatography (silica gel, EtOAc/hexane = 1/25); Colorless oil; IR (neat KBr,
1
/cm-1) 3033, 2960, 2903, 1733, 1618, 1371, 1325, 1252, 1164, 1068, 1018 cm-1; H NMR
spectroscopic data for the major diastereomer are as follows: 1H NMR (400 MHz, CDCl3, 30 °C)
 7.60-7.10 (overlap with minor isomer) (m, 9H), 5.23 (d, J = 10.0 Hz, 1H), 4.34–4.26 (m, 1H),
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3H), 0.05 (s, 9H); H NMR spectroscopic data for the minor diastereomer are as follows: H
NMR (400 MHz, CDCl3, 30 °C)  7.60-7.10 (overlap with major isomer) (m, 9H), 5.20 (d, J =
8.8 Hz, 1H), 3.99–3.89 (m, 2H), 3.79 (overlap with major isomer) (d, J = 8.8 Hz, 1H), 1.00 (t, J
= 7.2 Hz, 3H), –0.22 (s, 9H); Combined 13C{1H} NMR spectroscopic data for both diastereomers
are as follows: 13C{1H} NMR (100 MHz, CDCl3, 30 °C)  172.4, 171.6, 147.1, 146.1, 136.3,
134.7, 129.9, 129.6, 129.43, 129.38, 128.9, 128.7, 128.5, 128.3, 127.8, 127.6, 127.4, 127.2, 125.1,
124.8, 77.5, 76.5, 62.0, 61.3, 61.0, 60.8, 14.4, 13.9, –0.10, –0.32; HRMS (EI, m/z): [M]+
calculated for C21H25F3O3Si: 410.1525, found 410.1521.
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Ethyl 3-mesityl-2-phenyl-3-((trimethylsilyl)oxy)propanoate10 (8jf). Purified by flash column
chromatography (silica gel, EtOAc/hexane = 1/25); Colorless; IR (neat KBr, /cm-1) 3031, 2958,
2917, 2868, 1734, 1611, 1455, 1370, 1250, 1158, 1074, 842 cm-1; H NMR spectroscopic data
1
1
for the major diastereomer are as follows: H NMR (400 MHz, CDCl3, 30 °C)  7.40–7.10
(overlap with minor isomer) (m, 5H), 6.81 (s, 1H), 6.46 (s, 1H), 5.59 (d, J = 10.6 Hz, 1H), 4.37–
4.16 (overlap with minor isomer) (m, 3H), 2.68 (s, 3H), 2.19 (s, 3H), 1.75 (s, 3H), 1.34 (t, 3H, J
1
= 7.2 Hz), 0.01 (s, 9H); H NMR spectroscopic data for the minor diastereomer are as follows:
1H NMR (400 MHz, CDCl3, 30 °C)  7.59 (d, J = 7.2 Hz, 2H), 7.40–7.10 (overlap with major
isomer) (m, 3H), 6.84 (s, 1H), 6.78 (s, 1H), 5.50 (d, J = 9.6 Hz, 1H), 4.37–4.16 (overlap with
major isomer) (m, 1H), 2.64 (s, 3H), 2.52 (s, 3H), 2.26 (s, 3H), 0.88 (t, J = 7.2 Hz, 3H), –0.28 (s,
9H); Combined 13C{1H} NMR spectroscopic data for both diastereomers are as follows: 13C{1H}
NMR (100 MHz, CDCl3, 30 °C)  172.9, 171.8, 138.0, 137.4, 136.7, 136.4, 135.8, 135.0, 134.8,
133.7, 131.1, 130.7, 129.4, 129.3, 129.0, 128.8, 128.7, 128.5, 128.2, 128.0, 127.35, 127.33, 127.2,
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