Chiral phosphine oxide BINAPO as a Lewis base catalyst for asymmetric allylation and aldol reaction of trichlorosilyl compounds

Article abstract of DOI:10.1016/j.tet.2007.02.014

Chiral phosphine oxide BINAPO, which was readily prepared from chiral phosphine BINAP, exhibited good catalytic activities in the reaction of trichlorosilyl compounds via hypervalent silicate intermediates. The allylation of aldehydes with allyltrichloros

Full text of DOI:10.1016/j.tet.2007.02.014

Tetrahedron 63 (2007) 3122–3132
Chiral phosphine oxide BINAPO as a Lewis base catalyst for
asymmetric allylation and aldol reaction of trichlorosilyl
compounds
Shunsuke Kotani,a Shunichi Hashimotob and Makoto Nakajimaa,
*
aFaculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan
bFaculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo 060-0812, Japan
Received 9 January 2007; revised 3 February 2007; accepted 6 February 2007
Available online 9 February 2007
Abstract—Chiral phosphine oxide BINAPO, which was readily prepared from chiral phosphine BINAP, exhibited good catalytic activities in
the reaction of trichlorosilyl compounds via hypervalent silicate intermediates. The allylation of aldehydes with allyltrichlorosilanes in the
presence of a catalytic amount of BINAPO gave the allylated adducts in good enantioselectivities (up to 79% ee) wherein a combination of
diisopropylethylamine and tetrabutylammonium iodide as additives was crucial to accelerate the catalytic cycle. 31P NMR analysis of the
phosphine oxide suggested that the amine promoted the dissociation of phosphine oxide from silicon atom. BINAPO also promoted the enan-
tioselective aldol reaction of aldehydes with trichlorosilyl enol ethers in the presence of diisopropylethylamine as an additive to afford the
corresponding aldol adducts in high diastereo- and enantioselectivities (up to syn/anti¼1/25, 96% ee (anti)).
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
Enantioselective allylation of carbonyl compounds14 and
aldol reaction15,16 are powerful and important processes,
which are based on the nucleophilic addition to carbonyl de-
rivatives and yield optically active homoallylic alcohols and
b-hydroxy carbonyl compounds, respectively. The majority
of their asymmetric versions have been achieved utilizing
a chiral Lewis acid as a catalyst to activate the carbonyl
groups via an acyclic transition state to provide predomi-
nantly syn-adducts without reflecting the E/Z ratio of allyl
reagents or silyl enol ethers.
Numerous chiral base-catalyzed reactions have been devel-
oped, but most base catalysts are Brønsted bases, such as
amines or metal alkoxides.1 Recently Lewis base-catalyzed
reactions, utilizing the nucleophilicity toward a silicon atom
have attracted considerable attention.2,3 Lewis base catalysts
such as phosphoramides,4–6 pyridine N-oxides,7,8 sulf-
oxides,9 and formamides10 attack an electron-deficient sili-
con atom to form a hypervalent silicate, which undergoes
a reaction to release the product and the catalyst for further
turnover.
Kobayashi has reported that dimethylformamide activated
allyltrichlorosilanes to promote the allylation of alde-
hydes.17 The reaction proceeds via a six-membered transi-
tion state, which involves hypervalent silicate. Therefore,
the stereochemistry of the products can be controlled. (E)-
and (Z)-silane provide the anti- and syn-product, respec-
tively. Thereafter, various chiral Lewis base catalysts for
asymmetric allylation such as phosphoramides,4,5 form-
amides10 and pyridine N-oxides7a have been developed.
Denmark has reported the first asymmetric aldol reaction
Phosphine oxides possess a high nucleophilicity derived
from the polarization between P–O bond.11 This nucleophi-
licity allows phosphine oxides to act like other Lewis bases
and produces hypervalent silicates12 with trichlorosilyl
compounds. In addition, chiral phosphine oxides are readily
prepared from commercially available chiral phosphines.
However, little attention has been paid to phosphine oxides
as chiral Lewis base catalysts until recently when Kobaya-
shi13 reported the enantioselective allylation of benzoyl-
hydrazones with allyltrichlorosilanes promoted by phosphine
oxide, though more than a stoichiometric amount of phos-
phine oxide was required.
O
Ph
P
Ph
Ph
Ph
O
P
(S)-BINAPO (1)
* Corresponding author. E-mail: nakajima@gpo.kumamoto-u.ac.jp
Figure 1. Chiral phosphine oxide.
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.014

S. Kotani et al. / Tetrahedron 63 (2007) 3122–3132
Table 2. Screening of solvents
3123
of trichlorosilyl enol ethers promoted by a phosphoramide
catalyst.6 Similar to the allylation described above, this aldol
reaction proceeds via a chair-like transition state involving
a hypervalent silicate and yields products reflecting the
E/Z ratio of enol ethers.
(S)-1 (10 mol %)
i
Pr2NEt (5.0 eq)
Bu4N+I- (1.2 eq)
solvent, rt
OH
SiCl3
+
PhCHO
Ph
4aa
2a
3a
Herein we report the first example that employs chiral phos-
phine oxide BINAPO (1)18 as an organocatalyst19 in the
enantioselective allylation and aldol reaction of trichloro-
silyl compounds (Fig. 1).
Entry
Solvent
Time, h
Yield,a %
ee,b
%
1
2
3
CH2Cl2
Benzene
THF
CH3CN
CH2Cl2
4
24
48
24
24
92
11
8
96
7
43
10
16
44
—
4
5c
2. Results and discussion
a
Isolated yield.
Determined by HPLC (Daicel Chiralcel OD-H).
Triphenylphosphine oxide (0.2 equiv) was used as a catalyst.
b
c
2.1. Phosphine oxide-catalyzed allylation20
We initially examined (S)-1-catalyzed allylation of allyl-
trichlorosilane (2a) with benzaldehyde (3a) in dichloro-
methane at rt. The reaction proceeded to give corresponding
homoallylic alcohol (4), but the catalytic activity was quite
low compared to other Lewis bases4,7a (Table 1, entry 1).
To acquire a sufficient reactivity, we searched for an addi-
tive. We have previously investigated allylation catalyzed
by pyridine N-oxide,7a in which the addition of diisopro-
pylethylamine dramatically increased the activity of the cat-
alyst (entry 2). As another activator, Berrisford has shown
that tetrabutylammonium salts accelerate the allylation of
aldehydes with allyltrichlorosilanes.21 Although using either
diisopropylethylamine or tetrabutylammonium salts alone
did accelerate the reaction, the yields remained moderate
(entries 3 and 4). After considerable screening, we found
that the combination of diisopropylethylamine and tetra-
butylammonium iodide remarkably increased the catalytic
activity without decreasing the selectivity (entry 5).
Table 3 shows the results obtained in the present allylation
with various types of allyltrichlorosilanes. All the allyl-
trichlorosilanes smoothly react with aldehyde 3a to give
the corresponding homoallylic alcohols (4) in good yields
with g-selectivities. The syn-isomers were obtained from
(Z)-crotyltrichlorosilane, while the anti-isomers were pro-
duced from (E)-crotyltrichlorosilane with complete selectiv-
ities (entries 2 and 3). These results suggest that the reaction
proceeds via a six-membered chair-like transition state,
which involves hypervalent silicate (Fig. 2). (E)-Crotyltri-
chlorosilane gave a good enantioselectivity similar to allyl-
trichlorosilane (entry 3), while (Z)-crotyltrichlorosilane
Table 3. Asymmetric allylation of 3a with allyltrichlorosilanes (2) catalyzed
by (S)-1
(S)-1 (10 mol %)
i
Pr2NEt (5.0 eq)
R3
OH R3
Bu4N+I- (1.2 eq)
CH2Cl2, rt
R2
SiCl3
+
PhCHO
Ph
R1
R1 R2
4
2
Table 1. Effects of additives on chemical yield and enantioselectivity
(S)-1 (10 mol %)
3a
OH
additive
CH2Cl2, rt
Entry
Allyltrichlorosilane
R1
Time, h
Allylic alcohol
Yield,a % ee,b
4aa 92 43
SiCl3
+
PhCHO
R2
R3
%
Ph
4aa
2a
3a
1
2a
2b
2c
2d
2e
2f
H
H
H
4
4
2
4
1
1
3
2c
3e
4
Me
H
Me
H
H
H
H
H
Me
Ph
4ba 92d
4
46
4
Entry
Additivea
Time, h
Yield,b
%
ee,c %
Me
Me
H
4ca 87f
4da 63
4ea 73
4fa 80
4ga 81
1
2
3
4
5
None
24
24
12
6
32
79
54
32
92
36
37
46
42
43
iPr2NEt
Bu4N+Iꢀ
5
6
7
66
59
64
H
H
Bu4N+OTfꢀ
2g
H
–(CH2)4–
iPr2NEt, Bu4N+Iꢀ
4
a
Isolated yield.
Determined by HPLC.
E/Z¼1/99.
b
c
d
e
f
iPr2NEt: 5.0 equiv, ammonium salt: 1.2 equiv.
Isolated yield.
Determined by HPLC (Daicel Chiralcel OD-H).
a
b
c
syn/anti¼99/1.
E/Z¼77/23.
syn/anti¼23/77.
Next we screened solvents using diisopropylethylamine and
tetrabutylammonium iodide as additives (Table 2). Benzene
and tetrahydrofuran were not suitable as both gave low
yields and enantioselectivities (entries 2 and 3). Acetonitrile
gave a slightly higher yield, but the conversion took 24 h.
Thus, dichloromethane was the solvent of choice in terms
of both reactivity and enantioselectivity. Triphenylphos-
phine oxide, which is a typical monodentate phosphine
oxide, gave a lower chemical yield, suggesting that the
bidentate structure of the catalyst significantly influences
the reaction (entries 1 vs 5).
Ph
R1 Ph
Cl
P
O
R2
Ph
P
O
Si
Cl
Ph
O
H
Cl
Ph
Figure 2. Plausible transition state.

3124
S. Kotani et al. / Tetrahedron 63 (2007) 3122–3132
and prenyltrichlorosilane, which have steric hindrance in the
R1 position in Table 2, decreased the enantioselectivities (en-
tries 2 and 4). However, the most striking feature is that good
enantioselectivities were obtained in the reaction of b-
substituted allyltrichlorosilanes such as methallyltrichloro-
silane and b-phenylallyltrichlorosilane (entries 5–7), which
gave low enantioselectivities with other Lewis bases.4,7a
*
PO
Si
Cl–
Cl
PhCHO
3a
Cl3Si
PO
2a
Cl
1 + 2a
*
PO
PO
*
Cl
Cl–
PO
Si
PO
O
1
Table 4 summarizes the results obtained in the methallyla-
tion of various aldehydes catalyzed by BINAPO (1). Aro-
matic and unsaturated aldehydes underwent methallylation
in good yields (entries 1 and 2), although aliphatic aldehyde
decreased both the reactivity and enantioselectivity (entry
3). Aldehydes with electron-deficient substituents gave se-
lectivities similar to that of 3a (entry 4), while the introduc-
tion of electron-donating substituents into the p-position
slightly decreased the enantioselectivities (entry 5). Steric
hindrance in the o-position of benzaldehyde dramatically
decreased the enantioselectivities (entry 9). The best result
was obtained in the reaction of 3,5-dimethylbenzaldehyde
(3j) at ꢀ23 ꢁC (entry 11).
Ph
Cl
i
Pr2NEt
1 + 2a + 3a
*
OSiCl3
PO
Cl
Ph
silylated-4aa
Cl–
PO Si
O
Ph
Cl
Figure 3. Plausible reaction mechanism.
Table 5. 31P NMR analysis
Entry
Conditiona
31P NMR, ppm
1
2
3
4
5
6
1
28.6
43.3
40.9, 43.3
28.6
28.6
1+2a
1+2a+3a
Table 4. Asymmetric allylation of aldehydes (3) with 2e catalyzed by (S)-1
(S)-1 (10 mol %)
i
1+2a+3a+ Pr2NEt
1+2a+iPr2NEt
i
Pr2NEt (5.0 eq)
1+4aa+SiCl4+iPr2NEtb
40.7
Bu4N+I- (1.2 eq)
CH2Cl2, rt
OH
SiCl3
+
RCHO
1: 0.1 equiv, 2a: 1.1 equiv, 3a: 1.0 equiv, 4aa: 1.1 equiv, iPr2NEt:
5.0 equiv, SiCl4: 1.1 equiv.
a
R
4
2e
3
iPr2NEt: 1.1 equiv.
b
Entry
Aldehyde, R
Time, h
Yield,a %
ee,b
%
a new peak derived from the allylated product at 40.9 ppm
along with the previous peak at 43.3 ppm (entry 3). In the
control experiment, a mixture of 1, 4aa, SiCl4, and amine
gave a peak at 40.7 ppm (entry 6), which was derived from
the allylated product. Under the presence of diisopropyl-
ethylamine, 31P NMR peak in 1 appeared only at 28.6 ppm
(entry 4). These results suggest that the amine dissociates
1 from the silicon atom to reproduce free 1, which conse-
quently increases the catalytic efficiency.
1
2
3
4
5
6
7
8
3a
Ph
1
1
24
2
1
1
4
4
2
2
73
67
59
77
75
53
57
75
63
67
71
65
61
66
32
29
65
55
63
53
62
5
71
79
56
57
3b
3c
3d
3e
3f
3g
3h
3i
3j
3j
3k
3l
PhCH]CH
PhCH2CH2
4-Cl-C6H4
4-MeO-C6H4
2-Furyl
1-Naphthyl
2-Naphthyl
2,4,6-Me3-C6H2
3,5-Me2C6H3
3,5-Me2C6H3
3,5-(CF3)2C6H3
3,4,5-(MeO)3C6H2
9
10
11c
12
13
72
4
4
2.3. Phosphine oxide-catalyzed aldol reaction22
a
Isolated yield.
Determined by HPLC.
The reaction was conducted at ꢀ23 ꢁC.
b
c
We then investigated the asymmetric aldol reaction of
trichlorosilyl enol ethers catalyzed by phosphine oxide
BINAPO.
2.2. 31P NMR analysis
We initially examined the aldol reaction of 5a with 3a in the
presence of 10 mol % of 1 (Table 6, entry 1). The aldol ad-
duct was obtained in moderate yield and diastereoselectivity,
but a high enantioselectivity was observed in the anti-
adduct. To improve the yield and selectivity, we searched
for additives. The addition of 2-methyl-2-butene9b increased
both the reactivities and selectivities (entry 2), probably due
to its acid scavenging property, which neutralizes hydrogen
chloride produced by adventitious hydrolysis of trichloro-
silyl enol ethers. The addition of diisopropylethylamine
further accelerated the reaction rate, which suggests that
the amine works not only as an acid scavenger, but also
increases the catalytic activity as well as the allylation de-
scribed in Section 2.1 (entry 3). The addition of ammonium
salts promoted the formation of the dehydrated adduct,
which decreased the chemical yield of the aldol adduct
(entry 5).
Figure 3 shows a plausible reaction mechanism for Lewis
base-catalyzed allylation with allyltrichlorosilanes.17b The
binding of bidentate Lewis base to allyltrichlorosilane af-
fords a pentacoordinate silicon complex. Then aldehyde
attacks the enhanced electrophilic silicon to form a ternary
complex, which provides the silylated allylic alcohol via
a chair-like transition state and subsequently releases the
Lewis base for further turnover. In this process, the addition
of diisopropylethylamine increases the catalytic activity,
although the details are unclear. To clarify the role of amine,
we examined 31P NMR analysis of phosphine oxide 1 in
various steps of the reaction (Table 5). The 31P NMR peak
of pure 1 was observed at 28.6 ppm (entry 1), while signals
for the presence of allyltrichlorosilane were at 43.3 ppm
(entry 2), which suggest that phosphine oxide 1 coordinates
to allylsilane 2a. The addition of benzaldehyde (3a) gave

S. Kotani et al. / Tetrahedron 63 (2007) 3122–3132
3125
Table 6. Effects of additives on chemical yield and enantioselectivity
PhCHO (3a)
Table 8. Asymmetric aldol reactions of 3a with trichlorosilyl enol ethers (5)
catalyzed by (S)-1
(S)-1 (10 mol %)
OSiCl3
O
OH
O
OH
(S)-1 (10 mol %)
additive (1.2 eq)
i
OSiCl3
O
OH
Ph
O
OH
Ph
Pr2NEt (1.2 eq)
+
Ph
Ph
+
PhCHO
+
CH2Cl2, –78 °C
CH2Cl2, –78 °C
5a
syn-6aa
Time, Yield,a syn/antib ee,c %
anti-6aa
5
3a
syn-6
anti-6
Entry Additive
Entry
Trichlorosilyl
enol ether
Time, Yield,a syn/antib ee,c %
h
%
(anti)
h
%
(syn, anti)
1
2
3
4
5
None
2-Methyl-2-butene
2
1
58
96
1/2
86
84
87
87
82
1
2
5a
5b
0.25 94
1/14
1/17
71, 87
1/13
1/14
1/16
1/8
OSiCl3
iPr2NEt
0.25 94
i
2-Methyl-2-butene, Pr2NEt 0.25 94
iPr2NEt, Bu4N+Iꢀ
0.25 75
0.25 94
74, 69
59, 74
OSiCl3
OSiCl3
a
b
c
Isolated yield.
Determined by 1H NMR and HPLC.
Determined by HPLC (Daicel Chiralcel OD-H).
3d
5c
8
62
1/6
Et
OSiCl3
OSiCl3
4e
5
5d
5e
12
6
51
51
5/1
—
75, 14
95
To further optimize the aldol reaction, we next screened sol-
vents in the same transformation using 1 (Table 7). Changing
to either a more polar or less polar solvent dramatically de-
creased the chemical yields and stereoselectivities (entries
2–4). The reaction rate was also attenuated in a less polar sol-
vent (toluene), while employing polar solvents (tetrahydro-
furan and propionitrile) still provided moderate yields of
the corresponding aldol adducts.
Ph
tBu
a
b
c
d
e
Isolated yield.
Determined by 1H NMR and HPLC.
Determined by HPLC.
E/Z¼6.5/1.
E/Z¼1/>10.
Table 7. Screening of solvents
PhCHO (3a)
Table 9. Asymmetric aldol reaction of 3a with 7 catalyzed by (S)-1
(S)-1 (10 mol %)
OSiCl3
O
OH
Ph
O
OH
Ph
i
1) PhCHO (3a)
(S)-1 (10 mol %)
Pr2NEt (1.2 eq)
+
solvent, –78 °C
i
Pr2NEt (1.2 eq)
OMeOH
CH2Cl2, –78 °C, 1 h
5a
syn-6aa
anti-6aa
OSiCl3
nPent
MeO
nPent
8
Ph
2) MeOH, –78 °C, 45 min
3) rt, 30 min
Entry Solvent
Time, h Yield,a % syn/antib ee,c % (anti)
7
1
2
3
4
CH2Cl2
Toluene
THF
0.25
94
11
62
49
1/14
1/1
1/5
1/2
87
29
83
43
E/Z
Yield,a %
syn/antib
ee,c % (syn, anti)
1
1
2
>10/1
1/4
96
92
1/25
4/1
28, 12
31, 13
EtCN
a
b
c
Isolated yield.
a
Determined by 1H NMR and HPLC.
Determined by HPLC (Daicel Chiralcel OD-H).
Isolated yield.
Determined by 1H NMR and HPLC.
Determined by HPLC (Daicel Chiralcel OD-H).
b
c
With the optimized conditions in hand, we then investigated
the aldol reaction of various trichlorosilyl enol ethers with 3a
(Table 8). The trichlorosilyl enol ether derived from cyclo-
pentanone (5b) gave the anti-adduct as the major product
with a moderate enantioselectivity (entry 2). Although the
reactivities of enol ethers derived from acyclic ketones
were slightly lower (entries 3–5), the best enantioselectivity
of 95% ee was observed in the reaction of enol ether 5e,
which was derived from pinacolone (entry 5). It is notewor-
thy that the anti-adducts were predominantly obtained from
the (E)-enol ethers, while the corresponding syn-adducts
were predominantly produced from the (Z)-enol ethers.
reaction proceeds via a six-membered transition state as pro-
posed by Denmark.23
Table 10 summarizes the results obtained in the reactions of
aliphatic, a,b-unsaturated, and aromatic aldehydes with tri-
chlorosilyl enol ether 5a catalyzed by 1. All the reactions
resulted in high anti- and enantioselectivities, although the
reaction of aliphatic aldehyde proceeded rather slow (entry
3). All the a,b-unsaturated and aromatic aldehydes reacted
smoothly to produce the corresponding aldol adducts. In
the reaction of sterically congested aldehydes, high diaster-
eoselectivities were observed, but the enantioselectivities
somewhat decreased (entries 4 and 5). Aldehydes with elec-
tron-donating substituents gave slightly lower enantioselec-
tivities (entry 6), while aldehydes with electron-deficient
substituents gave high stereoselectivities (entries 8–10).
The best result was obtained in the reaction of p-nitrobenz-
aldehyde (3p) (entry 10).
To establish a mechanistic profile of the phosphine oxide cat-
alyzed process, we examined the aldol reactions of aldehyde
3a with (E)- and (Z)-trichlorosilyl enol ethers (7) derived
from heptanal (Table 9). These results indicate that the dia-
stereoselectivity of the aldol adducts is reflected in the E/Z
ratio of the enol ethers. These results suggest that the

3126
S. Kotani et al. / Tetrahedron 63 (2007) 3122–3132
4.1.1. Synthesis of (S)-BINAPO (1).24 H2O2 (30% aq,
1.74 mL, 1.61 mmol, 5.0 equiv) was added to a suspension
of (S)-BINAP (2.0 g, 0.32 mmol, 1.0 equiv) in acetone
(120 mL). After being stirred for 5 h, the reaction was
quenched with MnO2. Filtration through Celite and evapora-
tion of the solvent furnished the crude product, which was
purified by recrystallization (toluene/hex¼3/1, 20 mL) to
give (S)-BINAPO (1) (1.7 g, 81%) as pale yellowish prisms.
TLC: Rf 0.38 (EtOAc, UV). Mp: 260.5–261.5 ꢁC. [a]D25
–391.2 (c 0.5, benzene). 1H NMR (CDCl3): d 6.79 (d,
4H, J¼3.9 Hz), 7.22–7.44 (m, 20H), 7.66–7.71 (m, 4H),
7.79–7.85 (m, 4H).
Table 10. Asymmetric aldol reaction of aldehydes (3) with 5a catalyzed
by (S)-1
(S)-1 (10 mol %)
OSiCl3
O
OH
O
OH
i
Pr2NEt (1.2 eq)
+
+
RCHO
R
R
CH2Cl2, –78 °C
5a
3
syn-6
anti-6
Entry
Aldehyde, R
Time, Yield,a syn/antib ee,c %
h
%
(anti)
1
2
3
4
5
6
7
8
9
10
3a
Ph
0.25 94
1/14
1/7
1/6
1/34
1/48
1/6
87
81
90
55
74
78
83
89
93
96
3b
3c
3g
3i
PhCH]CH
PhCH2CH2
1-Naphthyl
2,4,6-Me3C6H2
4-MeO-C6H4
0.5
12
83
55
0.25 97
0.25 90
0.25 96
0.25 92
0.25 98
0.25 87
0.25 90
4.1.2. Synthesis of (Z)-crotyltrichlorosilane (2b).25 To a
suspensionoftrichlorosilane(6.9 mL, 51.1 mmol, 1.03 equiv)
and Pd(PPh3)4 (150 mg, 0.13 mmol, 0.26 mol %) in an argon
purged autoclave was added 1,3-butadiene (2.7 g, 50 mmol,
1.0 equiv) at ꢀ78 ꢁC. After being stirred for 30 min, the
mixture was allowed to warm to 100 ꢁC, then stirred for
1 h at the same temperature. Distillation of the reaction
mixture gave (Z)-crotyltrichlorosilane (2b) (4.48 g, 47%) as
3e
3m 4-Me-C6H4
1/7
3n
3o
3p
4-Br-C6H4
4-CF3-C6H4
4-NO2-C6H4
1/16
1/21
1/25
a
Isolated yield.
Determined by 1H NMR and HPLC.
Determined by HPLC.
b
c
1
a colorless oil. Bp: 140.0–141.0 ꢁC/760 mmHg. H NMR
(CDCl3): d 1.71 (m, 3H), 2.25 (m, 2H), 5.38 (m, 1H), 5.59
(m, 1H).
3. Conclusion
4.1.3. Synthesis of (E)-crotyltrichlorosilane (2c).26 To a
solution of CuCl (215 mg, 2.18 mmol, 5 mol %) and tri-
ethylamine (7.2 mL, 52.2 mmol, 1.2 equiv) in dry ether
(25 mL) was added a mixture of trichlorosilane (5.3 mL,
52.2 mmol, 1.2 equiv) and (E)-crotyl chloride (4.0 g,
43.5 mmol, 1.0 equiv, E/Z¼77/23) at 0 ꢁC and the mixture
was stirred for 2 h at rt. Filtration through Celite and the dis-
tillation of the filtrate afforded (E)-crotyltrichlorosilane (2c)
(5.5 g, 66%, E/Z¼77/23) as a colorless oil. Bp: 80.0–
81.0 ꢁC/50 mmHg. 1H NMR (CDCl3): d 1.67 (dd, 3H,
J¼0.7, 6.7 Hz), 2.35 (dd, 2H, J¼0.8, 8.9 Hz), 5.43 (m,
1H), 5.72 (m, 1H).
We have demonstrated catalytic, enantioselective methods
for the allylation and aldol reactions of trichlorosilyl com-
pounds using a phosphine oxide as an organocatalyst.
In these processes, phosphine oxide BINAPO gave anti-
adducts from (E)-silanes and syn-adducts from (Z)-silanes.
The employment of the appropriate additives dramatically
increased the catalytic activity. 31P NMR analysis of phos-
phine oxide revealed that the amine promotes the disso-
ciation of phosphine oxide from the silicon atom, which
increases the catalytic activity. The present reactions provide
the first examples that use a chiral phosphine oxide as a cat-
alyst for the enantioselective allylation and aldol reactions of
aldehydes. Further work on a more detailed mechanism is
currently in progress.
4.1.4. Prenyltrichlorosilane (2d).17b Bp: 113.0–114.0 ꢁC/
40 mmHg. H NMR (CDCl3): d 1.62 (s, 3H), 1.77 (s, 3H),
1
2.28 (d, 2H, J¼7.8 Hz), 5.13 (t, 1H, J¼7.8 Hz).
4. Experimental
4.1. General
4.1.5. Methallyltrichlorosilane (2e).26 Bp: 73.5–75.0 ꢁC/
95 mmHg. H NMR (CDCl3): d 1.87 (s, 3H), 2.37 (d, 2H,
1
J¼1.5 Hz), 4.84 (d, 1H, J¼0.8 Hz), 4.94 (dt, 1H, J¼1.5,
€
Melting points were measured using a Buchi 535 melting
0.8 Hz).
point apparatus and were not corrected. Optical rotations
were obtained on a JASCO DIP-370 digital polarimeter.
Infrared spectra were recorded on a JASCO FT/IR-5300.
1H NMR and 13C NMR spectra were recorded on a JEOL
EX-270 (1H, 270 MHz; 13C, 68 MHz) and AL-300 (1H,
300 MHz; 13C, 75 MHz) spectrometer. Chemical shift
values are expressed in parts per million relative to internal
tetramethylsilane. Coupling constants (J) are reported in
hertz (Hz). Abbreviations are as follows: s, singlet; d, dou-
blet; t, triplet; q, quartet; m, multiplet; br, broad. Mass spec-
tra were obtained by electron impact with ionization voltage
of 70 eV on JEOL JMS-DX303. HPLC was performed on
a JASCO PU-1580 with a JASCO UV-1575 (l¼254 nm)
and chiral separations were performed using Daicel Chiral-
pak or Chiralcel columns (f 0.46ꢂ25 cm). Allyltrichloro-
silane (2a) was purchased from TCI and was used without
further purification.
4.1.6. b-Phenylallyltrichlorosilane (2f). Trichlorosilane 2f
was prepared as described for 2c. Bp: 106.0–108.0 ꢁC/
1
20 mmHg. IR (neat): 1622, 899 cmꢀ1. H NMR (CDCl3):
d 2.85 (s, 2H), 5.25 (s, 1H), 5.47 (s, 1H), 7.33–7.50 (m,
5H). 13C NMR (CDCl3): d 32.0, 116.1, 126.6, 128.2,
128.6, 139.8, 140.6. MS (EI): m/z 250 (M+), 252. HRMS:
calcd for C9H9Cl3Si 249.9539, found 249.9533.
4.1.7. 1-(Trichlorosilylmethyl)cyclohexene (2g). Trichloro-
silane 2g was prepared as described for 2c. Bp: 106.5–
108.0 ꢁC/15 mmHg. IR (neat): 1662 cmꢀ1
.
1H NMR
(CDCl3): d 1.55–1.65 (m, 4H), 2.03–2.06 (m, 4H), 2.23
(s, 2H), 5.56 (s, 1H). 13C NMR (CDCl3): d 22.1,
23.1, 25.7, 30.6, 34.3, 126.1, 128.5. MS (EI): m/z 228
(M+), 230. HRMS: calcd for C7H11Cl3Si 227.9696, found
227.9700.

S. Kotani et al. / Tetrahedron 63 (2007) 3122–3132
3127
4.1.8. Representative procedure of asymmetric allylation
catalyzed by (S)-1. 1-Phenyl-3-buten-1-ol (4aa).27 To a
stirred solution of (S)-1 (30.8 mg, 0.047 mmol, 10 mol %),
tetrabutylammonium iodide (207 mg, 0.56 mmol, 1.2 equiv),
2a (50 mg, 0.47 mmol, 1.0 equiv), and diisopropylethyl-
amine (0.41 mL, 2.35 mmol, 5.0 equiv) in CH2Cl2 (0.5 mL)
was added allyltrichlorosilane in CH2Cl2 (1.12 M, 0.5 mL
0.56 mmol, 1.2 equiv) at rt, and the mixture was stirred at
the same temperature for 4 h. The reaction was quenched
with 10% NaOH (1 mL) and extracted with EtOAc
(50 mL). The organic layer was washed with 5% HCl
(15 mL), satd NaHCO3 (15 mL) and brine (15 mL), dried
over Na2SO4, and concentrated. The crude material was pu-
rified by column chromatography (hex/EtOAc¼15/1, SiO2,
7 g) to give corresponding homoallyl alcohol 4aa as an oil
(92%). (S)-1 (24.1 mg, 97%) was quantitatively recovered
by further elution with 3% EtOH in CH2Cl2 without any
loss of optical purity. TLC: Rf 0.29 (CH2Cl2, stained purple
with anisaldehyde). [a]2D3 +21.8 (c 0.88, benzene) for 43% ee
(CDCl3): d 1.81 (s, 3H), 2.11 (d, 1H, J¼1.8 Hz), 2.43 (d,
2H, J¼6.5 Hz), 4.83 (dt, 1H, J¼1.8, 6.5 Hz), 4.87 (d, 1H,
J¼1.9 Hz), 4.93 (d, 1H, J¼1.9 Hz), 7.28–7.38 (m, 5H).
HPLC: tR 30.8 min (minor, (S)-isomer), 35.2 min (major,
(R)-isomer) (Daicel Chiralcel OD-H, flow rate: 0.5 mL/
min, hex/IPA¼50/1).
4.1.13. 1,3-Diphenyl-3-buten-1-ol (4fa).30 TLC: Rf 0.34
(CH2Cl2, stained purple with anisaldehyde). [a]2D4 ꢀ16.7 (c
1
1.72, CHCl3) for 59% ee. H NMR (CDCl3): d 2.03 (d,
1H, J¼2.7 Hz), 2.88 (dd, 1H, J¼9.4, 14.1 Hz), 3.02 (dd,
1H, J¼4.0, 14.0 Hz), 4.73 (m, 1H), 5.18 (s, 1H), 5.43 (s,
1H), 7.29–7.47 (m, 10H). HPLC: tR 8.0 min (major, (R)-iso-
mer), 8.9 min (minor, (S)-isomer) (Daicel Chiralpak AD-H,
flow rate: 1.0 mL/min, hex/IPA¼9/1) (lit.30: tR 34.1 min (R)-
isomer, 38.2 min (S)-isomer) (Daicel Chiralpak AD, flow
rate: 0.5 mL/min, hex/IPA¼30/1).
4.1.14. (2-Methylenecyclohexyl)(phenyl)methanol (4ga).
TLC: Rf 0.36 (CH2Cl2, stained purple with anisaldehyde).
[a]2D2 +40.2 (c 1.17, CHCl3) for 64% ee. IR (neat): 3380,
1
(lit.27; [a]1D8 ꢀ48.7 (c 6.92, benzene) for (S)-isomer). H
NMR (CDCl3): d 2.02 (d, 1H, J¼3.2 Hz), 2.49–2.55 (m,
2H), 4.74 (m, 1H), 5.13–5.21 (m, 2H), 5.81 (m, 1H), 7.28–
7.37 (m, 5H). HPLC: tR 17.7 min (major, (R)-isomer),
20.5 min (minor, (S)-isomer) (Daicel Chiralcel OD, flow
rate: 1.0 mL/min, hex/IPA¼40/1).
4.1.9. syn-2-Methyl-1-phenyl-3-buten-1-ol (4ba).28 TLC:
Rf 0.34 (CH2Cl2, stained purple with anisaldehyde). [a]D23
ꢀ2.3 (c 0.56, CHCl3) for 4% ee (lit.28; [a]D25 ꢀ15.0 (c
0.93, CHCl3) for (1S,2R)-isomer of 55% ee). 1H NMR
(CDCl3): d 1.02 (d, 3H, J¼3.8 Hz), 1.93 (s, 1H), 2.61 (m,
1H), 4.62 (m, 1H), 5.04 (dd, 1H, J¼2.2, 3.3 Hz), 5.09 (dd,
1H, J¼2.2, 4.0 Hz), 5.77 (m, 1H), 7.24–7.38 (m, 5H).
HPLC: tR 16.3 min (minor, (1R,2S)-isomer), 18.9 min
(major, (1S,2R)-isomer) (Daicel Chiralcel OD, flow rate:
0.5 mL/min, hex/IPA¼19/1).
1645, 1449 cmꢀ1 1H NMR (CDCl3): d 1.21–1.61 (m,
.
5H), 1.76–1.85 (m, 1H), 2.26–2.33 (m, 3H), 2.41 (dt, 1H,
J¼10.4, 4.6 Hz), 4.74 (d, 1H, J¼10.4 Hz), 4.98 (s, 2H),
7.28–7.40 (m, 5H). 13C NMR (CDCl3): d 22.2, 28.3,
29.0, 32.7, 52.0, 72.9, 111.0, 127.1, 127.8, 128.3, 142.4,
149.6. HPLC: tR 11.0 min (minor, (ꢀ)-isomer), 13.2 min
(major, (+)-isomer) (Daicel Chiralpak AD, flow rate:
0.5 mL/min, hex/IPA¼3/1). MS (EI): m/z 96, 107, 202
(M+). HRMS: calcd for C14H18O 202.1358, found
202.1364.
4.1.15. 5-Methyl-1-phenyl-1,5-hexadien-3-ol (4eb).31
TLC: Rf 0.24 (CH2Cl2, stained purple with anisaldehyde).
[a]D22 +6.8 (c 0.39, benzene) for 32% ee (lit.31; [a]2D2 ꢀ19.4
(c 0.26, benzene) for (S)-isomer of 99% ee). 1H NMR
(CDCl3): d 1.82 (s, 3H), 1.86 (d, 1H, J¼3.2 Hz), 2.33 (d,
1H, J¼4.0 Hz), 2.36 (s, 1H), 4.43 (m, 1H), 4.87 (s, 1H),
4.93 (s, 1H), 6.24 (dd, 1H, J¼6.7, 15.9 Hz), 6.68 (d, 1H,
J¼15.9 Hz), 7.24–7.40 (m, 5H). HPLC: tR 13.2 min (major,
(R)-isomer), 15.6 min (minor, (S)-isomer) (Daicel Chiralcel
OD-H, flow rate: 1.0 mL/min, hex/IPA¼19/1).
4.1.16. 1-Phenyl-5-methyl-5-hexen-3-ol (4ec).31 TLC:
Rf 0.27 (CH2Cl2, stained purple with anisaldehyde). [a]D22
ꢀ5.7 (c 0.99, CHCl3) for 29% ee (lit.31; [a]D22 +15.8 (c
0.85, CHCl3) for (R)-isomer of 91% ee). 1H NMR
(CDCl3): d 1.71–1.83 (m, 6H), 2.15 (dd, 1H, J¼9.0,
13.2 Hz), 2.24 (dd, 1H, J¼3.3, 13.9 Hz), 2.64–2.89 (m,
2H), 3.76 (m, 1H), 4.81 (d, 1H, J¼2.0 Hz), 4.89 (d, 1H,
J¼2.0 Hz), 7.18–7.31 (m, 5H). HPLC: tR 14.6 min (major,
(S)-isomer), 21.1 min (minor, (R)-isomer) (Daicel Chiralcel
OD-H, flow rate: 0.5 mL/min, hex/IPA¼19/1).
4.1.10. anti-2-Methyl-1-phenyl-3-buten-1-ol (4ca).28
TLC: Rf 0.31 (CH2Cl2, stained purple with anisaldehyde).
[a]D25 +44.7 (c 0.75, CHCl3) for 46% ee (lit.28; [a]2D5 ꢀ73.4
1
(c 2.00, CHCl3) for (1S,2S)-isomer of 66% ee). H NMR
(CDCl3): d 0.87 (d, 3H, J¼6.5 Hz), 2.12 (d, 1H,
J¼2.1 Hz), 2.49 (m, 1H), 4.37 (dd, 1H, J¼2.1, 7.8 Hz),
5.17–5.23 (m, 2H), 5.78–5.88 (m, 1H), 7.28–7.35 (m, 5H).
HPLC: tR 34.3 min (minor, (1S,2S)-isomer), 41.3 min
(major, (1R,2R)-isomer) (Daicel Chiralcel OD-H, flow
rate: 1.0 mL/min, hex/IPA¼100/1).
4.1.11. 2,2-Dimethyl-1-phenyl-3-buten-1-ol (4da).29 TLC:
Rf 0.41 (CH2Cl2, stained purple with anisaldehyde). [a]D22
+2.3 (c 0.95, CHCl3) for 4% ee (lit.29; [a]D24 +22 (c 0.84,
CHCl3) for (R)-isomer of 78% ee). 1H NMR (CDCl3):
d 0.97 (s, 3H), 1.02 (s, 3H), 1.99 (d, 1H, J¼3.5 Hz), 4.44
(d, 1H, J¼3.5 Hz), 5.08 (dd, 1H, J¼3.3, 17.8 Hz), 5.15
(dd, 1H, J¼3.3, 11.3 Hz), 5.92 (dd, 1H, J¼11.3, 17.8 Hz),
7.28–7.30 (m, 5H). HPLC: tR 6.7 min (major, (R)-isomer),
9.4 min (minor, (S)-isomer) (Daicel Chiralcel OD-H, flow
rate: 1.0 mL/min, hex/IPA¼9/1).
4.1.17. 1-(4-Chlorophenyl)-3-methyl-3-buten-1-ol
(4ed).31 TLC: Rf 0.26 (CH2Cl2, stained purple with anisalde-
hyde). [a]2D2 +34.7 (c 0.55, benzene) for 65% ee (lit.31; [a]2D2
ꢀ44.5 (c 0.77, benzene) for (S)-isomer of 90% ee). 1H NMR
(CDCl3): d 1.80 (s, 3H), 2.13 (d, 1H, J¼1.9 Hz), 2.39 (d, 2H,
J¼6.5 Hz), 4.79 (m, 1H), 4.86 (d, 1H, J¼1.4 Hz), 4.94 (d,
1H, J¼1.4 Hz), 7.32 (m, 4H). HPLC: tR 27.2 min (minor,
(S)-isomer), 31.1 min (major, (R)-isomer) (Daicel Chiralcel
OJ-H, flow rate: 0.5 mL/min, hex/IPA¼50/1).
4.1.12. 3-Methyl-1-phenyl-3-buten-1-ol (4ea).27 TLC:
Rf 0.27 (CH2Cl2, stained purple with anisaldehyde). [a]D22
+51.8 (c 0.58, benzene) for 66% ee (lit.27; [a]D21 ꢀ46.6 (c
1.97, benzene) for (S)-isomer of 87% ee). 1H NMR

3128
S. Kotani et al. / Tetrahedron 63 (2007) 3122–3132
4.1.18. 1-(4-Methoxyphenyl)-3-methyl-3-buten-1-ol
(4ee).31 TLC: Rf 0.14 (CH2Cl2, stained purple with anis-
aldehyde). [a]2D2 +42.4 (c 0.45, CHCl3) for 55% ee
(lit.31; [a]D23 ꢀ67.9 (c 0.99, CHCl3) for (S)-isomer of
4.1.23. 1-(3,5-Dimethylphenyl)-3-methyl-3-buten-1-ol
(4ej). TLC: Rf 0.34 (CH2Cl2, stained purple with anisalde-
hyde). [a]2D3 +46.2 (c 1.19, CHCl3) for 79% ee. IR (neat):
1
3412, 1647, 1607, 1454 cmꢀ1. H NMR (CDCl3): d 1.81
1
94% ee). H NMR (CDCl3): d 1.79 (s, 3H), 2.04 (s, 1H),
(s, 3H), 2.06 (d, 1H, J¼2.2 Hz), 2.32 (s, 6H), 2.41 (d, 2H,
J¼6.3 Hz), 4.75 (dt, 1H, J¼2.2, 6.3 Hz), 4.88 (d, 1H,
J¼1.3 Hz), 4.93 (d, 1H, J¼1.3 Hz), 6.91 (s, 1H), 7.00 (s,
2H). 13C NMR (CDCl3): d 21.3, 22.3, 48.3, 71.4, 113.8,
123.5, 129.1, 137.9, 142.7, 144.0. HPLC: tR 11.8 min
(minor, (ꢀ)-isomer), 13.7 min (major, (+)-isomer) (Daicel
Chiralcel OD-H, flow rate: 0.5 mL/min, hex/IPA¼19/1).
MS (EI): m/z 107, 135, 190 (M+). HRMS: calcd for
C13H18O 190.1358, found 190.1366.
2.42 (d, 2H, J¼3.2 Hz), 3.81 (s, 3H), 4.78 (m, 1H), 4.85
(d, 1H, J¼1.3 Hz), 4.91 (d, 1H, J¼1.3 Hz), 6.89 (d, 2H,
J¼11.9 Hz), 7.30 (d, 2H, J¼11.9 Hz). HPLC: tR
14.4 min (major, (R)-isomer), 15.6 min (minor, (S)-isomer)
(Daicel Chiralcel OD-H, flow rate: 1.0 mL/min, hex/
IPA¼9/1).
4.1.19. 1-(2-Furyl)-3-methyl-3-buten-1-ol (4ef).31 TLC:
Rf 0.24 (CH2Cl2, stained purple with anisaldehyde). [a]D22
+31.7 (c 0.49, CHCl3) for 63% ee (lit.31; [a]D21 ꢀ49.2 (c
0.61, CHCl3) for (S)-isomer of 92% ee). 1H NMR (CDCl3):
d 1.76 (s, 3H), 2.05 (d, 1H, J¼4.0 Hz), 2.58 (d, 2H,
J¼7.9 Hz), 4.82–4.89 (m, 1H), 4.86 (d, 1H, J¼1.3 Hz),
4.91 (d, 1H, J¼1.3 Hz), 6.27 (d, 1H, J¼2.0 Hz), 6.34 (dd,
1H, J¼1.3, 2.0 Hz), 7.39 (d, 1H, J¼2.0 Hz). HPLC: tR
21.4 min (minor, (S)-isomer), 23.0 min (major, (R)-isomer)
(Daicel Chiralcel OD-H, flow rate: 0.5 mL/min, hex/
IPA¼40/1).
4.1.24. 1-[3,5-Bis(trifluoromethyl)phenyl]-3-methyl-3-
buten-1-ol (4ek). TLC: Rf 0.66 (CH2Cl2, stained purple
with anisaldehyde). [a]2D2 +26.4 (c 0.89, CHCl3) for 56%
ee. IR (neat): 3414, 1649, 1624, 1464 cmꢀ1 1H NMR
.
(CDCl3): d 1.85 (s, 3H), 2.32–2.40 (m, 2H), 2.47 (dd, 1H,
J¼4.0, 14.0 Hz), 4.90 (s, 1H), 4.95 (m, 1H), 5.02 (s, 1H),
7.79 (s, 1H), 7.85 (s, 2H). 13C NMR (CDCl3): d 22.1, 48.6,
70.0, 115.4, 121.3, 125.4, 126.0, 131.6 (t, J¼33 Hz),
141.2, 146.5. HPLC: tR 15.5 min (minor, (ꢀ)-isomer),
16.9 min (major, (+)-isomer) (Daicel Chiralpak AD-H,
flow rate: 0.5 mL/min, hex/IPA¼100/1). MS (EI): m/z 195,
243, 298 (M+). HRMS: calcd for C13H12F6O 298.0792,
found 298.0790.
4.1.20. 1-(1-Naphthyl)-3-methyl-3-buten-1-ol (4eg). TLC:
Rf 0.41 (CH2Cl2, stained purple with anisaldehyde). [a]D23
+59.8 (c 0.54, CHCl3) for 53% ee. IR (KBr): 3240,
1
1647 cmꢀ1. H NMR (CDCl3): d 1.92 (s, 3H), 2.27 (d,
1H, J¼1.9 Hz), 2.51 (dd, 1H, J¼9.7, 14.6 Hz), 2.69
(dd, 1H, J¼2.7, 14.6 Hz), 4.97 (s, 1H), 5.00 (s, 1H), 5.63
(dd, 1H, J¼2.7, 9.7 Hz), 7.47–7.56 (m, 3H), 7.73 (d, 1H,
J¼6.5 Hz), 7.79 (d, 1H, J¼7.8 Hz), 7.89 (dd, 1H, J¼2.4,
7.0 Hz), 8.08 (d, 1H, J¼7.8 Hz). 13C NMR (CDCl3):
d 22.4, 47.4, 68.2, 114.0, 122.7, 122.8, 125.4, 125.6,
126.0, 127.9, 129.0, 130.2, 133.8, 139.6, 142.8. HPLC: tR
7.3 min (minor, (ꢀ)-isomer), 13.6 min (major, (+)-isomer)
(Daicel Chiralcel OD-H, flow rate: 1.0 mL/min, hex/
IPA¼9/1). MS (EI): m/z 129, 157, 212 (M+). HRMS: calcd
for C15H16O 212.1201, found 212.1208.
4.1.25. 1-(3,4,5-Trimethoxyphenyl)-3-methyl-3-buten-1-
ol (4el). TLC: Rf 0.16 (hexane/EtOAc¼2/1, stained purple
with anisaldehyde). [a]2D2 +27.0 (c 1.15, CHCl3) for 57%
ee. IR (neat): 3478, 1647, 1593 cmꢀ1
.
1H NMR
(CDCl3): d 1.83 (s, 3H), 2.14 (d, 1H, J¼2.6 Hz), 2.42
(d, 2H, J¼6.6 Hz), 3.84 (s, 3H), 3.88 (s, 6H), 4.75 (dt,
1H, J¼2.0, 6.6 Hz), 4.90 (s, 1H), 4.96 (d, 1H,
J¼2.0 Hz), 6.62 (s, 2H). 13C NMR (CDCl3): d 22.3,
48.4, 56.1, 60.8, 71.5, 102.7, 114.1, 137.2, 139.8, 142.4,
153.2. HPLC: tR 13.5 min (minor, (ꢀ)-isomer), 18.3 min
(major, (+)-isomer) (Daicel Chiralcel OD-H, flow rate:
1.0 mL/min, hex/IPA¼19/1). MS (EI): m/z 169, 197, 252
(M+). HRMS: calcd for C14H20O4 252.1362, found
252.1356.
4.1.21. 1-(2-Naphthyl)-3-methyl-3-buten-1-ol (4eh). TLC:
Rf 0.34 (CH2Cl2, stained purple with anisaldehyde). [a]D22
+56.7 (c 0.51, CHCl3) for 62% ee. IR (KBr): 3416,
1
1649 cmꢀ1. H NMR (CDCl3): d 1.84 (s, 3H), 2.22 (d, 1H,
4.1.26. Synthesis of 1-cyclohexenyloxytrichlorosilane
(5a).6b Silicon tetrachloride (22.5 mL, 196 mmol, 2.0 equiv)
was added quickly to a suspension of Hg(OAc)2 (312 mg,
0.98 mmol, 1 mol %) in CH2Cl2 (100 mL). 1-Cyclohexe-
neyltrimethylsilane (16.7 g, 98 mmol, 1.0 equiv) was then
added to the solution dropwise over 15 min and the resulting
solution was stirred at rt for 12 h. The mixture was concen-
trated under reduced pressure (70 mmHg) and the resulting
oil was distilled to give the trichlorosilyl enol ether 5a
(11.9 g, 54%) as a colorless oil. Bp: 80.0–81.0 ꢁC/
J¼1.8 Hz), 2.52 (d, 2H, J¼7.3 Hz), 4.90 (s, 1H), 4.96 (s,
1H), 5.00 (dt, 1H, J¼1.8, 7.3 Hz), 7.46–7.53 (m, 3H),
7.83–7.85 (m, 4H). 13C NMR (CDCl3): d 22.3, 48.2, 71.5,
114.1, 124.0, 124.3, 125.7, 126.0, 127.6, 127.9, 128.1,
132.9, 133.3, 141.4, 142.3. HPLC: tR 28.7 min (minor,
(ꢀ)-isomer), 31.5 min (major, (+)-isomer) (Daicel Chiralcel
OD-H, flow rate: 0.5 mL/min, hex/IPA¼19/1). MS (EI): m/z
129, 157, 212 (M+). HRMS: calcd for C15H16O 212.1201,
found 212.1194.
1
20 mmHg. H NMR (C6D6): d 1.96–1.21 (m, 2H), 1.26–
1.35 (m, 2H), 1.70–1.73 (m, 2H), 1.90–1.97 (m, 2H), 5.21
4.1.22. 1-(2,4,6-Trimethylphenyl)-3-methyl-3-buten-1-ol
(4ei). TLC: Rf 0.38 (CH2Cl2, stained purple with anisalde-
(t, 1H, J¼3.9 Hz).
hyde). [a]2D2 ꢀ1.7 (c 0.81, CHCl3) for 5% ee. H NMR
1
(CDCl3): d 1.84 (s, 3H), 1.87 (d, 1H, J¼2.1 Hz), 2.24 (s,
3H), 2.28 (m,1H), 2.42 (s, 6H), 2.71 (dd, 1H, J¼10.5,
13.8 Hz), 4.92 (m, 2H), 5.26 (m, 1H), 6.82 (s, 2H), HPLC:
tR 11.8 min (minor, (+)-isomer), 13.3 min (major, (ꢀ)-iso-
mer) (Daicel Chiralcel OD-H, flow rate: 0.5 mL/min, hex/
IPA¼19/1).
4.1.27. 1-Cyclopentenyloxytrichlorosilane (5b).6c Bp:
1
60.0–61.0 ꢁC/8 mmHg. H NMR (C6D6): d 1.51 (m, 2H),
1.97 (m, 2H), 2.15 (m, 2H), 4.95 (t, 1H, J¼2.4 Hz).
4.1.28. [(1-(1,1-Dimethylethyl)ethenyl)oxy]trichloro-
silane (5e).6d Bp: 63.0–65.0 ꢁC/40 mmHg. 1H NMR (C6D6):

S. Kotani et al. / Tetrahedron 63 (2007) 3122–3132
3129
1
d 0.95 (s, 9H), 4.24 (d, 1H, J¼2.7 Hz), 4.46 (d, 1H,
J¼2.7 Hz).
(hex/EtOAc¼3/1, stained red with anisaldehyde). H NMR
(CDCl3): d 1.29–1.87 (m, 5H), 2.01–2.08 (m, 1H), 2.32–
2.63 (m, 2H), 2.60 (m, 1H), 3.00 (br s, 1H), 5.39 (s,
1H), 7.29–7.37 (m, 5H). HPLC: tR 8.5 min (syn-minor,
(2S,10S)-isomer), 9.7 min (syn-major, (2R,10R)-isomer),
10.9 min (anti-major, (2S,10R)-isomer), 15.9 min (anti-minor,
(2R,10S)-isomer) (Daicel Chiralcel OD-H, flow rate: 1.0 mL/
min, hex/IPA¼19/1).
4.1.29. Synthesis of (E)-1-trichlorosilyloxy-1-heptene
((E)-7).23 A solution of the (E)-1-trimethylsilyloxy-1-hep-
tene (5.5 g, 29.7 mmol, 1.0 equiv) in dry ether (75 mL)
was added to a cold solution of methyllithium in ether
(1.14 M, 39.7 mL, 44.6 mmol, 1.5 equiv) under argon atmo-
sphere. After being stirred for 0.5 h at 0 ꢁC, the reaction
mixture was allowed to reach rt and was stirred for 3 h.
The resulting solution was slowly added via cannula to
a cold (ꢀ78 ꢁC) solution of silicon tetrachloride (34.2 mL,
297 mmol, 10 equiv) in ether (70 mL). The reaction mixture
was slowly warmed to rt. Solvent and volatile materials
were removed under vacuum. The residue was distilled to
give trichlorosilyl enol ether (E)-7 (3.6 g, 49%, E/ZP10/1)
as a clear, colorless oil. Bp: 71.5–75.0 ꢁC/8 mmHg. 1H
NMR (C6D6): d 0.83 (t, 3H, J¼7.1 Hz), 1.08–1.20 (m,
6H), 1.56–1.64 (m, 2H), 5.25 (m, 1H), 5.98 (d, 1H,
J¼1.3 Hz).
4.1.34. 2-(Hydroxyphenylmethyl)cyclopentanone (6ba).33
anti-Isomer—TLC: Rf 0.33 (hex/EtOAc¼3/1, stained red
with anisaldehyde). [a]2D3 ꢀ86.7 (c 1.15, CHCl3) for
1
68% ee. H NMR (CDCl3): d 1.43–1.57 (m, 1H), 1.64–
1.81 (m, 2H), 1.92–2.01 (m, 1H), 2.17–2.31 (m, 1H),
2.39–2.49 (m, 2H), 4.56 (br s, 1H), 4.70 (d, 1H,
J¼9.2 Hz), 7.26–7.35 (m, 5H). syn-Isomer—TLC: Rf
1
0.36 (hex/EtOAc¼3/1, stained red with anisaldehyde). H
NMR (CDCl3): d 1.63–1.86 (m, 2H), 1.95–2.06 (m,
2H), 2.09–2.19 (m, 1H), 2.32–2.37 (m, 1H), 2.45–2.49 (m,
1H), 3.19 (s, 1H), 5.29 (br s, 1H), 7.24–7.29 (m, 5H).
HPLC: tR 14.6 min (syn-minor, (2S,10S)-isomer), 17.2 min
(syn-major, (2R,10R)-isomer), 20.4 min (anti-major,
(2S,10R)-isomer), 23.1 min (anti-minor, (2R,10S)-isomer)
(Daicel Chiralcel OD-H, flow rate: 0.5 mL/min, hex/
IPA¼9/1) (lit.33: tR 8.8 min (syn-minor, (2S,10S)-isomer),
10.6 min (syn-major, (2R,10R)-isomer), 12.9 min (anti-
major, (2S,10R)-isomer), 15.3 min (anti-minor, (2R,10S)-
isomer) (Daicel Chiralcel OD-H, flow rate: 1.0 mL/min,
hex/IPA¼9/1).
4.1.30. (E)-1-Ethyl-1-propenyloxytrichlorosilane (5c).32
1
Bp: 67.5–70.5 ꢁC/50 mmHg. H NMR (CDCl3): d 1.08 (t,
3H, J¼7.3 Hz), 1.59 (d, 3H, J¼6.8 Hz), 2.21 (q, 2H,
J¼7.3 Hz), 5.05 (q, 1H, J¼6.8 Hz).
4.1.31. (Z)-1-Phenyl-1-propenyloxytrichlorosilane (5d).6b
1
Bp: 103.0–105.5 ꢁC/7 mmHg. H NMR (C6D6): d 1.06 (d,
3H, J¼6.8 Hz), 5.23 (q, 1H, J¼6.8 Hz), 7.19–7.40 (m, 5H).
4.1.32. (Z)-1-Trichlorosilyloxy-1-heptene ((Z)-7).23 Bp:
74.0–77.0 ꢁC/8 mmHg. 1H NMR (C6D6): d 0.85 (t, 3H,
J¼7.1 Hz), 1.12–1.42 (m, 6H), 2.09–2.18 (m, 2H), 4.86
(dt, 1H, J¼4.8, 7.4 Hz), 6.25 (m, 1H).
4.1.35. 1-Hydroxy-2-methyl-1-phenyl-3-pentanone
(6ca).33 Diastereomeric mixture (syn/anti¼15/85)—TLC:
Rf 0.37 (hex/EtOAc¼3/1, stained gray with phosphomolyb-
dic acid/EtOH). 1H NMR (CDCl3): d 0.89 (d, 2.55H,
J¼7.2 Hz), 0.96 (t, 0.45H, J¼7.2 Hz), 1.03 (t, 2.55H,
J¼7.1 Hz), 1.08 (d, 0.45H, J¼7.2 Hz), 2.26–2.61 (m, 2H),
2.74–2.85 (m, 1H), 2.93 (m, 0.85H), 3.11 (d, 0.15H,
J¼2.4 Hz), 4.76 (d, 0.85H, J¼8.1 Hz), 5.07 (d, 0.15H,
J¼3.9 Hz), 7.27–7.39 (m, 5H). HPLC: tR 15.7 min (syn-
major), 18.4 min (anti-major), 20.9 min (syn-minor), 32.3 min
(anti-minor) (Daicel Chiralpak AS-H, flow rate: 1.0 mL/
min, hex/IPA¼30/1).
4.1.33. Representative procedure of asymmetric aldol
reaction catalyzed by (S)-1. 2-(Hydroxyphenylmethyl)-
cyclohexanone (6aa).16h A solution of benzaldehyde (3a) in
CH2Cl2 (0.378 M, 1.0 mL, 0.378 mmol, 1.0 equiv) and a
solution of diisopropylethylamine in CH2Cl2 (0.904 M,
0.5 mL, 0.452 mmol, 1.2 equiv) were added to a solution of
the (S)-1 (24.6 mg, 0.038 mmol, 10 mol %) in CH2Cl2
(2 mL) at ꢀ78 ꢁC. A solution of 1-cyclohexenyloxytrichloro-
silane (5a) in CH2Cl2 (0.904 M, 0.5 mL, 0.452 mmol,
1.2 equiv) was slowly added to the mixture. After being stirred
for 0.25 h, the reaction mixture was quickly poured into cold
(0 ꢁC) satd NaHCO3 (10 mL) and the slurry was stirred for
1 h. The mixture was filtered through Celite, and the filtrate
was extracted with CH2Cl2 (50 mL). The combined organic
layers were washed with brine (2ꢂ30 mL), dried over
Na2SO4, filtered, and concentrated. The crude product was
purified by column chromatography (hex/EtOAc¼6/1, SiO2,
10 g) to give the product as a diastereomeric mixture
(72.5 mg, 94%, syn/anti¼1/14, 71% ee (syn), 87% ee
(anti)). (S)-1 (24.1 mg, 97%) was quantitatively recovered
by further elution with 3% EtOH in CH2Cl2 without any
loss of optical purity. anti-Isomer—TLC: Rf 0.28 (hex/
EtOAc¼3/1, stained red with anisaldehyde). [a]2D4 +22.1 (c
1.00, CHCl3) for 87% ee (lit.16h: [a]D29 +20.1 (c 1.0, CHCl3)
for (2S,10R)-isomer of 93% ee). 1H NMR (CDCl3):
d 1.26–1.37 (m, 1H), 1.52–1.71 (m, 4H), 2.05–2.12 (m,
1H), 2.35–2.72 (m, 3H), 3.95 (br s, 1H), 4.78 (d, 1H,
J¼8.6 Hz), 7.29–7.35 (m, 5H). syn-Isomer—TLC: Rf 0.38
4.1.36. 1,3-Diphenyl-3-hydroxy-2-methylpropan-1-one
(6da).6b Diastereomeric mixture (syn/anti¼81/19)—TLC:
Rf 0.47 (hex/EtOAc¼3/1, stained purple with anisaldehyde).
1H NMR (CDCl3): d 1.07 (d, 0.6H, J¼7.2 Hz), 1.20 (d, 2.4H,
J¼7.2 Hz), 2.99 (m, 0.2H), 3.66–3.74 (m, 1.6H), 3.84 (m,
0.2H), 5.00 (m, 0.2H), 5.25 (m, 0.8H). 7.25–7.61 (m, 8H),
7.92–7.99 (m, 2H). HPLC: tR 9.5 min (syn-major),
11.1 min (syn-minor), 13.0 min (anti-minor), 15.2 min
(anti-major) (Daicel Chiralcel OD-H, flow rate: 1.0 mL/
min, hex/IPA¼19/1).
4.1.37. 1-Hydroxy-4,4-dimethyl-1-phenyl-3-pentanone
(6ea).6d TLC: Rf 0.44 (hex/EtOAc¼3/1, stained blue with
anisaldehyde). [a]D22 +56.2 (c 1.02, CHCl3) for 96% ee
(lit.6d: [a]D24 ꢀ33.9 (c 2.27, CHCl3) for (S)-isomer of 52%
ee). 1H NMR (CDCl3): d 1.13 (s, 9H), 2.88 (d, 2H,
J¼6.0 Hz), 3.56 (br s, 1H), 5.14 (t, 1H, J¼6.0 Hz), 7.25–
7.38 (m, 5H). HPLC: tR 10.7 min (major, (R)-isomer),
12.6 min (minor, (S)-isomer) (Daicel Chiralpak AD-H,
flow rate: 1.0 mL/min, hex/IPA¼19/1).

3130
S. Kotani et al. / Tetrahedron 63 (2007) 3122–3132
1
4.1.38. 2-[(E)-1-Hydroxy-3-phenyl-2-propenyl]cyclohex-
anone (6ab).16h anti-Isomer—TLC: Rf 0.19 (hex/EtOAc¼
3/1, stained violet with anisaldehyde). [a]2D3 ꢀ17.6 (c 0.72,
CHCl3) for 78% ee (lit.16h: [a]D29 ꢀ18.3 (c 1.0, CHCl3) for
CHCl3) for 77% ee. H NMR (CDCl3): d 1.26–1.81 (m,
5H), 2.05–2.11 (m, 1H), 2.34–2.64 (m, 3H), 3.80 (s, 3H),
3.92 (br s, 1H), 4.74 (d, 1H, J¼8.8 Hz), 6.86 (d, 2H,
J¼8.7 Hz), 7.24 (d, 2H, J¼8.7 Hz). syn-Isomer—TLC: Rf
0.32 (hex/EtOAc¼3/1, stained purple with anisaldehyde).
[a]2D6 +90.1 (c 0.52, CHCl3) for 87% ee. 1H NMR
(CDCl3): d 1.49–1.88 (m, 5H), 2.10 (m, 1H), 2.35–2.44
(m, 2H), 2.53–2.60 (m, 1H), 2.98 (br s, 1H), 3.80 (s, 3H),
5.32 (s, 1H), 6.87 (d, 2H, J¼8.8 Hz), 7.22 (d, 2H,
J¼8.8 Hz). HPLC: tR 41.6 min (syn-major), 48.6 min (syn-
minor), 77.0 min (anti-minor), 79.8 (anti-major) (Daicel
Chiralpak AD-H, flow rate: 0.5 mL/min, hex/IPA¼19/1).
1
(2S,10R)-isomer of 89% ee). H NMR (CDCl3): d 1.28–
1.91 (m, 4H), 2.08–2.14 (m, 2H), 2.34–2.52 (m, 3H), 3.67
(br s, 1H), 4.43 (t, 1H, J¼7.5 Hz), 6.19 (dd, 1H, J¼7.5, 15.9
Hz), 6.61 (d, 1H, J¼15.9 Hz), 7.23–7.40, (m, 5H). syn-
Isomer—TLC: Rf 0.24 (hex/EtOAc¼3/1, stained violet with
anisaldehyde). 1H NMR (CDCl3): d 1.25–1.93 (m, 5H), 2.06–
2.10 (m, 1H), 2.35–2.59 (m, 3H), 2.94 (br s, 1H), 4.77 (m,
1H), 6.21 (dd, 1H, J¼5.7, 15.6 Hz), 6.63 (dd, 1H, J¼1.1,
15.6 Hz), 7.20–7.39 (m, 5H). HPLC: tR 36.8 min (syn-
major), 45.0 min (syn-minor), 49.9 min (anti-major, (2S,10R)-
isomer), 59.6 min (anti-minor, (2R,10S)-isomer) (Daicel
Chiralpak AD-H, flow rate: 1.0 mL/min, hex/IPA¼40/1).
4.1.43. 2-[Hydroxy(p-tolyl)methyl]cyclohexanone (6am).
anti-Isomer—TLC: Rf 0.35 (hex/EtOAc¼2/1, stained violet
with anisaldehyde). [a]D23 +17.0 (c 0.41, CHCl3) for 83% ee.
Mp: 62.5–64.0 ꢁC. IR (CHCl3): 1694 cmꢀ1 1H NMR
.
4.1.39. 2-(1-Hydroxy-3-phenylpropyl)cyclohexanone
(6ac).16h Diastereomeric mixture (syn/anti¼15/85)—TLC:
Rf 0.33 (hex/EtOAc¼3/1, stained purple with anisaldehyde).
1H NMR (CDCl3): d 1.49–1.92 (m, 6H), 2.06–2.12 (m, 2H),
2.25–2.42 (m, 3H), 2.64–2.93 (m, 2.15H), 3.55 (br s, 0.85H),
3.72–3.78 (0.85H), 4.05–4.13 (m, 0.15H), 7.14–7.34 (m,
5H). HPLC: tR 59.9 min (anti-major), 64.5 min (syn-major),
71.0 min (anti-minor), 81.7 min (syn-minor) (Daicel Chiral-
cel OD-H and Chiralpak AD, flow rate: 0.5 mL/min, hex/
IPA¼30/1).
(CDCl3): d 1.28–1.37 (m, 1H), 1.54–1.82 (m, 4H), 2.07–
2.13 (m, 1H), 2.32–2.52 (m, 2H), 2.36 (s, 3H), 2.59–2.67
(m, 1H), 3.91 (br s, 1H), 4.78 (dd, 1H, J¼2.0, 8.6 Hz),
7.17 (d, 2H, J¼7.9 Hz), 7.23 (d, 2H, J¼7.9 Hz). 13C NMR
(CDCl3): d 21.2, 24.7, 27.8, 30.9, 42.7, 57.4, 74.5, 126.9,
129.0, 137.5, 138.0, 215.6. MS (EI): m/z 98, 119, 121, 232
(M+). HRMS: calcd for C14H18O2 218.1307, found
218.1306. syn-Isomer—TLC: Rf 0.46 (hex/EtOAc¼2/1,
stained violet with anisaldehyde). [a]2D5 +47.8 (c 0.11,
CHCl3) for 70% ee. Mp: 99.0–100.5 ꢁC. IR (CHCl3):
1691 cmꢀ1. 1H NMR (CDCl3): d 1.21–1.38 (m, 1H), 1.41–
1.80 (m, 4H), 1.98–2.04 (m, 1H), 2.31 (s, 3H), 2.24–2.54
(m, 3H), 2.89 (br s, 1H), 5.28 (s, 1H), 7.06 (d, 2H,
J¼7.8 Hz), 7.11 (d, 2H, J¼7.8 Hz). 13C NMR (CDCl3):
d 21.1, 24.9, 26.1, 28.0, 42.6, 57.2, 70.6, 125.7, 128.8,
136.5, 138.5, 214.8. MS (EI): m/z 98, 121, 232 (M+).
HRMS: calcd for C14H18O2 218.1307, found 218.1313.
HPLC: tR 21.6 min (syn-minor), 24.0 min (syn-major),
25.4 min (anti-major), 31.5 min (anti-minor) (Daicel Chiral-
pak AS-H, flow rate: 0.5 mL/min, hex/IPA¼9/1).
4.1.40. 2-[(1-Naphthyl)hydroxymethyl]cyclohexanone
(6ag).16h anti-Isomer—TLC: Rf 0.25 (hex/EtOAc¼3/1,
stained red with anisaldehyde). [a]2D3 +5.7 (c 1.02, CHCl3)
for 51% ee (lit.16h: [a]D28 +7.1 (c 1.0, CHCl3) for (2S,10R)-iso-
1
mer of 90% ee). H NMR (CDCl3): d 1.24–1.75 (m, 5H),
2.04–2.19 (m, 1H), 2.35–2.54 (m, 2H), 2.95–3.05 (m,
1H), 4.13 (br s, 1H), 5.58 (d, 1H, J¼8.7 Hz), 7.45–7.58
(m, 4H), 7.78–7.89 (m, 2H), 8.25 (d, 1H, J¼6.6 Hz). syn-
Isomer—TLC: Rf 0.34 (hex/EtOAc¼3/1, stained red with
anisaldehyde). 1H NMR (CDCl3): d 1.26–1.89 (m, 5H),
2.03–2.09 (m, 1H), 2.35–2.55 (m, 2H), 2.74–2.80 (m, 1H),
3.10 (br s, 1H), 6.25 (br s, 1H), 7.47–7.53 (m, 3H), 7.70
(d, 1H, J¼7.2 Hz), 7.77–7.87 (m, 2H), 7.87–7.91 (m, 1H).
HPLC: tR 29.7 min (syn-minor), 41.3 min (syn-major),
71.9 min (anti-minor, (2R,10S)-isomer), 85.6 min (anti-
major, (2S,10R)-isomer) (Daicel Chiralcel OD-H, flow rate:
0.5 mL/min, hex/IPA¼40/1).
4.1.44. 2-[4-Bromophenyl(hydroxy)methyl]cyclohexa-
none (6an).16h anti-Isomer—TLC: Rf 0.30 (hex/EtOAc¼
2/1, stained red with anisaldehyde). [a]2D9 +21.0 (c 1.02,
CHCl3) for 89% ee (lit.16h: [a]D +20.5 (c 1.7, CHCl3) for
1
(2S,10R)-isomer of >99% ee.). H NMR (CDCl3): d 1.25–
1.36 (m, 1H), 1.51–1.82 (m. 4H), 2.04–2.12 (m 1H), 2.29–
2.59 (m, 3H), 3.97 (d, 1H, J¼2.6 Hz), 4.74 (dd, 1H, J¼1.8,
8.6 Hz), 7.18 (d, 2H, J¼8.3 Hz), 7.47 (d, 2H, J¼8.3 Hz).
syn-Isomer: TLC: Rf 0.35 (hex/EtOAc¼2/1, stained red
with anisaldehyde). [a]2D9 +46.5 (c 0.27, CHCl3) for 60%
ee. 1H NMR (CDCl3): d 1.26–2.58 (m, 9H), 3.04 (br s, 1H),
5.34 (s, 1H), 7.17 (d, 2H, J¼8.3 Hz), 7.49 (d, 2H,
J¼8.3 Hz). HPLC: tR 10.6 min (syn-major), 12.6 min (syn-
minor), 17.0 min (anti-minor), 19.9 min (anti-major) (Daicel
Chiralpak AD-H, flow rate: 1.0 mL/min, hex/IPA¼9/1).
4.1.41. 2-[Hydroxy(mesityl)methyl]cyclohexanone (6ai).
anti-Isomer—TLC: Rf 0.41 (hex/EtOAc¼2/1, stained violet
with anisaldehyde). [a]D28 ꢀ40.8 (c 1.21, EtOH) for 74% ee.
IR (CHCl3): 1690 cmꢀ1. 1H NMR (CDCl3): d 1.20–1.25 (m,
1H), 1.53–1.76 (m, 4H), 2.04–2.11 (m, 1H), 2.24 (s, 3H),
2.40 (s, 6H), 2.33–2.52 (m, 2H), 3.02–3.07 (m, 1H), 3.55
(br s, 1H), 5.42 (d, 1H, J¼9.7 Hz), 6.81 (s, 2H). 13C NMR
(CDCl3): d 20.7, 21.0, 25.1, 27.8, 30.4, 42.6, 55.1, 69.8,
130.1, 132.9, 136.8, 136.9, 215.6. MS (EI): m/z 98, 149,
228, 246 (M+). HRMS: calcd for C16H22O2 246.1620, found
246.1608. HPLC: tR 12.9 min (syn-major), 15.0 min (syn-
minor), 17.5 min (anti-major), 20.9 min (anti-minor) (Dai-
cel Chiralpak AD-H, flow rate: 1.0 mL/min, hex/IPA¼49/1).
4.1.45. 2-{Hydroxy[(4-trifluoromethyl)phenyl]methyl}-
cyclohexanone (6ao).34 anti-Isomer—TLC: Rf 0.33 (hex/
EtOAc¼2/1, stained red with anisaldehyde). [a]2D5 +21.7 (c
0.84, CHCl3) for 93% ee. IR (CHCl3): 1691 cmꢀ1 1H
.
NMR (CDCl3): d 1.25–1.83 (m, 5H), 2.07–2.12 (m, 1H),
2.30–2.64 (m, 3H), 4.05 (d, 1H, J¼2.6 Hz), 4.85 (dd, 1H,
J¼2.6, 8.4 Hz), 7.44 (d, 2H, J¼7.9 Hz), 7.60 (d, 2H,
J¼7.9 Hz). 13C NMR (CDCl3): d 24.7, 27.7, 30.7, 42.6,
57.2, 74.2, 124.1 (q, J¼272 Hz), 125.2 (q, J¼4 Hz), 127.3,
4.1.42. 2-[Hydroxy(4-methoxyphenyl)methyl]cyclohexa-
none (6ae).16h anti-Isomer—TLC: Rf 0.19 (hex/EtOAc¼
3/1, stained purple with anisaldehyde). [a]2D6 +15.2 (c 1.23,

S. Kotani et al. / Tetrahedron 63 (2007) 3122–3132
3131
129.9 (q, J¼32.0 Hz), 145.0, 215.0. MS (EI): m/z 98, 127,
145, 254, 272 (M+). HRMS: calcd for C14H15O2F3
272.1024, found 272.1003. syn-Isomer—TLC: Rf 0.40
(hex/EtOAc¼2/1, stained red with anisaldehyde). [a]D23
Sports and Culture of Japan, the Novartis Foundation
(Japan) for the Promotion of Science and the SUNBOR
GRANT.
+44.0 (c 0.26, CHCl3) for 62% ee. IR (CHCl3): 1694 cmꢀ1
.
1H NMR (CDCl3): d 1.49–1.84 (m, 5H), 2.01–2.11 (m,
1H), 2.38–2.58 (m, 3H), 3.10 (d, 1H, J¼3.1 Hz), 5.44 (s,
1H), 7.42 (d, 2H, J¼8.5 Hz), 7.60 (d, 2H, J¼8.5 Hz). 13C
NMR (CDCl3): d 24.8, 24.9, 27.9, 42.7, 57.0, 70.2, 124.1
(q, J¼271 Hz), 125.2 (q, J¼4 Hz), 126.0, 129.2 (q,
J¼32 Hz), 145.0, 214.2. MS (EI): m/z 98, 145, 254, 272
(M+). HRMS: calcd for C14H15O2F3 272.1024, found
272.1018. HPLC: tR 8.7 min (syn-major), 10.0 min (syn-
major), 12.8 min (anti-minor), 15.7 min (anti-major) (Daicel
Chiralpak AD-H, flow rate: 1.0 mL/min, hex/IPA¼9/1).
References and notes
1. (a) List, B. Synlett 2001, 1675; (b) O’Brien, P. J. Chem. Soc.,
Perkin Trans. 1 1998, 1439; (c) Berrisford, D. J.; Horkan, C.;
Isherwood, M. L. Organic Synthetic Highlights III; Mulzer,
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3. Other types of Lewis base-catalyzed reactions: France, S.;
Guerin, D. J.; Miller, S. J.; Lectka, T. Chem. Rev. 2003, 103,
2985.
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4.1.46. 2-[Hydroxy(4-nitrophenyl)methyl]cyclohexanone
(6ap).35 anti-Isomer—TLC: Rf 0.13 (hex/EtOAc¼3/1,
stained red with anisaldehyde). [a]2D6 +10.6 (c 0.90,
CHCl3) for 96% ee (lit.35: [a]D +12.8 (c 1.1, CHCl3) for
1
(2S,10R)-isomer of 99% ee). H NMR (CDCl3): d 1.34–
1.84 (m, 5H), 2.07–2.13 (m, 1H), 2.24–2.68 (m, 3H), 4.08
(br s, 1H), 4.89 (dd, 1H, J¼2.2, 8.3 Hz), 7.49 (d, 2H,
J¼8.6 Hz), 8.20 (d, 2H, J¼8.6 Hz). syn-Isomer—TLC: Rf
5. (a) Iseki, K.; Kuroki, Y.; Takahashi, M.; Kobayashi, Y.
Tetrahedron Lett. 1996, 37, 5149; (b) Iseki, K.; Kuroki, Y.;
Takahashi, M.; Kishimoto, S.; Kobayashi, Y. Tetrahedron
1997, 53, 3513.
1
0.18 (hex/EtOAc¼3/1, stained red with anisaldehyde). H
NMR (CDCl3): d 1.28–1.89 (m, 5H), 2.08–2.16 (m, 1H),
2.43–2.69 (m, 3H), 3.17 (m, 1H), 5.49 (d, 1H, J¼0.4 Hz),
7.48 (d, 2H, J¼8.8 Hz), 8.21 (d, 2H, J¼8.8 Hz). HPLC: tR
11.8 min (syn-major), 12.3 min (syn-minor), 13.0 min (anti-
minor), 17.0 min (anti-major) (Daicel Chiralpak AD-H,
flow rate: 1.0 mL/min, hex/IPA¼4/1).
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4.1.47. Synthesis of 3,3-dimethoxy-2-pentyl-1-phenyl-1-
propanol (8).23 A solution of benzaldehyde (3a) in
CH2Cl2 (0.378 M, 1.0 mL, 0.378 mmol, 1.0 equiv) and a
solution of diisopropylethylamine in CH2Cl2 (0.904 M,
0.5 mL, 0.452 mmol, 1.2 equiv) were added to a solution
of the (S)-1 (24.6 mg, 0.038 mmol, 10 mol %) in CH2Cl2
(2 mL) at ꢀ78 ꢁC. A solution of (E)-1-trichlorosilyloxy-
1-heptene in CH2Cl2 (0.904 M, 0.5 mL, 0.452 mmol,
1.2 equiv) was slowly added to the mixture. After being
stirred for 1 h, MeOH (5 mL) was added and the reaction
mixture was stirred for 45 min. The reaction mixture was
allowed to warm to rt, then poured into cold (0 ꢁC) satd
NaHCO3 (5 mL) and was stirred for 2 h. The precipitate
was filtered through Celite and washed with CH2Cl2. The
organic phase was separated and the aqueous phase was
extracted with CH2Cl2 (3ꢂ10 mL). The combined organic
phases were washed with brine, dried over Na2SO4, and con-
centrated. The crude material was purified by column chro-
matography (SiO2, 8 g, hex/EtOAc¼8/1) to give the acetal
as a diastereomeric mixture. TLC: Rf 0.47 (hex/EtOAc¼
3/1, stained red with anisaldehyde). 1H NMR (CDCl3):
d 5.16 (syn-isomer, t, 1H, J¼2.6 Hz), 4.78 (anti-isomer, m,
1H). HPLC: tR 11.4 min (syn-minor), 13.7 min (anti-minor),
17.4 min (anti-major), 23.3 min (syn-major) (Daicel Chiral-
cel OD-H, flow rate: 1.0 mL/min, hex/IPA¼100/1).
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Kocovsky, P. Org. Lett. 2002, 4, 1047; (d) Shimada, T.; Kina,
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ꢁ
ꢀ
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of its conjugate acid is ꢀ2.1. (a) Smyth, C. P. J. Am. Chem. Soc.
Acknowledgements
This work was partly supported by a Grant-in-Aid for Scien-
tific Research from the Ministry of Education, Science,

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