Synthesis of novel silyl enol ethers from chlorodimethyl(naphthylphenylmethyl)silanes having a chiral centre and a ketone and their chirality transfer effects in crossed-aldol reactions

Article abstract of DOI:10.3184/030823409X393709

X-ray crystallography was used to determine the stereo structure of a novel chiral organosilicon compound, (2R)-(-)-(1-cyclohexenyloxy)dimethyl(1- naphthylphenylmethyl) silane, which has a chiral centre next to the silicon atom. The crossed-aldol reaction

Full text of DOI:10.3184/030823409X393709

46 RESEARCH PAPER
JANUARY, 46–51
JOURNAL OF CHEMICAL RESEARCH 2009
Synthesis of novel silyl enol ethers from chlorodimethyl(naphthyl-
phenylmethyl)silanes having a chiral centre and a ketone and their
chirality transfer effects in crossed-aldol reactions
Kenichi Miyakawa, Takeo Konakahara*, Norio Sakai, Kozo Kozawa, Takahiro Gunji and
Yukinori Nagao*
Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science (RIKADAI), Noda,
Chiba 278-8510, Japan
X-ray crystallography was used to determine the stereo structure of a novel chiral organosilicon compound, (2R)-
(–)-(1-cyclohexenyloxy)dimethyl(1-naphthylphenylmethyl) silane, which has a chiral centre next to the silicon atom.
The crossed-aldol reaction of the silyl enol ether with benzaldehyde gave the corresponding aldol products with
high chirality transfer.
Keywords: chirality, asymmetric synthesis, stereoselective synthesis, aldol reactions, organometallic reagents
O
OH
Previously, Hathaway and Paquette reported that the
chirality transfer reaction of the chiral allyl silane, (1S)-(–)-
allylmethyl(1-naphthyl)phenylsilane (1), with acetals showed
rather low ee values. (3.9–5.5%).1 Fry and co-workers2 also
demonstrated that the chirality transfer of alkyl aryl ketones
using (1S)-( + )-methyl(1-naphthyl)phenylsilane (2) in hydride
reduction resulted in 6.6–12.7%ee. In addition, Jung et al.3
reported that the enantioselectivity of a crossed Mukaiyama-
aldol reaction using (S)-binaphthylic cyclic silane 3 and
2-(hydroxyphenylmethyl)cyclohexanone showed relatively
low ee values (erythro: 17%, threo: 35%).4 Oestreich also
reported enhanced chiral transfer with a silane compound
4 that had a chiral centre on the Si atom (71%ee).5 Thus,
reactions, that use chiral organosilicon compounds and result
in greater asymmetric induction are highly desired.
TiCl4
CH2Cl2
0oC
Me
Me
Ph
+
PhCHO
PhCHO
Si
Ph
O
: 69%
7
5
erythro : threo = 1 : 0.4
trans, cis mixture
O
OH
*
Ph
Ph
Si
TiCl4
CH2Cl2
0oC
*
+
Ph
Me
O
: 44%
only erythro
7
6
cis mixture
Scheme 1
as shown in Scheme 2. To our knowledge, chiral transfer with
this type of a chiral organosilicon compound having high
enantioselectivity, has not previously been reported. This
paper details the results of this asymmetric synthesis.
H
Np
Me
Np Si
Ph
Si
Si
H
Me Si CH2CH CH2
Ph
Me
H
t-Bu
O
4
1
2
3
CH3
CH3
Si Cl
CH3
Si
O
*
*
7KHꢀVLJQL¿FDQWꢀUHVXOWꢀRIꢀWKHVHꢀSUHYLRXVꢀVWXGLHVꢀLVꢀWKDWꢀXVHꢀRIꢀ
an organosilicon compound, the whole molecule of which is
chiral, results in greater asymmetry than use of compounds
with a chiral centre only at the Si atom. Hence, the purpose
of the present study was to design a novel organosilicon
compound with a chiral centre next to the Si atom and
to investigate the asymmetric reaction using the novel
organosilicon compound.
Previously, we developed two novel silyl enol ethers 5 and
6, with a 2,5-dimethyl-1-phenyl-1-silacyclopentane6 unit and
a 2,5-diphenylsilacyclopent-3-ene7-11 moiety, respectively, and
examined the crossed-aldol reaction of the silyl enol ethers
with benzaldehyde (Scheme 1).12 When the reaction with silyl
ether 5 was performed, the corresponding aldol product 7 was
obtained as a mixture of erythro and threo adducts in good
yield. In contrast, the reaction using silyl enol ether 6 produced
only the erythro product 7 in moderate yield. The silane
compound 6 which contained a 2,5-diphenylsilacyclopentene
unit, showed good diastereomeric selectivity in the aldol
reaction. Unfortunately, because the starting material—silyl
enol ether 6—was not optically active, the reaction did
not show enantioselectivity. We now synthesise the novel
organosilicon compound 8 with a chiral centre next to the
silicon atom, chlorodimethyl(1-naphthylphenylmethyl)silane,
Base
CH3
Solvent
(
) 9
(-) 9
(
) 8
(-) 8
Scheme 2
,Qꢀ WKLVꢀ SDSHUꢁꢀ ZHꢀ ¿UVWꢀ GHVFULEHꢀ ERWKꢀ WKHꢀ SUHSDUDWLRQꢀ RIꢀ WKHꢀ
silane compounds and their molecular structure, as determined
by X-ray crystallography. We also describe the crossed-aldol
reactions of these chiral silyl enol ethers with benzaldehyde
in the presence of a Lewis acid, such as TiCl4, resulting in the
stereoselective production of the corresponding aldol products.
The crossed-aldol reaction using the chiral organosilicon
compound showed one of the greatest known rates of chiral
introduction into aldol products.
Results and discussion
According to the method reported in the literature,13-15 we
initially attempted to synthesise optically pure (2R)-(–)-
chlorodimethyl(1-naphthylphenylmethyl)silane ((–) 8) using
the reaction path shown in Scheme 3. The Grignard reagent
generated from 1-bromonaphthalene (10) was coupled with
benzyl chloride in the presence of Pd(PPh3)4 to produce
1-benzylnaphthalene (11) in 82% yield. The alkyllithium
* Correspondent. E-mail: konaka@rs.noda.tus.ac.jp

JOURNAL OF CHEMICAL RESEARCH 2009 47
Me Me
CO2CH3
Si
Br
Cl
12
1) Mg
2) PhCH2Cl
cat. Pd(PPh3)4
1) n-BuLi in THF
OH
2) Me2SiCl2 in hexane
imidazole
DMF
THF
82%
92%
87%
10
11
( ) 8
Me Me
Me Me
Me Me
Si
Si
Si
O
CO2CH3
O
CO2CH3
Cl
CH3COCl
ZnCl2 (cat)
Recrystallisation
Hexane/EtOAc, 9/1
87%
29%
13
14
(-) 8
Scheme 1
compound generated from naphthalene 11 with n-BuLi was
then treated with dichlorodimethylsilane to produce the
corresponding racemic chlorodimethyl(1-naphthylphenyl-
methyl)silane (( ) 8) in 92% yield. When the racemic-( )
8 was reacted with (S)-( + )-methylmandelate (12) in the
presence of imidazole in DMF at room temperature, the
expected [(1'S)-(methoxycarbonyl)phenylmethoxy]dimethy
(1-naphthylphenylmethyl)silane (13) was obtained in 87%
\LHOGꢀ ZLWKRXWꢀ SXUL¿FDWLRQꢂꢀ 7Rꢀ LVRODWHꢀ WKHꢀ GLDVWHUHRPHULFꢀ
products, we recrystallised the diastereomeric mixture 13
twice using solvent mixtures comprised of hexane and EtOAc
ꢃ¿UVWꢄꢀꢅꢆꢇꢅꢀDQGꢀVHFRQGꢄꢀꢆꢇꢅꢈꢀWRꢀDIIRUGꢀFU\VWDOOLQHꢀꢃ±ꢈꢉꢃꢊR,1'S)-
[(methoxycarbonyl)phenylmethoxy]dimethy(1-naphthylphenyl-
methyl)silane (14ꢈꢀLQꢀꢊꢆꢋꢀ\LHOGꢂꢀ7KHꢀDEVROXWHꢀFRQ¿JXUDWLRQꢀ
of 14 was unambiguously determined to be the R-form of
the diastereomer using X-ray structure analysis, as shown in
)LJꢂꢀꢊꢂꢀ7KHꢀUH¿QLQJꢀIDFWRUꢀRIꢀFU\VWDOOLQHꢀ14 was 4.6% and the
YDOXHꢀZDVꢀZHOOꢀUH¿QHGꢂꢀ)LQDOO\ꢁꢀZKHQꢀDꢀSUHYLRXVO\ꢀUHSRUWHGꢀ
method,13-15 was used to treat the silyl ether 14 with acetyl
chloride in the presence of ZnCl2, the desired chiral (2R)-(–)-
chlorodimethyl(1-naphthylphenylmethyl)silane ((–) 8) was
produced in 87% yield.
Fig. 2 Molecular structure of 14.
When the reaction of chloro(naphthylphenylmethyl)
silanes ( ) 8 and (–) 8 with cyclohexanone was examined
in the presence of a base, such as lithium diisopropylamide
(LDA) or triethylamine (Et3N), the corresponding starting
materials, silyl enol ethers ( ) 9 and (2R)-(–)-dimethyl(1-
cyclohexenyloxy)(1-naphthylphenylmethyl)silane ((–) 9),
were obtained in the yields shown in Table 1. The structure
of silyl enol ether ( ) 9 was characterised using spectral
GDWDꢁꢀ DQGꢀ VXEVHTXHQWO\ꢀ FRQ¿UPHGꢀ XVLQJꢀ ;ꢉUD\ꢀ VWUXFWXUHꢀ
DQDO\VLVꢂꢀ7KHꢀUH¿QHPHQWꢀIDFWRUꢀRIꢀFU\VWDOOLQHꢀ( ) 9 was 11.3%.
The molecular structure proved to be a pair of enantiomers,
as indicated in Fig. 3.
Next, the crossed-aldol reactions of the prepared enol ethers
( ) 9, (–) 9 and benzaldehyde were performed in the presence
of a stoichiometric amount of TiCl4 having no chirality
effect. Pure chirality transfer effects of novel organosilicon
compound having a chiral centre were checked by use
of TiCl4. All reactions proceeded cleanly to give the four
Fig. 3 Molecular structure of ( ) 9.
corresponding products in moderate yield with the formation
RIꢀ DQꢀ XQLGHQWL¿HGꢀ FRPSRXQGꢀ KDYLQJꢀ QDSKWK\Oꢁꢀ SKHQ\Oꢁꢀ
methylene ring and silylmethyl groups. For example, when
Table 1 Synthesis of silyl enol ether 9 from the chlorosilane 8a,b
Run
Chlorosilane
Base
Solv.
Temp./°C
Product
Yield/%
1a
2b
3b
( ) 8
( ) 8
(–) 8
Et3N
LDA
LDA
DMF
THF
THF
Reflux
–78
–78
( ) 9
( ) 9
(–) 9
63c
80c
70d
aMolar ratio: Chlorosilane (8): Cyclohexanone: Et3N = 1: 2: 2.
bMolar ratio: Chlorosilane (8): Cyclohexanone: LDA = 1: 1: 1.1.
cIsolated yields by crystallisation from EtOH after chromatographic purification (eluent: benzene).
dIsolated yields by chromatography (eluent: benzene).

48 JOURNAL OF CHEMICAL RESEARCH 2009
Table 2 Crossed-aldol reaction of silyl enol ether (–) 9 with benzaldehydea
Me Me
O
OH
O
OH
O
OH
O
OH
PhCHO H2O
Si
O
TiCl4
NaHCO3
CH2Cl2
(2S, 1'S)
(2R, 1'R)
(2R, 1'S)
(2S, 1'R)
(-) 9 (2'R)
(-)
erythro
(+)
(-)
threo
(+)
15
16
Run
Silyl
enol
ether
Temp./°C
Time/h
Product
Yieldd/%
drb
erc
ee/%
erc
ee/%
erythro: threo
15: 16
erythro 15
threo
(–: + )
16 (–: + )
1
2
(–) 9
(–) 9
–78
0
1
1
15 and 16
15 and 16
38
38
28: 72
31: 69
94:6
100:0
88
100
20:80
48:52
60
4
aReaction of silyl enol ether with TiCl4 at –78 or 0 °C for 1 h. Molar ratio: silyl enol ether: C6H5CHO: TiCl4 = 1:1.1:1.5.
bDiastereomer ratios were determined by 1H NMR analysis of the reaction mixtures before chromatographic separation.
cEnantiomer ratios were determined by HPLC using CSP column (eluent: hexane/i-PrOH = 19/1).
dIsolated yields by chromatography (eluent: hexane/EtOAc = 3/1).
The products were fully characterised by 1H NMR, 13C NMR and mass spectra.
the reaction was carried out with (–) 9, mixtures of the erythro
15 and threo 16 isomers were obtained in 38% yield in Table 2
(runs 1 and 2). Although the threo product was obtained prior
to the erythro product, enantiomer excess was not observed
for either the threo or erythro product. The enantiomeric
selectivity was determined by HPLC using a CSP column
after standard separation of the erythro and threo isomers.
In contrast, the reaction using silyl enol ether (–) 9 gave a
mixture of 15 and 16 in 38% yield (run 1). Neither the yield
nor the isomer ratio was improved when the similar reaction
was conducted at 0°C. The isomers were separated using silica
gel (eluent: hexane/EtOAc = 3/1). For threo isomer 16, the
enantiomer ratio (–)/( + ) is 48/52 in the reaction at 0°C. The
enantioselectivity, however, increased to 20/80 at –78°C. The
enantiomer excess of isolated 15 was 88%ee and that of 16
was 60%ee. Furthermore, when the reaction was conducted at
0°C, the enantiomer excess of 15 was dramatically enhanced,
such that only one diastereomer (–) 15 with high chiral purity
was obtained and that of 16 was 4%ee (run 2).
selectivity for asymmetric induction compared with
selectivity values previously reported for organosilicon
compounds with a chiral moiety. The most stable structure
for (–) 9 in the crystal, in which the cyclohexene and the
naphthyl ring on the silylether are located in nearly the same
plane, is shown in Fig. 3. Based on the ORTEP drawing, we
found that the 2S form of both the threo and erythro aldol
products more readily formed than the 2R form, because at
–78°C nucleophilic attack by the silyl enol ether occurred
at the hydrogen atom side, which is less sterically hindered
than the phenyl group side. To better illustrate the reason for
the superior enantiomeric selectivity, plausible transition-
states for the crossed-aldol reaction using (–) 9 are shown in
Fig. 4. The images in the left-side panel of Fig. 4 show the
transition-states for the reaction of 9, benzaldehyde and TiCl4,
and the right-side panel shows Newman drawings of the aldol
products. The transition-state I gives the erythro (–) isomer
15 by the reaction with the si-face of benzaldehyde and the
hydrogen atom side of the diasterotopic-face of the silyl enol
ether (–) 9. On the other hand, the transition state II gives the
erythro ( + ) isomer 15 by the reaction with the re-face of
benzaldehyde and the phenyl group side of the diasterotopic-
The reaction using silyl enol ether (–) 9 gave a threo-
rich isomer. As described above, the crossed-aldol reaction
with silyl enol ether (–) 9 showed the highest enantiomeric
Products
(aldol)
Transition-States
(-)-erythro 15 (+)-threo 16
O
O
H
(2S, 1'S)
(2S, 1'R)
H
OH
major
(H)
H
H
Cl4Ti
O
Ph
HO
2S
H
(Ph)
(IV)
I
Np
1'S (1'R)
Me
Me
H
Ph
(-)-erythro 15
(2S, 1'S)
(+)-threo 16
(2S, 1'R)
Si
O
H
1'R (1'S)
minor
(H)
Ph
O
O
H
Cl4Ti
O
2R
H
H
OH
H
H
(Ph)
(III)
II
OH
(-)-threo 16
(2R, 1'S)
(+)-erythro 15
(2R, 1'R)
(+)-erythro 15
(2R, 1'R)
(-)-threo 16
(2R, 1'S)
Fig. 4 Illustration of the transition-state of the crossed-aldol reaction of (–) 9.

JOURNAL OF CHEMICAL RESEARCH 2009 49
Fig. 5 Molecular structure of ( ) 15.
Fig. 6 Molecular structure of ( ) 16.
Chlorodimethyl(1-naphthylphenylmethyl)silanes ( ) 8 and (–) 8:
We have developed the general procedure for the preparation of (–) 8,
which was similar to a previously reported method,13-15 and is shown
in Scheme 3. The compound ( ) 8 was prepared using a method
described in the literature13-15ꢀZLWKꢀPLQRUꢀPRGL¿FDWLRQꢂ
face of (–) 9. Alternatively, III and IV give the desired threo
(–) or ( + ) isomers 16. The conformation of threo ( + ) 16
was the most stable structure and this aldol was obtained as
the major product. The erythro 15 and threo 16 isomers of the
aldols obtained from (–) 9 were liquid. However, crystals of
the aldols were easily obtained from the reaction of ( ) 9 and
benzaldehyde, because a pair of enantiomers of the aldols is
solid. Each the structure of crystallised 15 and 16 was directly
determined using X-ray structure analysis. The ORTEP
GUDZLQJVꢀDUHꢀVKRZQꢀLQꢀ)LJVꢀꢌꢀDQGꢀꢍꢂꢀ7KHꢀUH¿QHPHQWꢀIDFWRUVꢀ
of crystalline 15 and 16 were 7.3% and 6.6%, respectively.
7KHVHꢀYDOXHVꢀZHUHꢀZHOOꢀUH¿QHGꢂꢀ.LWDPXUDꢀDQGꢀKLVꢀFRZRUNHUꢀ
have reported crystal data of both racemic-erythro and
racemic-threo aldols.16 In the case of erythro 15, their crystal
data are almost same as ours. However, their crystal system
of threo 16 is different from ours. Although they reported the
crystal to be monoclinic, our crystal of threo 16 is seen to be
orthorhombic (see Experimental).
Benzylnaphthalene (11):13-15 To a THF solution (600 ml) containing
granular Mg was added 1-bromonaphthalene (10) (87.3 g, 432 mmol),
and the reaction was allowed to proceed for 30 min at room
temperature. The resulting Grignard reagent was added for 30 min to a
THF solution (200 ml) containing benzyl chloride (60.8 g, 480 mmol)
and palladium tetrakis(triphenylphosphine) (2.32 g, 2.00 mmol) at
room temperature, and the mixture was stirred for an additional 15 h.
The reaction was quenched by addition of water (20 ml) and 1N HCl
aq. (200 ml). The resulting organic layer was extracted with ether,
washed with 1N HCl aq. (200 ml), water (200 ml u 2) and brine
(200ml), anddriedoveranhydrousNa2SO4ꢂꢀ7KHꢀ¿OWUDWHꢀZDVꢀFRQGHQVHGꢀ
and distilled under reduced pressure (b.p. 160–175°C/0.2 mmHg)
to give 11. The distilled product was recrystallised from ethanol
at room temperature to give pure 11 in 82% yield. White solid,
m.p. 61.0–62.0°C. 1H NMR (500 MHz, CDCl3): G = 8.00–7.97
(m, 1 H, ArH), 7.86–7.83 (m, 1 H, ArH), 7.77–7.74 (m, 1 H, ArH),
7.46–7.39 (m, 3 H, ArH), 7.29–7.24 (m, 3 H, ArH), 7.20–7.16 (m,
2 H, ArH), 4.44 (s, 2 H, aliphatic CH2). 13C NMR (125 MHz, CDCl3):
G = 140.6, 136.6, 133.9, 132.1, 128.7, 128.7, 128.4, 127.3, 127.1,
126.0, 126.0, 125.5, 124.3, 39.0. MS (FAB): m/z (%) = 218 [M]+
(10), 207 (4), 147 (5), 129 (14), 128 (100), 127 (11), 73 (19), 59 (4).
Racemic-( )-chlorodimethyl(1-naphthylphenylmethyl)silane
(( ) 8):13-15 To a THF solution (80 ml) of 11 (16.4 g, 75.0 mmol), was
added dropwise 1.6 M n-butyl lithium in hexane (51.6 ml, 82.5 mmol)
for 30 min at –78°C.After heating a solution of dichlorodimethylsilane
(29.1 g, 225 mmol) in hexane (57 ml) to room temperature, the
synthesised lithium compound was added dropwise for 30 min
at –78°C; the mixture was stirred for an additional 15 h at room
temperature. The reaction mixture was evaporated and the residue
was distilled under reduced pressure (b.p. 156–170°C/0.2 mmHg)
to give racemic-( ) 8 in 92% yield. Pale white solid, m.p. 85.5–
86.2°C. 1H NMR (500 MHz, CDCl3): G = 8.09–8.06 (m, 1 H, ArH),
7.83–7.81 (m, 1 H, ArH), 7.76–7.71 (m, 2 H, ArH), 7.50–7.42 (m, 3
H, ArH), 7.33–7.30 (m, 2 H, ArH), 7.25–7.21 (m, 2 H, ArH), 7.14–
7.10 (m, 1 H, ArH), 4.55 (s, 1 H, SiCH aliphatic CH), 0.51 (s, 3H,
Si(CH3)2), 0.48 (s, 3H, Si(CH3)2). 13C NMR (125 MHz, CDCl3):
G = 140.3, 136.5, 134.5, 132.6, 128.9, 128.7, 128.4, 127.4, 127.3,
126.1, 125.7, 125.6, 125.1, 123.8, 41.7, 2.0, 1.9. 29Si NMR (99 MHz,
CDCl3): G = –22.43. MS (EI): m/z (%) = 310 [M]+ (100), 311 (35),
312 [M + 2]+ (55), 218 (98), 217 (64), 216 (83), 215 (93), 202 (100).
[(1'S)-(Methoxycarbonyl)dimethy(1-naphthylphenylmethyl)
phenylmethoxy]silane (13):13-15 To a DMF solution (50 ml) of a
mixture of ( + )-(S)-methylmandelate (12) (5.82 g, 35.0 mmol) and
imidazole (2.72 g, 40.0 mmol), was added to synthesised racemic-( )
8 (10.9 g, 32.0 mmol) at room temperature, followed by stirring for
15 h. The reaction mixture was neutralised by addition of saturated
NaHCO3 aq. (50 ml) at 0°C. Hexane/EtOAc = 1/1 was added to
the resulting organic layer. The extract was washed with saturated
NaHCO3 aq. (25 ml), water (25 ml u 2) and brine (25 ml u 2),
and dried over anhydrous Na2SO4ꢂꢀ 7KHꢀ PL[WXUHꢀ ZDVꢀ ¿OWHUHGꢀ DQGꢀ
condensed under reduced pressure to give crude 13 in 87% yield.
Pale yellow oil. 1H NMR (500 MHz, CDCl3): G = 8.09–8.05 (m, 1
H, ArH), 7.86–7.68 (m, 3 H, ArH), 7.46–7.05 (m, 13 H, ArH), 4.99
(s, 1 H [50%], OCH), 4.96 (s, 1 H [50%], OCH), 4.38 (s, 1 H [50%],
Conclusion
We developed a method for the preparation of novel racemic
silyl enol ethers, and the chiral silyl enol ether, (2R)-(–)-(1-
cyclohexenyloxy)dimethyl(1-naphthylphenylmethyl) silane,
starting from the precursor, chlorodimethyl(1-naphthylphenyl-
methyl)silane. The molecular structure of silyl enol ether ( ) 9
ZDVꢀXQDPELJXRXVO\ꢀFRQ¿UPHGꢀXVLQJꢀ;ꢉUD\ꢀVWUXFWXUHꢀDQDO\VLVꢂꢀ
Moreover, the crossed-aldol reaction of these silyl enol ethers
with benzaldehyde produced the corresponding aldols, the
stereoselectivity of which depended on the steric effect of
both the phenyl group and hydrogen atom of benzaldehyde.
The aldol reaction using (–) 9 in the presence of TiCl4,
produced threo aldols as the major product. We found that
the reaction using silyl enol ether (–) 9 gives the greatest
enantiomeric selectivity compared with selectivity values
previously reported for silyl enol ethers in similar reactions.
Experimental
General
All reactions were carried out under a nitrogen atmosphere, unless
otherwise noted. Column chromatography was performed using silica
gel (Wakogel C-200), and components were visualised using UV
light. 1H NMR (500 MHz), 13C NMR (125 MHz) and 29Si NMR (99
MHz) spectra were recorded using a JOEL EPC-500 spectrometer in
CDCl3. The stereochemistry of the isomers was assigned on the basis
of X-ray results, and the ratios of the diasteromer were determined
E\ꢀ 105ꢀ VSHFWUDꢀ SULRUꢀ WRꢀ SXUL¿FDWLRQꢂꢀ 7KHꢀ HQDQWLRVHOHFWLYLW\ꢀ ZDVꢀ
determined by HPLC analysis using a CSP column (Chiralcel OD-H,
Daicel Chemical Industries Ltd.). Commercially available TiCl4 was
distilled under a nitrogen atmosphere before use.

50 JOURNAL OF CHEMICAL RESEARCH 2009
SiCH), 4.34 (s, 1 H [50%], SiCH), 3.60 (s, 3 H [50%], CO2CH3),
3.57 (s, 3 H [50%], CO2CH3), 0.21 (s, 3 H [50%], Si(CH3)2), 0.18
(s, 3 H [50%], Si(CH3)2), 0.17 (s, 3 H [50%], Si(CH3)2), 0.15 (s, 3 H
[50%], Si(CH3)2).
141.9, 137.7, 134.4, 132.8, 128.8, 128.7, 128.1, 127.8, 126.6, 125.8,
125.2, 125.0, 124.1, 104.5, 40.5, 29.7, 23.8, 23.0, 22.2, –0.9, –1.3.
MS (FAB): m/z (%) = 373 [M + H]+ (27), 372 [M]+ (20), 275 (18),
217 (28), 215 (16), 197 (30), 155 (100), 75 (47). Anal. Calcd for
C25H28OSi: C, 80.59; H, 7.57. Found: C, 80.50; H, 7.52. Crystal data
for ( ) 9: C50H56O2Si2, M = 745.13, colourless crystal, 0.16 u 0.08 u
0.08 mm3, triclinic, space group P-1, a = 9.7708(16) Å, b = 13.425(2)
Å, c = 15.498(3) Å, D = 84.840(3)°, E = 80.970(3)°, J = 89.184(3)°,
V = 1999.5(6) Å3, Z = 4, Dc = 1.238 Mg/m3, F(000) = 800, Ac =
(–)-(2R,1'S)-[(Methoxycarbonyl)phenylmethoxy]dimethy(1-naphthyl-
phenylmethyl)silane (14):13-15 The synthesised 13 was recrystallised in
hexane/EtOAc = 95/5 to give crude 14, which was then recrystallised
in hexane/EtOAc = 90/10 to give pure 14 in 29% yield. White solid;
m.p. 112.5–113.5°C.1H NMR (500 MHz, CDCl3): G = 8.09–8.05
(m, 1 H, ArH), 7.84–7.78 (m, 2 H, ArH), 7.73–7.69 (m, 1 H, ArH),
7.47–7.38 (m, 3 H, ArH), 7.35–7.23 (m, 7 H, ArH), 7.18–7.13 (m,
2 H, ArH), 7.10–7.05 (m, 1 H, ArH), 4.99 (s, 1 H, OCH), 4.34 (s, 1 H,
SiCH), 3.62 (s, 3 H, CO2CH3), 0.21 (s, 3 H, Si(CH3)2), 0.15 (s, 3 H,
Si(CH3)2). Crystal data for 14: C28H28O3Si, M = 440.59, colourless
crystal, 0.50 u 0.15 u 0.10 mm3, monoclinic, space group P2(1),
a = 10.8990(14) Å, b = 8.3205(11) Å, c = 12.8498(17) Å, D = 90°,
E = 97.877(2)°, J = 90°, V = 1154.3(3) Å3, Z = 2, Dc = 1.268 Mg/m3,
F(000) = 468, Ac = 0.129 mm-1. Intensity data were collected on a
Smart-APEX diffractometer with graphite monochromated MoKD
radiation (O = 0.71073 Å) using the Z scan mode with 1.60°ꢀꢎꢀșꢀꢎꢀ
28.25°ꢂꢀꢏꢅꢊꢐꢂꢀ8QLTXHꢀUHÀHFWLRQVꢀZHUHꢀPHDVXUHGꢀDQGꢀUHÀHFWLRQVꢀZLWKꢀ
Iꢀ!ꢀꢊꢀıꢀꢃIꢈꢀZHUHꢀXVHGꢀLQꢀWKHꢀ)RXULHUꢀWHFKQLTXHVꢂꢀ7KHꢀ¿QDOꢀUH¿QHPHQWꢀ
converged to R = 0.0462 and wR = 0.1100.
0.130 mm-1. Intensity data were collected on
a Smart-APEX
diffractometer with graphite monochromated MoKD radiation
(O = 0.71073 Å) using the ZꢀVFDQꢀPRGHꢀZLWKꢀꢅꢂꢐꢓƒꢀꢎꢀșꢀꢎꢀꢊꢒꢂꢅꢌƒꢂꢀꢅꢑꢆꢐꢅꢂꢀ
8QLTXHꢀ UHÀHFWLRQVꢀ ZHUHꢀ PHDVXUHGꢀ DQGꢀ UHÀHFWLRQVꢀ ZLWKꢀ Iꢀ !ꢀ ꢊꢀ ıꢀ ꢃI)
ZHUHꢀ XVHGꢀ LQꢀ WKHꢀ )RXULHUꢀ WHFKQLTXHVꢂꢀ 7KHꢀ ¿QDOꢀ UH¿QHPHQWꢀ ZDVꢀ
converged to R = 0.1126 and wR = 0.3015.
(2R)-(–)-(1-Cyclohexenyloxy)dimethyl(1-naphthylphenylmethyl)
silane ((–)9): Pale yellow liquid. 1H NMR (500 MHz, CDCl3) G = 8.12–
8.09 (m, 1 H, ArH), 7.83–7.80 (m, 1 H, ArH), 7.76–7.71 (m, 2 H,
ArH), 7.48–7.40 (m, 3 H, ArH), 7.33–7.29 (m, 2 H, ArH), 7.23–7.18
(m, 2 H, ArH), 7.10–7.06 (m, 1 H, ArH), 4.79–4.76 (br, 1 H, vinyl
=CH), 4.42 (s, 1 H, aliphatic SiCH), 1.94–1.82 (m, 4 H, cyclohexane
like CH2), 1.58–1.38 (m, 4 H, cyclohexane like CH2), 0.24 (s, 3 H,
Si(CH3)2), 0.23 (s, 3H, Si(CH3)2). 13C NMR (125 MHz, CDCl3) G
= 150.3, 141.9, 137.7, 134.4, 132.8, 128.8, 128.7, 128.1, 127.8,
126.6, 125.8, 125.2, 125.0, 124.1, 104.5, 40.5, 29.7, 23.8, 23.0, 22.2,
–0.9, –1.2. MS (FAB): m/z (%) = 373 [M + H]+ (32), 372 [M]+ (26),
275 (30), 217 (43), 215 (31), 197 (68), 155 (100), 75 (78). Optical
rotation: [D]D25 = –18.8° (c = 2.0, CHCl3).
(2R)-(–)-Chlorodimethyl(1-naphthylphenylmethyl)silane ((–) 8)13-15
:
Acetyl chloride (2.98 g, 38.0 mmol) was added to the synthesised 14
(3.17 g, 7.20 mmol) to create a suspension, which was then cooled
to 0 °&ꢁꢀIROORZHGꢀE\ꢀDGGLWLRQꢀRIꢀꢑꢂꢌꢀ0ꢀ]LQFꢀFKORULGHꢀLQꢀ7+)ꢀꢃꢊꢒꢀȝOꢁꢀ
ꢅꢓꢂꢑꢀȝPROꢈꢂꢀ7KHꢀPL[WXUHꢀZDVꢀKHDWHGꢀWRꢀURRPꢀWHPSHUDWXUHꢀDQGꢀVWLUUHGꢀ
for 1 h, after which the reaction mixture became homogeneous and
was stirred for an additional 15 h. The excess acetyl chloride was
removed by distillation under reduced pressure. Hexane (1.7 ml) and
acetone (0.17 ml) were added, and the mixture was stirred for 45 min.
The solvent was removed by distillation under reduced pressure,
followed by distillation of the reaction mixture under reduced pressure
(b.p. 155–165°C/0.8 mmHg) to give (–) 8 in 87% yield. Pale yellow
oil. 1H NMR (500 MHz, CDCl3): G = 8.10–8.06 (m, 1 H, ArH), 7.84–
7.81 (m, 1 H, ArH), 7.77–7.70 (m, 2 H, ArH), 7.50–7.41 (m, 3 H,
ArH), 7.33–7.29 (m, 2 H, ArH), 7.26–7.22 (m, 2 H, ArH), 7.14–7.11
(m, 1 H, ArH), 4.55 (s, 1 H, SiCH), 0.51 (s, 3 H, Si(CH3)2), 0.48
(s, 3 H, Si(CH3)2). 13C NMR (125 MHz, CDCl3): G = 140.3, 136.5,
134.5, 132.6, 128.9, 128.7, 128.4, 127.4, 127.3, 126.1, 125.7, 125.6,
125.1, 123.8, 41.7, 2.0, 1.9. 29Si NMR (99 MHz, CDCl3): G = –22.43.
MS (EI): m/z (%) = 310 [M]+ (100), 311 (35), 312 [M + 2]+ (55), 218
(98), 215 (95), 216 (85), 217 (65), 202 (100).
Reaction of (1-cyclohexenyloxy)dimethyl(1-naphthylphenylmethyl)
silane with benzaldehyde in the presence of titanium tetrachloride
2-(hydroxyphenylmethyl)cyclohexanone (15, 16): To
a CH2Cl2
solution (15 ml) containing either dimethyl(1-cyclohexenyoxy)
(1-naphthylphenylmethyl)silane ( ) 9 or (–) 9 (745 mg, 2.00 mmol)
was added benzaldehyde (265 mg, 2.50 mmol) in dry methylene
chloride (5 ml) at 0°C or –78°C. TiCl4 (569 mg, 3.00 mmol) in
dry methylene chloride (5 ml) was added to the reaction mixture at
the same temperature and the reaction mixture was stirred for 1 h.
After hydrolysis and neutralisation by addition of aqueous NaHCO3
at either 0°C or –78°C, the resulting organic layer was extracted
with ether. The extract was then washed with water and dried over
anhydrous Na2SO4. The mixture was condensed under reduced
SUHVVXUHꢁꢀ DQGꢀ WKHꢀ UHVLGXHꢀ ZDVꢀ SXUL¿HGꢀ XVLQJꢀ VLOLFDꢀ JHOꢀ FROXPQꢀ
chromatography (hexane/EtOAc = 3/1) to afford the erythro and threo
aldol compounds, 15 and 16, respectively. The erythro (2R*,1'R*):
threo (2R*,1'S*) ratio was determined by 1H NMR analysis.
The enantio selectivities of the erythro and threo isomers were
determined using HPLC equipped with a CSP column; eluent, hexane/
iꢉ3U2+ꢀ ꢀꢅꢆꢇꢅꢔꢀÀRZꢀUDWHꢀ ꢀꢅꢂꢑꢀPOꢇPLQꢔꢀDQGꢀ89ꢀGHWHFWLRQꢀO = 265 nm.
The retention times for the isomers were determined previously to
be: t(–)-erythro = 10.67 min (2S,1'S), t(+)-erythro = 12.37 min (2R,1'R), t(+)-
threo = 14.87 min (2S,1'R), t(–)-threo = 20.27 min (2R,1'S).17-18
Reaction of 1-chlorosilanes with cyclohexanone using triethylamine
(1-cyclohexenyloxy)dimethyl(1-naphthylphenylmethyl)silane
(9):
ADMFsolution(2ml)of( )8(4.13g, 13.3mmol)wasaddeddropwise
to a DMF solution (2 ml) of triethylamine (2.69 g, 26.6 mmol),
and the reaction mixture was stirred. A DMF solution (2 ml) of
cyclohexanone (2.61 g, 26.6 mmol) was added to the former
VROXWLRQꢁꢀDQGꢀWKHꢀUHDFWLRQꢀPL[WXUHꢀZDVꢀVWLUUHGꢀXQGHUꢀUHÀX[ꢀIRUꢀꢍꢀKꢂꢀ
The mixture was cooled, and hexane was added to the solution.
7KHꢀSUHFLSLWDWHꢀZDVꢀUHPRYHGꢀE\ꢀ¿OWUDWLRQꢀDQGꢀSXUL¿HGꢀE\ꢀVLOLFDꢀJHOꢀ
column chromatography (benzene) to afford the corresponding silyl
enol ether ( ) 9 in 63.3% yield.
erythro-2-(Hydroxyphenylmethyl)cyclohexanone (15): White solid;
m.p. 102.5–103.5°C. UV (hexane/i-PrOH = 19/1): Omax = 265.5 nm.
1H NMR (500 MHz, CDCl3): G = 7.36–7.23 (m, 5 H, ArH), 5.41–
5.39 (br, 1 H, methine O–CH), 3.01 (d, 1 H, OH), 2.63–2.58 (m,
1 H, cyclohexanone CH–C=O), 2.48-2.44 (m, 1 H, cyclohexanone
CH2), 2.42–2.34 (m, 1 H, cyclohexanone CH2), 2.12–2.06 (m,
1 H, cyclohexanone CH2), 1.88–1.82 (m, 1 H, cyclohexanone
CH2), 1.78–1.70 (m, 2 H, cyclohexanone CH2), 1.70–1.63 (m, 1 H,
cyclohexanone CH2), 1.57–1.47 (m, 1 H, cyclohexanone CH2). 13C
NMR (125 MHz, CDCl3): G = 217.6, 141.6, 128.2, 127.0, 125.8, 70.6,
57.2, 42.69, 28.0, 26.0, 24.9.MS (FAB): m/z (%) = 205 [M + H]+ (20),
203 (12), 187 (100), 169 (24), 143 (18), 117 (13), 105 (20), 91 (25).
HRMS (Ion mode: FAB +) m/z (%): Found/205.1208 (100), Calcd for
C13H17O2/205.1229. Crystal data for ( )15: C26H32O4, M = 408.52,
colourless crystal, 0.33 u 0.32 u 0.27 mm3, monoclinic, space group
P2(1)/c, a = 25.796(6) Å, b = 5.7048(14) Å, c = 15.456(4) Å, D = 90°,
E = 106.433(4)°, J = 90°, V = 2181.7(9) Å3, Z = 4, Dc = 1.244 Mg
m-3, F(000) = 880, Ac = 0.082 mm-1. Intensity data were collected on
a Smart-APEX diffractometer with graphite monochromated MoKD
radiation (O = 0.71073 Å) using the ZꢀVFDQꢀPRGHꢀZLWKꢀꢅꢂꢍꢌƒꢀꢎꢀșꢀꢎꢀ
ꢊꢒꢂꢓꢑƒꢂꢀꢅꢊꢓꢅꢅꢂꢀ8QLTXHꢀUHÀHFWLRQVꢀZHUHꢀPHDVXUHGꢀDQGꢀUHÀHFWLRQVꢀZLWKꢀ
Iꢀ!ꢀꢊꢀıꢀꢃIꢈꢀZHUHꢀXVHGꢀLQꢀWKHꢀ)RXULHUꢀWHFKQLTXHVꢂꢀ7KHꢀ¿QDOꢀUH¿QHPHQWꢀ
was converged to R = 0.0730 and wR = 0.2133.
Reaction of chlorosilanes with cyclohexanone using lithium
diisopropylamide
(1-Cyclohexenyloxy)dimethyl(1-naphthylphenylmethyl)silane (9): A THF
solution (10 ml) of cyclohexanone (981 mg, 10.0 mmol) was
added dropwise to a THF solution (10 ml) of 1.5 M LDA (7.33 ml,
11.0 mmol) at –78°C, and the reaction mixture was stirred for 1 h at
this temperature. To this mixture was added a THF solution (10 ml)
of ( ) 8 (3.11 g, 10.0 mmol) and the resulting mixture was stirred at
–78°C. After 1–3 h, the resulting organic layer was extracted with
ether; the extract was washed with brine and dried over anhydrous
Na2SO4. The extract solution was condensed under reduced pressure,
DQGꢀWKHꢀUHVLGXHꢀZDVꢀSXUL¿HGꢀXVLQJꢀVLOLFDꢀJHOꢀFROXPQꢀFKURPDWRJUDSK\ꢀ
(benzene) to afford the corresponding silyl enol ether ( ) 9 (yield
79.6%). A single crystal of ( ) 9 was obtained by recrystallisation of
( ) 9 from ethanol. White solid; m.p. 92.5–94.5°C. IR (KBr): 1089
(Si-O) cm-1. 1H NMR (500 MHz, CDCl3): G = 8.12–8.09 (m, 1 H,
ArH), 7.83–7.80 (m, 1 H, ArH), 7.76–7.71 (m, 2 H, ArH), 7.48–7.40
(m, 3 H, ArH), 7.33–7.29 (m, 2 H, ArH), 7.23–7.18 (m, 2 H, ArH),
7.10–7.06 (m, 1 H, ArH), 4.79–4.76 (br, 1 H, vinyl =CH), 4.42 (s,
1 H, aliphatic SiCH), 1.94–1.82 (m, 4 H, cyclohexane like CH2),
1.58–1.38 (m, 4 H, cyclohexane like CH2), 0.24 (s, 3 H, Si(CH3)2),
0.23 (s, 3 H, Si(CH3)2). 13C NMR (125 MHz, CDCl3): G = 150.3,
threo-2-(Hydroxyphenylmethyl)cyclohexanone (16): White solid;
m.p. 70.5–71.5°C UV (hexane/i-PrOH = 19/1): Omax = 266.5 nm.
1H NMR (500 MHz, CDCl3): G = 7.37–7.27 (m, 5 H, ArH), 4.78
(dd, 1 H, methine O–CH), 3.96 (d, 1 H, OH), 2.65–2.59 (m, 1 H,

JOURNAL OF CHEMICAL RESEARCH 2009 51
References
cyclohexanone CH–C=O), 2.51-2.46 (m,
1 H, cyclohexanone
CH2), 2.40–2.33 (m, 1 H, cyclohexanone CH2), 2.12–2.05 (m,
1 H, cyclohexanone CH2), 1.82–1.76 (m, 1 H, cyclohexanone
CH2), 1.72–1.62 (m, 1 H, cyclohexanone CH2), 1.61–1.50 (m, 2 H,
cyclohexanone CH2), 1.35–1.25 (m, 1 H, cyclohexanone CH2). 13C
NMR (125 MHz, CDCl3): G = 215.6, 140.9, 128.4, 127.9, 127.0,
74.8, 57.4, 42.7, 30.9, 27.8, 24.7. MS (FAB): m/z (%) = 205 [M + H]+
(20),203 (12), 187 (100), 169 (24), 143 (18), 117 (13), 105 (20), 91
(25). HRMS (Ion mode: FAB +) m/z (%): Found/205.1225 (100),
Calcd for C13H17O2/205.1229. Crystal data for ( )16: C26H32O4,
M = 408.52, colourless crystal, 0.42 u 0.35 u 0.25 mm3, orthorhombic,
space group Pna2(1), a = 20.609(3) Å, b = 5.7569(8) Å, c = 18.451(3)
Å, D = 90°, E = 90°, J = 90°, V = 2189.1(5) Å3, Z = 4, Dc = 1.240 Mg/m3,
F(000) = 880, Ac = 0.082 mm-1. Intensity data were collected on a
Smart-APEX diffractometer with graphite monochromated MoKD
radiation (O = 0.71073 Å) using the Zꢀ VFDQꢀ PRGHꢀ ZLWKꢀ ꢅꢂꢆꢒƒꢀ ꢎꢀ șꢀ
ꢎꢀꢊꢒꢂꢓꢅƒꢂꢀꢅꢊꢍꢅꢆꢂꢀ8QLTXHꢀUHÀHFWLRQVꢀZHUHꢀPHDVXUHGꢀDQGꢀUHÀHFWLRQVꢀ
with Iꢀ !ꢀ ꢊꢀ ıꢀ ꢃIꢈꢀ ZHUHꢀ XVHGꢀ LQꢀ WKHꢀ )RXULHUꢀ WHFKQLTXHVꢂꢀ 7KHꢀ ¿QDOꢀ
UH¿QHPHQWꢀZDVꢀFRQYHUJHGꢀWRꢀR = 0.0659 and wR = 0.1662.
1
2
3
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This work was partially supported by a grant from the
Promotion and Mutual Aid Corporation for Private Schools
of Japan, and a fund for the “High-Tech Research Centre”
Project for Private Universities: a matching fund subsidy from
MEXT, 2000-2004, and 2005-2007, and by Toa Gousei Co.
Ltd. in Japan. We thank the IIF-FF and CDCH-UCV (grants
IIF: 04.2002, PG. 06-30-4590-2003), and CONICT (grant No.
/$%ꢉꢆꢏꢑꢑꢑꢍꢍꢌꢈꢀIRUꢀ¿QDQFLDOꢀVXSSRUWꢂ
Received 5 August 2008; accepted 19 October 2008
Paper 08/0091 doi:10.3184/030823409X393709
Published online: 23 January 2009