Silylative Kinetic Resolution of Racemic 1-Indanol Derivatives Catalyzed by Chiral Guanidine

Article abstract of DOI:10.1021/acs.joc.7b02493

Efficient kinetic resolution of racemic 1-indanol derivatives was achieved using triphenylchlorosilane by asymmetric silylation in the presence of chiral guanidine catalysts. The chiral guanidine catalyst (R,R)-N-(1-(β-naphthyl)ethyl)benzoguanidine was found to be highly efficient as only 0.5 mol % catalyst loading was sufficient to catalyze the reaction of various substrates with appropriate conversion and high s-values (up to 89). This catalyst system was successfully applied to the gram-scale silylative kinetic resolution of racemic 1-indanol with high selectivity.

Full text of DOI:10.1021/acs.joc.7b02493

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Note
Silylative Kinetic Resolution of Racemic 1-
Indanol Derivatives Catalyzed by Chiral Guanidine
Shuhei Yoshimatsu, Akira Yamada, and Kenya Nakata
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02493 • Publication Date (Web): 12 Dec 2017
Downloaded from http://pubs.acs.org on December 15, 2017
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The Journal of Organic Chemistry
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Silylative Kinetic Resolution of Racemic 1ꢀIndanol Derivatives Cataꢀ
lyzed by Chiral Guanidine
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Shuhei Yoshimatsu, Akira Yamada, and Kenya Nakata*
Department of Material Science, Interdisciplinary Graduate School of Science and Engineering, Shimane University, 1060
Nishikawatsu Matsue, Shimane 690ꢀ8504, Japan
Supporting Information Placeholder
ABSTRACT: Efficient kinetic resolution of racemic 1ꢀindanol derivatives was achieved using triphenylchlorosilane by
asymmetric silylation in the presence of chiral guanidine catalysts. The chiral guanidine catalyst, [(R,R)ꢀN
found to be highly efficient as only 0.5 mol% catalyst loading was sufficient to catalyze the reaction of various substrates
with appropriate conversion and high ꢀvalues (up to 89). This catalyst system was successfully applied to the gramꢀscale
silylative kinetic resolution of racemic 1ꢀindanol with high selectivity.
βNpEtBG] was
s
The kinetic resolution of racemic alcohols by enantioselective
acylation using enzyme1 and chiral nucleophilic organocatalyꢀ
sis2,3 has been intensively developed and widely utilized from
laboratory to industrial scale. Alternatively, kinetic resolution
of racemic alcohols by enantioselective silylation using nonꢀ
enzymatic catalysts4 has been drawing much attention, as silyl
ethers are ubiquitous hydroxyl protecting groups in organic
chemistry.5 In 2001, Ishikawa and coꢀworkers first reported
the asymmetric silylation of racemic alcohols using
chlorosilanes in the presence of stoichiometric amounts of
chiral guanidines.6 Oestreich and coꢀworkers reported the diaꢀ
stereoselective dehydrogenative coupling of racemic alcohols
with siliconꢀstereogenic silanes to achieve kinetic resolution.7
However, these examples required stoichiometric amounts of
chiral sources. In a breakthrough study by Hoveyda and Snapꢀ
per in 2006, the catalytic asymmetric silylation of alcohols
was achieved using an aminoꢀacidꢀbased chiral imidazole
catalyst.8,9 Tan and coꢀworkers reported the successful enantiꢀ
oselective desymmetrization and divergent resolution of alcoꢀ
hols using chlorosilanes and scaffolding organocatalysts.10 In
2011, Wiskur and coꢀworkers reported the silylative kinetic
resolution of monofunctional secondary alcohols and αꢀ
hydroxy carbonyl compounds11 using chiral isothiourea cataꢀ
lysts, which were also revealed to serve as efficient acyl transꢀ
fer catalysts for asymmetric acylation.12 Although significant
advances have been made in the chiral silylation of alcohols,
many of the examples require a relatively large catalyst loadꢀ
ing (≥ 20 mol%). Song and coꢀworkers reported the enantioseꢀ
lective silylation of benzylic alcohols using 1,1,1,3,3,3ꢀ
hexamethyldisilazane (HMDS) with an extremely low loading
(1 ppm) of a BINOLꢀbased polyether catalyst.13 List and coꢀ
workers also reported the asymmetric silylation of alcohols
with HMDS using a chiral Brønsted acid catalyst.14 Dehydroꢀ
genative SiꢀO coupling has been achieved by Oestreich and
coꢀworkers, who used transition metal catalysis with donorꢀ
functionalized alcohols,15 and various kinds of alcohols.16
Scheme 1. Previously reported study (a) and this study (b)
In our research group, chiral guanidineꢀbased catalyst (R)ꢀ
Nꢀmethylbenzoguanidine ((R)ꢀNMBG 1) was found to faciliꢀ
tate efficient acyl transfer for the kinetic resolution of racemic
benzylic alcohols via asymmetric esterification, in the presꢀ
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ence of pivalic anhydride.17 To demonstrate an application of
(8.4 and 8.7, respectively); however, considering both reactiviꢀ
ty and selectivity, toluene was selected as the most suitable
solvent and was adopted for the remainder of the study.
1
2
3
4
5
6
7
8
this protocol, we achieved an enantiodivergent synthesis of
both enantiomers of centrolobine using the developed catalyst
in the synthetic key step.18 Furthermore, we recently reported
the acylative kinetic resolution of racemic aromatic βꢀhydroxy
esters with cyclohexanecarboxylic anhydride in the presence
To evaluate the effect of the silyl chloride substitution on
selectivity, five silyl chlorides 5a–5e were applied to the siꢀ
lylative kinetic resolution of (±)ꢀ3 under the above mentioned
conditions (Table 2). Upon substitution of a phenyl group for a
methyl group at one or two positions, selectivity decreased
(entries 2 and 3), although reactivity did not diminish. When
the reaction was carried out using alkyl substituted silyl chloꢀ
rides such as 5d and 5e, the reaction appeared to be influenced
by steric effects: the triethyl substituted 5d showed fair reacꢀ
tivity but a low sꢀvalue, and the tertꢀbutyl dimethyl substituted
5e resulted in no reaction (entries 4 and 5). Among all the
entries, the highest sꢀvalue was obtained when using 5a (entry
1).
of (R)ꢀNMBG
1
and its derivative (R,R)ꢀNꢀ(1ꢀ(βꢀ
naphthyl)ethyl)benzoguanidine ((R,R)ꢀNβNpEtBG 2).19 Conꢀ
sidering Wiskur et al.’s asymmetric silylation utilizing an
isothioureaꢀbased catalyst (Scheme 1 (a)),11a we anticipated
that our guanidineꢀbased catalyst could also be a promising
candidate for asymmetric silylation (Scheme 1 (b)).
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Optically active 1ꢀindanol derivatives are important chiral
building blocks for the synthesis of biologically active comꢀ
pounds,20 with asymmetric reduction of prochiral carbonyl
compounds being the most common method of synthesis.21
Although several enzymatic21 and dynamic kinetic resolution
strategies using synergistic enzyme and metal catalyst sysꢀ
tems22 have been reported, the organocatalyzed acylative kiꢀ
netic resolution of racemic 1ꢀindanol (3) has remained a chalꢀ
lenge.11a Moreover, only one study16 has been recently pubꢀ
lished describing a practical method for the silylative kinetic
resolution of racemic 3 exceeding an sꢀvalue24 of 20.11a Thereꢀ
fore, we became interested in the development of an efficient
method for accessing chiral 1ꢀindanols. Here we report the
first practical kinetic resolution of a variety of racemic 1ꢀ
indanol derivatives with chlorosilanes by asymmetric silylaꢀ
tion using guanidineꢀtype catalysts (Scheme 1 (b)).
Table 2. Effect of silyl chloride substituents on reactivity
and selectivity
Entry R3SiCl 5
Conv
[%]a
ee
sꢀvaluea
(4; 3) [%]
1b
2
Ph3SiCl (5a)
62
53; 86
42; 69
24; 46
31; 47
–; –
8.4
4.8
2.4
2.9
–
Table 1. Solvent effect on the kinetic resolution of racꢀ1ꢀ
indanol ((±)ꢀ3) by asymmetric silylation
Ph2MeSiCl (5b) 62
3
PhMe2SiCl (5c)
Et3SiCl (5d)
66
60
4
5
tBuMe2SiCl (5e) NRc
a
Conversions and sꢀvalues were calculated using Kagan’s
equation.24 b Same as in Table 1, entry 4. c No reaction.
To further optimize the reaction conditions, we examined
the temperature effect and catalyst loading for the same reacꢀ
tion (Table 3). As the conversion exceeded 50% when the
reaction was performed at 0 °C (entry 1), it was proposed that
even lower reaction temperatures could be trialed. With each
decrease in reaction temperature (–20, –40, and –78 °C), there
was an increase in the sꢀvalue with no effect on reactivity (enꢀ
tries 2–4). The reaction was then carried out by incrementally
decreasing the catalyst loading from 20 mol% to 10, 5, and 1
mol% (entries 5–7). Interestingly, conversion was maintained
in each case, and generally, each decrease in catalyst loading
resulted in an increase in sꢀvalue. Although the exact reason
was not clear, with 1 mol% of the catalyst, the reaction gave
the highest conversion (68%), affording the recovered alcohol
(R)ꢀ3 in >99% ee. Since the sꢀvalue was not evaluated under
the conditions (entry 7), for convenience, it was calculated the
minimum value of >13 using the ee of the recovered alcohol
as 99%. The reaction was further investigated by reducing the
equivalents of 5 and iPr2NEt to 0.65, which resulted in a higher
sꢀvalue than that for entry 6 at 5 mol% catalyst loading (entry
8). In line with the noted trend, the reaction was repeated at a
low catalyst loading of 0.5 mol%, which gave the highest sꢀ
value (entry 9, s = 23), the as same as entry 8. As expected, the
control reaction performed in the absence of chiral catalyst 1
gave no appreciable background reaction (entry 10).
Entry
Solvent
Conv. [%]a
ee (4; 3) [%] sꢀvaluea
1
2
3
4
5
6
7
8
9
MeCN
DMF
1
66; 0.9
–; –
5.0
–
NRb
43
62
55
57
60
43
54
Hexane
Toluene
Et2O
33; 25
53; 86
53; 65
58; 78
48; 73
58; 44
57; 68
2.5
8.4
6.1
8.7
6.0
5.7
7.3
THF
CH2Cl2
(CH2Cl)2
EtOAc
a
Conversions and sꢀvalues were calculated using Kagan’s equaꢀ
tion.24 b No reaction.
In light of Wiskur et al.’s study, racemic 1ꢀindanol ((±)ꢀ3)
was chosen as a model substrate to facilitate direct comparison
with reported results. First, we examined solvent effects on the
silylative kinetic resolution of 3 with 0.75 equiv of Ph3SiCl (5)
as a silylation reagent and iPr2NEt as a coꢀbase in the presence
of 20 mol% of (R)ꢀNMBG 1 at 0 °C for 24 h (Table 1). The
reactivity appeared to be influenced by the polarity of the solꢀ
vent, as highꢀpolarity solvents such as MeCN and DMF led to
negligible conversion or no reaction (entries 1 and 2). In conꢀ
trast, the reaction proceeded smoothly with good conversion
(43–62%) in a number of other commonly used organic solꢀ
vents (entries 3–9). Both toluene and THF gave high sꢀvalues
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The Journal of Organic Chemistry
(R,R)ꢀconfiguration led to better results (entries 2 and 3).
1
2
3
4
5
6
However, the selectivity of both catalysts was much lower
than that of catalyst 1 (entry 1). Because of the higher perforꢀ
mance of the (R,R)ꢀstereochemistry at the two stereogenic
centers in the catalyst, we next applied (R,R)ꢀNβNpEtBG 2 to
the same reaction. The reaction proceeded smoothly to afford
the highest sꢀvalue (entry 4).
Table 3. Examination of temperature and catalyst loading on
conversion and selectivity
7
8
9
To assess the generality of this novel method, we screened
several racemic 1ꢀindanol derivatives 8a–8h under the optiꢀ
mized reaction conditions, using 0.5 mol% loading of (R,R)ꢀ
NβNpEtBG 2 (Scheme 2). However, the reactions of 4ꢀ
substituted 1ꢀindanol 8a and the fused aromatic 1ꢀindanol deꢀ
rivative 8h were performed in THF due to the poor solubility
of them in toluene. Interestingly, 4ꢀsubstituted 8a, 5ꢀ
substituted 8b–8d, and 6ꢀsubstituted 1ꢀindanols 8e and 8f,
proceeded with 52–54% conversion, and consistently high sꢀ
values were obtained in every case, irrespective of the substiꢀ
tution pattern and the electronic nature of the substituents. In
terms of selectivity, 6ꢀsubstituted 1ꢀindanols 8e and 8f outperꢀ
formed the rest, with outstanding sꢀvalues of 72 and 89 respecꢀ
tively. The reactions of 4ꢀ and 5ꢀsubstituted 1ꢀindanols 8a–8d
proceeded smoothly, resulting in sꢀvalues ranging from 43 to
60. The reaction of 3,3ꢀdisubstituted 1ꢀindanol 8g and the
fused aromatic 1ꢀindanol derivative 8h also afforded good sꢀ
values. Unfortunately, the reaction of 2,2ꢀdisubstututed 1ꢀ
indanol 8i did not proceed, probably because of the steric hinꢀ
drance of the 2,2ꢀdimethyl groups.
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Entry
n
Temp. Conv.
ee
sꢀvaluea
[mol%]
[°C]
[%]a
(4; 3) [%]
1b
2
20
20
20
20
10
5
0
62
57
62
63
61
60
68
59
59
<1h
53; 86
61; 80
59; 96
58; 98
64; 98
65; 99
47; >99
68; 98
68; 98
–; –
8
–20
–40
–78
–78
–78
–78
–78
–78
–78
10
14
17
20
23
>13
23
23
–
3
4
5
6
7c
8d
9d
10
1
1
0.5
g
–
a
Conversions and sꢀvalues were calculated using Kagan’s equaꢀ
tion.24 b Same as in Table 1, entry 4. c Average of two reactions. d
i
g
h
Using 0.65 equiv of 5 and Pr2NEt. Without catalyst. Deterꢀ
1
mined by H NMR analysis of the crude reaction mixture using
1ꢀbromonaphthalene as an internal standard.
Scheme 2. Silylative kinetic resolution of racemic 1ꢀindanol
derivatives
Table 4. Examination of chiral guanidine catalysts
Entry
Catalyst
Conv.
[%]a
ee
sꢀ
(4; 3) [%]
valuea
1b
2
3
4
1
59
54
57
68; 98
62; 72
64; 85
82; 92
23
9
12
32
(R,S)ꢀNPhEtBG 6
(R,R)ꢀNPhEtBG 7
(R,R)ꢀNβNpEtBG 2 53
a
Conversions and s-values were calculated using Kagan’s
equation.24 b Same as in Table 3, entry 9.
With the optimized reaction conditions in hand, we attemptꢀ
ed to further improve the selectivity. Thus, three further guanꢀ
idine catalysts, (R,S)ꢀNPhEtBG 6, (R,R)ꢀNPhEtBG 7, and
(R,R)ꢀNβNpEtBG 2 (previously reported by our research
group in application to acylative kinetic resolution),18 were
applied to the silylative kinetic resolution of (±)ꢀ3 (Table 4).
Comparison of the performance of diastereomeric catalysts
(R,S)ꢀNPhEtBG 6 and (R,R)ꢀNPhEtBG 7 revealed that the
a THF was used as solvent.
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(95.1 mg, 2.51 mmol). The reaction mixture was stirred for 30 min at
To elucidate the scalability of this method, a gramꢀscale
silylative kinetic resolution of racemic 1ꢀindanol (3) was perꢀ
formed, as shown in Scheme 3. The reaction carried out on a
10ꢀmmol scale under the optimized reaction conditions proꢀ
ceeded smoothly to afford the silyl ether (S)ꢀ4 in 53% yield
and 78% ee, along with the recovered alcohol (R)ꢀ3 in 47%
yield, 96% ee, and high selectivity. This result indicates the
potential utility of the present method for furnishing chiral
indanol derivatives on a large scale.
room temperature and then it was quenched with saturated aqueous
NH4Cl at 0 °C. The organic layer was separated and the aqueous layer
was extracted with EtOAc. The combined organic layer was dried
over Na2SO4. After filtration of evaporation of the solvent, the crude
product was purified by column chromatography on silica (hexꢀ
ane/EtOAc = 4/1) to afford 4ꢀmethylꢀ1ꢀindanol (8a) (285.4 mg, 92%).
1
2
3
4
5
6
7
8
Preparation of Racemic 8f (Scheme 2):
To a solution of 6ꢀhydroxyꢀ1ꢀindanone (296 mg, 2.00 mmol) in DMF
(4.0 mL) at 0 °C was added NaH (60%, 120 mg, 3.00 mmol). The
reaction mixture was stirred for 30 min and then MeI (187 ꢁL, 3.00
mmol) was added to the mixture. The whole mixture was stirred for
20.5 h at room temperature and then it was quenched with saturated
aqueous NH4Cl at 0 °C and diluted with H2O and EtOAc. After the
extraction with EtOAc, the combined organic layer was dried over
Na2SO4, filtered, and evaporated the solvent. The residue was purified
by column chromatography on silica (hexane/EtOAc = 9/1) to afford
6ꢀmethoxyꢀ1ꢀindanone as a white solid (318 mg, 98% yield), which
was subsequently reduced by the above method using NaBH4 to afꢀ
ford 8f (275 mg, 95% yield, 1.77 mmol scale).
9
Scheme 3. Gramꢀscale kinetic resolution of racemic 1ꢀ
indanol (3)
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Preparation of Racemic 8i (Scheme 2):
According to the literature procedure,25 to a solution of 1ꢀindanone
(463 mg, 3.50 mmol) in THF (7.0 mL) at 0 °C was added NaH (60%,
701 mg, 17.5 mmol). The reaction mixture was stirred for 10 min at
room temperature and then MeI (187 ꢁL, 3.00 mmol) was added to
the mixture at 0 °C. The whole mixture was stirred for 0.5 h at 40 °C
and continued stirring for 3 h at room temperature. Then it was
quenched with saturated aqueous H2O at 0 °C and diluted with
EtOAc. After the extraction with EtOAc, the combined organic layer
was dried over Na2SO4, filtered, and evaporated the solvent. The
residue was semiꢀpurified by column chromatography on silica (hexꢀ
ane/EtOAc = 9/1) to afford 3,3ꢀdimethylꢀ1ꢀindanone as a pale yellow
oil, which was subsequently reduced by the above method using
NaBH4 to afford 8i (485 mg, 85% yield for 2 steps).
In conclusion, we have developed a general method for the
nonꢀenzymatic kinetic resolution of racemic 1ꢀindanol derivaꢀ
tives with triphenylchlorosilane catalyzed by chiral guanidine,
(R,R)ꢀ
N
ꢀ(1ꢀ(
β
ꢀ1ꢀnaphthyl)ethyl)benzoguanidine [(R,R)ꢀ
N
β
NpEtBG], with high s
ꢀvalues (up to 89). The catalyst
was found to be a highly efficient, as only 0.5 mol% cataꢀ
lyst loading and slightly excess amount of silylchloride
(0.65 equiv) were required to achieve ≈50% conversion.
This protocol was also extended to the gramꢀscale silylative
kinetic resolution of racemic 1ꢀindanol with high selectivity.
Although the nonꢀenzymatic kinetic resolution of racemic
1ꢀindanol has presented a historically challenging issue in
organic chemistry, we have developed a highly promising
method to overcome this challenge. Further studies are in
progress in our laboratory to explore the scope and limitaꢀ
tion of this reaction, and to further develop novel chiral
catalysts that will be reported in due course.
1H NMR (CDCl3): δ 7.40–7.34 (m, 1H), 7.26–7.16 (m, 3H), 4.68 (d, J
= 5.0 Hz, 1H), 2.79 (d, J = 15.5 Hz, 1H), 2.67 (d, J = 15.5 Hz, 1H),
1.84 (br s, 1H), 1.19 (s, 3H), 1.04 (s, 3H); 13C NMR (CDCl3): δ 144.4,
141.8, 128.0, 126.5, 125.0, 124.4, 83.5, 44.8, 44.5, 26.7, 21.4.
Typical Procedure for the Silylative Kinetic Resolution of Raceꢀ
mic 1ꢀIndanol (Table 4, entry 4):
To a solution of racemic 1ꢀindanol (±)ꢀ3 (134.0 mg, 1.00 mmol) in
toluene (5.0 mL) at room temperature were successively added (R,R)ꢀ
EXPERIMENT SECTION
1
General Information. H and 13C NMR spectra were recorded with
i
NβNpEtBG 2 (2.0 mg, 5.1 ꢁmol) and Pr2NEt (113 ꢁL, 0.65 mmol).
tetramethylsilane (TMS) or chloroform (in chloroformꢀd) as internal
standard. Electrospray ionization mass (ESIꢀMS) spectra were recordꢀ
ed on a Bruker microTOFIIꢀSHIY3 mass spectrometer (Bruker,
Billerica, MA) using the positive mode ESIꢀTOF method for acetoniꢀ
trile solutions and sodium formate as the reference. Thin layer chroꢀ
matography was performed on Wakogel B5F. All reactions were
carried out under nitrogen atmosphere in dried glassware. Dichloroꢀ
methane and dichloroethane were distilled from diphosphorus pentoxꢀ
ide, then calcium hydride, and dried over MS 4Å. EtOAc was distilled
from diphosphorus pentoxide and dried over MS 4Å. Hexane, toluꢀ
ene, diethyl ether, THF, MeCN, and N,Nꢀdimethylformamide were
distilled from calcium hydride, and dried over MS 4Å. 1ꢀIndanol ((±)ꢀ
3) was purchased from Wako Pure Chemical Industries Ltd. and Toꢀ
kyo Chemical Industry Co., Ltd. Ph3SiCl (5a) was purchased from
Tokyo Kasei Kogyo Co., Ltd. All reagents were purchased from
commercial suppliers and used without further purification unless
otherwise noted.
After cooling to –78 °C, Ph3SiCl (5a) (191.9 mg, 0.65 mmol) was
added to the mixture. The reaction mixture was stirred for 24 h at the
same temperature and then it was quenched with saturated aqueous
NaHCO3 and diluted with EtOAc. After the extraction with EtOAc,
the combined organic layer was dried over Na2SO4, filtered, and
evaporated the solvent. The residue was purified by preparative thin
layer chromatography on silica (hexane/EtOAc = 4/1) to afford the
corresponding optically active (S)ꢀ4 and the recovered optically active
(R)ꢀ3 [53% conversion, s = 32].
Enantiomeric excess of (S)ꢀ4 has been determined after desilylation
into (S)ꢀ3 as followed: To a solution of the obtained silyl ether (S)ꢀ4
in THF (2.0 mL) at room temperature was added TBAF (1.5 mL, 1.0
M in THF). The reaction mixture was stirred for 2 h and then it was
quenched with saturated aqueous NH4Cl at 0 °C and diluted with
EtOAc. After the extraction with EtOAc, the combined organic layer
was dried over Na2SO4, filtered, and evaporated the solvent. The
residue was purified by preparative thin layer chromatography on
silica (hexane/EtOAc = 1/1) to afford the desilylated (S)ꢀ3.
Racemic 1ꢀindanols 8a, 8b, 8c, 8d, 8e, 8g, 8h were prepared by the
reduction of the corresponding commercially available ketones. Raꢀ
cemic 1ꢀindanols 8f and 8i were prepared by the reduction of the
corresponding synthesized ketones.
Gramꢀscale kinetic resolution of racemic 1ꢀindanol (3) (Scheme
3):
To a solution of racemic 1ꢀindanol ((±)ꢀ3) (1.34 g, 10.0 mmol) in
toluene (50 mL) at room temperature were successively added (R,R)ꢀ
NβNpEtBG 2 (19.5 mg, 0.05 mmol) and Pr2NEt (1.13 mL, 6.50
mmol). After cooling to –78 °C, Ph3SiCl (5a) (1.92 mg, 6.50 mmol)
Typical Procedure for the Preparation of Racemic 1ꢀIndanols 8a–
8e, 8g, 8h (Scheme 2):
To a solution of 4ꢀmethylꢀ1ꢀindanone (307.1 mg, 2.10 mmol) in
MeOH (4.2 mL) and CH2Cl2 (4.2 mL) at 0 °C was added NaBH4
i
was added to the mixture. The reaction mixture was stirred for 24 h at
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The Journal of Organic Chemistry
the same temperature and then it was quenched with saturated aqueꢀ
2.43 (m, 1H), 2.37 (s, 3H), 2.11 (br s, 1H), 1.99–1.89 (m, 1H); 13C
NMR (CDCl3): δ 145.1, 140.2, 136.3, 129.1, 124.7, 124.5, 76.3, 36.1,
29.3, 21.2.
ous NaHCO3 and diluted with EtOAc. After the extraction with
EtOAc, the combined organic layer was dried over Na2SO4, filtered,
and evaporated the solvent. The residue was purified by column
chromatography on silica (hexane/EtOAc = 20/1 to 9/1) to afford the
corresponding optically active (S)ꢀ4 (2.08 g, 53% yield, 78% ee) and
the recovered optically active (R)ꢀ3 (630 mg, 47% yield, 96% ee) [s =
31]. Enantiomeric excess of (S)ꢀ4 has been determined after desilylaꢀ
tion into (S)ꢀ3.
1
2
3
4
5
6
7
8
(R)ꢀ6ꢀmethoxyꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀol ((R)ꢀ8f)29
[Scheme 2, 97% ee]: [α]D23 = –32.8 (c 1.42, CHCl3); lit.,29 [α]D23 = –
20.0 (c 0.5, CHCl3), 94% ee for R; HPLC (CHIRALCEL ODꢀ3, iꢀ
PrOH/hexane = 1/30, flow rate = 0.6 mL/min): tR = 32.2 min (1.5%),
tR = 35.3 min (98.5%); 1H NMR (CDCl3): δ 7.14 (d, J = 8.5 Hz, 1H),
6.95 (d, J = 2.0 Hz, 1H), 6.82 (dd, J = 8.5, 3.0 Hz, 1H), 5.18 (dd, J =
7.0, 6.5 Hz, 1H), 3.80 (s, 3H), 2.96 (ddd, J = 15.5, 9.0, 4.5 Hz, 1H),
2.74 (dt, J = 15.5, 8.0 Hz, 1H), 2.54–2.44 (m, 1H), 2.11 (br s, 1H),
1.98–1.88 (m, 1H); 13C NMR (CDCl3): δ 158.9, 146.3, 135.0, 125.4,
114.9, 108.7, 76.5, 55.4, 36.4, 28.9.
[Optically Active (R)ꢀAlcohols 3, and 8a–8h]
(R)ꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀol ((R)ꢀ3)11a
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
[Table 4, Entry 4, 92% ee]: HPLC (CHIRALCEL ODꢀ3, iꢀ
PrOH/hexane = 1/30, flow rate = 0.5 mL/min): tR = 27.3 min (3.9%),
tR = 31.0 min (96.1%); 1H NMR (CDCl3): δ 7.43–7.39 (m, 1H), 7.30–
7.21 (m, 3H), 5.22 (t, J = 6.0 Hz, 1H), 3.05 (ddd, J = 16.0, 8.5, 5.0
Hz, 1H), 2.81 (dt, J = 16.0, 7.5 Hz, 1H), 2.52–2.42 (m, 1H), 2.19 (br
s, 1H), 1.99–1.88 (m, 1H); 13C NMR (CDCl3): δ 144.9, 143.2, 128.2,
126.6, 124.8, 124.1, 76.3, 35.8, 29.7.
(R)ꢀ3,3ꢀdimethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀol ((R)ꢀ8g)30
[Scheme 2, 83% ee]: [α]D21 = –15.5 (c 1.37, CHCl3); lit.,30 [α]D25 = –
27.1 (c 0.11, CHCl3), 90% ee for R; HPLC (CHIRALCEL ODꢀ3, iꢀ
PrOH/hexane = 1/30, flow rate = 0.5 mL/min): tR = 18.3 min (8.6%),
tR = 20.8 min (91.4%); 1H NMR (CDCl3): δ 7.39 (dd, J = 7.0, 1.0 Hz,
1H), 7.31 (dt, J = 1.0, 7.0 Hz, 1H), 7.26 (dt, J = 1.5, 7.5 Hz, 1H), 7.21
(d, J = 7.5 Hz, 1H), 5.30–5.21 (m, 1H), 2.38 (dd, J = 13.0, 7.0 Hz,
1H), 2.14 (br s, 1H), 1.84 (dd, J = 13.0, 6.0 Hz, 1H); 13C NMR
(CDCl3): δ 151.8, 143.6, 128.5, 126.9, 124.1, 122.2, 74.4, 51.8, 42.2,
29.9, 29.8.
Absolute configuration was determined by the comparison of the
HPLC retention time in Ref. 1.
(R)ꢀ4ꢀmethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀol ((R)ꢀ8a)26
[Scheme 2, 97% ee]: [α]D24 = –11.4 (c 1.46, CHCl3); lit.,26 [α]D23 = –
36.3 (c 1.5, CHCl3), 99% ee for R; HPLC (CHIRALPAK ODꢀ3, iꢀ
PrOH/hexane = 1/30, flow rate = 0.65 mL/min): tR = 23.9 min (1.7%),
tR = 30.0 min (98.3%); 1H NMR (CDCl3): δ 7.26 (d, J = 7.0 Hz, 1H),
7.18 (dt, J = 7.5, 7.0 Hz, 1H), 7.10 (d, J = 7.0 Hz, 1H), 5.24 (dd, J =
6.0, 5.5 Hz, 1H), 2.98 (ddd, J = 16.0, 8.5, 5.0 Hz, 1H), 2.73 (ddd, J =
16.0, 8.0, 7.0 Hz, 1H), 2.54–2.44 (m, 1H), 2.29 (s, 3H), 2.07 (br s,
1H), 1.99–1.90 (m, 1H); 13C NMR (CDCl3): δ 144.7, 142.1, 134.2,
129.0, 126.9, 121.5, 76.6, 35.3, 28.4, 18.7.
(R)ꢀ1,2ꢀdihydroacenaphthylenꢀ1ꢀol ((R)ꢀ8h)11a
[Scheme 2, 95% ee]: HPLC (CHIRALCEL ODꢀ3, iꢀPrOH/hexane =
1/30, flow rate = 0.65 mL/min): tR = 45.4 min (2.3%), tR = 52.2 min
1
(97.7%); H NMR (CDCl3): δ 7.76 (d, J = 8.0 Hz, 1H), 7.66 (d, J =
8.5 Hz, 1H), 7.59–7.46 (m, 3H), 7.30 (d, J = 7.0 Hz, 1H), 5.66 (s,
1H), 3.74 (ddd, J = 17.5, 7.0, 1.0 Hz, 1H), 3.18 (dd, J = 17.5, 2.0 Hz,
1H). 13C NMR (CDCl3): δ 145.6, 141.5, 137.1, 131.1, 128.2, 128.0,
124.9, 122.7, 120.3, 120.0, 74.2, 41.7.
(R)ꢀ5ꢀchloroꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀol ((R)ꢀ8b)27
22
25
Absolute configuration was determined by the comparison of the
HPLC retention time in Ref. 1.
[Scheme 2, 93% ee]: [α]D = –19.2 (c 0.74, CHCl3); lit.,27 [α]D
=
+30.10 (c 1.0, CHCl3), 99% ee for S; HPLC (CHIRALCEL ODꢀ3, iꢀ
PrOH/hexane = 1/30, flow rate = 0.5 mL/min): tR = 27.0 min (92.8%),
[Optically Active (S)ꢀSilyl Ethers 4, and 9a–9h]
1
tR = 30.1 min (7.2%); H NMR (CDCl3): δ 7.30 (d, J = 8.5 Hz, 1H),
(S)ꢀ((2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀyl)oxy)triphenylsilane ((S)ꢀ4)11a
[Table 4, Entry 4, 82% ee]: Enantiomeric excess of (S)ꢀ4 has been
determined after desilylation into (S)ꢀ3; HPLC (CHIRALCEL ODꢀ3,
iꢀPrOH/hexane = 1/30, flow rate = 0.5 mL/min): tR = 28.1 min
7.24–7.15 (m, 2H), 5.17 (t, J = 6.0 Hz, 1H), 3.00 (ddd, J = 16.0, 9.0,
5.0 Hz, 1H), 2.78 (dt, J = 16.0, 7.5 Hz, 1 H), 2.54–2.41 (m, 1H), 2.16
(br s, 1H), 1.99–1.87 (m, 1H); 13C NMR (CDCl3): δ 145.2, 143.4,
134.0, 126.9, 125.3, 125.0, 75.6, 36.0, 29.6.
1
(90.8%), tR = 32.1 min (9.2%); H NMR (CDCl3): δ 7.93–7.81 (m,
(R)ꢀ5ꢀbromoꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀol ((R)ꢀ8c)28
6H), 7.62–7.48 (m, 9H), 7.39–7.24 (m, 4H), 5.69–5.59 (m, 1H), 3.20–
3.08 (m, 1H), 2.90–2.77 (m, 1H), 2.48–2.36 (m, 1H), 2.31–2.15 (m,
1H); 13C NMR (CDCl3): δ 145.0, 142.8, 135.5, 134.6, 130.0, 127.84,
127.76, 126.4, 124.6, 124.4, 77.4, 36.3, 29.7.
22
25
[Scheme 2, 98% ee]: [α]D = –19.6 (c 1.00, CHCl3); lit.,28 [α]D
=
+15.8 (c 1.0, CHCl3), 98.1% ee for S; HPLC (CHIRALCEL ODꢀ3, iꢀ
PrOH/hexane = 1/30, flow rate = 0.5 mL/min): tR = 29.7 min (1.0%),
1
tR = 31.7 min (99.0%); H NMR (CDCl3): δ 7.42–7.31 (m, 2H), 7.23
(S)ꢀ((4ꢀmethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀyl)oxy)triphenylsilane
((S)ꢀ9a)
(d, J = 8.0 Hz, 1H), 5.22–5.09 (m, 1H), 3.08–2.93 (m, 1H), 2.85–2.71
(m, 1H), 2.53–2.40 (m, 1H), 2.35 (br s, 1H), 1.99–1.83 (m, 1H); 13C
NMR (CDCl3): δ 145.6, 143.9, 129.7, 128.0, 125.7, 122.2, 75.6, 35.9,
29.6.
25
[Scheme 2, 87% ee]: [α]D = –29.6 (c 1.0, CHCl3); white solid; Mp:
1
52–53 °C; IR (KBr): 1117, 700 cm–1; H NMR (CDCl3): δ 7.77–7.70
(m, 6H), 7.52–7.46 (m, 3H), 7.46–7.39 (m, 6H), 7.15–7.03 (m, 3H),
5.52 (t, J = 6.5 Hz, 1H), 2.98 (ddd, J = 16.0, 9.0, 3.5 Hz, 1H), 2.64
(dt, J = 16.0, 8.0 Hz, 1H), 2.36–2.25 (m, 3H), 2.28 (s, 3H), 2.27–2.06
(m, 1H); 13C NMR (CDCl3): δ 144.8, 141.7, 135.6, 134.7, 133.9,
130.0, 128.6, 127.8, 126.6, 121.8, 77.7, 35.7, 28.4, 18.7; Anal. Calcd
for C28H26OSi: C, 82.71; H, 6.45. Found: C, 82.63; H, 6.27.
Enantiomeric excess of (S)ꢀ9a has been determined after desilylation
into (S)ꢀ8a; HPLC (CHIRALCEL ODꢀ3, iꢀPrOH/hexane = 1/30, flow
rate = 0.65 mL/min): tR = 23.8 min (93.6%), tR = 30.6 min (6.4%).
(R)ꢀ5ꢀmethoxyꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀol ((R)ꢀ8d)27
25
25
[Scheme 2, 96% ee]: [α]D = –21.8 (c 1.23, CHCl3); lit.,27 [α]D
=
+27.6 (c 1.0, CHCl3), 99% ee for S; HPLC (CHIRALCEL ODꢀ3, iꢀ
PrOH/hexane = 1/30, flow rate = 0.6 mL/min): tR = 39.7 min (1.8%),
tR = 42.9 min (98.2%); 1H NMR (CDCl3): δ 7.30 (d, J = 9.5 Hz, 1H),
6.78 (d, J = 6.0 Hz, 2H), 5.17 (dd, J = 6.0, 5.0 Hz, 1H), 3.79 (s, 3H),
3.03 (ddd, J = 16.0, 8.5, 5.5 Hz,1 H), 2.78 (ddd, J = 16.0, 8.5, 6.5 Hz,
1H), 2.52–2.39 (m, 1H), 2.05 (br s, 1H), 1.99–1.89 (m, 1H); 13C NMR
(CDCl3): δ 160.1, 145.2, 137.3, 125.0, 112.9, 109.7, 75.7, 55.3, 36.2,
29.9.
(S)ꢀ((5ꢀchloroꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀyl)oxy)triphenylsilane ((S)ꢀ
9b)
(R)ꢀ6ꢀmethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀol ((R)ꢀ8e)26
[Scheme 2, 86% ee]: [α]D22 = –40.9 (c 1.00, CHCl3); white solid; Mp:
95–96 °C; IR (KBr): 1119, 716, 700 cm–1; 1H NMR (CDCl3): δ 7.75–
7.66 (m, 6H), 7.52–7.45 (m, 3H), 7.45–7.38 (m, 6H), 7.20 (s, 1H),
7.12 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 5.44 (dd, J = 6.5,
6.0 Hz, 1H), 3.00 (ddd, J = 16.0, 8.5, 4.0 Hz, 1H), 2.70 (dt, J = 16.0,
8.0, 8.0 Hz, 1H), 2.36–2.24 (m, 1H), 2.19–2.06 (m, 1H); 13C NMR
(CDCl3): δ 144.9, 143.6, 135.5, 134.4, 133.5, 130.1, 127.9, 126.6,
[Scheme 2, 99% ee]: [α]D22 = –48.0 (c 1.00, CHCl3); lit.,26 [α]D23 = –
36.3 (c 1.5, CHCl3), 99% ee for R; HPLC (CHIRALCEL ODꢀ3, iꢀ
PrOH/hexane = 1/30, flow rate = 0.5 mL/min): tR = 23.5 min (0.7%),
tR = 25.6 min (99.3%); 1H NMR (CDCl3): δ 7.24 (s, 1H), 7.15 (d, J =
7.5 Hz, 1H), 7.09 (d, J = 7.5 Hz, 1H), 5.20 (t, J = 6.0 Hz, 1H), 2.78
(ddd, J = 16.0, 8.5, 5.0 Hz, 1H), 2.78 (dt, J = 16.0, 8.0 Hz, 1H), 2.52–
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The Journal of Organic Chemistry
Page 6 of 8
125.5, 124.8, 76.7, 36.3, 29.6; HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd
for C27H23ClOSiNa 449.1099; Found 449.1097.
Enantiomeric excess of (S)ꢀ9b has been determined after desilylation
into (S)ꢀ8b; HPLC (CHIRALCEL ODꢀ3, iꢀPrOH/hexane = 1/30, flow
rate = 0.5 mL/min): tR = 26.9 min (3.6%), tR = 29.3 min (96.4%).
2.0 Hz, 1H), 2.03 (ddd, J = 12.5, 6.0, 2.0 Hz, 1H), 1.42 (d, J = 1.0 Hz,
3H), 1.14 (d, J = 1.0 Hz, 1H); 13C NMR (CDCl3): δ 151.5, 143.7,
135.6, 134.6, 130.0, 128.2, 127.8, 126.6, 124.5, 122.0, 75.4, 51.7,
42.1, 29.72, 29.68; HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd for
C29H28OSiNa 443.1802; Found 443.1805.
1
2
3
4
5
6
7
8
9
Enantiomeric excess of (S)ꢀ9g has been determined after desilylation
into (S)ꢀ8g; HPLC (CHIRALCEL ODꢀ3, iꢀPrOH/hexane = 1/30, flow
rate = 0.5 mL/min): tR = 18.3 min (92.9%), tR = 21.1 min (7.1%).
(S)ꢀ((5ꢀbromoꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀyl)oxy)triphenylsilane ((S)ꢀ
9c)
[Scheme 2, 83% ee]: [α]D22 = –39.0 (c 1.00, CHCl3); white solid; Mp:
80–81 °C; IR (KBr): 1119, 710, 700 cm–1; 1H NMR (CDCl3): δ 7.74–
7.65 (m, 6H), 7.51–7.44 (m, 3H), 7.44–7.37 (m, 6H), 7.34 (s, 1H),
7.30–7.23 (m, 1H), 6.97 (d, J = 8.0 Hz, 1H), 5.41 (dd, J = 7.0, 6.0 Hz,
1H), 2.99 (ddd, J = 16.0, 9.0, 4.0 Hz, 1H), 2.69 (dt, J = 16.0, 8.0 Hz,
1H), 2.32–2.22 (m, 1H), 2.16–2.04 (m, 1H); 13C NMR (CDCl3): δ
145.3, 144.1, 135.5, 134.4, 130.1, 129.5, 127.9, 127.8, 125.9, 121.7,
76.8, 36.3, 29.6; HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd for
C27H23BrOSiNa 493.0594; Found 493.0596.
(S)ꢀ((1,2ꢀdihydroacenaphthylenꢀ1ꢀyl)oxy)triphenylsilane
((S)ꢀ
9h)11a
[Scheme 2, 78% ee]: Enantiomeric excess of (S)ꢀ9h has been deterꢀ
mined after desilylation into (S)ꢀ9h; HPLC (CHIRALCEL ODꢀ3, iꢀ
PrOH/hexane = 1/30, flow rate = 0.65 mL/min): tR = 45.5 min
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
(89.0%), tR = 54.9 min (11.0%); H NMR (CDCl3): δ 7.82–7.75 (m,
6H), 7.73 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.5 Hz, 1H), 7.55–7.41 (m,
11H), 7.27–7.18 (m, 2H), 6.03 (d, J = 7.0 Hz, 1H), 3.62 (dd, J = 17.5,
7.0 Hz, 1H), 3.42 (d, J = 17.5 Hz, 1H); 13C NMR (CDCl3): δ 145.6,
141.7, 137.3, 135.6, 134.4, 131.1, 130.1, 127.9, 124.4, 122.6, 120.5,
119.3, 75.4, 42.0.
Enantiomeric excess of (S)ꢀ9c has been determined after desilylation
into (S)ꢀ8c; HPLC (CHIRALCEL ODꢀ3, iꢀPrOH/hexane = 1/30, flow
rate = 0.5 mL/min): tR = 29.2 min (91.5%), tR = 31.9 min (8.5%).
(S)ꢀ((5ꢀmethoxyꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀyl)oxy)triphenylsilane
((S)ꢀ9d)
ASSOCIATED CONTENT
[Scheme 2, 87% ee]: [α]D24 = –31.8 (c 1.03, CHCl3); white slurry; IR
Supporting Information
1
(KBr): 1090, 741, 704 cm–1; H NMR (CDCl3): δ 7.76–7.68 (m, 6H),
The Supporting Information is available free of charge on the
ACS Publications website.
7.51–7.45 (m, 3H), 7.45–7.38 (m, 6H), 7.06 (d, J = 8.5 Hz, 1H), 6.78
(s, 1H), 6.73 (dd, J = 8.5, 2.5 Hz, 1H), 5.47 (t, J = 6.0 Hz, 1H), 3.81
(s, 3H), 3.04 (ddd, J = 16.0, 9.0, 4.5 Hz, 1H), 2.71 (dt, 16.0, 8.0 Hz,
1H), 2.36–2.24 (m, 1H), 2.18–2.06 (m, 1H); 13C NMR (CDCl3): δ
159.9, 144.8, 137.3, 135.5, 134.7, 129.9, 127.8, 125.3, 112.6, 109.6,
76.9, 55.3, 36.5, 30.0; HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd for
C28H26O2SiNa 445.1594; Found 445.1599.
Enantiomeric excess of (S)ꢀ9d has been determined after desilylation
into (S)ꢀ8d; HPLC (CHIRALCEL ODꢀ3, iꢀPrOH/hexane = 1/30, flow
rate = 0.6 mL/min): tR = 39.9 min (93.5%), tR = 44.5 min (6.5%).
Copy of 1Hꢀ and 13CꢀNMR, and Copy of HPLC Analyses (PDF)
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: nakata@riko.shimaneꢀu.ac.jp.
Notes
The authors declare no competing financial interest.
(S)ꢀ((6ꢀmethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀyl)oxy)triphenylsilane
((S)ꢀ9e)
ACKNOWLEDGMENT
[Scheme 2, 87% ee]; [α]D23 = –31.0 (c 1.00, CHCl3); white solid; Mp:
1
91–92 °C; IR (KBr): 1115, 708 cm–1; H NMR (CDCl3): δ 7.78–7.71
The authors thank Dr. Michiko Egawa, Shimane University,
Japan, for her help with elemental analysis.
(m, 6H), 7.53–7.46 (m, 3H), 7.46–7.39 (m, 6H), 7.12 (d, J = 7.5 Hz,
1H), 7.05 (d, J = 7.5 Hz, 1H), 6.92 (s, 1H), 5.48 (t, J = 6.5 Hz, 1H),
2.99 (ddd, J = 16.0, 8.5, 3.5 Hz, 1H), 2.69 (dt, J = 16.0, 8.0 Hz, 1H),
2.34 –2.25 (m, 1H), 2.30 (s, 3H), 2,16–2.05 (m, 1H); 13C NMR
(CDCl3): δ 145.1, 139.8, 135.9, 135.6, 134.7, 130.0, 128.6, 127.8,
125.1, 124.3, 77.4, 36.5, 29.3, 21.2; HRMS (ESIꢀTOF) m/z: [M+Na]+
Calcd for C28H26OSiNa 429.1645; Found 429.1638.
Enantiomeric excess of (S)ꢀ9e has been determined after desilylation
into (S)ꢀ8e; HPLC (CHIRALCEL ODꢀ3, iꢀPrOH/hexane = 1/30, flow
rate = 0.5 mL/min): tR = 23.4 min (93.7%), tR = 26.0 min (6.3%).
REFERENCES
(1) For reviews, see: (a) Schoffers, E.; Golebiowski, A.; Johnson,
C. R. Tetrahedron 1996, 52, 3769–3826. (b) Ghanem, A.;
AboulꢀEnein, H. Y. Tetrahedron: Asymmetry 2004, 15, 3331–
3351. (c) Ghanem, A.; AboulꢀEnein, H. Y. Chirality 2005, 17,
1–15. (d) GotorꢀFernández, V.; Brieva, R.; Gotor, V. J. Mol.
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(S)ꢀ((6ꢀmethoxyꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀyl)oxy)triphenylsilane
((S)ꢀ9f)
[Scheme 2, 91% ee]: [α]D22 = –48.6 (c 1.00, CHCl3); white solid; Mp:
1
60–62 °C; IR (KBr): 1115, 702 cm–1; H NMR (CDCl3): δ 7.79–7.69
(m, 6H), 7.58–7.38 (m, 9H), 7.11 (d, J = 7.5 Hz, 1H), 6.83–6.75 (m,
1H), 6.64 (s, 1H), 5.48 (dd, J = 6.0, 5.0 Hz, 1H), 3.64 (s, 3H), 3.02–
2.89 (m, 1H), 2.66 (dt, J = 16.0, 8.0 Hz, 1H), 2.43–2.30 (m, 1H),
2.22–2.09 (m, 1H); 13C NMR (CDCl3): δ 158.7, 146.4, 135.6, 134.7,
134.6, 130.0, 127.9, 125.2, 114.8, 108.8, 77.5, 55.3, 36.7, 28.9;
HRMS (ESIꢀTOF) m/z: [M+Na]+ Calcd for C28H26O2SiNa 445.1594;
Found 445.1595.
Enantiomeric excess of (S)ꢀ9f has been determined after desilylation
into (S)ꢀ8f; HPLC (CHIRALCEL ODꢀ3, iꢀPrOH/hexane = 1/30, flow
rate = 0.6 mL/min): tR = 31.5 min (95.5%), tR = 36.5 min (4.5%).
(S)ꢀ((3,3ꢀdimethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀyl)oxy)triphenylsilane
((S)ꢀ9g)
(4) For highlights and reviews, see: (a) Rendler, S.; Oestreich, M.
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[Scheme 2, 86% ee]: [α]D22 = –18.4 (c 0.90, CHCl3); white solid; Mp:
1
89–91 °C; IR (KBr): 1117, 700 cm–1; H NMR (CDCl3): δ 7.75–7.68
(m, 6H), 7.50–7.44 (m, 3H), 7.44–7.38 (m, 6H), 7.30–7.24 (m, 1H),
7.20–7.10 (m, 3H), 5.51 (t, J = 6.5 Hz, 1H), 2.16 (ddd, J = 12.5, 7.0,
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