Asymmetric synthesis of enantiomerically pure spiro [((2S)- hydroxy)indane-1,4'-piperidine]

Article abstract of DOI:10.1016/S0957-4166(99)00172-X

We report herein, efficient and practical synthetic methods for the preparation of enantiomerically pure spiro[((2S)-hydroxy)indane-1,4'- piperidine] (S)-1, a key intermediate for the synthesis of a tachykinin receptor antagonist, using catalytic asymmetric reduction or catalytic asymmetric epoxidation as a key step.

Full text of DOI:10.1016/S0957-4166(99)00172-X

Pergamon
Tetrahedron: Asymmetry 10 (1999) 1787–1793
Asymmetric synthesis of enantiomerically pure
spiro[((2S)-hydroxy)indane-1,40-piperidine]
Toshiyasu Takemoto, Katsuyoshi Nakajima, Yukiko Iio, Masakazu Tamura and
Takahide Nishi ∗
Medicinal Chemistry Research Laboratories, Sankyo Co. Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan
Received 12 April 1999; accepted 30 April 1999
Abstract
We report herein, efficient and practical synthetic methods for the preparation of enantiomerically pure
spiro[((2S)-hydroxy)indane-1,40-piperidine] (S)-1, a key intermediate for the synthesis of a tachykinin receptor
antagonist, using catalytic asymmetric reduction or catalytic asymmetric epoxidation as a key step. © 1999 Elsevier
Science Ltd. All rights reserved.
1. Introduction
Spiro-substituted piperidine analogues are important compounds as subunits in a number of biologi-
cally active compounds. Spiro[(2-hydroxy)indane-1,40 -piperidine] 1 has been known as a component
of growth hormone secretagogues,1 and also as one of the key constituents of a tachykinin receptor
antagonist.2 In the course of our studies on tachykinin receptor antagonists, we have synthesized
a variety of spiro-substituted piperidine analogues. Among these analogues, the compounds which
possess properties such as spiro[((2S)-hydroxy)indane-1,40 -piperidine] (S)-1 or spiro[benzo[c]thiophene-
1(3H),40-piperidine]-(2S)-oxide (S)-23 moiety had strong binding affinities to the tachykinin receptor.
Preliminary studies indicated that the stereochemistry of the hydroxy group of 1 and sulfoxide of 2 has
great impact on the binding activity to tachykinin receptor, and the (S)-configuration has been shown to
be an essential requirement for more potent binding affinities.
∗
Corresponding author. E-mail: takahi@shina.sankyo.co.jp
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00172-X

1788
T. Takemoto et al. / Tetrahedron: Asymmetry 10 (1999) 1787–1793
The conformations of these spiro-piperidine analogues clearly play a key role in binding to the
tachykinin receptor. The aromatic rings of (S)-1 and (S)-2 are required to exploit a hydrophobic or π–π
interaction with the receptor, and the secondary hydroxy group of 1 and sulfoxide of 2 are needed for
high affinity to the receptor, probably through their actions as hydrogen bond acceptors or donors, or due
to the steric effect. In fact, geometry optimizations of 1 and 2 were carried out using the semiempirical
molecular orbital method PM3 in the program SPARTAN. It was found that both compounds have very
similar conformations, as shown in Fig. 1.
Figure 1. Stereoview of the superimposition of stable conformers of (S)-1 (bold line) and (S)-2 (solid line)
In a previous paper,1 racemic N-Boc-(RS)-1 was prepared by hydroboration of indene analogue
3 as a mixture with the 3-hydroxy derivative. Studies to date have yet to address successfully the
enantioselective preparation of both enantiomers of 1. We report herein, efficient and practical synthetic
methods for the preparation of enantiomerically pure (S)-1. The key features of our approach are Corey’s
CBS-oxazaborolidine-catalyzed reduction of ketone 5, and Jacobsen’s asymmetric epoxidation of indene
derivative 3 followed by reductive opening of the epoxide (Scheme 1).
Scheme 1.
2. Results and discussion
At first, we focused on the asymmetric reduction of ketone 5. Ketone 5 was synthesized according
to Scheme 2. Epoxide 4 was obtained in 95% yield by treating indene 34 with aqueous H2O2 and
pyridine in the presence of a catalytic amount of methyltrioxorhenium(VII) in CH2Cl2,5 and subsequent
regioselective reductive opening6 of the epoxide produced racemic N-Boc-(RS)-1 in 86% yield. Next,
N-Boc-(RS)-1 was oxidized to ketone 5 with pyridinium chlorochromate (PCC) in 86% yield. While
there are a great number of chiral reducing agents described in the literature, we focused our attention on
CBS (Corey–Bakshi–Shibata)-oxazaborolidine catalysts,7 an extremely important class of asymmetric
reducing catalysts. Actually, by treating ketone 5 with 5.0 mol% of (R)-2-methyl-CBS-oxazaborolidine
6 as catalyst and BH3–THF (0.5 equiv.) as the reducing reagent in THF at room temperature for 30 min,
we obtained N-Boc-(S)-1 with 89% ee in quantitative yield (Scheme 2). This synthesis also led to the
synthesis of N-Boc-(R)-1 with the opposite configuration by using (S)-2-methyl-CBS-oxazaborolidine
instead of (R)-2-methyl-CBS-oxazaborolidine.

T. Takemoto et al. / Tetrahedron: Asymmetry 10 (1999) 1787–1793
1789
Scheme 2. Reagents: (a) methyltrioxorhenium(VII) (2 mol%), H2O2, pyridine, CH2Cl2 (95%); (b) 5% Pd–C, HCO2NH4,
dioxane, 80°C (86%); (c) PCC, MS 4A, CH2Cl2 (86%); (d) (R)-2-methyl-CBS-oxazaborolidine 6 (5 mol%), BH3–THF, THF
(100%, 89% ee)
The ee of N-Boc-(S)-1 could be determined by HPLC analysis. The secondary alcohol was converted
to the 4-nitrobenzoate with 4-nitrobenzoyl chloride and triethylamine in CH2Cl2, and the resulting
4-nitrobenzoate was analyzed by chiral HPLC (column, CHIRALPAK AD (4.6φ×250 mm); eluent,
50:50 n-hexane:2-propanol mixture; flow rate, 0.5 mL/min; tR of (S)-isomer, 10.1 min; tR of (R)-
isomer, 17.1 min). The stereochemistry of (S)-1 was confirmed by X-ray analysis of α-methoxy-α-
trifluoromethylphenylacetic acid (MTPA) amide of (S)-1. A single-crystal X-ray structure determination
of (R)-MTPA amide of (S)-1 unambiguously established the relative configuration, and hence, the
absolute stereochemistry of the hydroxy group is S, as shown in Fig. 2.8
Figure 2. X-Ray ORTEP of (R)-MTPA amide of (S)-1
As an alternative method, asymmetric epoxidation of 3 followed by reductive epoxide opening is a
straightforward route to N-Boc-(S)-1. In the past few years, a number of highly promising strategies
for asymmetric epoxidation catalysis have been successfully developed. Among these strategies, the
use of Jacobsen’s (salen)Mn(III)Cl9 complexes is effective for the catalysis of the asymmetric epo-
xidation. High enantioselectivities and yields are obtained for a variety of substrates, especially cis-
alkenes. Asymmetric epoxidation of 3 using Jacobsen’s (S,S)-N,N0-bis(3,5-di-tert-butylsalicylidene)-
1,2-cyclohexanediaminomanganese(III) chloride 7 was investigated in various combinations of solvent,
oxidant, and additive, and selected results are summarized in Table 1.
High enantioselectivities and moderate chemical yields were obtained under a variety of conditions. A
screening of appropriate solvents for oxidation showed a dramatic solvent effect, and the best solvent was
dichloromethane. On the other hand, the oxidants and additives had little effect on the enantioselectivities.
The ee of (2R,3S)-4 could be determined directly by chiral HPLC analysis (column, CHIRALCEL OD
(4.6φ×250 mm); eluent, 80:20 n-hexane:2-propanol mixture; flow rate, 0.5 mL/min; tR of (2S,3R)-
isomer, 10.7 min; tR of (2R,3S)-isomer, 13.2 min). This method also led to the synthesis of N-Boc-(R)-1
with the opposite configuration by using (R,R)-(salen)Mn(III)Cl.

1790
T. Takemoto et al. / Tetrahedron: Asymmetry 10 (1999) 1787–1793
Table 1
Asymmetric epoxidation of 3
The resulting epoxide (2R,3S)-4 was then subjected to reductive opening with 5% Pd–C and HCO2NH4
in dioxane at 80°C to provide the desired N-Boc-(S)-1 in 86% yield. Thus, two complementary
approaches to the conversion of 3 to N-Boc-(S)-1 were explored. Single recrystallization of the resulting
N-Boc-(S)-1 (87–93% ee) from n-hexane and ethyl acetate produced enantiomerically pure N-Boc-(S)-
24
1 (>99% ee) as white crystals (mp 105–107°C, [α]D +50.0 (c 1.0, MeOH)) in 70–80% recovery.
Subsequent deprotection of the Boc group with 4 N HCl/dioxane produced (S)-1 HCl salt as white
crystals (mp 246–248°C, [α]D24 +46.2 (c 0.5, MeOH)) in 93% yield (Scheme 3).
Scheme 3. Reagents: (a) 5% Pd–C, HCO2NH4, dioxane, 80°C (86%); (b) 4 N HCl/dioxane, room temperature (93%)
In conclusion, potentially useful and effective methods for the preparation of (S)-1 have been achieved.
The enantiomerically pure (S)-1 prepared by the above methods has been successfully incorporated into
a number of tachykinin receptor antagonists. The results of this work will be published elsewhere.
3. Experimental
3.1. General
All melting points were measured on a Yanaco MP-500D micro melting point apparatus and are
uncorrected. Optical rotations were measured with a JASCO P-1030 digital polarimeter. The IR spectra

T. Takemoto et al. / Tetrahedron: Asymmetry 10 (1999) 1787–1793
1791
were measured on a JASCO FT/IR 8300 spectrophotometer as KBr plates, and peaks are reported in
cm−1. 1H NMR spectra were recorded on a JEOL JNM-GSX 400 spectrometer in CDCl3 or DMSO-d6.
1H NMR chemical shifts are reported in ppm downfield of internal tetramethylsilane. Mass spectra were
recorded using a JEOL JMS-BU 20 or JMS-700 spectrometer. Thin layer chromatography (TLC) was
used routinely to monitor the progress and purity of compounds and was performed on Merck Kieselgel
60 F254 plates. For flash column chromatography, silica gel (Kieselgel 60, 230–400 mesh) was employed.
3.2. N-tert-Butoxycarbonyl-spiro[((2,3)-epoxy)indane-1,40 -piperidine] 4
N-tert-Butoxycarbonyl-spiro(1H-indene-1,40 -piperidine) 3 (10.0 g, 35.1 mmol) and 174 mg (0.70
mmol, 2.0 mol%) of methyltrioxorhenium(VII) were dissolved in 20 mL of CH2Cl2. To this solution,
0.67 mL (8.40 mmol, 24.0 mol%) of pyridine was added, and then 7.90 mL (70.0 mmol, 1.5 equiv.) of
30% aqueous H2O2 was added dropwise from a syringe at 0°C over a period of 10 min. The resulting
mixture was stirred for 5 h at rt. After the addition of 70.0 mL (70.0 mmol) of a 1.0 M aqueous solution
of sodium hypochlorite, the resulting mixture was stirred for 1 h. Water was added and the resulting
mixture was extracted with AcOEt. The organic extract was washed with brine and then dried over
anhydrous Na2SO4. The solvent was then removed in vacuo, and the residue was purified by silica gel
flash column chromatography (eluent, n-hexane:AcOEt=2:1) to obtain 4 (10.0 g, 95% yield) as white
crystals. Mp 148–150°C. IR (KBr) νmax: 2949, 1679, 1424, 1365, 1244, 1168, 765 cm−1; 1H NMR (400
MHz, CDCl3): δ 7.49 (1H, d, J=7.3 Hz), 7.32–7.15 (3H, m), 4.28 (1H, d, J=2.9 Hz), 4.11 (1H, d, J=2.9
Hz), 4.30–4.03 (2H, m), 3.15 (2H, broad t, J=12.0 Hz), 1.95–1.74 (3H, m), 1.51 (9H, s), 1.58–1.50 (1H,
m); MS (EI) m/z: 301 (M+). Anal. calcd for C18H23NO3: C, 71.74; H, 7.69; N, 4.65. Found: C, 71.59; H,
7.54; N, 4.64.
3.3. N-tert-Butoxycarbonyl-spiro[(2-hydroxy)indane-1,40 -piperidine] N-Boc-(RS)-1
N-tert-Butoxycarbonyl-spiro[((2,3)-epoxy)indane-1,40 -piperidine] 4 (10.0 g, 33.2 mmol) was dissolv-
ed in 1,4-dioxane (200 mL). To the resulting solution, 12.0 g of ammonium formate and 300 mg of
5% palladium–carbon were added, followed by stirring at 80°C for 1 h. To the reaction mixture, 6.0 g
of ammonium formate and 150 mg of 5% palladium–carbon were added and the resulting mixture was
stirred for 1 h. After the reaction mixture was allowed to stand at rt, it was filtered. The solvent of the
filtrate was removed in vacuo, and the residue was purified by silica gel flash column chromatography
(eluent, n-hexane:AcOEt=3:1) to obtain N-Boc-(RS)-1 (8.60 g, 86% yield) as white crystals. IR (KBr)
ν
max: 3349, 2934, 1698, 1425, 1367, 1168, 1162 cm−1; 1H NMR (400 MHz, CDCl3): δ 7.28–7.18 (4H,
m), 4.50 (1H, dd, J=4.9, 1.9 Hz), 4.07–3.83 (2H, m), 3.32 (1H, dd, J=16.7, 4.9 Hz), 3.30–3.12 (2H, m),
2.86 (1H, dd, J=16.7, 1.9 Hz), 2.08–1.99 (1H, m), 1.89–1.78 (1H, m), 1.49 (9H, s), 1.64–1.42 (2H, m);
MS (FAB) m/z: 304 (M+H)+. Anal. calcd for C18H25NO3: C, 71.26; H, 8.31; N, 4.62. Found: C, 70.99;
H, 8.24; N, 4.68.
3.4. N-tert-Butoxycarbonyl-spiro[(2-indanone)-1,40 -piperidine] 5
N-tert-Butoxycarbonyl-spiro[(2-hydroxy)indane-1,40 -piperidine] N-Boc-(RS)-1 (8.10 g, 26.7 mmol)
was dissolved in 160 mL of CH2Cl2. To the resulting solution, 8.10 g of molecular sieves (4 Å, powder)
and 11.5 g (53.4 mmol) of pyridinium chlorochromate were added under ice-cooling, followed by stirring
for 30 min at rt. After the addition of 250 mL of Et2O to the reaction mixture, the resulting mixture was
filtered through Celite. The filtrate was concentrated under reduced pressure, and the residue was purified

1792
T. Takemoto et al. / Tetrahedron: Asymmetry 10 (1999) 1787–1793
by silica gel flash column chromatography (eluent, n-hexane:AcOEt=5:1) to afford 5 (6.91 g, 86% yield)
as white crystals. IR (KBr) νmax: 2931, 1749, 1686, 1417, 1366, 1178, 1150, 1031, 757 cm−1; 1H NMR
(400 MHz, CDCl3): δ 7.46–7.22 (4H, m), 3.93 (2H, broad s), 3.60 (2H, s), 3.52 (2H, broad s), 1.79–1.76
(4H, m), 1.50 (9H, s); MS (EI) m/z: 301 (M+). Anal. calcd for C18H23NO3: C, 71.74; H, 7.69; N, 4.65.
Found: C, 71.75; H, 7.79; N, 4.57.
3.5. N-tert-Butoxycarbonyl-spiro[((2S)-hydroxy)indane-1,40 -piperidine] N-Boc-(S)-1
To 0.42 mL (0.42 mmol) of a 1.0 M toluene solution of (R)-2-methyl-CBS-oxazaborolidine, a THF
(8.30 mL) solution of 2.50 g (8.30 mmol) of N-tert-butoxycarbonyl-spiro[(2-indanone)-1,40 -piperidine]
5 and 4.20 mL of a 1.0 M THF solution of BH3–THF complex were added, each at a rate of 1.0 mL/min.
The resulting mixture was stirred at rt for 1 h, followed by the addition of water under ice-cooling. After
extraction of the reaction mixture with AcOEt, the organic extract was washed with brine and dried over
anhydrous Na2SO4. The solvent was then removed in vacuo, and the residue was purified by silica gel
flash column chromatography (eluent, n-hexane:AcOEt=1:1) to afford N-Boc-(S)-1 (2.51 g, 100% yield)
as white crystals of optical purity 89% ee. The resulting crystals were dissolved in 5.0 mL of AcOEt under
heating in a water bath. After the addition of 150 mL of n-hexane, the resulting mixture was allowed to
stand to yield 1.91 g of white crystals. The same procedure was repeated again to furnish 1.52 g (yield:
61%, >99% ee) of N-Boc-(S)-1 as white crystals. The ee of N-Boc-(S)-1 was determined by subjecting
the 4-nitrobenzoate to chiral HPLC analysis [column, CHIRALPAK AD (4.6φ×250 mm); eluent, 50:50
n-hexane:2-propanol mixture; flow rate, 0.5 mL/min; tR(S)=10.1 min, tR(R)=17.1 min]. Mp 105–107°C.
[α]D24 +50.0 (c 1.0, MeOH); IR (KBr) νmax: 3349, 2934, 1698, 1425, 1367, 1168, 1162 cm−1; 1H NMR
(400 MHz, CDCl3): δ 7.28–7.18 (4H, m), 4.50 (1H, dd, J=4.9, 1.9 Hz), 4.07–3.83 (2H, m), 3.32 (1H, dd,
J=16.7, 4.9 Hz), 3.30–3.12 (2H, m), 2.86 (1H, dd, J=16.7, 1.9 Hz), 2.08–1.99 (1H, m), 1.89–1.78 (1H,
m), 1.49 (9H, s), 1.64–1.42 (2H, m); MS (FAB) m/z: 304 (M+H)+. Anal. calcd for Cl8H25NO3: C, 71.26;
H, 8.31; N, 4.62. Found: C, 70.99; H, 8.24; N, 4.68.
3.6. N-tert-Butoxycarbonyl-spiro[((2R,3S)-epoxy)indane-1,40 -piperidine] (2R,3S)-4
N-tert-Butoxycarbonyl-spiro(1H-indene-1,40 -piperidine) 3 (100 mg, 0.35 mmol) was dissolved in
CH2Cl2 (2.0 mL). To the resulting solution, 11.4 mg (0.018 mmol) of (S,S)-(+)-N,N0-bis(3,5-di-tert-
butylsalicylidene)-1,2-cyclohexanediaminomanganese(III) chloride was added, followed by the addition
of 19.0 mg (0.11 mmol) of 4-phenylpyridine N-oxide. The resulting mixture was stirred for 10 min.
After the addition of 0.7 mL (0.7 mmol) of a 1.0 M aqueous solution of sodium hypochlorite, the
resulting mixture was stirred for 2 h. Water was added and the resulting mixture was extracted with
AcOEt. The organic extract was washed with brine and dried over anhydrous Na2SO4. The solvent
was removed in vacuo, and the residue was purified by silica gel flash column chromatography (eluent,
n-hexane:AcOEt=2:1) to afford (2R,3S)-4 (53.6 mg, 51% yield) as white crystals of 91% ee. The ee
of (2R,3S)-4 was determined by chiral HPLC analysis [column, CHIRALCEL OD (4.6φ×250 mm);
eluent, 80:20 n-hexane:2-propanol mixture; flow rate, 0.5 mL/min; tR(2S,3R)=10.7 min, tR(2R,3S)=13.2
min]. Single recrystallization of the resulting (2R,3S)-4 (87–93% ee) from n-hexane and AcOEt yielded
24
enantiomerically pure (2R,3S)-4 (>99% ee) as white crystals. Mp 148–150°C. [α]D +62.2 (c 1.0,
MeOH). IR (KBr) νmax: 2949, 1679, 1424, 1365, 1244, 1168, 765 cm−1; 1H NMR (400 MHz, CDCl3):
δ 7.49 (1H, d, J=7.3 Hz), 7.32–7.15 (3H, m), 4.28 (1H, d, J=2.9 Hz), 4.11 (1H, d, J=2.9 Hz), 4.30–4.03
(2H, m), 3.15 (2H, broad t, J=12.0 Hz), 1.95–1.74 (3H, m), 1.51 (9H, s), 1.58–1.50 (1H, m); MS (EI)
m/z: 301 (M+). Anal. calcd for Cl8H23NO3: C, 71.74; H, 7.69; N, 4.65. Found: C, 71.62; H, 7.67; N, 4.59.

T. Takemoto et al. / Tetrahedron: Asymmetry 10 (1999) 1787–1793
1793
3.7. N-tert-Butoxycarbonyl-spiro[((2S)-hydroxy)indane-1,40 -piperidine] N-Boc-(S)-1
According to a similar procedure for the preparation of N-Boc-(RS)-1, N-Boc-(S)-1 (109 mg) was
prepared in 86% yield from (2R,3S)-4 (125 mg, 0.42 mmol) as white crystals. The physiochemical
properties of this compound were the same as those of the product produced as described in Section 3.5.
3.8. Spiro[((2S)-hydroxy)indane-1,40 -piperidine] hydrochloride (S)-1·HCl
N-tert-Butoxycarbonyl-spiro[((2S)-hydroxy)indane-1,40 -piperidine] N-Boc-(S)-1 (1.50 g, 4.95 mmol)
was dissolved in EtOH (12.4 mL). To the resulting solution, 6.20 mL of 4 N solution of hydrogen chloride
in 1,4-dioxane was added under ice-cooling, followed by stirring at rt for 5 h. The solvent was removed in
vacuo, and the residue was washed with Et2O to afford (S)-1·HCl (1.10 g, 93% yield) as white crystals.
24
Mp 246–248°C. [α]D +46.2 (c 0.50, MeOH); IR (KBr) νmax: 3413, 3269, 2937, 1607, 1431, 1074,
765 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 8.98 (2H, m), 7.22–7.17 (4H, m), 5.20 (1H, d, J=5.0 Hz),
4.40–4.37 (1H, m), 3.26–3.13 (5H, m), 2.77 (1H, dd, J=16.5, 3.2 Hz), 2.07 (1H, d, J=14.0 Hz), 1.99–1.82
(2H, m), 1.60 (1H, d, J=14.0 Hz); MS (EI) m/z: 203 ((M+); free form). Anal. calcd for C13H18NOCl: C,
65.13; H, 7.57; N, 5.84; Cl, 14.79. Found: C, 64.89; H, 7.48; N, 5.82; Cl, 15.01.
Acknowledgements
We are grateful to Mr. Yoji Furukawa for the X-ray analysis.
References
1. Tata, J. R.; Nargund, R. P.; Murphy, M. M.; Johnston, D. B. R.; Patchett, A. A.; Cheng, K.; Wei, L.; Chan, W. W.-S.; Butler,
B.; Jacks, T. M.; Hickey, G.; Smith, R. Bioorg. Med. Chem. Lett. 1997, 7, 663–668.
2. Unpublished studies.
3. Nishi, T.; Fukazawa, T.; Ishibashi, K.; Nakajima, K.; Sugioka, Y.; Iio, Y.; Kurata, H.; Itoh, K.; Mukaiyama, O.; Satoh,
Y.; Yamaguchi, T. Bioorg. Med. Chem. Lett. 1999, 9, 875–880. Synthesis: Nishi, T.; Nakajima, K.; Iio, Y.; Ishibashi, K.;
Fukazawa, T. Tetrahedron: Asymmetry 1998, 9, 2567–2570.
4. Chambers, M. S.; Baker, R.; Billington, D. C.; Knight, A. K.; Middlemiss, D. N.; Wong, E. H. F. J. Med. Chem. 1992, 35,
2033–2039.
5. Rudolph, J.; Reddy, K. L.; Chiang, J. P.; Sharpless, K. B. J. Am. Chem. Soc. 1997, 119, 6189–6190.
6. Varghese, J. P.; Sudalai, A.; Iyer, S. Synth. Commun. 1995, 25, 2267–2273.
7. (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987, 109, 5551–5553. (b) Corey, E. J.; Bakshi, R. K.;
Shibata, S.; Chen, C.-P.; Singh, V. K. J. Am. Chem. Soc. 1987, 109, 7925–7926. The asymmetric reduction using chirally
modified borohydride as a catalyst has been in use since 1981 (Hirao, A.; Itsuno, S.; Nakahama, S.; Yamazaki, N. J. Chem.
Soc., Chem. Commun. 1981, 315–317). For a review on asymmetric boron-catalyzed reactions, see: Deloux, L.; Srebnik,
M. Chem. Rev. 1993, 93, 763–784.
8. Crystal data of (R)-MTPA amide of (S)-1: C23H24NO3F3, MW=419.4, T=298 K, CuKα radiation, λ=1.5418 Å;
monoclinic, space group P21, a=14.923(4) Å, b=7.121(4) Å, c=19.863(3) Å, β=91.27(2)°, V=2110(1) Å3, Z=4, Dc=1.32
g/cm3, R=0.065. Full X-ray crystallographic data will be deposited with the Cambridge Crystallographic Data Centre.
9. (a) Palucki, M.; McCormik, G. J.; Jacobsen, E. N. Tetrahedron Lett. 1995, 36, 5457–5460. (b) Jacobsen, E. N.; Zhang,
W.; Muci, A. R.; Ecker, J. R.; Deng, L. J. Am. Chem. Soc. 1991, 113, 7063–7064. (c) Zhang, W.; Jacobsen, E. N. J. Org.
Chem. 1991, 56, 2296–2298. For a review on recent progress in asymmetric epoxidation, see: Jacobsen, E. N. In Catalytic
Asymmetric Synthesis; Ojima, I., Ed; VCH: New York, 1993; Chapter 4.2, pp. 159–202 and references cited therein.