Syntheses of chiral β-amino α-perfluoroalkylpropanol derivatives

Article abstract of DOI:10.1016/j.tetasy.2007.11.011

Chiral β-amino α-perfluoroalkylpropanol derivatives were synthesized from N-Boc-l-phenylalanine methyl ester by substitution of the methoxy group into the corresponding perfluoroalkyl chain, followed by reduction and deprotection. Among them, a Schiff bas

Full text of DOI:10.1016/j.tetasy.2007.11.011

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 18 (2007) 2768–2772
Syntheses of chiral b-amino a-perfluoroalkylpropanol derivatives
Masaaki Omote, Yusuke Eto, Atsushi Tarui, Kazuyuki Sato and Akira Ando*
Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata 573-0101, Japan
Received 31 August 2007; accepted 7 November 2007
Abstract—Chiral b-amino a-perfluoroalkylpropanol derivatives were synthesized from N-Boc-L-phenylalanine methyl ester by substitu-
tion of the methoxy group into the corresponding perfluoroalkyl chain, followed by reduction and deprotection. Among them, a Schiff
base prepared by condensation of (2S,3S)-2-amino-3-perfluorooctyl-1-phenylpropan-3-ol, (2S,3S)-1, and 1-naphthaldehyde catalyzed
the asymmetric ethyl addition reaction of diethylzinc with the aldehyde to afford the product up to 93% ee.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
the a-perfluoroalkylated-alkoxide was expected to show
higher Lewis acidity than the original one. Further-
more, the hydroxy group would become less sensitive
toward oxidation and dehydration. On the basis of these
expectations, we designed four b-amino a-Rf -alcohols
carrying perfluorobutyl or perfluorooctyl chain, (2S,3S)-
or (2S,3R)-2-amino-3-perfluoroalkyl-1-phenylpropan-3-ol
(Fig. 1). Herein, we report the syntheses of these b-amino
a-Rf -alcohols, 1 and 2, and the preliminary results on their
application in the asymmetric addition reaction of diethyl-
zinc with benzaldehyde.
The discovery of a b-amino alcohol-catalyzed dialkylzinc
alkylation by Oguni1 opened up a new field of asymmetric
synthesis. Diverse chiral b-amino alcohols, especially de-
signed for the asymmetric alkylation with dialkylzinc, have
been elaborated from commercially available chiral sources
such as amino acid,2 camphor,3,4 and sugar derivatives.5
Other useful derivatives such as salen, oxazoline, and
dipeptides have also been well studied and shown outstand-
ing activity.6 In contrast to these, some challenges, how-
ever, still remain with Schiff base-type ligand. Low
coordination property of the Schiff base to diethylzinc
requires use of Lewis acid such as Ti(OiPr)4.7,8 Recently,
Schiff base ligands derived from [2.2]paracyclophane were
reported with high catalytic performance in the same asym-
metric ethyl addition using diethylzinc to afford a product
of 93% ee without any help of a Lewis acid.9 We expected
that the catalytic reactivity of the Schiff base ligands would
be mainly influenced by the neighboring hydroxy group,
which participates in the chelation with zinc. Our previous
study on chiral ligands containing perfluoroalkyl carbinol
moieties10 led to a chiral b-amino a-perfluoroalkylated-
alcohol (b-amino a-Rf -alcohol) for Schiff base ligands.
The following advantages are expected in the b-amino
a-Rf-alcohol. The higher acidic a-perfluoroalkylated-
alcohol compared with the non-fluorinated one allows easy
ligand replacement with Lewis acidic metals such as
Ti(OiPr)4 or Et2Zn. The resulting chelate complex containing
NH2
NH2
C8F17
C8F17
OH
)-1
OH
)-1
(2
S,3
S
(2
S,3
R
NH2
NH2
C4F9
C4F9
OH
)-2
OH
)-2
(2
S,3
S
(2
S,3
R
Figure 1. Structures of perfluoroalkyl substituted b-amino alcohols.
2. Results and discussion
We started the synthesis of 1 and 2 from the introduction
of the Rf chain into N-Boc-L-phenylalanine methyl ester,
(S)-3. The introduction of the Rf group was conducted
by using Hultin’s method.11 Following the literature, RfLi
*
Corresponding author. Tel.: +81 72 866 3140; fax: +81 72 850 7020;
e-mail: aando@pharm.setsunan.ac.jp
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.11.011

M. Omote et al. / Tetrahedron: Asymmetry 18 (2007) 2768–2772
2769
prepared by the reaction of methyllithium with the corre-
sponding RfI was examined for Rf-introduction. However,
easy decomposition of the RfLi to a carbene species or the
b-elimination decreased a chemical yield in that reac-
tion.12,13 The problem was solved by using RfMgBr pre-
pared in the same manner with ethylmagnesium bromide
instead of methyllithium. RfMgBr was stable below
ꢀ65 ꢁC14 and no decomposition was observed. The reac-
tions of RfMgBr with (S)-3 were successful for obtaining
products, (S)-4 and 5, with different lengths of the Rf group
(Scheme 1). In this reaction, the second addition of an Rf
group to 4 or 5 was prevented, probably due to the stable
tetrahedral intermediate of the first adduct. In this process,
control of the reaction temperature and time was impor-
tant to avoid racemization of the a-carbon. Chiral HPLC
analysis indicated that no racemization was observed when
the reaction temperature reached to 0 ꢁC; however, elonga-
tion of the reaction time to 2 h at room temperature caused
complete racemization. Products 4 and 5 were subjected to
reduction of the Rf ketones with NaBH4 and subsequent
acid treatment. The reduction proceeded so fast that no
racemization was observed in chiral HPLC analysis. The
diastereomers in 1 or 2 were easily separated by silica-gel
column chromatography to give enantiomerically pure
(2S,3R)- and (2S,3S)-1 or 2, respectively. 1H NMR analysis
of 1 showed a broad singlet peak assigned to three protons
of the amino and hydroxy groups around 2 ppm. That
peak demonstrates the possibility of intramolecular hydro-
gen bonding between the amino and hydroxy groups. The
hydrogen bonding would decrease the basicity of the nitro-
gen, thus allowing easy handling under air. The configura-
tions of diastereomers of 1 were determined according to
Kitazume’s method.15 They reported the typical H–H cou-
pling constant between H4 and H5 in 5-trifluoro-
methyloxazolidinone derivatives. Namely, the coupling
constant in the cis-configuration is larger than that of the
trans one. For the determination, both diastereomers of 1
were converted to oxazolidinone derivatives, 6 and 7, by
reaction with triphosgene. The 1H NMR study of their
derivatives identified their configuration as shown in
Scheme 2.
operations owing to their instability toward moisture.
These freshly prepared and purified Schiff bases, 8 and 9,
were employed directly as ligand for diethylzinc in the
asymmetric ethyl addition reaction. The results on the ethyl
addition reaction are summarized in Table 1. Some types of
Schiff base ligands were prepared while searching the effec-
tive backbone structure of Schiff base ligand. Salicylalde-
hyde, 2-pyridinecarbaldehyde, and benzaldehyde were
chosen for that purpose. Ligand 8a prepared by condensa-
tion of (2S,3S)-1 and salicylaldehyde showed low catalytic
reactivity. The phenolic alcohol allowing the r bond with
zinc might concern with the low ee (Table 1, entries 1
and 2). In the case of 2-pyridinecarbaldehyde, 8b capable
of coordinating zinc slightly improved the catalytic reactiv-
ity (entries 3 and 4).
A considerable improvement in both the catalytic and
asymmetric performance was achieved by 8c prepared from
1 and benzaldehyde. Concerning the two stereoisomers
(2S,3S)- and (2S,3R)-8c, we recognized a large difference
in their asymmetric induction. The former exhibited out-
standing performance in the asymmetric reaction to afford
86% ee of the product. The stereochemistry of the product
was controlled by the geometry of the alcohol carrying a
perfluoroalkyl-tail in the ligand. On the basis of these re-
sults, we carried on searching for a superior Schiff base li-
gand by changing the aldehyde moiety as well as changing
the length of Rf chain. To determine electrostatic and steric
effects of the benzene ring on its asymmetric performance,
substituted benzaldehydes were tested. Ligands 8–9d with
an electron-donating methyl group and 8–9e with elec-
tron-withdrawing fluorine showed almost the same perfor-
mance between the corresponding d and e products (entries
7–14). This suggests that the electrostatic effect of the aryl
moiety is negligible for asymmetric induction. Next, the
steric effect of the aryl moiety was investigated. 1- and 2-
Naphthaldehydes were chosen for that. Ligand (2S,3S)-8f
revealed the best performance in the asymmetric reaction
to afford 93% ee of the product in quantitative yield (entry
15). Compared with (2S,3S)-8f, (2S,3S)-9f, with a short-
ened Rf chain, afforded the product with an ee which
slightly decreased to 89% (entry 17). This suggests that
the length of the Rf chain was also an important factor
for acquiring high asymmetric performance of the ligand.
In the cases of 8–9g, small decreases were observed on
the asymmetric inductions of them compared with the cor-
responding 8–9f. Among Schiff base ligands, the one de-
rived from [2.2]paracyclophane has been reported to give
an outstanding asymmetric performance in the same ethyl
addition to give 93% ee of the product. However, a long
reaction time (15 h at room temperature) is required for
obtaining a high chemical yield. Schiff base ligand
(2S,3S)-8f was able to catalyze the reaction with the same
To estimate the asymmetric inductions of 1 and 2, several
Schiff bases were prepared by condensation with the appro-
priate aldehydes in the presence of anhydrous MgSO4. The
suspended material was filtered off and purified through
short silica-gel column chromatography to give Schiff base,
1
8 or 9. H NMR analysis and low resolution MS spectra
indicated the formation of 8 or 9, and the peaks that orig-
inated during the formation of oxazolidine derivative were
not observed. The purities of 8 and 9 after the purification
step were confirmed immediately by GC to be more than
95%, however, they were hydrolyzed gradually during
(
S
)-1 (90%)
RfI (3.0 eq.)
EtMgBr (3.0 eq.)
NHBoc
Rf
NHBoc
OMe
1) NaBH4 (2.0 eq.)
THF
(2
S
,3
R
)/(2 ,3 ) = 58:42
S S
Bn
Bn
(
R
S)-2 (90%)
Et2O, -78 ºC
2) TFA, CH2Cl2
O
(2S
,3
)/(2 ,3 ) = 55:45
S S
O
(S)-3
(
(
S
S
)-4 Rf = C8F17 (68%)
)-5 Rf = C4F9 (60%)
Scheme 1.

2770
M. Omote et al. / Tetrahedron: Asymmetry 18 (2007) 2768–2772
Jvic = 3.7 Hz
O
Jvic = 7.8 Hz
O
(CCl3O)2CO
DIPEA
(CCl3O)2CO
DIPEA
HN
H4
Bn
O
H5
C8F17
HN
H4
Bn
O
H5
C8F17
(2S,3S)-1
(2S,3R)-1
4
5
5
4
6
7
Scheme 2.
Table 1. Asymmetric induction of Schiff base ligands, 8 and 9, for Et2Zn in the reaction with benzaldehyde
Rf
Bn
OH
*
MgSO4
MeOH
RCHO
(1.0 equiv.)
1
+
N
8 Rf = C8F17
9 Rf = C4F9
R
OH
8 or 9 (10 mol%)
Et2Zn
PhCHO
+
(2.5 equiv.)
PhCH3, 0 ˚C to rt, 6 h
*
Ph
Et
Entry
Ligand
R of 8 or 9
Yield (%)
eea (%)
Config.b
1
2
3
4
5
6
7
8
(2S,3S)-8a
(2S,3R)-8a
(2S,3S)-8b
(2S,3R)-8b
(2S,3S)-8c
(2S,3R)-8c
(2S,3S)-8d
(2S,3R)-8d
(2S,3S)-9d
(2S,3R)-9d
(2S,3S)-8e
(2S,3R)-8e
(2S,3S)-9e
(2S,3R)-9e
(2S,3S)-8f
(2S,3R)-8f
(2S,3S)-9f
(2S,3R)-9f
(2S,3S)-8g
(2S,3R)-8g
(2S,3S)-9g
(2S,3R)-9g
2-Hydroxyphenyl
38
99
82
99
94
99
91
90
96
94
90
89
82
94
99
99
97
95
97
98
99
97
18
19
42
52
86
44
77
42
78
50
78
49
73
55
93
67
89
69
82
44
81
49
(S)
(R)
(S)
(R)
(S)
(R)
(S)
(R)
(S)
(R)
(S)
(R)
(S)
(R)
(S)
(R)
(S)
(R)
(S)
(R)
(S)
(R)
2-Pyridyl
Phenyl
3-Methylphenyl
9
10
11
12
13
14
15
16
17
18
19
20
21
22
3-Fluorophenyl
1-Naphthyl
2-Naphthyl
a Determined by chiral GC analysis.
b Determined by comparing the sign of the specific rotation with reported ones.
asymmetric performance and also shorten the reaction time
to 6 h at room temperature. The short reaction time, which
might be given by perfluoroalkylcarbinol, is an advantage
of using 8f.
reaction to benzaldehyde. Further applications of this
ligand to other aldehydes and asymmetric syntheses are
now in progress.
4. Experimental
4.1. General
3. Conclusions
In conclusion, we have succeeded in the syntheses of 1 and
2 which possess perfluorooctyl and perfluorobutyl chains,
respectively. The Rf chains were effectively introduced into
(S)-3 by using Grignard reagents prepared by the corres-
ponding perfluoroalkyl iodide and ethylmagnesium bromide.
Subsequent reduction of the Rf ketone and deprotection
afforded 1 and 2. Schiff base (2S,3S)-8f obtained by con-
densation of (2S,3S)-1 and 1-naphthaldehyde was an effec-
tive ligand for diethylzinc in the asymmetric ethyl addition
All reactions were conducted under an argon atmosphere
unless noted otherwise. Chemicals were treated as follows:
THF, ether, and toluene were distilled from Na/benzophe-
1
none; other chemicals were used as received. H and 13C
NMR spectra were recorded on GSX-400 (400 MHz,
JEOL) or ECA-600 (600 MHz, JEOL) Spectrometers and
19F NMR spectra were recorded on FT-NMR R-
1500 (60 MHz, Hitachi) or ECP-600 (600 MHz, JEOL)

M. Omote et al. / Tetrahedron: Asymmetry 18 (2007) 2768–2772
2771
Spectrometers at ambient probe temperature and refer-
3.0 mmol) in THF (6 mL) was added NaBH4 (227 mg,
6.0 mmol) at 0 ꢁC after which the mixture was warmed to
room temperature. After stirring the mixture for 3 h at
the same temperature, the reaction was quenched by add-
ing saturated aqueous NH4Cl. After separation of the lay-
ers, the aqueous layer was extracted with CHCl3. The
combined organic layers were dried over MgSO4, filtered,
and condensed in vacuo to give the crude product. The
crude product was dissolved in CH2Cl2 (3 mL) and TFA
(3 mL, 40 mmol). After stirring for 30 min at room temper-
ature, aqueous 10% NaOH was added to the solution to
adjust the pH to 8 to allow precipitation of the product.
The precipitate was collected by suction filtration and the
solid was purified by silica-gel column chromatography
(MeOH/CHCl3 = 2:98) and obtained as a white solid
1
enced as follows: H and 13C, TMS; 19F, BTF. IR spectra
were measured on an Hitachi 270-30 IR Spectrophotome-
ter. Mass spectra were recorded on JMS-DX-300 or
JMS-700 T (JEOL) Spectrometers. Ee was determined by
GLC with GAMMA DEXTM 225 Capillary Column
(30 m · 0.25 mm · 0.25 lm). Optical rotations were mea-
sured by DIP-140 (JASCO).
4.1.1. (S)-(1-Benzyl-3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-hep-
tadecafluoro-2-oxo-decyl)-carbamic acid tert-butyl ester
(S)-4. To
a
solution of ethylmagnesium bromide
(7.2 mL, 3.0 M in Et2O, 21.6 mmol) in Et2O (50 mL) was
slowly added a solution of C8F17I (11.8 g, 21.6 mmol) in
Et2O (35 mL) keeping the temperature below ꢀ65 ꢁC under
an atmosphere of Ar. After stirring for 30 min at ꢀ78 ꢁC, a
solution of (S)-3 (2.0 g, 7.2 mmol) in Et2O (15 mL) was
added to the solution at the same temperature. The solu-
tion was stirred for 1 h at ꢀ70 ꢁC and then warmed to
0 ꢁC. The reaction was then quenched by the addition of
saturated aqueous NH4Cl when the solution temperature
was reached to 0 ꢁC. After separation of the layers, the
aqueous layer was extracted with CHCl3. The combined
organic layers were dried over MgSO4, filtered, and con-
densed in vacuo to give the crude product. The desired
product was purified by silica-gel column chromatography
(0.63 g for (2S,3S)-1, 0.87 g for (2S,3R)-1, 90% total).
24
(2S,3S)-1: White solid; mp 92.5–93.1 ꢁC. ½aꢁD ¼ ꢀ3:7 (c
1.04, CHCl3). 1H NMR (CDCl3) d: 7.22–7.37 (5H, m),
3
3
3.89 (1H, dd, JH,F = 23.9 Hz, JH,H = 4.2 Hz), 3.67–3.70
2
3
(1H, m), 2.90 (1H, dd, JH,H = 13.9 Hz, JH,H = 5.6 Hz),
2
3
2.72 (1H, dd, JH,H = 14.2 Hz, JH,H = 9.8 Hz), 1.81 (3H,
br). 13C NMR (CDCl3, 1H19F-COM) d: 137.0, 129.2,
129.0, 127.2, 117.2, 116.8, 111.5, 111.2, 110.9, 110.8,
110.3, 108.4, 69.1, 49.4, 40.5. 19F NMR (CDCl3) d: ꢀ63.3
(2F, m), ꢀ61.7 (1F, d, J = 281.9 Hz), ꢀ59.8 (2F, m),
ꢀ58.1 to ꢀ59.2 (8F, m), ꢀ54.4 (1F, d, J = 282.8 Hz),
ꢀ18.0 (3F, t, J = 10.3 Hz). IR (KBr) cmꢀ1: 3027, 2694,
1701, 1601, 1201. MS m/z: 570 (M++H). HRMS Calcd
for C17H13F17NO: 570.0726 (M++H). Found: 570.0729
(M++H). (2S,3R)-1: White solid; mp 108.7–110.0 ꢁC.
(CHCl3/hexane = 3:7) and obtained as a white solid (2.8 g,
24
68%). White solid; mp 73.8–74.4 ꢁC. ½aꢁD ¼ þ16:3 (c 1.07,
CHCl3). 1H NMR (CDCl3) d: 7.14–7.35 (5H, m), 5.08
3
3
(1H, dd, JH,H = 12.9 Hz, JH,H = 7.1 Hz), 4.89 (1H, d,
24
3JH,H = 7.9 Hz), 3.24 (1H, dd, JH,H = 14.0 Hz, JH,H
=
½aꢁD ¼ ꢀ72:5 (c 1.00, CHCl3). H NMR (CDCl3) d: 7.20–
2
3
1
2
3
3
3
5.0 Hz), 2.90 (1H, dd, JH,H = 13.9 Hz, JH,H = 7.9 Hz),
7.36 (5H, m), 4.20 (1H, dt, JH,F = 24.2 Hz, JH,H =
3.2 Hz), 3.38 (1H, dt, JH,H = 11.0 Hz, JH,H = 3.4 Hz),
3.13 (1H, d, JH,H = 14.2 Hz), 2.68 (1H, ddd, JH,H =
1.38 (s, 9H). 13C NMR (CDCl3, H19F-COM) d: 193.5,
1
3
3
2
2
154.6, 134.4, 129.4, 128.9, 127.5, 119.9, 117.2, 116.9,
114.5, 110.9, 110.7, 110.2, 109.5, 108.4, 56.8, 36.8, 28.1.
19F NMR (CDCl3) d: ꢀ63.3 (2F, m), ꢀ58.3 to ꢀ59.9
(11F, m), ꢀ56.8 (1F, dt, J = 294.0 Hz, J = 12.9 Hz),
ꢀ54.2 (1F, dt, J = 294.0 Hz, J = 12.1 Hz), ꢀ18.0 (3F, t,
J = 15.8 Hz). IR (KBr) cmꢀ1: 3370, 2984, 1770, 1703,
1521, 1200. MS m/z: 667 (M+). HRMS Calcd for
C22H18F17NO3: 667.1015 (M+). Found: 667.1007 (M+).
3
4
14.6 Hz, JH,H = 12.2 Hz, JH,H = 1.6 Hz), 2.04 (3H, br).
13C NMR (CDCl3, H19F-COM) d: 137.7, 129.2, 129.0,
1
127.1, 117.3, 111.4, 111.2, 110.9, 110.8, 110.3, 110.2,
108.4, 69.8, 54.2, 38.0. 19F NMR (CDCl3) d: ꢀ64.3 (1F,
d, J = 284.5 Hz), ꢀ63.4 (2F, m), ꢀ59.9 (2F, m), ꢀ58.3 to
ꢀ59.4 (8F, m), ꢀ57.3 (1F, d, J = 279.3 Hz), ꢀ18.0 (3F, t,
J = 9.5 Hz). IR (KBr) cmꢀ1: 3358, 3098, 1665, 1614,
1201. MS m/z: 570 (M++H). HRMS Calcd for
C17H13F17NO: 570.0726 (M++H). Found: 570.0718
(M++H).
4.1.2.
(S)-(1-Benzyl-3,3,4,4,5,5,6,6,6-nonafluoro-2-oxo-
hexyl)-carbamic acid tert-butyl ester ((S)-5). The
procedure was the same as in the case of (S)-4. Mp 87.9–
24
1
88.7 ꢁC. ½aꢁD ¼ þ29:6 (c 1.00, CHCl3). H NMR (CDCl3)
4.1.4. (2S,3S)- and (2S,3R)-2-Amino-4,4,5,5,6,6,7,7,7-nona-
fluoro-1-phenylheptan-3-ol ((2S,3S)- and (2S,3R)-2). The
procedure was the same as in the case of 1. (2S,3S)-2.
3
d: 7.14–7.35 (5H, m), 5.07 (1H, dd, JH,H = 16.0 Hz,
3JH,H = 6.8 Hz), 4.88 (1H, d, JH,H = 7.6 Hz), 3.24 (1H,
3
24
2
3
1
dd, JH,H = 14.5 Hz, JH,H = 4.7 Hz), 2.89 (1H, dd,
Mp 74.7–75.1 ꢁC. ½aꢁD ¼ ꢀ3:7 (c 1.05, CHCl3). H NMR
2JH,H = 14.8 Hz, JH,H = 7.3 Hz), 1.38 (s, 9H). 13C NMR
(CDCl3) d: 7.21–7.37 (5H, m), 3.89 (1H, dd,
3
(CDCl3, H19F-COM) d: 193.4, 154.7, 134.5, 129.5, 128.9,
3JH,F = 24.2 Hz, JH,H = 4.2 Hz), 3.66–3.70 (1H, m), 2.90
1
3
2
3
127.6, 117.3, 114.6, 110.3, 109.5, 108.6, 56.9, 36.8, 28.2.
19F NMR (CDCl3) d: ꢀ62.7 (2F, m), ꢀ59.8 (2F, m),
ꢀ56.9 (1F, dt, J = 295.7 Hz, J = 12.1 Hz), ꢀ54.4 (1F, dt,
J = 294.8 Hz, J = 12.1 Hz), ꢀ18.2 (3F, t, J = 9.5 Hz). IR
(KBr) cmꢀ1: 3369, 2987, 1762, 1699, 1518, 1251. MS m/z:
467 (M+). HRMS Calcd for C18H18F9NO3: 467.1143
(M+). Found: 467.1138 (M+).
(1H, dd, JH,H = 13.9 Hz, JH,H = 5.6 Hz), 2.72 (1H, dd,
2JH,H = 14.2 Hz, JH,H = 9.5 Hz), 2.00 (3H, br). 13C
3
NMR (CDCl3, H19F-COM) d: 137.0, 129.2, 129.0, 127.2,
1
117.5, 116.7, 112.3, 108.8, 69.1, 49.3, 40.6. 19F NMR
(CDCl3) d: ꢀ64.5 (1F, d, J = 286.2 Hz), ꢀ64.0 to ꢀ64.6
(2F, m), ꢀ62.3 to ꢀ62.9 (2F, m), ꢀ59.5 to ꢀ60.7 (2F,
m), ꢀ57.4 (1F, d, J = 297.6 Hz), ꢀ18.2 (3F, t,
J = 11.4 Hz). IR (KBr) cmꢀ1: 3029, 2688, 1599, 1457,
1221. MS m/z: 370 (M++H). HRMS Calcd for
C13H13F9NO: 370.0853 (M++H). Found: 370.0855
(M++H). (2S,3R)-2: White solid; mp 96.1–96.7 ꢁC.
4.1.3. (2S,3S)- and (2S,3R)-2-Amino-4,4,5,5,6,6,7,7,8,
8,9,9,10,10,11,11,11-heptadecafluoro-1-phenyl-undecan-3-ol
(2S,3S)- and (2S,3R)-1. To a solution of (S)-4 (2.0 g,

2772
24
M. Omote et al. / Tetrahedron: Asymmetry 18 (2007) 2768–2772
1
2. (a) Delair, P.; Einhorn, C.; Einhorn, J.; Luche, J. L. J. Org.
Chem. 1994, 59, 4680–4682; (b) Beliczey, J.; Giffels, G.; Kragl,
U.; Wandrey, C. Tetrahedron: Asymmetry 1997, 8, 1529–
1530; (c) Sibi, M. P.; Chen, J.-X.; Cook, G. R. Tetrahedron
Lett. 1999, 40, 3301–3304; (d) Dai, W.-M.; Zhu, H. J.; Hao,
X.-J. Tetrahedron: Asymmetry 1995, 6, 1857–1860; (e) Soai,
K.; Ookawa, A.; Kaba, T.; Ogawa, K. J. Am. Chem. Soc.
1987, 109, 7111–7115; (f) Yang, X.; Shen, J.; Da, C.; Wang,
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Asymmetry 1999, 10, 133–138; (g) Kawanami, Y.; Mitsuie, T.;
Miki, M.; Sakamoto, T.; Nishitani, K. Tetrahedron 2000, 56,
175–178; (h) Huang, H.-L.; Lin, Y.-C.; Chen, S.-F.; Wang,
C.-L.; Liu, L. T. Tetrahedron: Asymmetry 1996, 7, 3067–3070.
3. (a) Kitamura, M.; Suga, S.; Kawai, K.; Noyori, R. J. Am.
Chem. Soc. 1986, 108, 6071–6072; (b) Genov, M.; Kostova,
K.; Dimitrov, V. Tetrahedron: Asymmetry 1997, 8, 1869–
1876; (c) Nugent, W. A. J. Chem. Soc., Chem. Commun. 1999,
½aꢁD ¼ ꢀ12:9 (c 1.01, CHCl3). H NMR (CDCl3) d: 7.19–
3
3
7.36 (5H, m), 4.23 (1H, dtd, JH,F = 24.0 Hz, JH,H
=
4
3
3.8 Hz, JH,H = 1.2 Hz), 3.37 (1H, dt, JH,H = 11.3 Hz,
3JH,H = 3.5 Hz), 3.12 (1H, d, JH,H = 14.6 Hz), 2.67 (1H,
2
2
3
4
ddd, JH,H = 14.0 Hz, JH,H = 12.4 Hz, JH,H = 1.4 Hz),
2.44 (3H, br). 13C NMR (CDCl3, H19F-COM) d: 138.3,
1
129.2, 128.9, 126.9, 117.5, 117.4, 110.9, 108.9, 70.3, 54.0,
38.6. 19F NMR (CDCl3) d: ꢀ64.0 to ꢀ64.6 (2F, m),
ꢀ62.3 to ꢀ62.9 (2F, m), ꢀ61.8 (1F, d, J = 283.6 Hz),
ꢀ59.3 to ꢀ60.8 (2 F, m), ꢀ54.9 (1F, d, J = 299.4 Hz),
ꢀ18.2 (3F, t, J = 10.2 Hz). IR (KBr) cmꢀ1: 3070, 2858,
1613, 1456, 1230. MS m/z: 370 (M++H). HRMS Calcd
For C13H13F9NO: 370.0853 (M++H). Found: 370.0851
(M++H).
1369–1370; (d) Knollmuller, M.; Ferencic, M.; Ga¨rtner, P.;
¨
4.1.5. General procedure for asymmetric ethyl addition
(Table 1). To a suspension of MgSO4 (100 mg) in metha-
nol (1 mL) was added 1 (0.05 mmol) and the appropriate
aldehyde (0.05 mmol) under atmosphere of Ar. After stir-
ring for 30 min at room temperature, the solid was filtered
off and the filtrate was evaporated. The crude 8 or 9 was
purified by short silica-gel column chromatography with
chloroform (if necessary, a small amount of methanol)
and the fractions containing 8 or 9 were collected. After
removal of the solvent in vacuo, 8 (or 9) was subjected
directly to the next reaction. All amounts of diethylzinc,
aldehyde, and solvent were adjusted based on that of 8
or 9 obtained. To the solution of 8 or 9 (0.05 mmol) in tol-
uene (0.3 mL) was added diethylzinc (2.5 mmol, 1.0 M in
hexane solution) at 0 ꢁC. After stirring for 30 min at the
same temperature, a solution of benzaldehyde (0.5 mmol)
in toluene (0.1 mL) was added slowly. The mixture was
stirred for 6 h at room temperature. The reaction was
quenched by the addition of 10% of aqueous HCl and
the organic layer was collected. The aqueous layer was ex-
tracted with ether and the combined organic layers were
dried over MgSO4. After filtration of the solid, the solvent
was removed in vacuo to give the crude product. The de-
sired product was purified by silica-gel column chromato-
graphy (ether/hexane = 1:9) and the chemical yield and
ee were detected. (S)-1-Phenylpropan-1-ol: 93% ee
determined by chiral GC analysis. Retention time:
tminor = 5.7 min, and tmajor = 6.9 min (120 ꢁC).
Mereiter, K.; Noe, C. R. Tetrahedron: Asymmetry 1998, 9,
4009–4020; (e) Chelucci, G.; Soccolini, F. Tetrahedron:
Asymmetry 1992, 3, 1235–1238; (f) Collomb, P.; von
Zelewsky, A. Tetrahedron: Asymmetry 1998, 9, 3911–3917.
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30, 49–69.
5. (a) Cho, B. T.; Kim, N. J. Chem. Soc., Perkin Trans. 1 1996,
2901–2907; (b) Cho, B. T.; Kim, N. Synth. Commun. 1995, 25,
167–175; (c) Cho, B. T.; Kim, N. Tetrahedron Lett. 1994, 35,
4115–4118; (d) Yang, W. K.; Cho, B. T. Tetrahedron:
Asymmetry 2000, 11, 2947–2953; (e) Cho, B. T.; Chun, Y.
S. Tetrahedron: Asymmetry 1998, 9, 1489–1492; (f) Cho, B.
T.; Chun, Y. S.; Yang, W. K. Tetrahedron: Asymmetry 2000,
11, 2149–2157; (g) Ikota, N.; Inaba, H. Chem. Pharm. Bull.
1996, 44, 587–589.
6. Lin Pu, L.; Yu, H.-B. Chem. Rev. 2001, 101, 757–824.
7. Mino, T.; Oishi, K.; Yamashita, M. Synlett 1998, 965–966.
8. Fleischer, R.; Braun, M. Synlett 1998, 1441–1443.
9. Danilova, T. I.; Rozenberg, V. I.; Sergeeva, E. V.; Zoya, A.;
Starikova, Z. A.; Bra¨se, S. Tetrahedron: Asymmetry 2003, 14,
2013–2019.
10. (a) Omote, M.; Nishimura, Y.; Sato, K.; Ando, A.; Kuma-
daki, I. Tetrahedron 2006, 62, 1886–1894; (b) Sokeirik, Y. S.;
Omote, M.; Sato, K.; Kumadaki, I.; Ando, A. Tetrahedron:
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11. Hein, J. E.; Geary, L. M.; Jaworski, A. A.; Hultin, P. G.
J. Org. Chem. 2005, 70, 9940–9946.
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