The pentafluorophenyl group as a module for the direct modification of chiral diamines for asymmetric catalysis

Article abstract of DOI:10.1016/j.tetasy.2008.02.024

A pentafluorophenyl group embedded in a chiral diamine allows the direct modification of an aryl group. The diamine is readily converted into para-disubstituted diamines. Although the electronic effect of the modified diamine somewhat lowers the catalytic

Full text of DOI:10.1016/j.tetasy.2008.02.024

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 695–700
The pentafluorophenyl group as a module for the direct modification
of chiral diamines for asymmetric catalysis
Toshinobu Korenaga,* Kenji Nomura, Shinichi Minami, Hitomi Sasaki and Takashi Sakai*
Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University,
3-1-1 Tsushima-naka, Okayama 700-8530, Japan
Received 16 January 2008; accepted 22 February 2008
Abstract—A pentafluorophenyl group embedded in a chiral diamine allows the direct modification of an aryl group. The diamine is read-
ily converted into para-disubstituted diamines. Although the electronic effect of the modified diamine somewhat lowers the catalytic
activity of BINAP–Ru–diamine-catalyzed asymmetric hydrogenation, the enantioselectivity of the product is higher than that obtained
by using a typical chiral diamine. Such an easy and direct modification of the chiral ligand has the potential to facilitate the optimization
of the steric effect of chiral ligands in asymmetric catalysis.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Indirect modification
X
Asymmetric catalysts are crucial to the synthesis of useful
chiral compounds. Typically, a homogeneous asymmetric
catalyst is a metal complex containing one or more organic
chiral ligands, which control the electronic and steric (chi-
ral) environment of the metal catalyst.1 Therefore, the
development of the chiral ligand plays an important role
in the development of an asymmetric catalyst. In many
cases, many chiral ligands are screened in order to achieve
high activity with high enantioselectivity in asymmetric
catalysis. Although the electronic effect of the ligand often
influences the enantioselectivity, stereo-regulation is mainly
achieved by utilizing the repulsive interactions between the
ligand and the reactive substrate. Accordingly, partial
modification of chiral ligands to tune the steric effect is
required in order to improve the enantioselectivity in asym-
metric catalysis. However, the preparation of the modified
ligands is often complicated and hinders research. For
example, 1,2-diphenylethylenediamine (DPEN 1, Scheme
1) is one of the most useful chiral ligands for asymmetric
catalysis. However, DPEN analogues bearing substituted
aryl groups cannot be prepared directly from 1 (Scheme
1). Instead, they must be synthesized via inconvenient
asymmetric synthesis using individual starting materials,
such as imines.2 If a direct modification of the original chi-
X
NH2
NH2
H2N
H2N
(S,S)-DPEN 1
X
DPEN analogues
X
NR
Direct modification
F
F
F
F
X
F
F
F
F
F
F
F
F
F
NH2
NH2
X
F
F
F
X
H2N
H2N
F
F
(S,S)-2
(S,S)-3
Scheme 1. Direct modification of diamines bearing the C6F5 group.
ral ligand is possible, optimization of the chiral ligand in
asymmetric catalysis will be facilitated. For this reason,
we have focused on a pentafluorophenyl (C6F5) group as
a modifiable module in a chiral ligand, because this group
is readily attacked by various nucleophiles to afford the
para-substituted tetrafluorophenyl group (Scheme 1).3
*
Corresponding authors. Tel./fax: +81 86 251 8092; e-mail: tsakai@cc.
okayama-u.ac.jp
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.02.024

696
T. Korenaga et al. / Tetrahedron: Asymmetry 19 (2008) 695–700
Herein, we report the effectiveness of the C6F5 group
embedded in the chiral ligand as a modifiable unit. The chi-
ral diamine 2 bearing two C6F5 groups4 is used as the ori-
ginal ligand for self-modification at the para-position. The
modified diamines 3 are used as ligands for Noyori–Ohku-
ma’s asymmetric hydrogenation catalyst5 to find the di-
amine ligand that exhibits an effective steric environment
at the para-positions of the aryl groups.6
of 6a was improved when increasing the amount of KOH
(Table 1, entries 2–4).11 As a result, when 4a with 8 equiv
of KOH for the Ru complex was used for the hydrogena-
tion of 5a, 6a was obtained in 95% yield (Table 1, entry
4). Although a marginal negative phenomenon was caused
by the electronic effect of 3a, the catalytic system of 4a with
KOH acted as a suitable hydrogenation catalyst.
Table 1. Catalytic activities of catalysts 4a and 7
4a
RuCl2[(S)-binap][(S,S)-3a]
or
RuCl2[(S)-binap][(S,S)-1]
2. Results and discussion
7
OH
O
Chiral diamine 2 was readily converted into para-disubsti-
tuted (S,S)-3. The modification of 2 was performed using
an alkoxide to avert the necessity of protection of the ami-
no groups of 2.7 For example, (S,S)-2 was exposed to
KOH/methanol at room temperature for 3 h to afford
(S,S)-3a in a quantitative yield. The modification of
(S,S)-2 afforded 11 types of para-disubstituted diamines
3a–k (Scheme 2). However, substitution with tert-butoxy
group was unsuccessful. The direct modification of 2 with
alkoxide was found to be limited to primary or secondary
alkoxides. Consequently, we could obtain a series of dia-
mines 3 for screening the ligands in asymmetric catalysis
within a short period of time.
(S/C 1000)
KOH
2-propanol
H2, 8 atm
27°C, 1h
5a
6a
Entry
Catalysts
KOH (equiv)
Yield (%)
1
2
3
4
5
4a
4a
4a
4a
7
2
4
6
8
2
39
79
89
95
>99
Asymmetric hydrogenations of 5a were studied by using
RuCl2[(S)-binap](dmf)n and (S,S)-3a–k, which afforded
RuCl2[(S)-binap][(S,S)-3a–k] 4a–k in situ, to explore the
most sterically favored substituent at the para-position of
the aryl groups in 3, affording the highest enantioselectivity
in the product. All the reactions were performed with
8 equiv of KOH for the Ru complex in 2-propanol under
H2 (8 atm) at 27 °C for 4 h to afford 6a in a quantitative
yield. All the products showed higher enantioselectivities
than those obtained by using 7, which afforded 6a in 82%
ee (Table 2, entries 1–11 vs 13). Even the use of 4a, which
F
F
F
RO
F
F
F
F
F
F
NH2
NH2
ROH
KOH
F
F
F
H2N
H2N
F
F
F
F
F
F
OR
(S,S)-2
(S,S)-3
3e:
RO-
Ph
Ph
3a: MeO-
3b: iPrO-
3c:
3d:
O
O
O
O
Table 2. Asymmetric hydrogenation of acetophenone
RuCl2[(S)-binap](dmf)
n4
/ (S,S)-3
3g:
3h:
3f:
3i:
O
O
or
RuCl2[(S)-binap](dmf)
n 7
OH
O
/ (S,S)-1
Ph
Ph
H
Me
(S/C 1000)
3j:
3k:
O
H
O
(S)-
O
(R)-
Me
KOH
2-propanol
H2, 8 atm
27°C, 4 h
5a
(R)-6a
quant.
Scheme 2. Easy modification of the diamine at the para-position of the
C6F5 group.
Entry
Catalysts (diamine)
ee of 6a (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
4a [(S,S)-3a]
4b [(S,S)-3b]
4c [(S,S)-3c]
4d [(S,S)-3d]
4e [(S,S)-3e]
4f [(S,S)-3f]
4g [(S,S)-3g]
4h [(S,S)-3h]
4i [(S,S)-3i]
4j [(S,S,S)-3j]
4k [(S,S,R)-3k]
4l [(S,S)-3l]
7 [(S,S)-1]
87
92
90
89
90
91
91
89
90
88
90
84
82
Before screening the ligands for asymmetric hydrogena-
tion, we verified the electronic influence of the fluorinated
diamine 3 on the Ru catalyst.8,9 Diamine 3a was complexed
with RuCl2[(S)-binap](dmf)n in CDCl3 to afford RuCl2[(S)-
binap][(S,S)-3a] 4a quantitatively,10 although 3a had a
weak electron-donating ability. Unfortunately, the hydro-
genation of acetophenone 5a using 4a with 2 equiv of
KOH with respect to the Ru complex in 2-propanol under
8 atm of H2 at 27 °C for 1 h afforded alcohol 6a in a low
yield (39%), although the reaction using RuCl2[(S)-binap]-
[(S,S)-1] 7 afforded 6a in a quantitative yield under the
same conditions (Table 1, entry 1 vs 5). However, the yield

T. Korenaga et al. / Tetrahedron: Asymmetry 19 (2008) 695–700
697
had the smallest alkoxy substituents, afforded 6a with 87%
ee (Table 2, entry 1). The reason for the high enantioselec-
tivity obtained when using 4 as compared with that ob-
tained when using 7 is assumed to be the steric effect of
the para-substituent of 3, because the hydrogenation using
4l included 2,3,5,6-tetrafluorophenyl analogue 3l, which
was synthesized by the reductive defluorination of 2
(Scheme 3),12 gave only 84% ee of 6a (Table 2, entry 12).
Among diamines 3, the hydrogenation using 4b, which in-
cluded 3b bearing an isopropoxy substituent, showed the
highest enantioselectivity of 92% ee (Table 2, entry 2).
Therefore, we performed the hydrogenation of the other
ketones 5b–i using 4b (Table 3). The enantioselectivities
of 6, excluding those of the ortho-substituted aromatics
6h and 6i, were higher than that using 7. The results indi-
cated that we could easily find out the generally effective li-
gand whose ability is greater than that of DPEN 1.
diamine (S,S)-3b, which has an influential steric effect for
the Noyori–Ohkuma asymmetric hydrogenation, can be
easily found after the screening reaction using RuCl2[(S)-
binap][(S,S)-3]. The pentafluorophenyl group in the chiral
diamine facilitated the ligand screening process in the
asymmetric hydrogenation. Although the electronic effect
of the para-substituted tetrafluorophenyl group in the
ligand must be considered, the introduction of a pentaflu-
orophenyl group as a modifiable module into other chiral
ligands may turn into one method for avoiding the compli-
cated screening required for tuning the steric effect of the
chiral ligands for asymmetric catalyses.
4. Experimental
Asymmetric hydrogenations were carried out with de-
gassed solvents under an argon atmosphere. Dehydrated
2-propanol was purchased from Kanto Chemical Co. and
stored in Schlenk tubes under an argon atmosphere after
degassing via freeze–thaw cycles. Reagents were purchased
at the highest commercial quality and used without further
purification, unless otherwise stated. Preparative column
chromatography was carried out by using silica gel (Fuji
Silysia BW-127 ZH, 100–270 mesh) or neutral silica gel
(nacalai tesque Silica Gel 60, spherical, neutrality). HPLC
analysis was carried out by using Daicel CHIRALCEL
OD-H, U 4.6 mm ꢀ 25 cm, with the mixed solvent indi-
cated. 1H and 13C NMR spectra were measured at
300 MHz and 75 MHz, respectively, and chemical shifts
are given relative to tetramethylsilane (TMS). 19F NMR
spectra were measured at 282 MHz, and chemical shifts
are given relative to CCl3F using C6F6 as a secondary ref-
erence (ꢁ162.9 ppm). 31P NMR spectra were measured at
121 MHz, and chemical shifts are given relative to H3PO4
as an external standard.
H
F
F
F
NH2
Zn
(S,S)-2
F
F
NH3 / H2O
H2N
THF
F
F
rt, 3 days
F
H
(S,S)-3l
Scheme 3. Synthesis of (S,S)-3l by reductive defluorination of (S,S)-2.
Table 3. Asymmetric hydrogenation of aromatic ketones
RuCl2[(S)-binap](dmf)n
4b
/ (S,S)-3b
or
RuCl2[(S)-binap](dmf)n
7
OH
O
/ (S,S)-1
(S/C 1000)
KOH
2-propanol
H2, 8 atm
27°C, 4 h
4.1. Preparation of diamine 3
X
X
5b-i
(R)-6b-i
quant.
4.1.1. (1S,2S)-1,2-Bis(4-methoxy-2,3,5,6-tetrafluorophenyl)-
ethane-1,2-diamine (S,S)-3a.
Entry
X
Catalysts
ee (%)
A
mixture of (S,S)-2
(19.6 mg, 0.0500 mmol) and KOH (28.2 mg, 0.500 mmol)
in methanol (1.0 mL) was stirred at room temperature for
3 h. The solvent was removed under reduced pressure.
The residue was poured into water (5 mL) and extracted
with Et2O (3 ꢀ 5 mL). The combined organic extract was
washed with brine. The organic layer was dried over
MgSO4, and concentrated under reduced pressure to afford
a crude oil, which was purified by column chromatography
(neutral SiO2, CH2Cl2/MeOH, 30:1) to give (S,S)-3a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
4-Me (5b)
4-Me (5b)
4-MeO (5c)
4-MeO (5c)
4-F (5d)
4b
7
84 (6b)
79 (6b)
87 (6c)
80 (6c)
73 (6d)
73 (6d)
91 (6e)
88 (6e)
87 (6f)
84 (6f)
81 (6g)
70 (6g)
92 (6h)
93 (6h)
42 (6i)
77 (6i)
4b
7
4b
7
4-F (5d)
3-Me (5e)
3-Me (5e)
3-MeO (5f)
3-MeO (5f)
3-F (5g)
4b
7
4b
7
(20.8 mg, 0.0500 mmol) in 100% yield: white solid; mp
4b
7
20
56–58 °C; ½aꢂD ¼ ꢁ85:8 (c 0.50, MeOH); IR (KBr, cmꢁ1
)
3-F (5g)
3371, 2957, 1651, 1495, 1196, 1128, 978; 1H NMR
(300 MHz, CDCl3) d 4.45 (s, 2H), 4.02 (t, J = 1.5 Hz,
6H), 2.03 (br, 4H); 13C NMR (75 MHz, CDCl3 (except
for C6F4)) d 62.0, 52.5; 19F NMR (282 MHz, CDCl3) d
ꢁ145.7 to ꢁ145.6 (m, 4F), ꢁ158.7 to ꢁ158.6 (m, 4F); Anal.
Calcd for C16H12F8N2O2: C, 46.17; H, 2.91; N, 6.73;
Found: C, 46.27; H, 3.04; N, 6.70. HLPC analysis:
2-Me (5h)
2-Me (5h)
2-MeO (5i)
2-MeO (5i)
4b
7
4b
7
3. Conclusion
hexane/i-PrOH/Et2NH (70:30:0.2), 0.5 mL minꢁ1
, UV
Herein, we have demonstrated that (S,S)-2 was readily con-
verted into 11 types of para-disubstituted (S,S)-3, and then
254 nm, retention time (tR); (S,S)-3a: 22.3 min (>99%),
(R,R)-3a: 36.1 min (0%).

698
T. Korenaga et al. / Tetrahedron: Asymmetry 19 (2008) 695–700
4.1.2. (1S,2S)-1,2-Bis(4-isopropoxy-2,3,5,6-tetrafluorophen-
yl)ethane-1,2-diamine (S,S)-3b. Compound (S,S)-3b was
prepared from (S,S)-2 (19.6 mg, 0.0500 mmol), KOH
(56.1 mg, 1.00 mmol), and 2-propanol (1.0 mL) in 98%
was prepared from (S,S)-2 (19.6 mg, 0.0500 mmol), KOH
(56.1 mg, 1.00 mmol), and 2,2-dimethyl-1-propanol
(2.00 g, 22.7 mmol) in 91% yield (24.0 mg, 0.0454 mmol)
by the procedure described for (S,S)-3a at 55 °C for 18 h:
30
yield (23.2 mg, 0.0491 mmol) by the procedure described
yellow oil; ½aꢂD ¼ ꢁ89:2 (c 0.45, MeOH); IR (neat, NaCl
30
for (S,S)-3a: colorless oil; ½aꢂD ¼ ꢁ92:5 (c 0.21, MeOH);
plate, cmꢁ1) 3387, 3310, 2962, 1651, 1504, 1366, 1265,
IR (neat, NaCl plate, cmꢁ1) 3387, 3325, 2986, 1651,
1134, 986; H NMR (300 MHz, CDCl3) d 4.45 (s, 2H),
1
1
1489, 1381, 1242, 1103, 980; H NMR (300 MHz, CDCl3)
3.79 (s, 4H), 2.08 (br, 4H), 1.01 (s, 18H); 13C NMR
(75 MHz, CDCl3 (except for C6F4)) d 84.9, 52.6, 32.7,
26.0; 19F NMR (282 MHz, CDCl3) d ꢁ145.9 to ꢁ145.8
(m, 4F), ꢁ157.9 to ꢁ157.8 (m, 4F); Anal. Calcd for
C24H28F8N2O2: C, 54.54; H, 5.34; N, 5.30; Found: C,
54.76; H, 5.54; N, 4.97. HLPC analysis: hexane/i-PrOH/
Et2NH (70:30:0.4), 0.5 mL minꢁ1, UV 254 nm, retention
time (tR); (S,S)-3e: 16.1 min (>99%), (R,R)-3e: 24.5 min
(0%).
d 4.47 (m, 2H), 4.42 (s, 2H), 2.03 (br, 4H), 1.29 (d,
J = 6.2 Hz, 12H); 13C NMR (75 MHz, CDCl3 (except for
C6F4)) d 78.0, 52.8, 22.1; 19F NMR (282 MHz, CDCl3) d
ꢁ145.9 to ꢁ145.8 (m, 4F), ꢁ157.0 to ꢁ156.9 (m, 4F); Anal.
Calcd for C20H20F8N2O2: C, 50.85; H, 4.27; N, 5.93;
Found: C, 50.58; H, 4.26; N, 5.75. HLPC analysis:
hexane/i-PrOH/Et2NH (70:30:0.2), 0.5 mL minꢁ1
, UV
254 nm, retention time (tR); (S,S)-3b: 18.1 min (>99%),
(R,R)-3b: 32.6 min (0%).
4.1.6. (1S,2S)-1,2-Bis(4-cyclopentyloxy-2,3,5,6-tetrafluoro-
phenyl)ethane-1,2-diamine (S,S)-3f. Compound (S,S)-3f
was prepared from (S,S)-2 (9.8 mg, 0.0250 mmol), KOH
(28.1 mg, 0.500 mmol), and cyclopentanol (0.70 mL) in
82% yield (10.7 mg, 0.0204 mmol) by the procedure
4.1.3. (1S,2S)-1,2-Bis(4-(pentan-3-yloxy)-2,3,5,6-tetrafluoro-
phenyl)ethane-1,2-diamine (S,S)-3c. Compound (S,S)-3c
was prepared from (S,S)-2 (19.6 mg, 0.0500 mmol), KOH
(56.1 mg, 1.00 mmol), and 3-pentanol (1.0 mL) in 97% yield
(25.5 mg, 0.0483 mmol) by the procedure described for
described for (S,S)-3a at 50 °C for 6 h: yellow oil;
16
31
(S,S)-3a at 50 °C for 6 h: yellow oil; ½aꢂD ¼ ꢁ51:4 (c 1.6,
½aꢂD ¼ ꢁ77:2 (c 0.54, MeOH); IR (neat, NaCl plate,
MeOH); IR (neat, NaCl plate, cmꢁ1) 3387, 3302, 2970,
cmꢁ1) 3387, 3310, 2939, 1651, 1489, 1373, 1242, 1134,
1
1
1651, 1489, 1381, 1242, 1134, 980; H NMR (300 MHz,
980; H NMR (300 MHz, CDCl3) d 4.78–4.84 (m, 2H),
CDCl3) d 4.41 (s, 2H), 4.13 (quint, J = 5.7 Hz, 2H), 2.07
(br, 4H), 1.57–1.61 (m, 8H), 0.91–0.97 (m, 12H); 13C NMR
(75 MHz, CDCl3 (except for C6F4)) d 87.8, 52.8, 26.2, 9.1;
19F NMR (282 MHz, CDCl3) d ꢁ146.0 to ꢁ145.9 (m 4F),
ꢁ156.9 to ꢁ156.8 (m, 4F); Anal. Calcd for C24H28F8N2O2:
C, 54.54; H, 5.34; N, 5.30; Found: C, 54.41; H, 5.47; N,
5.07. HLPC analysis: hexane/i-PrOH/Et2NH (70:30:0.4),
0.5 mL minꢁ1, UV 254 nm, retention time (tR); (S,S)-3c:
18.1 min (>99%), (R,R)-3c: 31.0 min (0%).
4.41 (s, 2H), 2.08 (br, 4H), 1.61–1.83 (m, 16H); 13C NMR
(75 MHz, CDCl3 (except for C6F4)) d 87.1, 52.8, 32.7,
23.2; 19F NMR (282 MHz, CDCl3) d ꢁ146.0 to ꢁ145.9
(m, 4F), ꢁ157.2 to ꢁ157.1 (m, 4F); Anal. Calcd for
C24H24F8N2O2: C, 54.96; H, 4.61; N, 5.34; Found: C,
55.14; H, 4.91; N, 4.98. HLPC analysis: hexane/i-PrOH/
Et2NH (70:30:0.4), 0.5 mL minꢁ1, UV 254 nm, retention
time (tR); (S,S)-3f: 21.7 min (>99%), (R,R)-3f: 37.0 min
(0%).
4.1.4. (1S,2S)-1,2-Bis(4-benzhydryloxy-2,3,5,6-tetrafluoro-
phenyl)ethane-1,2-diamine (S,S)-3d. A mixture of (S,S)-2
(4.9 mg, 0.0125 mmol), KOH (14.0 mg, 0.250), and benzhy-
drol (0.500 g, 2.71 mmol) in DMF (0.10 mL) was stirred at
50 °C for 24 h. To the reaction mixture was added water,
and the organic layer was extracted with Et2O
(3 ꢀ 2 mL). The combined organic extract was washed
with brine. The organic layer was dried over MgSO4, and
concentrated under reduced pressure to afford a crude
oil, which was purified by column chromatography (neu-
4.1.7. (1S,2S)-1,2-Bis(4-cyclohexyloxy-2,3,5,6-tetrafluoro-
phenyl)ethane-1,2-diamine (S,S)-3g. Compound (S,S)-3g
was prepared from (S,S)-2 (19.6 mg, 0.0500 mmol), KOH
(56.1 mg, 1.00 mmol), and cyclohexanol (1.4 mL) in 77%
yield (21.2 mg, 0.0384 mmol) by the procedure described
32
for (S,S)-3a at 50 °C for 6 h: yellowish oil; ½aꢂD ¼ ꢁ80:2
(c 0.13, MeOH); IR (neat, NaCl plate, cmꢁ1) 3389, 3317,
2939, 1651, 1489, 1373, 1242, 1134, 980; 1H NMR
(300 MHz, CDCl3) d 4.41 (s, 2H), 4.14–4.21 (m, 2H),
1.98 (br, 4H), 1.57–1.88 (m, 8H), 1.51–1.57 (m, 6H),
1.25–1.35 (m, 6H); 13C NMR (75 MHz, CDCl3 (except
for C6F4)) d 82.9, 52.9, 32.0, 25.3, 23.4; 19F NMR
(282 MHz, CDCl3) d ꢁ146.0 to ꢁ145.9 (m, 4F), ꢁ156.9
to ꢁ156.8 (m, 4F); Anal. Calcd for C26H28F8N2O2: C,
56.52; H, 5.11; N, 5.07; Found: C, 56.91; H, 5.32; N,
4.71. HLPC analysis: hexane/i-PrOH/Et2NH (70:30:0.4),
0.5 mL minꢁ1, UV 254 nm, retention time (tR); (S,S)-3g:
21.4 min (>99%), (R,R)-3g: 39.4 min (0%).
tral SiO2, CH2Cl2/MeOH, 30:1) to give (S,S)-3d (8.10 mg,
32
0.0112 mmol) in 90% yield: yellow oil; ½aꢂD ¼ ꢁ41:9 (c
0.19, MeOH); IR (neat, NaCl plate, cmꢁ1) 3395, 3325,
3031, 2962, 1651, 1489, 1265, 1126, 988; 1H NMR
(300 MHz, CDCl3) d 7.28–7.42 (m, 20H), 6.35 (s, 2H),
4.31 (s, 2H), 1.94 (br, 4H); 13C NMR (75 MHz, CDCl3 (ex-
cept for C6F4)) d 139.4, 128.5, 127.0, 86.8, 52.5; 19F NMR
(282 MHz, CDCl3) d ꢁ145.9 to ꢁ145.8 (m, 4F), ꢁ155.1 to
ꢁ155.0 (m, 4F); Anal. Calcd for C40H28F8N2O2: C, 66.67;
H, 3.92; N, 3.89; Found: C, 66.87; H, 4.23; N, 3.79. HLPC
4.1.8.
(1S,2S)-1,2-Bis(2,3,5,6-tetrafluoro-4-(3,3,5,5-tetra-
analysis: hexane/i-PrOH/Et2NH (60:40:0.1), 0.5 mL minꢁ1
,
methylcyclohexyloxy)phenyl)ethane-1,2-diamine (S,S)-3h.
Compound (S,S)-3h was prepared from (S,S)-2 (19.6 mg,
0.0500 mmol), KOH (56.1 mg, 1.00 mmol), 3,3,5,5-tetra-
methylcyclohexanol (2.00 g, 12.8 mmol), and DMF
(0.40 mL) in 58% yield (19.4 mg, 0.0292 mmol) by the pro-
cedure described for (S,S)-3d at 50 °C for 24 h: yellow oil;
UV 254 nm, retention time (tR); (S,S)-3d: 14.8 min (>99%),
(R,R)-3d: 21.9 min (0%).
4.1.5.
(1S,2S)-1,2-Bis(4-neopentyloxy-2,3,5,6-tetrafluoro-
phenyl)ethane-1,2-diamine (S,S)-3e. Compound (S,S)-3e

T. Korenaga et al. / Tetrahedron: Asymmetry 19 (2008) 695–700
699
32
½aꢂD ¼ ꢁ95:8 (c 0.78, MeOH); IR (neat, NaCl plate, cmꢁ1
)
7.34 (m, 10H), 5.39 (q, J = 6.3 Hz, 2H), 4.32 (s, 2H), 1.93
(s, 4H), 1.65 (d, J = 6.3 Hz, 6H); 13C NMR (75 MHz,
CDCl3 (except for C6F4)) d 140.5, 128.6, 128.5, 126.2,
82.5, 52.5, 22.9; 19F NMR (282 MHz, CDCl3) d ꢁ146.1
to ꢁ146.0 (m, 4F), ꢁ156.0 to ꢁ155.9 (m, 4F); Anal. Calcd
for C30H24F8N2O2: C, 60.40; H, 4.06; N, 4.70; Found: C,
60.47; H, 4.13; N, 4.37. HLPC analysis: hexane/i-PrOH/
Et2NH (60:40:0.1), 0.5 mL minꢁ1, UV 254 nm, retention
time (tR); (S,S)-3k: 15.0 min (>99%), (R,R)-3k: 21.9 min
(0%).
1
3402, 3317, 2954, 1651, 1489, 1366, 1242, 1134, 988; H
NMR (300 MHz, CDCl3) d 4.39–4.44 (m, 2H), 4.41 (s,
2H), 1.93 (br, 4H), 1.72–1.80 (m, 4H), 1.07–1.27 (m, 8H),
0.98 (s, 12H), 0.95 (s, 12H); 13C NMR (75 MHz, CDCl3 (ex-
cept for C6F4)) d 80.3, 52.9, 51.3, 45.0, 35.0, 32.6, 27.6; 19
F
NMR (282 MHz, CDCl3) d ꢁ146.0 to ꢁ145.9 (m, 4F),
ꢁ156.9 to ꢁ156.8 (m, 4F); Anal. Calcd for C34H44F8N2O2:
C, 61.43; H, 6.67; N, 4.21; Found: C, 61.82; H, 6.82; N, 4.08.
HLPC analysis: hexane/i-PrOH/Et2NH (70:30:0.4),
0.5 mL minꢁ1, UV 254 nm, retention time (tR); (S,S)-3h:
12.4 min (>99%), (R,R)-3h: 17.0 min (0%).
4.1.12. (1S,2S)-1,2-Bis(2,3,5,6-tetrafluorophenyl)ethane-1,2-
diamine (S,S)-3l. To a solution of (S.S)-2 (20.0 mg,
0.0510 mmol) in THF (0.21 mL) were added zinc powder
(0.500 g, 7.65 mmol), NH4Cl (0.206 g, 3.85 mmol), and
28% aqueous ammonia (2.1 mL). The resulting mixture
was stirred at room temperature for 3 days. Unconsumed
zinc was separated, and filtrate was extracted with ether
(3 ꢀ 5 mL). The combined organic layer was dried over
MgSO4, and concentrated under reduced pressure to afford
crude oil, which was purified by column chromatography
(neutral SiO2, CH2Cl2/MeOH, 30:1) to give (S,S)-3l
4.1.9.
2,3,5,6-tetrafluorophenyl)ethane-1,2-diamine
Compound (S,S)-3i was prepared from (S,S)-2 (19.6 mg,
0.0500 mmol), KOH (56.1 mg, 1.00 mmol), 2-indanol
(2.00 g, 14.9 mmol), and DMF (0.40 mL) in 71% yield
(1S,2S)-1,2-Bis(4-(2,3-dihydro-1H-inden-2-yloxy)-
(S,S)-3i.
(22.0 mg, 0.0355 mmol) by the procedure described for
32
(S,S)-3d at 50 °C for 24 h: yellowish oil; ½aꢂD ¼ ꢁ72:8 (c
0.18, MeOH); IR (neat, NaCl plate, cmꢁ1) 3395, 3317,
3024, 2954, 1651, 1489, 1358, 1134, 980; 1H NMR
(300 MHz, CDCl3) d 7.15–7.44 (m, 8H), 5.17–5.22 (m,
2H), 4.44 (s, 2H), 3.09–3.23 (m, 8H), 1.74 (br, 4H); 13C
NMR (75 MHz, CDCl3 (except for C6F4)) d 139.7, 126.9,
124.7, 85.3, 52.8, 40.0, 39.8; 19F NMR (282 MHz, CDCl3)
d ꢁ145.5 to ꢁ145.4 (m, 4F), ꢁ157.0 to ꢁ156.8 (m, 4F);
Anal. Calcd for C32H24F8N2O2: C, 61.94; H, 3.90; N,
4.51; Found: C, 61.75; H, 4.28; N, 4.15. HLPC analysis:
(11.3 mg, 0.0317 mmol) in 62% yield: colorless oil;
18
½aꢂD ¼ ꢁ61:9 (c 1.8, MeOH); IR (neat, NaCl plate, cmꢁ1
)
3387, 3306, 3084, 2974, 1616, 1502, 1387, 1254, 1175,
920, 851; 1H NMR (300 MHz, CDCl3) d 6.83–6.94 (m,
2H), 4.53 (s, 2H), 2.07 (br, 4H); 13C NMR (75 MHz,
CDCl3 (except for C6F4)) d 105.3, 52.8; 19F NMR
(282 MHz, CDCl3) d ꢁ139.6 to ꢁ139.5 (m, 4F), ꢁ144.5
to ꢁ144.4 (m, 4F); Anal. Calcd for C14H8F8N2: C, 47.20;
H, 2.26; N, 7.86; Found: C, 47.23; H, 2.48; N, 7.67. HLPC
hexane/i-PrOH/Et2NH (60:40:0.1), 0.5 mL minꢁ1
254 nm, retention time (tR); (S,S)-3i: 26.9 min (>99%),
(R,R)-3i: 48.4 min (0%).
, UV
analysis: hexane/i-PrOH/Et2NH (60:40:0.1), 0.5 mL minꢁ1
,
UV 254 nm, retention time (tR); (S,S)-3l: 13.8 min (>99%),
(R,R)-3l: 21.3 min (0%).
4.1.10. (1S,2S)-1,2-Bis(4-((S)-1-phenylethoxy)-2,3,5,6-tetra-
fluorophenyl)ethane-1,2-diamine
(S,S)-3j was prepared from
(S,S,S)-3j. Compound
(S,S)-2 (15.7 mg,
4.2. General procedure for the asymmetric hydrogenation of
ketones
0.0400 mmol), KOH (44.9 mg, 0.800 mmol), and (S)-1-
phenylethanol (1.0 mL) in 86% yield (20.4 mg,
0.0342 mmol) by the procedure described for (S,S)-3a at
RuCl2[(S)-binap](dmf)n (7.5 mg, 8.0 lmol), (S,S)-diamine
3b (3.8 mg, 8.0 lmol), 2-propanol (6.4 mL), and a solution
of KOH/2-propanol (0.5 M, 128 lL, 64 lmol) were placed
in an autoclave under a stream of argon. The mixture was
stirred at room temperature for 30 min. Acetophenone 5a
(0.93 mL, 8.0 mmol) was added to the mixture at room
temperature under a stream of argon, and then hydrogen
was introduced at a pressure of 8 atm. After having vigor-
ously stirred at 27 °C for 4 h, the solvent was removed un-
der reduced pressure. The residue was filtered through a
short column packed with silica gel. Chemical yield and
enantiomeric ratio of phenethyl alcohol 6a were deter-
mined by chiral GC (>99%, 92% ee (R)). GC (column
32
50 °C for 24 h: yellowish oil; ½aꢂD ¼ ꢁ177:3 (c 0.23,
MeOH); IR (neat, NaCl plate, cmꢁ1) 3395, 3317, 3032,
2986, 1651, 1489, 1381, 1211, 1134, 980; 1H NMR
(300 MHz, CDCl3) d 7.28–7.35 (m, 10H), 5.38 (q,
J = 6.6 Hz, 2H), 4.31 (s, 2H), 1.71 (br, 4H), 1.66 (d,
J = 6.6 Hz, 6H); 13C NMR (75 MHz, CDCl3 (except for
C6F4)) d 140.4, 128.7, 128.5, 126.2, 82.5, 52.5, 22.9; 19F
NMR (282 MHz, CDCl3) d ꢁ146.1 to ꢁ146.0 (m, 4F),
ꢁ156.0 to ꢁ155.9 (m, 4F); Anal. Calcd for C30H24F8N2O2:
C, 60.40; H, 4.06; N, 4.70; Found: C, 60.72; H, 4.19; N,
4.82. HLPC analysis: hexane/i-PrOH/Et2NH (60:40:0.1),
0.5 mL minꢁ1, UV 254 nm, retention time (tR); (S,S)-3j:
13.5 min (>99%), (R,R)-3j: 20.9 min (0%).
CP-Cyclodextrin-b-2,3,6-M-19,
i.d.
0.25 mm ꢀ 25 m,
CHROMPACK; carrier gas, helium (80 KPa); column
temperature, 100 °C; injection temp, 250 °C; split ratio,
50:1), retention time (tR); (R)-(+)-6a: 23.4 min (96.1%),
(S)-(ꢁ)-6a: 26.2 min (3.9%), 5a: 13.2 min (0%).
4.1.11. (1S,2S)-1,2-Bis(4-((R)-1-phenylethoxy)-2,3,5,6-tet-
rafluorophenyl)ethane-1,2-diamine (S,S,R)-3k. Compound
(S,S)-3k was prepared from (S,S)-2 (15.7 mg,
0.0400 mmol), KOH (44.9 mg, 0.800 mmol), and (R)-1-
phenylethanol (1.0 mL) in 93% yield (22.1 mg,
0.0370 mmol) by the procedure described for (S,S)-3a at
Acknowledgments
32
50 °C for 24 h: yellowish oil; ½aꢂD ¼ þ63:9 (c 0.55, MeOH);
IR (neat, NaCl plate, cmꢁ1) 3402, 3310, 3031, 2986, 1651,
This work was supported by a Grant-in-Aid for Young Sci-
entists (B) (No. 16750082) from the Ministry of Education,
1489, 1242, 1134, 980; 1H NMR (300 MHz, CDCl3) d 7.28–

700
T. Korenaga et al. / Tetrahedron: Asymmetry 19 (2008) 695–700
complex: Jing, Q.; Sandoval, C. A.; Wang, Z.; Ding, K. Eur.
J. Org. Chem. 2006, 3606–3616.
7. Free amino groups under the basic conditions and at high
temperature attack the perfluoro aromatic groups: Sandford,
G.; Tadeusiak, A.; Yufit, D. S.; Howard, J. A. K. J. Fluorine
Chem. 2007, 128, 1216–1220.
Culture, Sports, Science and Technology, Japan. We thank
1
the SC-NMR Laboratory of Okayama University for H,
13C, 19F, and 31P NMR measurements.
References
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1
10. The formation of complex 4a was confirmed by H and 31P
NMR spectra without purification. In particular, 4a is clearly
identified as a single complex (d 45.8, s) by 31P NMR spectra.
11. KOH is used for the deprotonation of an amino proton of 4a
to give active species (Ref. 5c). The reason for the necessity of
such a large amount of KOH in the case of 4a is assumed to
be due to a relatively weak coordination between Ru and 3a,
which prevents to increase the amino proton acidity by
complexation (Ref. 5c). The distance between the Ru and N
atoms of 4a is longer than that of RuCl2[(S)-binap][(S,S)-1] 7
˚
˚
(2.199 A for 4a vs 2.178 A for 7) by the DFT calculations at
the B3LYP/6-31G* (LANL2DZ for Ru) using GAUSSIAN 03.
In addition, N–H stretching vibration values of 4a (3341,
3279 cmꢁ1) are larger than those of 7 (3335, 3260 cmꢁ1) by
measurement of IR spectra (KBr), which indicates that the
N–H bond of 4a is stronger than that of 7.
5. (a) Noyori, R.; Okhuma, T. Angew. Chem., Int. Ed. 2001, 40,
40–73; (b) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.;
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Chem. Soc. 2003, 125, 13490–13503.
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