Practical synthesis of optically active amino alcohols via asymmetric transfer hydrogenation of functionalized aromatic ketones

Article abstract of DOI:10.1021/jo011076w

2-Substituted acetophenones such as 2-cyano-, 2-azido-, or 2-nitroacetophenones were effectively reduced with a mixture of HCOOH/N(C₂H₅)₃ containing a chiral Ru(II) catalyst, RuCl[(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine](p-cymene), giving the corresponding optically active alcohols, which can be converted to optically active amino alcohols with excellent ee's. Similarly, the reaction of 2-benzoylacetophenone with the same Ru catalyst gave a quantitative yield of the corresponding optically active 1,3-diol with 99% ee.

Full text of DOI:10.1021/jo011076w

1712
J . Org. Chem. 2002, 67, 1712-1715
Sch em e 1
P r a ctica l Syn th esis of Op tica lly Active
Am in o Alcoh ols via Asym m etr ic Tr a n sfer
Hyd r ogen a tion of F u n ction a lized Ar om a tic
Keton es
Masahito Watanabe,† Kunihiko Murata,†,‡ and
Takao Ikariya*,‡
Central Research Laboratory of Kanto Chemical Corp., Inc.,
1-7-1 Inari, Soka, Saitama, J apan, and Graduate School of
Science and Engineering, Tokyo Institute of Technology,
CREST, 2-12-1 O-okayama, Meguro-ku,
Tokyo 152-8552, J apan
tikariya@o.cc.titech.ac.jp
Received November 14, 2001
Abstr a ct: 2-Substituted acetophenones such as 2-cyano-,
2-azido-, or 2-nitroacetophenones were effectively reduced
with a mixture of HCOOH/N(C2H5)3 containing a chiral Ru-
(II) catalyst, RuCl[(S,S)-N-(p-toluenesulfonyl)-1,2-diphenyl-
ethylenediamine](p-cymene), giving the corresponding op-
tically active alcohols, which can be converted to optically
active amino alcohols with excellent ee’s. Similarly, the
reaction of 2-benzoylacetophenone with the same Ru catalyst
gave a quantitative yield of the corresponding optically active
1,3-diol with 99% ee.
Ta ble 1. Asym m etr ic Tr a n sfer Hyd r ogen a tion of
2-Su bstitu ted Acetop h en on es Ca ta lyzed by Ch ir a l Ru (II)
a
Ca ta lyst (1) w ith a Mixtu r e of HCOOH/N(C2H5)3
T, time, yield,b ee,b
ketone S/C HCOOH/N(C2H5)3 °C
h
%
%
configc
2a
1000
100
100
100
100
100
200
500
200
200
200
3.1:2.6
d
30 24
30 24
30 24
30 24
30 16
30 16
30 16
30 16
30 16
30 16
40 24
100
<1
33
65
18
87
90
58
95
67
99
98
S
2a
2b
3.1:2.6
3.1:5.2
3.1:2.6
6.0:2.4
6.0:2.4
6.0:2.4
6.0:2.4
6.0:2.4
4.4:2.6
91
92
R
R
2b
2c
96f Rg
97f Rg
98f Rg
98f Rg
2ce
2ce
2ce
2d e
2ee
2fe
Coordinatively saturated 18-electron chiral Ru(II) com-
plexes bearing optically active diamines, RuCl(Tsdpen)-
(η6-arene) (TsDPEN: N-(p-toluenesulfonyl)-1,2-diphenyl-
ethylenediamine) have been extensively investigated as
practical asymmetric reduction catalysts to produce
optically active alcohols or amines.1 Thanks to the
characteristic properties of chiral Ru catalysts, function-
alized aromatic ketones bearing neighboring functional
groups at the R or â position of the carbonyl group could
be readily reduced to optically active alcohols with
extremely high ee’s. The functional groups of these com-
pounds are free from the metal center. In fact, reactions
of benzils or benzoins,1g 2-amido-2-phenyl-acetophenone,
acetylpyridines,1h or â-ketoesters1e,2 proceeded smoothly
under mild conditions to give optically active diols or
alcohols with up to 99% ee in almost quantitative yields.
We now describe a practical asymmetric transfer hydro-
genation of 2-cyano-, 2-azido-, or 2-nitroacetophenone
(2a -c) in a mixture of formic acid and triethylamine with
chiral diamine-based Ru(II) catalysts, leading to optically
active alcohols. These aromatic alcohols can be readily
96f
h
95f Rg
99i S,Sj
a
The reaction of aromatic ketones (1.0-3.0 mmol) was carried
out in a mixture of HCOOH and N(C2H5)3 containing (S,S)-Ru
b
catalyst (1). Unless otherwise noted, yields were determined by
1H NMR using 1,3,5-trimethoxybenzene as an internal standard,
and ee values were determined by HPLC analysis using Daicel
Chiralcel OB, OD, and OJ , Chiralpak AD column. c Unless oth-
erwise noted, determined from the sign of rotation of the isolated
d
product. Reaction in 2-propanol, conditions: (S,S)-Ru amide
complex, 0.1 M in 2-propanol. e Reaction in 1.0 M DMF. f Deter-
mined after reduction to the corresponding amino alcohol with H2-
g
Pd/C and subsequent monobenzoylation. Αbsolute configration
was determined from the sign of rotation after reduction to the
h
corresponding amino alcohol with H2-Pd/C. Not determined.
i
j
Determined after derivatization to acetal. dl/meso ) 94/6.
reduced with conventional reducing systems to the cor-
responding optically active amino alcohols with excellent
enantiomeric purities.
A well-defined chiral Ru catalyst, RuCl[(S,S)-Tsdpen]-
(p-cymene) (1) effected asymmetric transfer hydrogena-
tion of 2-cyanoacetophenone (2a ) with HCOOH as a
hydrogen source, giving (S)-1-phenyl-2-cyano-1-ethanol
(3a ) with excellent enantioselectivity (Scheme 1). As
shown in Table 1, the reaction with a substrate to
catalyst molar ratio (S/C) of 1,000:1 in a mixture of
HCOOH/N(C2H5)3 (ketone/HCOOH/N(C2H5)3 molar ratio
) 1:3.1:2.6) proceeded smoothly at 30 °C to give the
corresponding reduction product in an almost quantita-
tive yield and with up to 98% ee.3 The sense of enantio-
† Central Research Laboratory of Kanto Chemical Corp. Inc.
‡ Tokyo Institute of Technology.
(1) (a) Hashiguchi, S.; Fujii, A.; Takehara, J .; Ikariya, T.; Noyori,
R. J . Am. Chem. Soc. 1995, 117, 7562-7563. (b) Haack, K.-J .;
Hashiguchi, S.; Fujii, A.; Ikariya, T.; Noyori, R. Angew. Chem., Int.
Ed. Engl. 1997, 36, 285-288. (c) Hashiguchi, S.; Fujii, A.; Haack, K.-
J .; Matsumura, K.; Ikariya, T.; Noyori, R. Angew. Chem., Int. Ed. Engl.
1997, 36, 288-290. (d) Matsumura, K.; Hashiguchi, S.; Ikariya, T.;
Noyori, R. J . Am. Chem. Soc. 1997, 119, 8738-8739. (e) Noyori, R.;
Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97-102. (f) Murata, K.;
Ikariya, T.; Noyori, R. J . Org. Chem. 1999, 64, 2186-2187. (g) Murata,
K.; Okano, K.; Miyagi, M.; Iwane, H.; Noyori, R.; Ikariya, T. Org. Lett.
1999, 1, 1119-1121. (h) Okano, K.; Murata, K.; Ikariya, T. Tetrahedron
Lett. 2000, 41, 9277-9280. (i) Koike, T.; Murata, K.; Ikariya, T. Org.
Lett. 2000, 2, 3833-3836.
(3) Enantioselective biochemical reduction of 2-cyanoketone, 2a to
(S)-3a : Dehli, J . R.; Gotor, V. Tetrahedron: Asymmetry 2000, 11,
3693-3700.
(2) Palmer, M. J .; Wills, M. Tetrahedron: Asymmetry 1999, 10,
2045-2061.
10.1021/jo011076w CCC: $22.00 © 2002 American Chemical Society
Published on Web 02/08/2002

Notes
J . Org. Chem., Vol. 67, No. 5, 2002 1713
Sch em e 2
Sch em e 3
face selection in this reaction was the same as that
attained in the reaction of acetophenone.1a The neighbor-
ing cyano group did not affect seriously the outcome of
the reaction. Formic acid is the best choice for hydrogen
sources. Attempted transfer hydrogenation of 2a with
2-propanol and a Ru amide catalyst, Ru[(S,S)-Tsdpen]-
(p-cymene)1b or 1/KOt-Bu catalyst system, gave less than
1% of the reduction product. Asymmetric hydrogenation
of 2a in 2-propanol with the practical stereoselective
hydrogenation catalyst, RuCl2[(S)-binap][(S,S)-dpen]4
and KOt-Bu, (S/C ) 200, H2 10 atm, 30 °C, 24 h), did not
proceed. The alcohol product (S)-3a was readily reduced
with conventional reducing agents, BH3/S(CH3)2 in THF
to give optically active 1-phenyl-3-amino-1-propanol (S)-
4a , which is an intermediate of (S)-fluoxetin,5 in 90%
yield and with 98% ee as shown in Scheme 2.
is easily hydrogenated over Pd/C to give the optically
active 2-amino alcohol 4b with 92% ee (Scheme 3).9,10
The reaction of the nitro group substituted acetophe-
none 2c with a mixture of HCOOH and N(C2H5)3 in a
3.1:2.6 molar ratio did not give a satisfactory yield albeit
with an excellent enantioselectivity (3c, 18% yield, 96%
ee). However, the use of DMF or CH2Cl2 as a solvent as
well as an increase in the molar ratio of HCOOH to
N(C2H5)3 to 6.0:2.4 resulted in a significant increase in
the product yield of up to 90%. The enantiomeric excess
of the reduction product was determined to be 98% ee
after the nitro alcohol was reduced to 2-amino alcohol
4b by H2-Pd/C. Para-substituted 2-nitroacetophenones
are consistently convertible to the alcohols with excellent
ee’s. For example, an electron-withdrawing fluoro group
on the aromatic ring in 2d increases the yield of 3d up
to 96%, as expected. 2-Nitroacetophenone with an electron-
donating methyl group, 2e, is also reducible to the
corresponding optically active alcohol with a high ee and
a moderate yield (Table 1).
Among the notable features of this asymmetric transfer
hydrogenation promoted by chiral Ru catalyst is the
carbonyl group selectivity. The neighboring groups at the
R or â position of the carbonyl group do not interact with
the metal center because of the coordinatively saturated
nature of the diamine-based Ru(II)-arene complexes,
leading to excellent enantioselectivity. Such unique
catalyst properties were also demonstrated by the reac-
tion of 2-benzoylacetophenone (1,3-diphenyl-1,3-propane-
dione 2f) under reaction conditions similar to those
described in Table 1. The reaction of 1,3-diketone in a
mixture of HCOOH/N(C2H5)3 (4.4/2.6) containing catalyst
1 gave a quantitative yield of the corresponding optically
active 1,3-diol (3f) with 99% ee and in 99% yield (dl:meso
) 94:6).11 However, 1,3-pentanedione did not give the
reduction product under the same conditions.
Similarly, 2-azidoacetophenone (2b) and 2-nitroaceto-
phenone (2c) were reducible with the same catalyst 1 in
a mixture of formic acid and N(C2H5)3 to the correspond-
ing optically active alcohol 3b and 3c, respectively, with
an excellent enantioselectivity.6,7 The outcome of these
reactions was greatly influenced by the reaction condi-
tions. The reaction of 2b with a mixture of HCOOH and
N(C2H5)3 ) 3.1:2.6 proceeded sluggishly because the
reactant is labile under the reaction conditions and there
is a serious product inhibition effect. In fact, an addition
of the product alcohol 3b (2b/rac-3b ) 1:1) to the reaction
mixture caused a significant decrease in the product yield
to ca. 10%.8 Increasing the amount of N(C2H5)3 from
HCOOH/N(C2H5)3 ) 3.1:2.6 to 3.1:5.2 resulted in an
improvement of the yield from 33 to 65% without any
change in the ee value. The azido group in the product
(4) (a) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori,
R. J . Am. Chem. Soc. 1995, 117, 2675-2676. (b) Doucet, H.; Ohkuma,
T.; Murata, M.; Yokozawa, T.; Kozawa, M.; Katayama, E.; England,
A. F.; Ikariya, T.; Noyori, R. Angew. Chem., Int. Ed. Engl. 1998, 37,
1703-1707. (c) Ohkuma, T.; Koizumi, M.; Doucet, H.; Pharm, T.;
Kozawa, M.; Murata, K.; Katayama, E.; Yokozawa, T.; Ikariya, T.;
Noyori, R. J . Am. Chem. Soc. 1998, 120, 13529-13530. (d) Noyori, R.;
Ohkuma, T. Angew. Chem., Int. Ed. Engl. 2001, 40, 40-73.
(5) Preparation of optically active floxetine. (a) Enantioselective
reduction of â-chloropropiophenone by chiral borane catalyst: Corey,
E. J .; Reichard, G. A. Tetrahedron Lett. 1989, 30, 5207-5210. (b)
Enantioselective hydrogenation of â-amino ketone derivative by chiral
Rh complex: Sakuraba, S.; Achiwa, K. Synlett 1991, 689-690. (c)
Optical resolution and derivatization of 2b: Koenig, T. M.; Mitchell,
D. Tetrahedron Lett. 1994, 35, 1339-1342. (d) Enantioselective
synthesis of 2-aryloxyester and derivatization: Devine, P. N.; Heid,
R. M.; Tschaen, D. M. Tetrahedron 1997, 53, 6739-6746. (e) Enanti-
oselective hydrogenation of â-ketoester and derivatization: Huang, H.-
L.; Liu, L. T.; Chen, S.-F.; Ku, H. Tetrahedron: Asymmetry 1998, 9,
1637-1640.
(6) (a) Pamies, O.; Ba¨ckvall, J .-E, J . Org. Chem. 2001, 66, 4022-
4025. (b) Kawamoto, A.; Wills, M. Tetrahedron: Asymmetry 2000, 11,
3257-3261. (b) Yadav, J . S.; Reddy, P. T.; Hashim, S. R. Synlett 2000,
1049-1051.
(7) Preparation of optically active nitro alcohols with chiral metal
catalysts: (a) Sasai, H.; Suzuki, T.; Arai, S.; Arai, T.; Shibasaki, M. J .
Am. Chem. Soc. 1992, 114, 4418-4420. (b) Molinari, F.; Occhiato, E.
G.; Aragozzini, F.; Guarna, A. Tetrahedron: Asymmetry 1998, 9, 1389-
1394.
This work presents the successful reductive transfor-
mation of 2-cyano-, 2-azido-, or 2-nitroacetophenone via
asymmetric transfer hydrogenation to optically active
(9) Preparation of optically active 2-amino alcohol. Biochemical
redution of 2b to optically active 3b and subsequent derivatization to
4b: Yadav, J . S.; Reddy, P. T.; Nanda, S.; Rao, A. B. Tetrahedron:
Asymmetry 2001, 12, 63-67.
(10) â-Adrenergic blockers, (a) Wang, Y.-F.; Izawa, T.; Kobayashi,
S.; Ohno, M. J . Am. Chem. Soc. 1982, 104, 6465-6466. (b) Takaoka,
E.; Yoshikawa, N.; Yamada, Y. M. A.; Sasai, H.; Shibasaki, M.
Heterocycles 1997, 46, 157-163.
(8) Kenny, J . A.; Palmer, M. J .; Smith, A. R. C.; Walsgroue, T.; Wills,
M. Synlett 1999, 1615-1617.

1714 J . Org. Chem., Vol. 67, No. 5, 2002
Notes
(m, 2H, CH2NH2), 2.90-3.10 (m, 2H, CH2CH(OH)), 4.95 (dd, J
) 3.0, 8.6 Hz, 1H, CHOH), 7.20-7.40 (m, 5H, aromatic protons).
Asym m etr ic Tr a n sfer Hyd r ogen a tion of 2-Azid oa ceto-
p h en on e (2b) Ca ta lyzed by Ch ir a l Ru (II) (1) Lea d in g to
(R)-1-P h en yl-2-a zid o-1-eth a n ol (3a ). A mixture of triethyl-
amine (0.72 mL, 5.2 mmol) and formic acid (0.12 mL, 3.1 mmol)
was added to 2-azidoacetophenone (2b) (161 mg, 1.0 mmol) and
(S,S)-Ru (1) (6.4 mg, 0.010 mmol), and the mixture was then
stirred at 30 °C for 24 h. After the reaction, the reaction mixture
was neutralized with NaHCO3 (aq) and diluted with ethyl
acetate, and the organic layer was washed with water. The
organic layer was dried over Na2SO4, passed through a silica
gel pad, and concentrated under reduced pressure to give (R)-
1-phenyl-2-azido-1-ethanol (3b) with 92% ee in 65% yield. (R)-
3b: 1H NMR (400 MHz, CDCl3) δ 2.29 (brs, 1H, OH), 3.45 (m,
2H, CH2N3), 4.87 (dd, J ) 4.0, 7.9 Hz, 1H, CHOH), 7.25-7.50
primary amino alcohols. Optically active amino alcohols
as well as optically active diols obtained here are useful
building blocks for the synthesis of various biologically
active compounds or chiral auxiliaries and have been
prepared by stoichiometric or catalytic asymmetric syn-
thetic methods.12 The present asymmetric transfer hy-
drogenation procedure serves as a useful practical method
for these important class of compounds.
(m, 5H, aromatic protons); [R]25D -89.3 (c 0.80, CHCl3) (lit.9 [R]25
D
-80.1 (c 0.78, CHCl3, (R))).
According to a literature procedure,9 (R)-3b was hydrogenated
with H2-Pd/C in methanol to give 1-phenyl-3-amino-1-ethanol,
(R)-4b with 92% ee, quantitatively: 1H NMR (400 MHz, CDCl3)
δ 2.17 (brs, 3H, OH, NH2), 2.80 (dd, J ) 7.6, 13.0 Hz, 1H,
CHHNH2), 2.97 (dd, J ) 3.9, 13.0 Hz, 1H, CHHNH2), 4.61 (dd,
Exp er im en ta l Section
2-Cyanoacetophenone, 1,3-diphenyl-1,3-propanedione, triethy-
lamine, formic acid (>98%), and dry DMF were purchased from
Kanto Chemical Co., Inc. 2-Nitroacetophenone was purchased
from Aldrich. 2-Azidoacetophenone was synthesized according
to the published procedure.13 4′-Fluoro-2-nitroacetophenone, and
4′-methyl-2-nitroacetophenone were synthesized from the reac-
tion of substituted benzaldehyde and nitromethane in the
presence of K2CO3 and J ones oxidation.14 Asymmetric reduction
of ketones with chiral Ru catalysts was conducted in an
atmosphere of dry Argon. The typical experimental procedures
including analytical and spectroscopic data are as follows.
Asym m etr ic Tr a n sfer Hyd r ogen a tion of 2-Cya n oa ceto-
p h en on e (2a ) Ca ta lyzed by Ru Cl[(1S,2S)-N-(p-tolu en e-
su lfon yl)-1,2-d ip h en yleth ylen ed ia m in e](η6-p-cym en e) (1)
Lea d in g to (S)-1-P h en yl-2-cya n o-1-eth a n ol (3a ). A mixture
of triethylamine (1.09 mL, 7.8 mmol) and formic acid (0.35 mL,
9.3 mmol) was added to 2-cyanoacetophenone (2a ) (435 mg, 3.0
mmol) and (S,S)-Ru (1) (1.9 mg, 0.003 mmol), and the mixture
was then stirred at 30 °C for 24 h. After the reaction, the reaction
mixture was neutralized with NaHCO3 (aq) and diluted with
ethyl acetate, and the organic layer was washed with water. The
organic layer was dried over Na2SO4, passed through a silica
gel pad, and concentrated under reduced pressure to give (S)-
1-phenyl-2-cyano-1-ethanol (3a ) with 98% ee in almost quantita-
tive yield.
J
) 3.9, 7.6 Hz, 1H, CHOH), 7.20-7.45 (m, 5H, aromatic
protons); [R]20 -39.1 (c 1.30, C2H5OH) (lit.16 [R]20 -42.2 (c 1,
D
D
C2H5OH, 95% ee (R))).
Asym m etr ic Tr a n sfer Hyd r ogen a tion of 2-Nitr oa ceto-
p h en on e (2c) to (R)-1-P h en yl-2-n itr o-1-eth a n ol (3c) Ca ta -
lyzed by Ch ir a l Ru (II) (1) Lea d in g to (R)-1-P h en yl-2-n itr o-
1-eth a n ol (3c). A mixture of triethylamine (0.33 mL, 2.4 mmol)
and formic acid (0.23 mL, 6.0 mmol) was added to 2-nitroac-
etophenone (2c) (165 mg, 1.0 mmol) and (S,S)-Ru (1) (3.2 mg,
0.005 mmol) in 1.0 mL of DMF, and the mixture was stirred at
30 °C for 16 h, neutralized with NaHCO3 (aq), and diluted with
ethyl acetate, and the organic layer was washed with water. The
organic layer was dried over Na2SO4, passed through a silica
gel pad, and concentrated under reduced pressure to give (R)-
1-phenyl-2-nitro-1-ethanol (3c) with 98% ee in 90% yield. (R)-
3c: 1H NMR (400 MHz, CDCl3) δ 2.80 (d, J ) 3.4 Hz, 1H, OH),
4.52 (dd, J ) 3.0, 13.4 Hz, 1H, CHHNO2), 4.61 (dd, J ) 9.5,
13.4 Hz, 1H, CHHNO2), 5.46 (m, 1H, CHOH), 7.30-7.55 (m, 5H,
aromatic protons);7a,17 [R]20 -20.2 (c 1.0, C2H5OH). absolute
D
configuration was determined from the sign of rotation after
reduction to amino alcohol with H2-Pd/C.
According the literature method,10b the alcohol product (R)-
3c was readily reduced with H2-Pd/C in methanol to give (R)-
1-phenyl-2-amino-1-ethanol, (R)-4b, in an almost quantitative
yield and with 98% ee.16
(S)-3a : 1H NMR (400 MHz, CDCl3) δ 2.51 (brs, 1H, OH), 2.76
(m, 2H, CH2CN), 5.04 (t, J ) 6.0 Hz, 1H, CHOH), 7.35-7.50
(m, 5H, aromatic protons); [R]20 -52.5 (c 2.60, C2H5OH) (lit.3
D
[R]20 -57.7 (c 2.6, C2H5OH, >96% ee (S))).
D
Similarly, the alcoholic products 3d and 3e were obtained by
asymmetric reduction of 2d and 2c and were hydrogenated with
H2-Pd/C in methanol to give quantitatively 4d and 4e, respec-
tively.
According to a literature procedure, the alcohol product (S)-
3a was reduced with BH3/S(CH3)2 in THF to give optically active
1-phenyl-3-amino-1-propanol, (S)-4a in 90% yield and with 98%
ee.3 4a : [R]25 -46.3 (c 1.46, CH3OH) (lit.15 [R]25 -43.65 (c 1,
D
D
CH3OH, 100% ee (S))); 1H NMR (400 MHz, CDCl3) δ 1.70-1.90
Op t ica lly a ct ive 1-(4′-flu or op h en yl)-2-n it r o-1-et h a n ol
(3d ): 1H NMR (400 MHz, CDCl3) δ 2.86 (d, J ) 3.6 Hz, 1H, OH),
4.49 (dd, J ) 3.0, 13.4 Hz, 1H, CHHNO2), 4.58 (dd, J ) 9.5,
13.4 Hz, 1H, CHHNO2), 5.45 (m, 1H, CHOH), 7.00-7.25, 7.30-
7.50 (m, 4H, aromatic protons); 13C NMR (100 MHz, CDCl3) δ
70.3, 116.0 (d, J CF ) 21.5 Hz), 127.7 (d, J CF ) 8.2 Hz), (CH2),
81.1 (CH), 133.9, 162.9 (d, J CF ) 247.8 Hz), (C); MS (EI, 70 eV)
(11) Part of the results were reported at the 2000 International
Chemical Congress of Pacific Basin Societies at Honolulu (ORGN 1064,
2000), and full details of the reaction will be published separately.
During the preparation of this manuscript, similar results on the
asymmetric transfer hydrogenation of 1,3-diketones were reported.
Cossy, J .; Eustache, F.; Daiko, P. I. Tetrahedron Lett. 2001, 42, 5005-
5007.
185 (M+), 167 (-F), 140, 138, 125, 123, 121, 109, 101; [R]25
-19.1 (c 1.04, C2H5OH).
D
(12) Asymmetric catalytic hydrogenation of amino ketones: (a)
Hayashi, T.; Katsumura, A.; Konishi, M.; Kumada, M. Tetrahedron
Lett. 1979, 425-428. (b) Kitamura, M.; Ohkuma, T.; Inoue, S.; Sayo,
N.; Kumobayashi, H.; Akutagawa, S.; Ohta, T.; Takaya, H.; Noyori,
R. J . Am. Chem. Soc. 1988, 110, 629-631. (c) Yoshikawa, K.; Yama-
moto, N.; Murata, M.; Awano, K.; Morimoto, T.; Achiwa, K. Tetrahe-
dron: Asymmetry 1992, 3, 13-16. (d) Mashima, K.; Kusano, K.; Sato,
N.; Matsumura, Y.; Nozaki, K.; Kumobayashi, H.; Sayo, N.; Hori, Y.;
Ishizaki, T.; Akutagawa, S.; Takaya, T. J . Org. Chem. 1994, 59, 3064-
3076. (e) Devocelle, M.; Agbossou, F.; Mortreux, A. Synlett 1997, 1306-
1308. (f) Pasquier, C.; Naili, S.; Pelinski, L.; Brocard, J .; Mortreux, A.;
Agbossou. F. Tetrahedron: Asymmetry 1998, 9, 193-196. (g) Ohkuma,
T.; Ishii, D.; Takeno, H.; Noyori, R. J . Am. Chem. Soc. 2000, 122, 6510-
6511. Asymmetric aminohydroxylation of olefins: Chang, L. G.,
Sharpless, K. G. Angew. Chem., Int. Ed. Engl. 1996, 35, 451-454.
(13) Ackrell, J .; Muchowski, J .; Galeazzi, E.; Guzman, A. J . Org.
Chem. 1986, 51, 3374-3376.
Op tica lly a ctive 1-(4′-flu or op h en yl)-2-a m in o-1-eth a n ol
(4d ):18 1H NMR (400 MHz, CDCl3) δ 2.18 (brs, 3H, OH, NH2),
2.76 (dd, J ) 7.8, 12.7 Hz, 1H, CHHNH2), 2.98 (dd, J ) 3.9,
12.7 Hz, 1H, CHHNH2), 4.61 (dd, J ) 3.9, 7.8 Hz, 1H, CHOH),
6.90-7.15, 7.20-7.45 (m, 4H, aromatic protons); [R]20D -40.8 (c
1.68, C2H5OH).
(15) Mitchell, D.; Koenig, T. M. Synth. Commun. 1995, 25, 1231-
1238.
(16) Izumi, T.; Fukaya, K. Bull. Chem. Soc. J pn. 1993, 66, 1216-
1221.
(17) Oshida, J .; Okamoto, M.; Azuma, S.; Tanaka, T. Tetrahedron:
Asymmetry 1997, 8, 2579-2584.
(18) Fuller, R. W.; Marsh, M. M. J . Med. Chem. 1972, 15, 1068-
1069.
(14) Luzzio, F. A. Tetrahedron 2001, 57, 905-945.

Notes
J . Org. Chem., Vol. 67, No. 5, 2002 1715
Op t ica lly a ct ive 1-(4′-m et h ylp h en yl)-2-n it r o-1-et h a n ol
2.96 (dd, J ) 3.9, 12.9 Hz, 1H, CHHNH2), 4.59 (dd, J ) 3.9, 7.6
(3e):19 1H NMR (400 MHz, CDCl3) δ 2.36 (s, 3H, CH3), 2.72 (brs,
1H, OH), 4.49 (dd, J ) 2.9, 13.2 Hz, 1H, CHHNO2), 4.60 (dd, J
) 9.5, 13.2 Hz, 1H, CHHNO2), 5.42 (dd, J ) 2.9, 9.5 Hz, 1H,
Hz, 1H, CHOH), 7.05-7.40 (m, 4H, aromatic protons); [R]20
D
-42.5 (c 1.48, C2H5OH) (lit.20 [R]20D -42.5 (c 0.6, (C2H5)2O, (R))).
(S,S)-1,3-Dip h en yl-1,3-p r op a n ed iol (3f): 1H NMR (400
MHz, CDCl3); δ 2.18 (t, J ) 5.8 Hz, 2H, CH2), 2.87 (brs, 2H,
OH), 4.98 (t, J ) 5.8 Hz, 2H, CHOH), 7.30-7.40 (m, 10H,
aromatic protons); [R]28D -68.2 (c 1.12, CH3OH) (lit.21 [R]23D +52
(c 0.5, CHCl3), >99% ee (R,R))).
CHOH), 7.15-7.40 (m, 4H, aromatic protons); [R]25 -23.0 (c
D
0.95, C2H5OH).
Op tica lly a ctive 1-(4′-m eth ylp h en yl)-2-a m in o-1-eth a n ol
(4e): 1H NMR (400 MHz, CDCl3) δ 2.07 (brs, 3H, OH, NH2),
2.34 (s, 3H, CH3), 2.80 (dd, J ) 7.6, 12.9 Hz, 1H, CHHNH2),
Ack n ow led gm en t. This work was financially sup-
ported by grant-in-aid from the Ministry of Education,
Science, Sports and Culture of J apan (No. 09238104,
No. 12305057).
(19) Nikalje, M. D.; Ali, I. S.; Dewkar, G. K.; Sudalai, A. Tetrahedron
Lett. 2000, 41, 959-961.
(20) Ziegler, T.; Ho¨rsch, B.; Effenberger, F. Synthesis 1990, 575-
578.
(21) Corey, E. J .; Chen. Z. Tetrahedron Lett. 1994, 35, 8731-8734.
J O011076W