Enantioselective addition of diethylzinc to aldehydes catalyzed by titanium(IV) complexes of N-sulfonylated amino alcohols with two stereogenic centers

Article abstract of DOI:10.1016/S0957-4166(01)00522-5

Bidentate N-sulfonylated amino alcohols with one or two stereogenic centers were prepared and applied as chiral ligands in the titanium(IV)-catalyzed asymmetric addition of diethylzinc to aldehydes, affording excellent enantioselectivities of up to 98% e.e.

Full text of DOI:10.1016/S0957-4166(01)00522-5

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 2971–2975
Enantioselective addition of diethylzinc to aldehydes catalyzed by
titanium(IV) complexes of N-sulfonylated amino alcohols with
two stereogenic centers
Jing-Song You,† Ming-Yuan Shao and Han-Mou Gau*
Department of Chemistry, National Chung-Hsing University, Taichung 402, Taiwan
Received 28 September 2001; accepted 10 November 2001
Abstract—Bidentate N-sulfonylated amino alcohols with one or two stereogenic centers were prepared and applied as chiral
ligands in the titanium(IV)-catalyzed asymmetric addition of diethylzinc to aldehydes, affording excellent enantioselectivities of up
to 98% e.e. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
diethylzinc to aldehydes catalyzed by titanium(IV) com-
plexes of the chiral N-sulfonylated amino alcohols was
carried out and proceeded with excellent enantioselec-
tivities (up to 98% e.e.).
The application of chiral b-amino alcohols as versatile
ligands for a variety of asymmetric reactions has been
extensively studied.1 Most notable among these reac-
tions are the asymmetric additions of organometallic
reagents to aldehydes.2 Traditionally, Grignard and
alkyllithium reagents have been used together with
amino alcohols in stoichiometric amounts to obtain
high enantioselectivity.3 Over the past 10 years, the
asymmetric addition of organozinc reagents to alde-
hydes in the presence of a catalytic amount of chiral
ligand has attracted much attention, and many excel-
lent ligands inducing high enantioselectivity have been
reported.4 Chiral titanium complexes have proven
remarkably successful in the asymmetric addition of
dialkylzinc to aldehydes and the effective catalytic sys-
tems were, in general, prepared in situ by mixing a
chiral ligand with excess Ti(O-i-Pr)4.5–8 The most suc-
cessful catalysts in these reactions have been titanium
complexes which employ chiral diol-based or bis(sul-
fonamide) ligand systems.
2. Results and discussion
We first prepared the N-sulfonylated amino alcohols
(S)-1a–c with only one stereogenic center from
L-
phenylglycine, -alanine or -phenylalanine, respec-
L
L
tively. The asymmetric addition of diethylzinc to
aldehydes using titanium complex systems prepared in
situ from Ti(O-i-Pr)4 and the bidentate N-sulfonylated
amino alcohols (S)-1 were examined (Eq. (1)) and the
results are listed in Table 1. It was found that these
catalytic systems afforded poor enantioselectivities with
an e.e. value of 18% (R) (entry 1) when (S)-1a (R=
CH3) was used as a ligand and no enantioselectivity for
(S)-1b (R=Ph; entry 2). For (S)-1c with R=PhCH2
(entry 3), moderate enantioselectivity was obtained with
an e.e. of 64% (R). The above results prompted us to
synthesize a series of amino alcohols with two stereo-
genic centers, hoping to improve the enantioselectivity
and to learn more about the structural features of the
ligand that influences the enantioselectivity and cata-
lytic activity.
Following our interest in developing the titanium lig-
and chemistry,9 we report herein the synthesis of biden-
tate N-sulfonylated amino alcohols with one or two
stereogenic centers. The asymmetric additions of
HO
Ph
NHTs
R
1a: R = CH3
1b: R =Ph
* Corresponding author. Tel.: +886-4-22878615; fax: +886-4-
22862547; e-mail: hmgau@dragon.nchu.edu.tw
Ph
1c: R =PhCH2
† Postdoctoral research fellow from the Department of Chemistry,
Sichuan University, PR China.
(S)-1
0957-4166/01/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00522-5

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J.-S. You et al. / Tetrahedron: Asymmetry 12 (2001) 2971–2975
OH
stituent in (R,S)-3b, the asymmetric addition reaction
also gave excellent enantioselectivity of 94% e.e. (entry
7). However, when R% was an aliphatic substituent such
as cyclohexyl [(R,S)-3c] or t-Bu [(R,S)-3d], very poor
enantioselectivities were obtained (8% e.e. of the (S)-
configured product and 4% e.e. of the (R)-configured
product, respectively, entries 8 and 9). When R and R%
were both phenyl groups, the reaction gave an of the
(R)-configured product with e.e. of 90% (entry 10). The
above study clearly demonstrates that differences in the
ligand structure strongly influence the enantioselectivity
of the substitution reaction. For substitution at the
hydroxyl-bearing stereogenic center, several trends were
noted for the asymmetric alkylation reactions. First,
changing the tertiary alcohol functionality to a sec-
ondary alcohol led to a significant improvement in the
enantioselectivity (entry 4 versus 1). Second, the pres-
ence of aryl substituents on the hydroxyl-bearing
stereogenic center proved to be much superior to alkyl
groups (entries 4 and 7 versus entries 8 and 9). Third,
substitution of the flexible benzyl group in (R,S)-3a for
a rigid phenyl group in (R,S)-3e resulted in a slight
drop in the e.e. (entry 4 versus entry 10). These results
indicate that the enantioselectivity relies mainly on the
stereogenic center bearing the hydroxyl group rather
than the one bearing the amino group. In addition, the
effect of changing the solvent on the asymmetric addi-
tion was examined employing (R,S)-3a as a ligand and
CH2Cl2 was found to be the best solvent for these
reactions.
Chiral Ligand/Ti(O-i-Pr)4
RCHO + ZnEt2
R
(1)
Table 1. Enantioselective addition of diethylzinc to benz-
aldehyde catalyzed by bidentate N-sulfonylated amino
alcohol ligands/Ti(O-i-Pr)4 in situ-formed systemsa,b,c
Entry
Ligand
(mol%)
Ti(O-i-Pr)4
(mmol)
Yield (%)
% e.e.
1
2
3
4
5
6
7
8
1a (10)
1b (10)
1c (10)
3a (10)
3a (20)
3a (5)
3b (10)
3c (10)
3d (10)
3e (10)
0.5
0.5
0.5
0.5
1.0
0.25
0.5
0.5
0.5
0.5
96
100
93
100
100
96
100
75
81
18 (R)
0
64 (R)
96 (R)
\99 (R)
91 (R)
94 (R)
8 (S)
9
10
4 (R)
90 (R)
100
a Reaction conditions: Under a nitrogen atmosphere, the ligand and
Ti(O-i-Pr)4 were mixed in dry dichloromethane at room tempera-
ture. The mixture was stirred for 1 h and Et2Zn (1.0 M solution in
hexane, 0.75 mmol) was added at 0°C. After 30 min, benzaldehyde
(0.5 mmol) was added and the mixture was allowed to react at 0°C
for 12 h.
b The yields were based on the 1H NMR spectra.
c The e.e. values were determined by HPLC with a Chiralcel-OD
column from Daicel. The absolute configurations of the products
were derived by comparison of optical rotation data with literature
values.
Based on the route described by Reetz et al.,10 amino
alcohols (R,S)-2 with two stereogenic centers were syn-
thesized and an array of bidentate N-sulfonylated
amino alcohols (R,S)-3 were synthesized by condensa-
tion of amino alcohols with TsCl in the presence of an
excess of triethylamine and a catalytic amount of
DMAP (4-dimethylaminopyridine).
We subsequently explored the scope of the asymmetric
addition of diethylzinc to aldehydes using the best
performing ligand (R,S)-3a, and the results are listed in
Table 2. For aromatic aldehyde substrates such as
4-chlorobenzaldehyde, 1-naphthaldehyde or 2-naph-
thaldehyde as excellent enantioselectivities of 96, 94,
and 98% e.e. (entries 2–4) of the (R)-configured product
When 10 mol% of (R,S)-3a was used as a ligand in the
asymmetric reaction under the same conditions as used
for entries 1–3, with a molar ratio of Ti(O-i-Pr)4/(R,S)-
3a of 10, the reaction gave (R)-1-phenyl-1-propanol in
100% yield with an excellent e.e. of 96% (entry 4).
When 20 mol% of (R,S)-3a was used, the addition of
diethylzinc to benzaldehyde gave the product in 100%
yield with an e.e. value of 99% (entry 5). On reducing
the loading of (R,S)-3a to 5 mol%, excellent enantiose-
lectivity of 91% e.e. was still obtained (entry 6). When
the phenyl group R% was replaced with a p-tolyl sub-
were obtained, respectively. For aromatic aldehydes
bearing an electron-donating substituent such as 2-
methoxybenzaldehyde (entry 5) or 4-methoxybenzalde-
hyde (entry 6), the reaction gave the desired chiral
product in slightly lower yield but with excellent enan-
tioselectivities of 95 and 97% e.e., respectively. The
reactions of aldehydes with an alkyl group between the
aromatic ring and the carbonyl group, such as trans-
cinnamaldehyde or 3-phenylpropionaldehyde and n-
hexaldehyde were also examined. The catalytic reaction
gave 96% e.e. for trans-cinnamaldehyde as the substrate

J.-S. You et al. / Tetrahedron: Asymmetry 12 (2001) 2971–2975
2973
Table 2. Enantioselective addition of diethylzinc to alde-
hydes catalyzed by 3a/Ti(O-i-Pr)4 in situ-formed systema,b,c
4.2. Physical measurements
1H NMR spectra were obtained with a Varian Mer-
cury-400 (400 MHz) or a Varian Gemini-200 (200
MHz) spectrometer and 13C NMR spectra were
recorded with the Varian Mercury-400 (100.70 MHz) or
the Varian Gemini-200 (50.289 MHz) spectrometer.
Entry
Aldehyde
Yield (%)
% e.e.
1
2
3
4
5
6
7
8
9
Benzaldehyde
4-Chlorobenzaldehyde
1-Naphthaldehyde
100
100
100
100
90
96 (R)
96 (R)
94 (R)
98 (R)
95 (R)
97 (R)
96 (R)
94 (R)
79 (R)d
1
The H and 13C NMR chemical shifts were measured
2-Napthaldehyde
relative to tetramethylsilane as the internal reference.
Melting points were taken on a Bu¨chi 535 instrument
and are uncorrected. Elemental analyses were per-
formed using a Heraeus CHN-O-RAPID instrument.
The high resolution FAB-mass spectra and EI-mass
spectra were obtained using a JEOL JMS-SX/SX 102A
instrument. Optical rotations were determined on a
Perkin–Elmer 241 polarimeter.
2-Methyoxybenzaldehyde
4-Methyoxybenzaldehyde
trans-Cinnamaldehyde
3-Phenylpropionaldehyde
n-Hexaldehyde
94
100
100
94
a The same conditions as described in the footnote of Table 1.
b The yields were based on the 1H NMR spectra.
c The e.e. values were determined by HPLC with a Chiralcel-OD
column from Daicel. The absolute configurations of the products
were derived by comparison of optical rotation data with literature
values.
4.3. General procedures for the addition of Et2Zn to
aldehydes
d Reaction time of 24 h. The alcohol was converted to the benzoate
ester for HPLC analysis.
Under a dry nitrogen atmosphere, the ligand and Ti(O-
i-Pr)4 were mixed in dry (1.5 mL) dichloromethane at
room temperature. After stirring the mixture for 1 h, a
solution of Et2Zn (1.0 M in hexane, 0.75 mmol) was
added at 0°C. The mixture was stirred for 0.5 h and the
resulting orange solution cooled to 0°C and treated
with the aldehyde (0.5 mmol). The mixture was allowed
to react at 0°C for 12 h and quenched with 1N aqueous
HCl. The aqueous phase was extracted with ethyl ace-
tate (3×5 mL). The combined organic phase was dried
over MgSO4, filtered and concentrated. Chromatogra-
phy of the residue on silica gel (elution with 5:1 hexane/
ethyl acetate) gave the carbinol. The enantiomeric
purity of the product was determined by HPLC.
(entry 7). However, in the reaction of n-hexaldehyde, a
lower e.e. of 79% was obtained (entry 9). Because high
enantioselectivity is generally more difficult to achieve
with aliphatic aldehydes than with benzaldehydes, we
were delighted to find that the addition to 3-phenylpro-
pionaldehyde also proceeded in 94% e.e. (entry 8).
3. Conclusion
In summary, we have developed a family of N-sulfonyl-
ated amino alcohols with two stereogenic centers for
application as chiral ligands. The titanium complexes of
these bidentate ligands are demonstrated as excellent
catalysts in the addition of diethylzinc to aldehydes at
the convenient temperature of 0°C. The (R,S)-3a/Ti(O-
i-Pr)4 catalytic system also works successfully with 3-
phenylpropionaldehyde.
4.4. General procedures for synthesis of (S)-sulfonyl-
amino alcohols, (S)-1
L
-Amino acid (50.0 mmol) was dissolved in aqueous
sodium hydroxide (1.67 M, 60 mL) at 0°C. An ethereal
solution of p-toluenesulfonyl chloride (50.0 mmol) was
added dropwise with stirring over 4 h. The ethereal
solution was then separated off and the aqueous solu-
tion was acidified to pH 2.0 with hydrochloric acid. The
product crystallized immediately and was collected by
filtration to give the (S)-N-sulfonylated amino acid.
4. Experimental
4.1. Reagents and general techniques
L
-Phenylalanine, L-alanine, L-phenylglycine, DMAP (4-
dimethylaminopyridine), sulfur trioxide pyridine com-
plex, and diethylzinc (1.0 M solution in hexane) were
purchased from Fluka and were used directly. Ti(O-i-
Pr)4 was freshly distilled prior to use. Aldehydes were
distilled or recrystallized before use. (1R,2S)-2-Amino-
1,2-diphenylethanol, Grignard reagents, p-toluenesul-
fonyl chloride (TsCl) and 20% Pd(OH)2–C were
purchased from Aldrich and used without further
purifications. Amino alcohols (R,S)-2a–2d were synthe-
sized according to literature procedures.10 Solvents were
dried by heating under refluxing for at least 24 h over
P2O5 (dichloromethane), sodium/benzophenone (n-hex-
ane, diethyl ether, THF or toluene) or sodium
(methanol) and were freshly distilled prior to use. All
syntheses and manipulations were carried out under a
dry nitrogen atmosphere.
The (S)-N-p-toluenesulfonylated amino acid (12.3
mmol) was suspended in methanol (45 mL) and cooled
to 0°C in an ice bath. SOCl2 (1.4 mL) was then added
dropwise at this temperature. The mixture was stirred
at room temperature for 24 h, and the solvent was then
removed. The product was dried in vacuo to give the
(S)-N-p-toluenesulfonyl amino acid methyl ester as a
pale yellow solid. The crude (S)-N-p-toluenesulfonyl
amino acid methyl ester (12.1 mmol) was dissolved in
dry THF (80 mL) and then phenylmagnesium bromide
(1.0 M solution in THF, 50 mL) was added dropwise
under a nitrogen atmosphere at 0°C over 0.5 h. The
resulting solution was stirred for 24 h at room tempera-
ture. The reaction mixture was cooled to 0°C and
hydrolyzed with a saturated aqueous NH4Cl solution
(20 mL). The organic layer was separated and the

2974
J.-S. You et al. / Tetrahedron: Asymmetry 12 (2001) 2971–2975
aqueous layer was extracted with THF (3×30 mL). The
combined organic extracts were washed with saturated
brine (2×50 mL), dried over anhydrous MgSO4 and
filtered. The solvent was removed under reduced pres-
sure to give a yellow oil, which was recrystallized from
CH2Cl2/hexane for (S)-1a and (S)-1b or EtOAc for
(S)-1c to afford white needles.
NaHCO3 (2×20 mL) and saturated brine (2×30 mL).
The organic phase was dried over MgSO4 and concen-
trated under reduced pressure to give the crude
product.
4.5.1. (1R,2S)-2-(p-Toluenesulfonylamino)-1,3-diphenyl-
1-propanol, (R,S)-3a. Recrystallized from EtOAc/hex-
ane to afford white needles (81% yield), mp 116–117°C.
[h]2D5 −21.2 (c=0.5, CH2Cl2). 1H NMR (200 MHz,
CDCl3): l 2.37 (s, 3H, CH3), 2.44 (dd, J=9.8, 4.4 Hz,
1H, PhCHAHB), 2.49 (dd, J=9.8, 4.4 Hz, 1H,
PhCHAHB), 3.57 (m, 1H, CHN), 4.83 (d, J=7.4 Hz,
1H, PhCHOH), 5.10 (d, J=2.8 Hz, 1H, NH), 6.76–7.38
(m, 14H, 3Ph) ppm. 13C{1H} NMR (50.289 MHz,
CDCl3): l 21.44, 34.30, 61.06, 75.06, 126.16, 126.24,
126.79, 127.66, 128.38, 128.98, 129.46, 136.24, 136.93,
140.11, 142.97 ppm. HRMS (FAB) calcd for
4.4.1.
(S)-2-(p-Toluenesulfonylamino)-1,1-diphenyl-1-
propanol, (S)-1a. White needles (67% yield), mp 108–
110°C. [h]2D5 +7.7 (c=0.5, CH2Cl2). 1H NMR (200
MHz, CDCl3): l 1.07 (d, J=6.4 Hz, 3H, CH3CH), 2.40
(s, 3H, CH3 in Ts), 4.36 (m, 1H, CHN), 4.76 (d, J=8.2
Hz, 1H, NH), 7.12–7.53 (m, 14H, 3Ph) ppm. 13C{1H}
NMR (50.289 MHz, CDCl3): l 17.19, 21.48, 55.65,
80.38, 125.65, 125.71, 126.89, 126.97, 127.19, 128.25,
128.35, 129.54, 137.79, 143.01, 143.84, 143.91 ppm.
HRMS (FAB) calcd for C22H23N1O3S1Na ([M+Na]+):
404.1296, found: 404.1306. Anal. calcd for
C22H23N1O3S1: C, 69.27; H, 6.08; N, 3.67%. Found: C,
68.99; H, 6.09; N, 3.79%.
C22H23N1O3S1Na
([M+Na]+):
404.1296.
Found:
404.1288. Anal. calcd for C22H23N1O3S1: C, 69.27; H,
6.08; N, 3.67. Found: C, 69.10; H, 6.28; N, 3.71%.
4.5.2. (1R,2S)-2-(p-Toluenesulfonylamino)-3-phenyl-1-
(p-tolyl)-1-propanol, (R,S)-3b. Recrystallized from
EtOAc/hexane to afford white needles (78% yield), mp
4.4.2.
(S)-2-(p-Toluenesulfonylamino)-1,1,2-triphenyl-
ethanol, (S)-1b. White needles (74% yield), mp 215–
1
1
216°C. [h]2D5 −251.4 (c=0.5, CH2Cl2). H NMR (200
137–138°C. [h]2D5 −12.2 (c=0.5, CH2Cl2). H NMR (200
MHz, CDCl3): l 2.29 (s, 3H, CH3), 2.61 (s, br, 1H,
OH), 5.29 (d, J=8.00 Hz, 1H, CHN), 5.44 (d, J=7.6
Hz, 1H, NH), 6.72–7.60 (m, 19H, 4Ph) ppm. 13C{1H}
NMR (50.289 MHz, CDCl3): l 21.33, 63.19, 80.93,
125.62, 126.62, 126.86, 127.01, 127.41, 127.47, 127.80,
128.54, 128.77, 128.89, 135.46, 137.43, 142.54, 143.25,
143.72 ppm. HRMS (FAB) calcd for C27H25N1O3S1Na
([M+Na]+): 466.1453; found: 466.1451. Anal. calcd for
C27H25N1O3S1: C, 73.11; H, 5.68; N, 3.16. Found: C,
73.27; H, 5.96; N, 3.27%.
MHz, CDCl3): l 2.34 (s, 3H, CH3), 2.36 (s, 3H, CH3),
2.44 (dd, J=9.6, 4.4 Hz, 1H, PhCHAHB), 2.51 (dd,
J=9.6, 4.4 Hz, 1H, PhCHAHB), 3.56 (m, 1H, CHN),
4.82 (d, J=7.8 Hz, 1H, p-CH3PhCHOH), 5.01 (d,
J=2.8 Hz, 1H, NH), 6.77–7.36 (m, 13H, 3Ph) ppm.
13C{1H} NMR (50.289 MHz, CDCl3): l 21.09, 21.44,
34.49, 61.02, 74.91, 126.10, 126.22, 126.80, 128.36,
129.06, 129.41, 136.37, 137.00, 137.09, 137.31, 142.90
ppm. HRMS (FAB) calcd for C23H25N1O3S1Na ([M+
Na]+): 418.1453. Found: 418.1462. Anal. calcd for
C23H25N1O3S1: C, 69.85; H, 6.37; N, 3.54. Found: C,
69.74; H, 6.42; N, 3.50%.
4.4.3. (S)-2-(p-Toluenesulfonylamino)-1,1,3-triphenyl-1-
propanol, (S)-1c. White needles (62% yield), mp 120–
121°C. [h]2D5 +86.4 (c=0.5, CH2Cl2). 1H NMR (200
MHz, CDCl3): l 2.35 (s, 3H, CH3), 2.54 (s (br), 1H,
OH), 2.79 (dd, J=5.8, 3.8 Hz, 1H, PhCHAHB), 2.86
(dd, J=5.4, 3.8 Hz, 1H, PhCHAHB), 4.61 (m, 1H,
CHN), 4.88 (d, J=8.2 Hz, 1H, NH), 6.93–7.51 (m,
19H, 4Ph) ppm. 13C{1H} NMR (50.289 MHz, CDCl3):
l 21.41, 37.80, 61.25, 80.95, 125.38, 126.07, 126.57,
126.81, 127.41, 128.13, 128.45, 128.69, 129.33, 129.73,
137.13, 137.43, 142.46, 143.74, 143.88 ppm. HRMS
(FAB) calcd for C28H27N1O3S1Na ([M+Na]+): 480.1609,
found: 480.1618. Anal. calcd for C28H27N1O3S1: C,
73.50; H, 5.95; N, 3.06. Found: C, 73.72; H, 5.78; N,
3.50%.
4.5.3. (1R,2S)-2-(p-Toluenesulfonylamino)-1-cyclohexyl-
3-phenyl-1-propanol, (R,S)-3c. Recrystallized from
EtOAc/hexane to afford white needles (66% yield), mp
1
117–118°C. [h]2D5 −25.8 (c=0.5, CH2Cl2). H NMR (200
MHz, CDCl3): l 1.02–2.04 (m, 11H, cyclohexyl), 2.39
(s, 3H, CH3), 2.54 (dd, J=9.6, 3.4 Hz, 1H, PhCHAHB),
2.61 (dd, J=9.8, 3.6 Hz, 1H, PhCHAHB), 3.48 (m, 2H,
CHN and CHCHOH), 4.64 (d, J=6.8 Hz, 1H, NH),
6.88–7.36 (m, 9H, 2Ph) ppm. 13C{1H} NMR (50.289
MHz, CDCl3): l 21.46, 25.57, 25.81, 26.21, 28.61,
29.62, 33.43, 39.73, 56.87, 126.30, 126.81, 128.47,
129.14, 129.43, 136.60, 137.30, 142.84 ppm. HRMS
(FAB) calcd for C22H30N1O3S1 ([MH]+): 388.1946.
Found: 388.1950. Anal. calcd for C22H29N1O3S1: C,
68.19; H, 7.54; N, 3.61%. Found: C, 68.61; H, 7.77; N,
3.64%.
4.5. General procedures for the synthesis of bidentate
sulfonylamino alcohols 3
The amino alcohol (R,S)-2 (1 mmol), NEt3 (3.0 mmol),
and a catalytic amount of DMAP were combined in
CH2Cl2 (10 mL) and cooled to −78°C. TsCl (1.05
mmol) in CH2Cl2 (10 mL) was added dropwise to the
cooled, magnetically stirred solution over 20 min. After
the addition was complete, the solution was allowed to
stay at 0°C overnight. The resulting mixture was
washed with 1N HCl (2×20 mL), saturated aqueous
4.5.4. (3R,4S)-4-(p-Toluenesulfonylamino)-2,2-dimethyl-
5-phenyl-3-pentanol, (R,S)-3d. Recrystallized from hex-
ane to afford white needles (77% yield), mp 86–88°C.
[h]2D5 −55.2 (c=0.5, CH2Cl2). 1H NMR (200 MHz,
CDCl3): l 1.06 (s, 9H, 3CH3), 1.97 (s, br, OH, 1H),
2.37 (s, H, CH3), 2.52 (dd, J=10.6, 3.0 Hz, 1H,
PhCHAHB), 2.59 (dd, J=11.4, 2.8 Hz, 1H, PhCHAHB),
3.51 (m, H, CHN), 3.84 (d, J=1.4 Hz, 1H, CHCHOH),

J.-S. You et al. / Tetrahedron: Asymmetry 12 (2001) 2971–2975
2975
4.84 (d, J=7.0 Hz, 1H, NH), 6.82–7.26 (m, 9H, 2Ph)
ppm. 13C{1H} NMR (50.289 MHz, CDCl3): l 21.43,
27.13, 34.78, 35.10, 57.32, 81.61, 126.14, 126.79, 128.42,
128.89, 129.34, 136.26, 137.72, 142.69 ppm. HRMS
(FAB) calcd for C20H28N1O3S1 ([MH]+): 362.1790.
Found: 362.1794. Anal. calcd for C20H27N1O3S1: C,
66.45; H, 7.53; N, 3.87. Found: C, 66.70; H, 7.71; N,
3.62%.
1369; (e) Kitamura, M.; Oka, H.; Noyori, R. Tetrahedron
1999, 55, 3605; (f) Reddy, K. S.; Sola, L.; Moyano, A.;
Pericas, M. A.; Riera, A. J. Org. Chem. 1999, 64, 3969;
(g) Kawanami, Y.; Mitsuie, T.; Miki, M.; Sakamoto, T.;
Nishitani, K. Tetrahedron 2000, 56, 175; (h) Hanyu, N.;
Aoki, T.; Mino, T.; Sakamoto, M.; Fujita, T. Tetra-
hedron: Asymmetry 2000, 11, 4127; (i) Zhao, G.; Li,
X.-G.; Wang, X.-R. Tetrahedron: Asymmetry 2001, 12,
399; (j) Wu, X.-W.; Hou, X.-L.; Dai, L.-X.; Tao, J.; Cao,
B.-X.; Sun, J. Tetrahedron: Asymmetry 2001, 12, 529.
5. Duthaler, R. O.; Hafner, A. Chem. Rev. 1992, 92, 807.
6. For diols as ligands: (a) Seebach, D.; Beck, A. K.;
Schmidt, B.; Wang, Y. M. Tetrahedron 1994, 50, 4363;
(b) Waldmann, H.; Weigerding, M.; Dreisbach, C.; Wan-
drey, C. Helv. Chim. Acta 1994, 77, 2111; (c) Oguni, N.;
Satoh, N.; Fujii, H. Synlett 1995, 1043; (d) Mori, M.;
Nakai, T. Tetrahedron Lett. 1997, 38, 6233; (e) Kotsuki,
H.; Hayakawa, H.; Tateishi, H.; Wakao, M.; Shiro, M.
Tetrahedron: Asymmetry 1998, 9, 3203; (f) Sellner, H.;
Seebach, D. Angew. Chem., Int. Ed. Engl. 1999, 38, 1918;
(g) Yang, X. W.; Sheng, J. H.; Da, C. S.; Wang, H. S.;
Su, W.; Wang, R.; Chan, A. S. C. J. Org. Chem. 2000, 65,
295; (h) Nakamura, Y.; Takeuchi, S.; Ohgo, Y.; Curran,
D. P. Tetrahedron Lett. 2000, 41, 57.
7. For disulfonamides as ligands: (a) Takahashi, H.;
Kawakita, T.; Ohno, M.; Yoshioka, M.; Kobayashi, S.
Tetrahedron 1992, 48, 5691; (b) Cernerud, M.; Skrinning,
A.; Be´rge`re, I.; Moberg, C. Tetrahedron: Asymmetry
1997, 8, 3437; (c) Qiu, J.; Guo, C.; Zhang, X. J. Org.
Chem. 1997, 62, 2665; (d) Lutz, C.; Knochel, P. J. Org.
Chem. 1997, 62, 7895; (e) Paquette, L. A.; Zhou, R. J.
Org. Chem. 1999, 64, 7929; (f) Balsells, J.; Walsh, P. J. J.
Am. Chem. Soc. 2000, 122, 3250.
8. Others: (a) Ramo´n, D.; Yus, M. Tetrahedron Lett. 1998,
39, 1239; (b) Shibata, T.; Tabira, H.; Soai, K. J. Chem.
Soc., Perkin Trans. 1 1998, 177; (c) Shi, M.; Sui, W.-S.
Tetrahedron: Asymmetry 2000, 11, 835.
4.5.5. (1R,2S)-2-(p-Toluenesulfonylamino)-1,2-diphenyl-
ethanol, (R,S)-3e. The resulting reaction mixture was
filtered to afford the insoluble white product. The crude
solid was washed with dichloromethane and dried
under reduced pressure (85% yield), mp 211–212°C.
[h]2D5 −25.0 (c=0.5, acetone). 1H NMR (200 MHz,
CDCl3): l 2.26 (d, J=3.8 Hz, 1H, OH), 2.34 (s, 3H,
CH3), 4.52 (dd, J=4.8, 4.4 Hz, 1H, CHN), 4.99 (t,
J=4.4 Hz, 1H, PhCHOH), 5.18 (d, J=4.2 Hz, 1H,
NH), 6.95–7.16 (m, 14H, 3Ph) ppm. 13C{1H} NMR
(50.289 MHz, CDCl3): l 21.30, 64.67, 77.18, 127.53,
127.63, 127.75, 127.99, 128.05, 128.51, 129.55, 129.95
138.75, 140.00, 142.66, 143.22 ppm. HRMS (FAB)
calcd for C21H21N1O3S1Na ([M+Na]+): 390.1140.
Found: 390.1147. Anal. calcd for C21H21N1O3S1: C,
68.64; H, 5.76; N, 3.81. Found: C, 68.10; H, 6.00; N,
4.18%.
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