Enantioselective synthesis of 1-arylethanediols by rhodium-catalyzed transfer hydrogenation of α-tosyloxyarylketones

Article abstract of DOI:10.1007/s00706-008-0009-2

Catalytic transfer hydrogenation of α-tosyloxyarylketones mediated by a chiral rhodium complex using an azeotropic mixture of formic acid/triethylamine afforded the corresponding 1-arylethanediol monotosylates in excellent yield with high enantioselectivity.

Full text of DOI:10.1007/s00706-008-0009-2

Monatsh Chem (2009) 140:73–78
DOI 10.1007/s00706-008-0009-2
ORIGINAL PAPER
Enantioselective synthesis of 1-arylethanediols
by rhodium-catalyzed transfer hydrogenation
of a-tosyloxyarylketones
Do-Min Lee Æ Gullapalli Kumaraswamy Æ
Kee-In Lee
Received: 29 April 2008 / Accepted: 20 May 2008 / Published online: 20 September 2008
Ó Springer-Verlag 2008
Abstract Catalytic transfer hydrogenation of a-tosyloxy-
arylketones mediated by a chiral rhodium complex using
an azeotropic mixture of formic acid/triethylamine affor-
ded the corresponding 1-arylethanediol monotosylates in
excellent yield with high enantioselectivity.
arylketones, a-, and b-ketoesters, a,b-unsaturated ketones,
1,2-diketones with high optical and chemical yields, while
Rh-catalysts are preferable, notably in the reduction of
a-chloroketones [4, 5]. In general, ATH rather offers an
operational simplicity, since the reaction does not involve
molecular hydrogen and is insensitive to air oxidation, so it
is particularly valuable in scale-up synthesis of active
pharmaceutical ingredients [6].
Keywords 1-Arylethanediol ꢀ Rhodium ꢀ
Asymmetric transfer hydrogenation ꢀ
a-Tosyloxyarylketone
Previously, we have reported the asymmetric transfer
hydrogenation of 2-tosyloxy-1-(4-hydroxyphenyl)ethanone
derivatives with TsDPEN-Rh-catalyst in formic acid/
triethylamine and their further applications to the synthesis
of b-adrenergic agonists [7]. This represented a simple
and highly efficient procedure for the preparation of
chiral alcohols from a-tosyloxyketones under catalytic
transfer hydrogenation. Indeed, a-sulfonyloxyketones are
particularly interesting as versatile intermediates for the
preparation of a large group of anti-depressants and a- and
b-adrenergic drugs [8, 9]. However, they have not received
much attention in asymmetric transfer hydrogenation to
date [10, 11]. Herein, we report the asymmetric transfer
hydrogenation of various a-tosyloxyarylketones with
structural diversity, which may provide their facile entry to
many biologically active compounds containing 1,2-ami-
noalcohol functionality.
Introduction
Asymmetric transfer hydrogenation (ATH) has been
broadening its applications to enantioselective hydrogena-
tion of unsaturated carbonyl and imine groups [1–3]. The
catalysts generally consist of bidentate ligands based on
1,2-aminoalcohols or diamines, bound to ruthenium, rho-
dium, or iridium. The transfer reaction is routinely carried
out under isopropanol/base or a formic acid/triethylamine
mixture as hydrogen donors. It has been proved that (1S,2S)-
or (1R,2R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenedi-
amine (TsDPEN) is an excellent ligand for the catalytic
transfer hydrogenation of aryl ketones [1]. The TsDPEN-Ru
catalysts efficiently reduced activated ketones, such as
D.-M. Lee ꢀ K.-I. Lee (&)
Results and discussion
Bio-Organic Science Division, Korea Research Institute
of Chemical Technology, PꢀO. Box 107, Yusong,
Taejon 305-600, South Korea
The starting a-tosyloxyketones 2a–2t were conveniently
prepared by a-sulfonyloxylation of the corresponding
arylketones 1a–1t, which are either commercially available
or easily accessible in a few steps, with [hydroxy(tosyl-
oxy)iodo]benzene in refluxing acetonitrile [12]. The
compounds 1l–1n were conveniently obtained starting from
e-mail: kilee@krict.re.kr
G. Kumaraswamy
Organic Division III,
Indian Institute of Chemical Technology,
Hyderabad 500 007, India
123

74
D.-M. Lee et al.
Scheme 1
Ts
N
Rh
.
Ph
Ph
Cl
N
H
2
(S,S)-3
(S,S)-3,
O
O
OH
HCO H/Et N,
PhI(OTs)OH,
MeCN, reflux
2
3
OTs
OTs
EtOAc, rt.
R
R
R
(R)-4
1
2
Table 1 Rhodium catalyzed transfer hydrogenation of a-tosyloxy-
ketones 2
1-(4-hydroxyphenyl)ethanone, and 1t was prepared via
acetylation of 1-methoxy-4-methylbenzene with acetic acid
in the presence of LiClO4 [13]. Thus, we extended Rh-cat-
alyzed transfer hydrogenation of a-tosyloxyarylketones by a
substituent variation in the aryl part, as shown in Scheme 1.
Here, the sense of asymmetric induction has not been
changed as observed with a-chloroarylketones, and the
results are summarized in Table 1. The reduction of o-
substituted acetophenones (2b and 2i) showed a decrease in
enantioselectivity, while m- and p-substituted derivatives
(2c–2d and 2j–2k) regained. The observation suggests that
the introduction of o-substituents brings about steric
demand to disturb toward catalytic complex structure. The
ketones with electron-withdrawing groups such as p-F (2g)
and –CF3 (2h) showed a decreased enantioselectivity.
However, p-OMe substrate (2k) was cleanly reduced to
afford (R)-4k in 94% ee by (S,S)-3 at S/C = 1,000, while
15% ee was previously observed with the same catalyst at
S/C = 200 [7, 11]. The high enantioselectivity was also
observed in the cases of p-OBn (2l), –OTBS (2m) and
–OAc (2n). The substrates with electron-donating substit-
uents proceeded in a more precisely controlled manner to
provide a higher ee. This informs us that an attractive
interaction between arene ligand and aryl substrate is
favorable, presumably due to the contribution of a rela-
tively electron-rich aryl substrate.
Entrya
R
Time/ Conv/ 4
hb
%
Yield/ eed [a]D
%
/
(R)/
25
cm2 g-1 (S)e
c
2a
H
4
4
100
100
65
97
95
42
99
94
12
96
98
95
99
96
92
94
85
60
95
97
98
94
94
98
77
95 -51.1
R
Sf
R
R
R
R
R
R
R
R
R
R
Sf
R
R
R
R
R
R
R
R
Sf
95 ?51.2
62 -37.8
95 -42.1
93 -44.8
85 -37.7
88 -31.6
93 -34.8
69 -23.6
85 -47.9
94 -37.5
94 -50.7
94 ?50.9
95 -42.5
96 -37.3
96 -41.2
98 -47.8
2b
2c
2d
2e
2f
o-Cl
24
2
m-Cl
100
100
32
p-Cl
2
o-Br
24
2
m-CF3
p-F
100
100
100
100
100
100
100
95
2g
2h
2i
1
p-NO2
o-OMe
m-OMe
p-OMe
2
4
2j
2
2k
18
18
18
2
2l
p-OBn
2m
2n
2o
2p
2q
2r
2s
2t
p-OTBS
90
p-OAc
2
100
100
100
100
100
100
87
p-Me
2
30,40-C4H4
30,40-O(CH2)2O
30,40-(OMe)2
30-NO2-40-OMe
20-OMe-50-Me
3
92 -50.0
g
5
–
-36.9
8
90 -27.0
84 -36.3
90h ?32.8
While a -chloroketones are addressed as superior sub-
strates in the Rh-catalyzed transfer hydrogenation [4, 5],
they suffer from severe drawbacks for commercial appli-
cations, causing irritation to the skin and eyes and being
light-sensitive [14]. Furthermore, the chloride in a reduced
halohydrin is a poor leaving group; so far, it routinely
transformed either to styrene oxide [4, 5] for subsequent
regioselective ring-opening with amine or to iodide [15] for
amine displacement.
3
9
a
Unless otherwise indicated, reaction conditions are as follows:
ketone 2 (1 mmol), (S,S)-3 (S/C = 1,000), HCO2H/Et3 N (molar
ratio = 5/2, 0.2 cm3), 2 cm3 EtOAc
b
Time taken to reach the conversion specified
c
Isolated yield
d
The % ee values were measured using a chiral stationary phase
e
The absolute configuration was determined by comparing the sign
of the specific rotation with the literature data
In this study, we have achieved a highly enantioselective
transfer hydrogenation of a-tosyloxyarylketones to pro-
duce optically active 1-arylethanediol monotosylates. The
products mostly exist in a crystalline solid; so far, they are
f
(R,R)-3 was used instead of (S,S)-3
g
Separation failed
h
Measured as the corresponding acetate
123

Enantioselective synthesis of 1-arylethanediols
75
(m, 7H), 4.99 (d, J = 8.7 Hz, 1H), 4.17 (dd, J = 10.2,
3.3 Hz, 1H), 4.07 (dd, J = 10.2, 8.7 Hz, 1H), 2.55 (d,
J = 3.0 Hz, 1H), 2.44 (s, 3H) ppm; 13C NMR (75 MHz,
CDCl3) d 145.0, 138.1, 132.6, 129.9, 128.6, 128.5, 126.1,
74.3, 71.9, 21.6 ppm; MS (EI, 70 eV) m/z (%) 292 (7)
[M]?; HRMS Calcd for C15H16O4S: 292.0769, found
292.0769.
easy to handle and/or enrich optical purity, if necessary.
This may provide new opportunities for industrial synthe-
sis of active pharmaceutical ingredients, in particular,
optically active 2-amino-1-arylethanols with structural
diversity.
(R)-1-(2-Chlorophenyl)-2-(p-tolylsulfonyloxy)ethanol
(4b, C15H15ClO4S)
Experimental
25
Yield: 42%; yellow oil; [a]D -37.8 cm2 g-1 (c 2.45,
The catalytic reactions were carried out under an argon
atmosphere with oven-dried glassware. The reactions were
monitored by TLC using silica gel plates, and the products
were purified by flash column chromatography on silica gel
(230–400 mesh). Melting points were measured on an
electrothermal apparatus. NMR spectra were recorded at
1
CHCl3); 62% ee; H NMR (300 MHz, CDCl3) d 7.78 (d,
J = 8.1 Hz, 2H), 7.57 (d, J = 8.1 Hz, 2H), 7.34–7.23 (m,
5H), 5.35 (dd, J = 8.1, 3.0 Hz, 1H), 4.27 (dd, J = 10.5,
2.7 Hz, 1H), 3.98 (dd, J = 10.5, 8.4 Hz, 1H), 2.77 (d,
J = 3.6 Hz, 1H), 2.45 (s, 3H) ppm; 13C NMR (75 MHz,
CDCl3): d = 145.0, 135.6, 132.5, 131.8, 129.9, 129.4, 129.4,
127.98, 127.8, 127.2, 72.7, 68.8, 21.6 ppm; MS (EI, 70 eV)
m/z (%) 141 (100) [M–CH2OTs]?, 143 (35) [M–CH2OTs]?.
1
300 MHz for H and 75 or 125 MHz for 13C. Mass spectra
were recorded on a GC/MS operating system at an ionization
potential of 70 eV. Optical rotations were measured on a
high-resolution digital polarimeter. The ee values of the
samples were determined by HPLC analysis using Daicel
Chiralcel OD-H chiral column [250 9 4.6 mm, ethanol/
n-hexane (v/v) = 1-5/99-95, flow rate 0.5–1.2 cm3/min].
The starting a-tosyloxyketones 2a-2t were conveniently
prepared by a-tosyloxylation of the corresponding ace-
tophenones 1a-2t with [hydroxy(tosyloxy)iodo]benzene in
refluxing acetonitrile [7, 10–12, 14]. The chiral rhodium
complex (S,S)-3 was prepared from the reaction of
dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer
(99%) and (1S,2S)-N-(p-toluenesulfonyl)-1,2-diphenyl-
ethylenediamine (98%) in dichloromethane in the presence
of triethylamine, according to [16]. The formic acid/tri-
ethylamine (molar ratio = 5/2) azeotrope was prepared by
double distillation of the mixture [17]. All reagent-grade
chemicals and anhydrous solvents were purchased from
commercial suppliers and used without further purification.
(R)-1-(3-Chlorophenyl)-2-(p-tolylsulfonyloxy)ethanol
(4c, C15H15ClO4S)
Yield: 99%; pale yellow oil; [a]D25 –42.1 cm2 g-1 (c 0.98,
1
CHCl3); 95% ee; H NMR (300 MHz, CDCl3) d 7.76 (d,
J = 8.1 Hz, 2H), 7.35–7.18 (m, 6H), 4.96 (dt, J = 8.1,
3.3 Hz, 1H), 4.14 (dd, J = 10.5, 3.3 Hz, 1H), 4.02 (dd,
J = 10.5, 8.4 Hz, 1H), 2.61 (d, J = 3.6 Hz, 1H), 2.46 (s,
3H) ppm; 13C NMR (75 MHz, CDCl3) d 145.2, 140.3,
138.5, 137.4, 134.6, 132.3, 129.9, 129.9, 128.5, 127.9,
126.3, 124.3, 71.8, 71.2, 21.6 ppm; MS (EI, 70 eV) m/z (%)
141 (100) [M–CH2OTs]?, 143 (28) [M–CH2OTs]?; Anal.
Calcd for C15H15ClO4S: C, 55.13; H, 4.63. Found: C,
55.27, H, 4.76.
(R)-1-(4-Chlorophenyl)-2-(p-tolylsulfonyloxy)ethanol
(4d, C15H15ClO4S)
25
Yield: 94%; white solid; mp 91–92 °C; [a]D
-44.8 cm2 g-1 (c 2.52, CHCl3); 93% ee; 1H NMR
(300 MHz, CDCl3) d 7.75 (d, J = 8.1 Hz, 2H), 7.35–7.23
(m, 6H), 4.96 (dt, J = 8.1, 3.3 Hz, 1H), 4.14 (dd, J = 10.5,
3.3 Hz, 1H), 4.02 (dd, J = 10.5, 8.1 Hz, 1H), 2.59 (d,
J = 3.3 Hz, 1H), 2.45 (s, 3H) ppm; 13C NMR (75 MHz,
CDCl3) d 145.1, 136.7, 134.2, 132.4, 129.9, 128.7, 127.8,
127.5, 73.9, 71.25, 21.6 ppm; MS (EI, 70 eV) m/z (%) 141
(100) [M–CH2OTs]?, 143 (60) [M–CH2OTs]?.
General procedure for asymmetric transfer
hydrogenation of a-tosyloxyarylketones
Using the protocol previously described [7], the reduction
of 1 mmol of ketone with (S,S)-3 (S/C = 1,000) was car-
ried out using a formic acid/triethylamine mixture (molar
ratio = 5/2, 0.2 cm3) in 2 cm3 ethyl acetate for the time
indicated in Table 1 at ambient temperature to afford the
corresponding alcohol. The Rh-catalyst effectively per-
formed in transfer hydrogenation of a-tosyloxyketones
2a-2t to produce optically active a-tosyloxyalcohols 4a-4t.
(R)-1-(2-Bromophenyl)-2-(p-tolylsulfonyloxy)ethanol
(4e, C15H15BrO4S)
Yield: 12%; yellow oil; [a]D -37.7 cm2 g-1 (c 0.28,
25
1
CHCl3); 85% ee; H NMR (300 MHz, CDCl3) d 7.78 (d,
J = 8.3 Hz, 2H), 7.57 (d, J = 7.7 Hz, 1H), 7.47 (d,
J = 7.9 Hz, 1H), 7.34–7.30 (m, 3H), 7.17 (t, J = 7.7 Hz,
1H), 5.31–5.29 (m, 1H), 4.27 (dd, J = 10.5, 2.6 Hz, 1H),
3.97 (dd, J = 10.5, 8.3 Hz, 1H), 2.86 (bs, 1H), 2.44 (s, 3H)
ppm; 13C NMR (75 MHz, CDCl3) d 145.0, 137.1, 132.7,
(S)-1-Phenyl-2-(p-tolylsulfonyloxy)ethanol
(4a, C15H16O4S)
25
Yield: 95%; white solid; mp 69–71 °C; [a]D
?51.2 cm2 g-1 (c 2.52, CHCl3); 95% ee; 1H NMR
(300 MHz, CDCl3) d 7.78 (d, J = 8.4 Hz, 2H), 7.36–7.27
123

76
D.-M. Lee et al.
132.56, 129.9, 129.8, 128.1, 128.0, 127.8, 121.8, 72.7,
71.0, 21.6 ppm; MS (EI, 70 eV) m/z (%) 370 (19) [M]?,
372 (21) [M]?; HRMS Calcd for C15H15BrO4S: 369.9874,
found 369.9875.
144.7, 132.8, 129.7, 129.3, 127.9, 127.4, 126.1, 120.8,
110.3, 73.0, 68.2, 55.2, 21.6 ppm; MS (EI, 70 eV) m/z (%)
322 (60) [M]?.
(R)-1-(3-Methoxyphenyl)-2-(p-tolylsulfonyloxy)ethanol
(4j, C16H18O5S)
(R)-1-(3-Trifluoromethylphenyl)-2-
25
(p-tolylsulfonyloxy)ethanol (4f, C16H15F3O4S)
Yield: 96%; white solid; mp 52–54 °C; [a]D
Yield:96%;whitesolid;mp89–92 °C;[a]D25 -31.6 cm2 g-1
(c 2.42, CHCl3); 88% ee; 1H NMR (300 MHz, CDCl3) d 7.74
(d, J = 8.4 Hz, 2H), 7.58–7.43 (m, 4H), 7.33 (d,
J = 8.14 Hz, 2H), 5.05 (dt, J = 8.1, 3.3 Hz, 1H), 4.16 (dd,
J = 10.5, 3.6 Hz, 1H), 4.05 (dd, J = 10.5, 8.1 Hz, 1H), 2.89
(d, J = 3.3 Hz, 1H), 2.44 (s, 3H) ppm; 13C NMR (75 MHz,
CDCl3) d 145.3, 139.3, 132.3, 131.4, 131.1, 129.9, 129.6,
129.1, 127.8, 125.2, 123.0, 73.8, 71.3, 21.6 ppm; MS (EI,
70 eV) m/z (%) 360 (14) [M]?; HRMS Calcd for
C16H15F3O4S: 360.0643, found 360.0644.
-37.5 cm2 g-1 (c 2.56, CHCl3); 94% ee; 1H NMR
(300 MHz, CDCl3) d 7.77 (d, J = 8.4 Hz, 2H), 7.33 (d,
J = 8.1 Hz, 2H), 7.27–7.22 (m, 1H), 6.88–6.82 (m, 3H),
4.95 (d, J = 8.7, 3.0 Hz, 1H), 4.15 (dd, J = 10.5, 3.3 Hz,
1H), 4.04 (dd, J = 10.5, 8.7 Hz, 1H), 2.53 (d, J = 3.3 Hz,
1H), 2.45 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3) d
159.8, 145.7, 239.8, 132.5, 129.9, 129.7, 127.9, 118.4,
114.0, 111.5, 74.3, 71.8, 55.2, 21.6 ppm; MS (EI, 70 eV)
m/z (%) 322 (46) [M]?.
(R)-1-(4-Methoxyphenyl)-2-(p-tolylsulfonyloxy)ethanol
(4k, C16H18O5S)
(R)-1-(4-Fluorophenyl)-2-(p-tolylsulfonyloxy)ethanol
(4g, C15H15FO4S)
25
Yield: 92%; white solid; mp 71–72 °C; [a]D
Yield: 98%; white solid; mp 66–68 °C; [a]D
-50.7 cm2 g-1 (c 0.79, CHCl3); 94% ee; 1H NMR
(300 MHz, CDCl3) d 7.77 (d, J = 8.3 Hz, 2H), 7.33 (d,
J = 8.1 Hz, 2H), 7.23 (d, J = 6.9 Hz, 2H), 6.86 (d,
J = 6.8 Hz, 2H), 4.92 (dd, J = 8.4, 3.5 Hz, 1H), 4.11
(dd, J = 10.3, 3.5 Hz, 1H), 4.03 (dd, J = 10.4, 8.5 Hz,
1H), 3.79 (s, 3H), 2.45 (s, 3H) ppm; 13C NMR (125 MHz,
CDCl3) d 159.7, 145.0, 132.6, 130.3, 129.9, 127.9, 127.4,
114.0, 74.2, 71.4, 55.2, 21.6 ppm; MS (EI, 70 eV) m/z (%)
322 (44) [M]?; HRMS Calcd for C16H18O5S: 322.0875,
found 322.0875.
25
-34.8 cm2 g-1 (c 1.59, CHCl3); 93% ee; 1H NMR
(300 MHz, CDCl3) d 7.76 (d, J = 8.2 Hz, 2H), 7.35–7.28
(m, 4H), 7.01 (t, J = 8.6 Hz, 2H), 4.96 (dt, J = 8.2,
3.0 Hz, 1H), 4.11 (dd, J = 10.5, 3.5 Hz, 1H), 4.02 (dd,
J = 10.2, 8.3 Hz, 1H), 2.68 (d, J = 3.1 Hz, 1H), 2.45 (s,
3H) ppm; 13C NMR (125 MHz, DMSO-d6) d 162.5, 144.8,
136.8, 132.1, 130.0, 127.5, 125.4, 114.9, 74.1, 69.1, 21.0
ppm; MS (EI, 70 eV) m/z (%) 125 (100) [M–CH2OTs]?;
Anal. Calcd for C15H15FO4S: C, 58.05; H, 4.87. Found: C,
58.47; H, 5.01.
(R)-1-(4-Benzyloxyphenyl)-2-(p-tolylsulfonyloxy)ethanol
(4l, C22H22O5S)
(R)-1-(4-Nitrophenyl)-2-(p-tolylsulfonyloxy)ethanol
(4h, C15H15NO6S)
28
Yield: 85%; white solid; mp 91–92 °C; [a]D
25
Yield: 95%; white solid; mp 174–175 °C; [a]D
-42.5 cm2 g-1 (c 0.79, CHCl3); 95% ee; 1H NMR
(300 MHz, CDCl3) d 7.77 (d, J = 8.4 Hz, 2H), 7.43–7.31
(m, 6H), 7.23 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.8 Hz,
2H), 5.05 (s, 2H), 4.92 (dt, J = 8.3, 3.0 Hz, 1H), 4.11 (dd,
J = 10.3, 3.5 Hz, 1H), 4.02 (dd, J = 10.3, 8.5 Hz, 1H),
2.47 (d, J = 3.0 Hz, 1H), 2.44 (s, 3H) ppm; 13C NMR
(75 MHz, DMSO-d6) d 158.9, 145.0, 136.7, 132.6, 130.5,
129.9, 128.5, 128.0, 127.9, 127.5, 127.4, 114.9, 74.2, 71.4,
69.9, 21.6 ppm; MS (EI, 70 eV) m/z (%) 398 (1) [M]?;
HRMS Calcd for C16H18O5S: 398.1188, found 398.1191.
-23.6 cm2 g-1 (c 1.06, acetone); 69% ee; 1H NMR
(300 MHz, CDCl3) d 8.19 (d, J = 8.6 Hz, 2H,), 7.75 (d,
J = 8.1 Hz, 2H), 7.52 (d, J = 8.5 Hz, 2H), 7.33 (d,
J = 8.0 Hz, 2H), 5.13–5.10 (m, 1H), 4.20 (dd, J = 10.6,
3.4 Hz, 1H), 4.10–4.04 (m, 1H), 2.82 (d, J = 3.1 Hz, 1H),
2.45 (s, 3H) ppm; 13C NMR (125 MHz, DMSO-d6) d
148.3, 146.8, 144.8, 131.9, 129.9, 127.5, 123.1, 73.7, 69.0,
21.0 ppm; MS (EI, 70 eV) m/z (%) 152 (74) [M–
CH2OTs]?; Anal. Calcd for C15H15NO6S: C, 53.40; H,
4.48. Found: C, 53.97; H, 5.04.
(R)-1-(4-tert-Butyldimethylsilyloxyphenyl)-2-
(p-tolylsulfonyloxy)ethanol (4m, C21H30O5SSi)
(R)-1-(2-Methoxyphenyl)-2-(p-tolylsulfonyloxy)ethanol
(4i, C16H18O5S)
Yield: 60%; yellow oil; [a]D -37.3 cm2 g-1 (c 1.02,
29
25
1
Yield: 99%; white solid; mp 53–55 °C; [a]D
CHCl3); 96% ee; H NMR (300 MHz, CDCl3) d 7.78 (d,
-47.9 cm2 g-1 (c 2.54, CHCl3); 85% ee; 1H NMR
(300 MHz, CDCl3) d 7.76 (d, J = 8.1 Hz, 2H), 7.38–7.24
(m, 4H), 6.95 (t, J = 7.5 Hz, 1H), 6.82 (d, J = 8.1 Hz,
1H), 5.17 (dd, J = 8.1, 3.3 Hz, 1H), 4.28 (dd, J = 10.2,
3.3 Hz, 1H), 4.05 (dd, J = 10.2, 8.1 Hz, 1H), 3.77 (s, 3H),
2.44 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3) d 156.1,
J = 8.3 Hz, 2H), 7.34 (d, J = 8.6 Hz, 2H), 7.16 (d,
J = 8.3 Hz, 2H), 6.79 (d, J = 8.6 Hz, 2H), 4.92–4.89
(m, 1H), 4.11 (dd, J = 10.3, 3.3 Hz, 1H), 4.02 (dd,
J = 10.3, 8.5 Hz, 1H), 2.48 (d, J = 2.8 Hz, 1H), 2.44 (s,
3H), 0.96 (s, 9H), 0.17 (s, 6H) ppm; 13C NMR (75 MHz,
CDCl3): d = 155.9, 145.0, 132.6, 130.8, 129.9, 127.9,
123

Enantioselective synthesis of 1-arylethanediols
77
127.4, 120.2, 74.3, 71.5, 25.6, 21.6, 18.1, -4.4 ppm; MS
(EI, 70 eV) m/z (%) 422 (1) [M]?; HRMS Calcd for
C21H30O5SSi: 422.1583, found 422.1587.
116.1, 75.5, 72.4, 64.2, 21.6 ppm; MS (EI, 70 eV) m/z (%)
350 (1) [M]?.
(R)-1-(3,4-Dimethoxyphenyl)-2-(p-tolylsulfonyloxy)ethanol
(4r, C17H20O6S)
(R)-1-(4-Acetoxyphenyl)-2-(p-tolylsulfonyloxy)ethanol
(4n, C17H18O6S)
Yield: 94%; pale yellow oil; [a]D25 -27.0 cm2 g-1 (c 0.83,
Yield: 95%; pale yellow oil; [a]D25 -41.2 cm2 g-1 (c 1.09,
CHCl3); 90% ee; H NMR (300 MHz, CDCl3) d 7.32 (d,
1
1
CHCl3); 96% ee; H NMR (300 MHz, CDCl3) d 7.77 (d,
J = 8.2 Hz, 2H), 7.75 (d, J = 8.3 Hz, 2H), 6.85–6.82 (m,
3H), 4.92 (dd, J = 8.1, 3.7 Hz, 1H), 4.12 (dd, J = 10.4,
3.7 Hz, 1H), 4.05 (dd, J = 10.2, 8.1 Hz, 1H), 3.86 (s, 3H),
3.84 (s, 3H), 2,44 (s, 3H) ppm; MS (EI, 70 eV) m/z (%) 352
(3) [M]?.
J = 8.3 Hz, 2H), 7.34 (d, J = 8.6 Hz, 2H), 7.33 (d,
J = 8.7 Hz, 2H), 7.06 (d, J = 8.6 Hz, 2H), 4.99 (dt,
J = 8.5, 3.2 Hz, 1H), 4.12 (dd, J = 10.4, 3.3 Hz, 1H), 4.01
(dd, J = 10.4, 8.5 Hz, 1H), 2.61 (d, J = 3.2 Hz, 1H), 2.45
(s, 3H), 2.29 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3) d
169.4, 150.6, 145.1, 145.7, 132.4, 129.9, 127.9, 127.3,
121.8, 74.1, 74.3 21.6, 21.0 ppm; MS (EI, 70 eV) m/z (%)
165 (39) [M–CH2OTs]?; Anal. Calcd for C17H18O6S: C,
58.27; H, 5.18. Found: C, 60.01, H, 5.08.
(R)-1-(3-Nitro-4-methoxyphenyl)-2-
(p-tolylsulfonyloxy)ethanol (4s, C16H17NO7S)
25
Yield: 98%; white solid; mp 92–93 °C; [a]D
-36.3 cm2 g-1 (c 2.49, CHCl3); 84% ee; 1H NMR
(300 MHz, CDCl3) d 7.78 (s, 1H), 7.75 (d, J = 8.4 Hz,
2H), 7.54 (d, J = 8.4 Hz, 1H), 7.34 (d, J = 8.1 Hz, 2H),
7.06 (d, J = 8.7 Hz, 1H), 5.00–4.98 (m, 1H), 4.13 (dd,
J = 10.5, 3.9 Hz, 1H), 4.04 (dd, J = 10.5, 7.8 Hz, 1H),
3.96 (s, 3H), 2.73 (bs, 1H), 2.46 (s, 3H) ppm; 13C NMR
(75 MHz, CDCl3) d 152.8, 145.3, 139.3, 132.2, 132.0,
130.8, 130.0, 127.8, 123.5, 113.6, 73.5, 70.4, 56.6, 21.6
ppm; MS (EI, 70 eV) m/z (%) 182 (100) [M–CH2OTs]?.
(R)-1-(4-Methylphenyl)-2-(p-tolylsulfonyloxy)ethanol
(4o, C16H18O4S)
25
Yield: 97%; white solid; mp 85–86 °C; [a]D
-47.8 cm2 g-1 (c 1.27, CHCl3); 98% ee; 1H NMR
(500 MHz, CDCl3) d 7.76 (d, J = 8.3 Hz, 2H), 7.32 (d,
J = 8.1 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 7.14 (d,
J = 7.7 Hz, 2H), 4.94–4.92 (m, 1H), 4.12 (dd, J = 10.4,
3.2 Hz, 1H), 4.03 (dd, J = 10.4, 8.6 Hz, 1H), 2.59 (s, 1H),
2.44 (s, 3H), 2.33 (s, 3H) ppm; 13C NMR (75 MHz,
CDCl3) d 145.0, 138.3, 135.2, 132.0, 129.9, 129.3, 127.9,
126.7, 126.0, 74.3, 71.7, 21.6, 21.1 ppm; MS (EI, 70 eV)
m/z (%) 121 (100) [M–CH2OTs]?; Anal. Calcd for
C16H18O4S: C, 62.72; H, 5.92. Found: C, 61.98; H, 5.97.
(S)-1-(2-Methoxy-5-methylphenyl)-2-
(p-tolylsulfonyloxy)ethanol (4t, C17H20O5S)
25
Yield: 77%; yellow oil; [a]D ?32.8 cm2 g-1 (c 1.06,
CHCl3); 90% ee; 1H NMR (300 MHz, CDCl3) d 7.76
(d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.15 (d,
J = 1.9 Hz, 1H), 7.05 (dd, J = 8.7, 1.7 Hz, 1H), 6.71 (d,
J = 8.3 Hz, 1H), 5.15–5.10 (m, 1H), 4.25 (dd, J = 10.1,
3.4 Hz, 1H), 4.05 (dd, J = 10.1, 8.1 Hz, 1H), 3.73 (s, 3H),
2.82 (d, J = 5.3 Hz, 1H), 2.44 (s, 3H), 2.26 (s, 3H) ppm;
MS (EI, 70 eV) m/z (%) 336 (2) [M]?.
(R)-1-(2-Naphthyl)-2-(p-tolylsulfonyloxy)ethanol
(4p, C19H18O4S)
25
Yield: 98%; white solid; mp 116–118 °C; [a]D
-50.0 cm2 g-1 (c 2.50, CHCl3); 92% ee; 1H NMR
(300 MHz, CDCl3) d 7.83–7.72 (m, 6H), 7.51–7.47 (m,
2H), 7.38 (d, J = 8.7 Hz, 1H), 7.27–7.25 (m, 2H), 5.15
(dd, J = 8.1, 3.3 Hz, 1H), 4.25 (dd, J = 10.5, 3.6 Hz, 1H),
4.14 (dd, J = 10.5, 8.1 Hz, 1H), 2.65 (bs, 1H), 2.41 (s, 3H)
ppm; 13C NMR (75 MHz, CDCl3) d 145.0, 135.6, 133.2,
133.1, 132.5, 129.8, 128.4, 127.9, 127.8, 127.6, 127.3,
126.3, 125.4, 123.6, 74.2, 72.0, 21.6 ppm; MS (EI, 70 eV)
m/z (%) 157 (100) [M–CH2OTs]?; Anal. Calcd for
C19H18O4S: C, 66.65; H, 5.30. Found: C, 66.72; H, 5.81.
Acknowledgments This work was supported by a grant for Indus-
trial Technology Development Programs (TS062-03) from the
Ministry of Commerce, Industry and Energy of Korea and a Brain-
Pool fellowship to G.K. (052-1-4) from the Korean Federation of
Science and Technology Societies.
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