Enantioselective Rh-catalyzed transfer hydrogenation of α-sulfonyloxy heteroaryl ketones; asymmetric synthesis of (S)-bufuralol

Article abstract of DOI:10.1016/j.tetasy.2009.11.002

Asymmetric transfer hydrogenation of α-sulfonyloxy heteroaryl ketones mediated by Cp*RhCl[(S,S)-TsDPEN] using an azeotropic mixture of formic acid/triethylamine afforded the corresponding diol-2-monosulfonates in excellent yield with high enantioselectivity. This led to the asymmetric synthesis of (S)-bufuralol.

Full text of DOI:10.1016/j.tetasy.2009.11.002

Tetrahedron: Asymmetry 20 (2009) 2639–2645
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantioselective Rh-catalyzed transfer hydrogenation of a-sulfonyloxy
heteroaryl ketones; asymmetric synthesis of (S)-bufuralol
Se Hun Kwak a,b, Do-Min Lee a, Kee-In Lee a,b,
*
a Bio-Organic Science Division, Korea Research Institute of Chemical Technology, PO Box 107, Yusong, Taejon 305-600, Republic of Korea
b Department of Medicinal and Pharmaceutical Chemistry, University of Science and Technology, Gwahangno 113, Yusong, Taejon 305-333, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Asymmetric transfer hydrogenation of
a-sulfonyloxy heteroaryl ketones mediated by Cp*RhCl[(S,S)-
Received 21 September 2009
Accepted 4 November 2009
Available online 26 November 2009
TsDPEN] using an azeotropic mixture of formic acid/triethylamine afforded the corresponding
diol-2-monosulfonates in excellent yield with high enantioselectivity. This led to the asymmetric synthe-
sis of (S)-bufuralol.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
thiophene, and benzofuran.9 Previously, we reported the asymmet-
ric transfer hydrogenation of 2-tosyloxy-1-phenylethanone deriva-
Amino alcohols have been identified as rich resources in organic
and medicinal chemistry. Amino alcohols are often found not only in
the structural units of many building blocks, chiral auxiliaries, and
ligands in organic transformations,1 but also in the structural motifs
ofmanybiologicallyactivecompounds. Inparticular, opticallyactive
alcohols or amines containing heteroaryl moieties are of great
importance as key intermediates for the synthesis of biologically ac-
tive compounds, such as bufuralol, duloxetine, zileuton, MK-0417,
andL-770644.2 Muchattentionhasbeenpaidtotheenantioselective
preparation of chiral precursors under asymmetric catalysis, classi-
cal/enzymatic resolution and biotransformative pathways. A num-
ber of studies have disclosed the methods comprising of the
oxazaborolidine-catalyzed reduction of ketones,3 asymmetric
hydrogenation of aminoketones,4 and asymmetric epoxidation of
allylic alcohols.5 Moreover, there have been many reports on the
synthesis of such an important class of compounds; however, the
application has been rather limited to aromatic and olefinic ketones.
Recently, heteroaryl-containing alcohols and amines have been
prepared through biotransformation; lipase-mediated resolution
tives with TsDPEN-Rh catalyst in formic acid/triethylamine and
further applications to the synthesis of b-adrenergic agonists.10 In
continuation of our earlier efforts toward the preparation of biolog-
ically important compounds, particularly those possessing a chiral
aminoalcohol unit, we herein report an enantioselective Rh-cata-
lyzed transfer hydrogenation of
a-sulfonyloxy heteroaryl ketones
and further elaborate to access the facile synthesis of (S)-bufura-
lol,9c,11 a non-selective b-adrenergic antagonist.
2. Results and discussion
2.1.
a-Sulfonyloxylation of heteroaryl ketones
The
a-sulfonyloxy heteroaryl ketones were prepared by sulfo-
nyloxylation of the corresponding ketones and their trimethylsilyl
enol ethers with [hydroxy(tosyloxy)iodo]benzene (PhI(OH)OTs) or
[hydroxy(mesyloxy)iodo]benzene (PhI(OH)OMs).12 The starting
ketones were either commercially available or easily accessible in
a few steps.
Thus, 2-mesyloxy-1-(furan-2-yl)ethanone 2a was conveniently
prepared in 73% yield from the corresponding 2-acetylfuran 1a
with PhI(OH)OMs in refluxing acetonitrile (route A), as shown in
of b-cyano-,
mediated reduction of
c
-chloro-, and
c
-azidoalcohols6a–d, and Baker’s yeast-
a
-hydroxyketone derivatives.6e,f
Asymmetric transfer hydrogenation (ATH) has had its applica-
tions broadened to the enantioselective hydrogenation of unsatu-
rated carbonyl and imine groups.7 In general, ATH offers an
operational simplicity, since the reaction does not involve molecular
hydrogen and is insensitive to air oxidation, hence it proves particu-
larly valuable in the scale-up synthesis of active pharmaceutical
ingredients.8 However, this approach has only rarely been used for
simple heteroaryl ketones, mostly as the 2-acetyl analogues of furan,
Scheme 1. It is known that the a-mesyloxylation of methylketones
is initiated by the electrophilic addition of [PhI(OH)]+OMsꢀ to enol-
izable ketones to give aldol adducts, followed by nucleophilic dis-
placement by the nearby mesyloxy anion to result in the observed
products. The above-mentioned procedure is quite general for the
a-sulfonyloxylation of thiophene, benzofuran, and benzothiophene
derivatives, however, the reaction of 1-(5-methoxybenzofuran-
2-yl)ethanone 1e with either PhI(OH)OTs or PhI(OH)OMs was
problematic, resulting in very poor yield and several majorly
decomposed products. A similar phenomenon was also observed
* Corresponding author. Tel.: +82 42 860 7186; fax: +82 42 860 7160.
E-mail address: kilee@krict.re.kr (K.-I. Lee).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.11.002

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S. H. Kwak et al. / Tetrahedron: Asymmetry 20 (2009) 2639–2645
route A
O
O
Ph
I
O
PhI(OH)OMs
MeCN, reflux
O
O
O
OMs
+
OH2
-OMs
1a
2a (73%)
route B
O
OTBS
O
O
OTs
O
O
ii, PhI(OH)OTs
i, TBSOTf, i-Pr2NEt
CH2Cl2, 0ºC
MeO
MeO
MeO
2h (61%)
1e
Scheme 1.
a-Sulfonyloxylation of heteroaryl ketones.
for substrates possessing an electron-donating group, such as 1g
and 1h, and the reaction was not successful. Presumably, the elec-
tron-rich species hampered the initial formation of enol-tautomer,
which is crucial for certain types of aldol condensation.
Alternatively, the reaction of PhI(OH)OMs with the TBS enolate
of 1e in dichloromethane furnished 2-mesyloxy-1-(5-meth-
oxybenzofuran-2-yl)ethanone 2g in 61% yield (route B). Thus, the
limitation could be overcome indirectly by means of their silyl eno-
lates, derived from the corresponding methylketones with TBSOTf,
which were then trapped with either PhI(OH)OTs or PhI(OH)OMs
of 1 mmol of 2a with (S,S)-Rh (substrate/catalyst molar ratio = 500)
and formic acid/triethylamine mixture (molar ratio = 5/2,
a
0.2 mL), stirring in ethyl acetate (4 mL) for 1 h at ambient temper-
ature resulted in (R)-3a in 92% yield with 98% enantiomeric excess
(ee). It should be noted that the observed enantioselectivity was
similar to that reported in the corresponding
a
-chloroketone.9b
The ee values were measured by chiral HPLC analysis using a
Daicel Chiralcel OD-H or OJ-H column. The racemic alcohols ( )-3
were prepared by the sodium borohydride reduction of 2 in THF,
and used as standards for ee determination.
to afford the desired
a
-sulfonyloxy ketones in moderate yields. Fol-
We examined the 2- and 3-iomeric heterocyclic substrates dif-
ferentiated by electronically demanding groups using the same
protocol and the results are summarized in Table 1. For a given cat-
alytic system, the value of enantioselectivity was not much sensi-
tive to the structural patterns, although the yield did decrease in
the cases of the 3-isomers. Only the reduction of 5-nitrobenzofuran
2f showed a decrease in enantioselectivity when compared to
those of the corresponding congeners 2h and 2i. This result indi-
cates that an attractive interaction between arene ligand and het-
eroaryl substrate is still favorable, presumably due to the
contribution of a relatively electron-rich substrate. The overall
results again suggest that the reduction of heteroaryl ketones oper-
ates in the same way as that of aryl ketones. The Rh-catalyst
lowing the above-mentioned procedures, some heteroaryl ketones
(Fig. 1) were prepared and readily used for the asymmetric transfer
hydrogenation.
2.2. Asymmetric transfer hydrogenation of
heteroaryl ketones
a-sulfonyloxy
The Rh-catalyst, Cp*RhCl[(S,S)-TsDPEN], was prepared from the
reaction of dichloro(pentamethylcyclopentadienyl)rhodium(III)
dimer and (1S,2S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenedi-
amine in dichloromethane in the presence of triethylamine.13
The formic acid/triethylamine (molar ratio = 5/2) azeotrope was
prepared by double distillation of the mixtures.14 Upon reduction
performed effectively in the transfer hydrogenation of a-sulfonyloxy
O
O
O
O
X
X
R1
X
X
1b: X = S
1
1j:
1k: X = O
1l: X = S
X = S
1c:
X = O; R = H
1d: X = O; R1 = 5-NO2
1f: X = O; R1 = 5-Br
1
1g:
X = O; R = 7-Et
1h: X = O; R1 = 7-OMe
1
1i:
X = S; R = H
O
O
O
O
OR2
OR2
OR2
X
OR2
X
R1
X
X
2o-2p
2a-2d
2e-2m
2n
Figure 1. Substrates prepared for transfer hydrogenation. Route A: 2b (72%), 2c (81%), 2d (87%), 2e (69%), 2f (66%), 2i (62%), 2m (60%), 2n (58%), 2o (62%), 2p (64%). Route B:
2g (61%); 2j (52%); 2k (54%); 2l (53%); the structures of 2a–2p are shown in Table 1.

S. H. Kwak et al. / Tetrahedron: Asymmetry 20 (2009) 2639–2645
2641
Table 1
Catalytic transfer hydrogenation of a-sulfonyloxy heteroaryl ketones
OH
O
Ts
N
)-Rh
(S,S
X
X
.
OR2
OR2
Ph
Ph
HCO2H/Et3N, EtOAc
(S/C = 500)
Rh
Cl
N
H2
R1
R1
Cp*RhCl[(S,S)-TsDPEN]
2
3
Entrya
X
R1
R2
Time (h)
Alcohol
Yield (%)
eeb (%)
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
O
S
—
—
—
—
H
Ms
Ts
Ms
Ts
Ts
Ts
Ms
Ts
Ts
Ms
Ts
Ts
Ts
Ts
Ts
Ts
1
1
1
1
1
2
3
2
1
1
1
2
2
4
2
2
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
92
98
95
97
96
90
90
99
95
97
94
91
91
85
84
83
98
99
95
96
c
O
—
5-NO2
88
96
96
94
97d
95d
96
96
96
95
93
5-OMe
5-OMe
5-Br
7-Et
7-Et
7-OMe
H
—
—
—
S
S
O
S
a
b
c
Reaction conditions are as follows: ketone 2 (1 mmol), (S,S)-Rh (substrate/catalyst = 500), HCO2H/Et3N (molar ratio = 5/2, 0.2 mL), EtOAc (4 mL).
The % ee values were determined by HPLC analysis using a Daicel Chiralcel OD-H column unless otherwise indicated.
Separation failed.
Chiralcel OJ-H column used.
d
heteroaryl ketones with an azeotropic mixture of formic acid/tri-
ethylamine to produce the corresponding 1,2-diol monosulfonates
in excellent yield with high enantioselectivity. This represents a
simple and highly efficient procedure for the preparation of chiral
diols containing heteroaryl moieties, which could be used as pre-
cursors to access aminoalcohols.
ethers, depending on their electronic nature. The asymmetric
transfer hydrogenation of -sulfonyloxy heteroaryl ketones medi-
a
ated by the Rh-catalyst using an azeotropic mixture of formic acid/
triethylamine afforded the corresponding diol-2-monosulfonates
in excellent yield with high enantioselectivity. The enantioselectiv-
ity appears to be little affected by the properties of the heteroaryl
moiety. This represents a useful approach to the preparation of chi-
ral alcohols from heteroaryl ketones, particularly those possessing
a chiral aminoalcohol unit. This approach has led to the efficient
synthesis of (S)-bufuralol.
2.3. Asymmetric synthesis of (S)-bufuralol9c,11
Bufuralol,
1-(7-ethylbezofuran-2-yl)-2-tert-butylamino-1-
hydroxyethane, is a potent non-selective b-adrenoreceptor antago-
nist and administered as a racemic mixture. However, it is known
that the b-blocking potency of (S)-bufuralol is approximately 100
times greater than that of the (R)-enantiomer.15 With (S)-2-mesyl-
oxyethanol 3j in hand, we were able to access (S)-bufuralol as
shown in Scheme 2. As already established, the reaction of (S)-3j
with tert-butylamine in refluxing ethanol provided (S)-bufuralol
4. Experimental
4.1. Preparation of
a
-sulfonyloxy heteroaryl ketones
According to the known procedure,
a-sulfonyloxy heteroaryl
ketones 2a–2p were prepared by the sulfonyloxylation of the
corresponding ketones or their trimethylsilyl enol ethers with
[hydroxy(tosyloxy)iodo]benzene (PhI(OH)OTs) or [hydroxy(mesyl-
oxy)iodo]benzene (PhI(OH)OMs),12 where the starting ketones
were either commercially available or easily accessible in a few
steps. The 2-acetylbenzofuran derivatives 1e16 and 1g11b were
prepared, respectively, fromthecorresponding2-hydroxybenzaldehyde
4, ½a 2D0
¼ ꢀ54:5 (c 0.37, CHCl3), with 99% ee in 45% yield.
ꢁ
3. Conclusion
The -sulfonyloxy heteroaryl ketones were prepared by the sul-
a
fonyloxylation of the corresponding ketones or trimethylsilyl enol
OH
OH
H
N
OMs
t-BuNH2
EtOH, reflux
O
O
Et
Et
3j
4: (S)-Bufuralol
Scheme 2. Asymmetric synthesis of (S)-bufuralol.

2642
S. H. Kwak et al. / Tetrahedron: Asymmetry 20 (2009) 2639–2645
derivatives, and 3-acetylbenzofuran 1k17 from 1-(2-methoxy-
phenyl)-2-propanone with dimethylformamide dimethyl acetal,
according to the known protocols.
113.6, 69.7, 21.7; EIMS (70 eV) m/z (rel intensity) 410 (M+ 39),
,
408 (M+ 35), 223 (100), 167 (17), 155 (34), 91 (28).
,
4.1.8. 2-Tosyloxy-1-(2-benzothiophenyl)ethanone 2m
4.1.1.
a
-Sulfonyloxylation of ketone (route A): representative
Yield = 60%, 1H NMR (300 MHz, CDCl3) d 8.03 (s, 1H), 7.88 (m,
4H), 7.47 (m, 2H), 7.35 (d, 2H, J = 8.2 Hz), 5.19 (s, 2H), 2.44 (s,
3H); 13C NMR (75 MHz, CDCl3) d 185.5, 145.4, 139.3, 138.0,
136.4, 132.5, 131.6, 129.9, 128.2, 126.1, 125.9,125.3, 122.2, 70.4,
procedure for the preparation of 2-mesyloxy-1-(2-
furanyl)ethanone 2a12c
A
mixture of [hydroxy(mesyloxy)iodo]benzene (4.31 g,
9.08 mmol) and 1a (1 g, 9.1 mmol) in acetonitrile (25 mL) was stir-
red at reflux for 1 h. After cooling to rt, the reaction mixture was
concentrated in vacuo. The resulting mixture was diluted with
ethyl acetate (30 mL) and then was washed with saturated NaHCO3
(2 ꢂ 10 mL) and brine (10 mL). The organic phase was dried over
Na2SO4 and concentrated to give a residue. The residue was puri-
fied by column chromatography on silica gel (hexane/ethyl ace-
tate = 2/1) to give 1.36 g (73%) of 2a: 1H NMR (300 MHz, CDCl3) d
7.65 (s, 1H), 7.34 (dd, 1H, J = 3.6 and 0.6 Hz), 6.63 (dd, 1H, J = 3.6
and 1.6 Hz), 5.35 (s, 2H), 3.27 (s, 3H); 13C NMR (75 MHz, CDCl3) d
180.3, 149.8, 147.3, 118.6, 112.8, 69.4, 39.0; EIMS (70 eV) m/z (rel
intensity) 204 (M+, 88), 95 (M+ꢀCH2OMs, 100).
21.6; EIMS (70 eV) m/z (rel intensity) 346 (M+ 9), 161 (100), 147
,
(5), 133 (15), 89 (28).
4.1.9. 2-Tosyloxy-1-(3-thiophenyl)ethanone 2n18
Yield = 58%; 1H NMR (300 MHz, CDCl3) d 8.14 (d, 1H, J = 4.2 Hz),
7.85 (d, 2H, J = 8.4 Hz), 7.51 (d, 1H, J = 6.3 Hz), 7.36–7.33 (m, 3H),
5.07 (s, 2H), 2.45 (s, 3H); 13C NMR (75 MHz, CDCl3) d 184.9,
145.4, 138.2, 133.4, 132.5, 129.9, 128.2, 126.9, 126.7, 70.3, 21.7;
EIMS (70 eV) m/z (rel intensity) 296 (M+, 3), 218 (3), 141 (6), 111
(100), 91 (18). Anal. Calcd for C13H14O4S2: C, 52.69; H, 4.08; S,
21.64. Found: C, 52.01; H, 4.47; S, 22.26.
4.1.10. 2-Tosyloxy-1-(3-benzofuranyl)ethanone 2o
4.1.2. 2-Tosyloxy-1-(2-furanyl)ethanone 2b12c
Yield = 62%; 1H NMR (300 MHz, CDCl3) d 8.47(s, 1H), 8.15 (m,
1H), 7.84 (d, 2H, J = 8.7 Hz), 7.54 (m, 1H), 7.37 (m, 4H), 4.95 (s,
2H), 2.42 (s, 3H); 13C NMR (75 MHz, CDCl3) d 187.0, 155.0, 152.2,
145.7, 132.2, 130.1, 128.1, 126.1, 124.9, 123.9, 122.7, 119.1,
Yield = 72%; 1H NMR (300 MHz, CDCl3) d 8.14 (d, 1H, J = 3.0 Hz),
7.85 (d, 2H, J = 8.4 Hz), 7.51 (d, 1H, J = 5.1 Hz), 7.36–7.33 (m, 3H),
5.07 (s, 2H), 2.45 (s, 3H); EIMS (70 eV) m/z (rel intensity) 280
(M+, 38), 95 (100), 65 (42).
111.5, 71.0, 21.7; EIMS (70 eV) m/z (rel intensity) 330 (M+ 16),
,
175 (9), 145 (100), 89 (35).
4.1.3. 2-Mesyloxy-1-(2-thiophenyl)ethanone 2c12a
Yield = 81%; 1H NMR (300 MHz, CDCl3) d 7.78–7.75 (m, 2H),
7.21–7.18 (m, 1H), 5.38 (s, 2H), 3.27 (s, 3H); 13C NMR (75 MHz,
CDCl3) d 184.2, 139.4, 135.2, 132.5, 128.6, 69.6, 39.1; EIMS
(70 eV) m/z (rel intensity) 220 (M+, 32), 124 (60), 111 (100),
83(49). Anal. Calcd for C7H8O4S2: C, 38.17; H, 3.66; S, 29.11. Found:
C, 37.01; H, 3.63; S, 27.74.
4.1.11. 2-Tosyloxy-1-(3-benzothiophenyl)ethanone 2p
Yield = 64%; 1H NMR (300 MHz, CDCl3) d 8.59 (d, 1H, J = 7.5 Hz),
8.34 (s, 1H), 7.85(m, 3H), 7.46 (m, 2H), 7.30 (d, 2H, J = 7.8 Hz), 5.16
(s, 2H), 2.39 (s, 3H); EIMS (70 eV) m/z (rel intensity) 346 (M+ 13),
,
161 (100), 147 (5), 133 (14), 89 (29).
4.1.12.
a-Sulfonyloxylation of silyl enol ether (route B):
4.1.4. 2-Tosyloxy-1-(2-thiophenyl)ethanone 2d12b,c
representative procedure for the preparation of 2-tosyloxy-1-
Yield = 87%; 1H NMR (300 MHz, CDCl3) d 7.85 (d, 2H, J = 8.1 Hz),
7.79 (d, 1H, J = 3.9 Hz), 7.73 (d, 1H, J = 4.8 Hz), 7.36 (d, 2H,
J = 8.4 Hz), 7.15 (t, 1H, J = 4.5 Hz), 5.08 (s, 2H), 2.45 (s, 3H); 13C
NMR (75 MHz, CDCl3) d 183.7, 145.4, 140.4, 135.1, 133.2, 132.4,
130.0, 128.5, 128.2, 69.9, 21.7; EIMS (70 eV) m/z (rel intensity)
296 (M+, 8), 111 (100). Anal. Calcd for C13H12O4S2: C, 52.69; H,
4.08; S, 21.64. Found: C, 52.99; H, 4.14; S, 21.84.
(5-methoxybenzofuran-2-yl)ethanone 2h
To a solution of 1e (750 mg, 3.94 mmol) in anhydrous dichloro-
methane (4 mL) in an ice-bath was added DIPEA (1.03 mL,
5.92 mmol) via a syringe. To this solution, TBSOTf (0.83 mL,
4.73 mmol) was slowly added via a syringe. The resulting mixture
was stirred for 30 min at 0 °C and then allowed to warm to room
temperature. To this mixture was added [hydroxy(tosyl-
oxy)iodo]benzene (2.32 g, 5.92 mmol) and the resulting mixture
was stirred for 1 h. The resulting mixture was diluted with ethyl
acetate (10 mL) and then washed with brine (10 mL). The organic
phase was dried over Na2SO4 and concentrated to give a residue.
The residue was purified by column chromatography on silica gel
(hexane/ethyl acetate = 2/1) to give 867 mg (61%) of 2h: 1H NMR
(300 MHz, CDCl3) d 7.88 (d, 2H, J = 8.1 Hz), 7.58 (s, 1H), 7.44 (d,
1H, J = 9.0 Hz), 7.37 (d, 2H, J = 8.1 Hz), 7.14–7.08 (m, 2H), 5.21 (s,
2H), 3.86 (s, 3H), 2.45 (s, 3H); EIMS (70 eV) m/z (rel intensity)
360 (M+, 9), 175 (100), 119 (19), 91 (12).
4.1.5. 2-Tosyloxy-1-(2-benzofuranyl)ethanone 2e
Yield = 69%; 1H NMR (300 MHz, CDCl3) d 7.89 (d, 2H, J = 8.4 Hz),
7.73 (d, 1H, J = 7.8 Hz), 7.64 (s, 1H), 7.55–7.51 (m, 2H), 7.37–7.31
(m, 3H), 5.22 (s, 2H), 2.45 (s, 3H); EIMS (70 eV) m/z (rel intensity)
330 (M+, 100), 252 (5), 145 (55), 89 (25). Anal. Calcd for C17H14O5S:
C, 61.81; H, 4.27; S, 9.71. Found: C, 62.27; H, 4.61; S, 8.16.
4.1.6. 2-Tosyloxy-1-(5-nitrobenzofuran-2-yl)ethanone 2f
Yield = 66%, 1H NMR (300 MHz, CDCl3) d 8.71 (d, 1H, J = 2.3 Hz),
8.44 (dd, 1H, J = 9.1 and 2.3 Hz), 7.88 (d, 2H, J = 8.4 Hz), 7.79 (m,
1H), 7.70 (d, 1H, J = 9.3 Hz), 7.39 (d, 2H, J = 8.3 Hz), 5.22 (s, 2H),
2.47 (s, 3H); 13C NMR (75 MHz, CDCl3) d 181.5, 157.8, 152.2,
145.7, 145.1, 132.3, 130.1, 128.2, 126.9, 124.2, 120.3, 114.8,
4.1.13. 2-Mesyloxy-1-(5-methoxybenzofuran-2-yl)ethanone 2g
Yield = 61%; 1H NMR (300 MHz, CDCl3) d 7.58 (s, 1H), 7.47 (d,
1H, J = 9.1 Hz), 7.17–7.10 (m, 2H), 5.47 (s, 2H), 3.86 (s, 3H), 3.30
(s, 3H); EIMS (70 eV) m/z (rel intensity) 284 (M+, 17), 209 (13),
175 (100), 119 (45).
113.2, 69.7, 21.7; EIMS (70 eV) m/z (rel intensity) 375 (M+ 37),
,
297 (7), 190 (100), 154 (88), 143 (29), 91 (46).
4.1.7. 2-Tosyloxy-1-(5-bromobenzofuran-2-yl)ethanone 2i
Yield = 62%, 1H NMR (300 MHz, CDCl3) d 7.88 (m, 3H), 7.60 (m,
2H), 7.45 (d, 1H, J = 8.6 Hz), 7.37 (d, 2H, J = 7.8 Hz), 5.21 (s, 2H),
2.46 (s, 3H); 13C NMR (75 MHz, CDCl3) d 181.5, 154.3, 150.6,
145.5, 132.5, 132.1, 130.0, 128.5, 128.2, 126.1, 117.5, 114.0,
4.1.14. 2-Mesyloxy-1-(7-ethylbenzofuran-2-yl)ethanone 2j
Yield = 52%; 1H NMR (300 MHz, CDCl3) d 7.65 (s, 1H), 7.57 (d,
1H, J = 8.0 Hz), 7.31 (m, 2H), 5.51 (s, 2H), 3.31 (s, 3H), 2.98 (q,
2H, J = 7.5 Hz), 1.37 (t, 3H, J = 7.5 Hz); EIMS (70 eV) m/z (rel inten-
sity) 282 (M+, 11), 186 (10), 173 (100), 115 (13).

S. H. Kwak et al. / Tetrahedron: Asymmetry 20 (2009) 2639–2645
2643
4.1.15. 2-Tosyloxy-1-(7-ethylbenzofuran-2-yl)ethanone 2k
Yield = 54%; 1H NMR (300 MHz, CDCl3) d 7.89 (d, 2H, J = 8.4 Hz),
7.63 (s, 1H), 7.55 (d, 1H, J = 7.2 Hz), 7.38–7.24 (m, 4H), 5.25 (s, 2H),
2.96 (q, 2H, J = 7.72 Hz), 2.45 (s, 3H), 1.35 (t, 3H, J = 8.4 Hz); 13C
NMR (75 MHz, CDCl3) d 181.4, 154.4, 149.5, 145.4, 132.6, 129.9,
129.0, 128.2, 128.0, 126.3, 124.5, 121.0, 115.0, 69.6, 22.6, 21.7,
13.9; EIMS (70 eV) m/z (rel intensity) 358 (M+, 14), 203 (14), 186
(23), 173 (100), 115 (34), 91 (53).
4.2.3. (S)-2-Mesyloxy-1-(2-thiophenyl)ethanol 3c
Yield = 95%; 1H NMR (300 MHz, CDCl3) d 7.32 (d, 1H, J = 5.0 Hz),
7.07 (d, 1H, J = 3.3 Hz), 7.02 (dd, 1H, J = 5.0 and 3.5 Hz), 5.32–5.27
(m, 1H), 4.42 (dd, 1H, J = 10.9 and 4.0 Hz), 4.36 (dd, 1H, J = 10.9
and 7.4 Hz), 3.06 (s, 3H), 2.89 (d, 1H, J = 4.0 Hz); 13C NMR
(75 MHz, CDCl3) d 141.5, 127.0, 125.7, 125.1, 73.2, 68.3, 37.6; EIMS
(70 eV) m/z (rel intensity) 222 (M+, 1), 113 ((M+ꢀOMs, 100), 85
(34); ½a 2D7
¼ ꢀ33:2 (c 0.56 CHCl3); 94.7% ee.
ꢁ
4.1.16. 2-Tosyloxy-1-(7-methoxybenzofuran-2-yl)ethanone 2l
Yield = 53%; 1H NMR (300 MHz, CDCl3) d 7.89 (d, 2H, J = 9.1 Hz),
7.62 (s, 1H), 7.36 (d, 2H, J = 7.7 Hz), 7.27 (m, 2H), 6.97 (dd, 1H,
J = 7.27 and 1.6 Hz), 5.29 (s, 2H), 4.02 (s, 3H), 2.45 (s, 3H); 13C
NMR (75 MHz, CDCl3) d 181.4, 150.1, 146.0, 145.5, 145.3, 132.6,
129.9, 128.3, 128.2, 128.5, 115.3, 114.6, 110.0, 69.8, 56.1, 21.7;
EIMS (70 eV) m/z (rel intensity) 360 (M+, 81), 175 (100), 155 (20),
119 (27), 91 (49).
4.2.4. (S)-2-Tosyloxy-1-(2-thiophenyl)ethanol 3d20
Yield = 97%; 1H NMR (300 MHz, CDCl3) d 7.80 (d, 2H, J = 8.4 Hz),
7.35 (d, 2H, J = 8.1 Hz), 7.28–7.26 (m, 1H), 6.98–6.95 (m, 2H), 5.25–
5.20 (m, 1H), 4.23 (dd, 1H, J = 10.2 and 3.6 Hz), 4.17–4.08 (m, 1H),
2.67 (s, 1H, J = 3.9 Hz), 2.45 (s, 3H); 13C NMR (75 MHz, CDCl3) d
145.2, 141.5, 132.6, 130.0, 128.0, 127.0, 125.6, 125.0, 73.7, 68.3,
21.7; EIMS (70 eV) m/z (rel intensity) 172 (100), 113 ((M+ꢀCH2OTs,
5), 91 (100). Anal. Calcd for C13H14O4S2: C, 52.33; H, 4.73; S, 21.49.
Found: C, 51.97; H, 4.69; S, 22.14; ½a D27
¼ ꢀ31:3 (c 1.12, CHCl3);
ꢁ
4.2. Asymmetric transfer hydrogenation of
heteroaryl ketones
a-sulfonyloxy
lit.20 for (R)-3d, ½a 2D2
¼ þ34:2 (c 1.05, CHCl3); 95.9% ee.
ꢁ
4.2.5. (S)-2-Tosyloxy-1-(2-benzofuranyl)ethanol 3e
General. The catalyst, Cp*RhCl[(S,S)-TsDPEN] was prepared from
the reaction of dichloro(pentamethylcyclopentadienyl)rhodium(III)
dimer and (1S,2S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenedi-
amine in dichloromethane in the presence of triethylamine, accord-
ing to the literature procedure.13 It should be noted that the catalyst
was used without any purification, so the catalyst includes an equal
molar of hydrochloride/triethylamine salt. This catalyst mixture is
very stable and insensitive to atmospheric manipulations, and does
not show any deterioration in the catalytic activity compared to that
prepared from recrystalization.10b The formic acid/triethylamine
(molarratio = 5/2)azeotropewas prepared bythedouble distillation
ofthemixtures, accordingtotheliteratureprocedure.14 Theabsolute
configuration was determined by comparing the sign of the specific
rotation with the literature data or chemical modification to the
known compounds. Unless otherwise indicated, the absolute stereo-
chemistrywas assignedfromthesamesignof rotationoftheisolated
product.
Yield = 96%; 1H NMR (300 MHz, CDCl3) d 7.74 (d, 2H, J = 8.4 Hz),
7.54–7.51 (m, 1H), 7.38 (d, 1H, J = 8.1 Hz), 7.30–7.21 (m, 4H), 6.70
(s, 1H), 5.10 (dd, 1H, J = 10.5 and 5.7 Hz), 4.42 (dd, 1H, J = 10.5 and
3.9 Hz), 4.34 (dd, 1H, J = 10.5 and 6.6 Hz), 2.66 (d, 1H, J = 5.4 Hz),
2.41 (s, 3H); EIMS (70 eV) m/z (rel intensity) 332 (M+, 100), 161
(84), 146 (96), 118 (84), 102 (61), 89 (89); ½a D27
¼ ꢀ28:98 (c 0.98,
ꢁ
CHCl3).
4.2.6. (S)-2-Tosyloxy-1-(5-nitrobenzofuran-2-yl)ethanol 3f
Yield = 90%; 1H NMR (300 MHz, CDCl3) d 8.47 (d, 1H, J = 2.1 Hz),
8.22 (d, 1H, J = 9.0 and 2.3 Hz), 7.77–7.75 (m, 2H), 7.48 (d, 1H,
J = 9.0 Hz), 7.32–7.26 (m, 2H), 6.88–6.87 (m, 1H), 5.19–5.13 (m,
1H), 4.45 (dd, 1H, J = 10.6 and 3.7 Hz), 4.35 (dd, 1H, J = 10.6 and
6.4 Hz), 2.92 (d, 1H, J = 5.8 Hz), 2.43 (s, 3H); 13C NMR (75 MHz,
CDCl3) d 157.6, 157.5, 145.4, 144.3, 132.1, 130.0, 128.1, 127.9,
120.5, 117.8, 111.7, 105.5, 70.8, 66.5, 21.7; EIMS (70 eV) m/z (rel
intensity) 377 (M+, 2), 360 (6), 205 (24), 192 (100), 176 (30), 155
(99), 146(74). Anal. Calcd for C17H15NO7S: C, 54.11; H, 4.01; N,
3.71; S, 8.50. Found: C, 54.25; H, 4.11; N, 3.67; S, 8.16;
4.2.1. Representative procedure for the synthesis of (S)-2-
mesyloxy-1-(2-furanyl)ethanol 3a
½
a 2D0
ꢁ
¼ ꢀ18:0 (c 0.6, CHCl3); 88.02% ee.
Into a two-neck flask, were added (S,S)-Rh (1.6 mg, equivalent
to 0.002 mmol) and 2a (204 mg, 1 mmol) under a slight stream
of argon. To this mixture, ethyl acetate (2 mL) and then an azeotro-
pic mixture of HCO2H/Et3N (molar ratio = 5/2, 0.2 mL) were added
via a syringe. The combined contents were stirred for 0.5 h. The
reaction mixture was diluted with ethyl acetate (10 mL) and
washed with water (3 ꢂ 5 mL). The organic layer was dried over
anhydrous sodium sulfate, filtered, and concentrated and then
the residue was purified by column chromatography on silica gel
(chloroform/ethyl acetate = 10/1) to give 190 mg (92%) of (S)-3a:
1H NMR (300 MHz, CDCl3) d 7.40 (s, 1H), 6.38–6.37 (m, 2H), 5.03
(t, 1H, J = 5.5 Hz), 4.47–4.45 (m, 2H), 3.04 (s, 3H); 13C NMR
(75 MHz, CDCl3) d 151.3, 142.7, 110.5, 107.9, 71.1, 66.0, 37.5; EIMS
(70 eV) m/z (rel intensity) 206 (M+, 1), 110 (22), 97 ((M+ꢀCH2OMs,
4.2.7. (S)-2-Mesyloxy-1-(5-methoxybenzofuran-2-yl)ethanol 3g
Yield = 90%; 1H NMR (300 MHz, CDCl3) d 7.34 (d, 1H, J = 8.9 Hz),
7.01–7.00 (m, 1H), 6.90 (dd, 1H, J = 8.9 and 2.5 Hz), 6.71 (s, 1H),
5.16–5.12 (m, 1H), 4.62–4.51 (m, 2H), 3.93 (s, 3H), 3.06 (s, 3H),
2.87 (d, 1H, J = 5.4 Hz); 13C NMR (75 MHz, CDCl3) d 156.2, 154.7,
149.9, 128.3, 113.6, 111.8, 104.9, 103.7, 71.1, 66.8, 55.9, 37.7; EIMS
(70 eV) m/z (rel intensity) 286 (M+, 10), 190 (26), 177 (100), 161
(10), 121 (15), 91 (12). Anal. Calcd for C12H14O6S: C, 50.34; H,
4.93; S, 11.20. Found: C, 50.43; H, 5.53; S, 10.81; ½a D30
¼ ꢀ32:0 (c
ꢁ
1.0, CHCl3); 96.38% ee.
4.2.8. (S)-2-Tosyloxy-1-(5-methoxybenzofuran-2-yl)ethanol 3h
Yield = 99%; 1H NMR (300 MHz, CDCl3) d 7.74 (d, 2H, J = 8.3 Hz),
7.28–7.24 (m, 3H), 6.98 (d, 1H, J = 2.3 Hz), 6.87 (dd, 1H, J = 8.9 and
2.5 Hz), 6.64 (s, 1H), 5.07 (dd, 1H, J = 5.9 and 4.0 Hz), 4.40 (dd, 1H,
J = 10.4 and 4.0 Hz), 4.31 (dd, 1H, J = 10.4 and 6.8 Hz), 3.83 (s, 3H),
2.42 (s, 3H); 13C NMR (75 MHz, CDCl3) d; EIMS (70 eV) m/z (rel
intensity) 362 (M+, 3), 190 (59), 177 (100), 161 (11), 121 (9), 91
100); ½a 2D7
¼ ꢀ30:7 (c 1.01, CHCl3); 98.42% ee.
ꢁ
4.2.2. (S)-2-Tosyloxy-1-(2-furanyl)ethanol 3b19a,b
Yield = 98%; 1H NMR (300 MHz, CDCl3) d 7.79 (d, 2H, J = 8.4 Hz),
7.36–7.34 (m, 3H), 6.33 (s, 2H), 5.00–4.53 (m, 1H), 4.30 (dd, 1H,
J = 10.4 and 4.3 Hz), 4.24 (dd, 1H, 10.4 and 7.1 Hz), 2.45 (s, 3H), 2.41
(d, 1H, J = 5.1 Hz); 13C NMR (75 MHz, CDCl3) d 151.3, 145.0, 142.6,
132.4, 129.9, 127.9, 110.3, 107.9, 71.4, 65.8, 21.6; EIMS (70 eV) m/z
(rel intensity) 97 ((M+ꢀCH2OTs, 100), 110 (100), 91 (75);
(23); ½a 2D7
¼ ꢀ23:15 (c 0.97, CHCl3); 96.28% ee.
ꢁ
4.2.9. (S)-2-Tosyloxy-1-(5-bromobenzofuran-2-yl)ethanol 3i
Yield = 95%; 1H NMR (300 MHz, CDCl3) d 7.73 (d, 2H, J = 8.2 Hz),
7.65 (d, 1H, J = 1.5 Hz), 7.37 (dd, 1H, J = 6.75 and 1.98 Hz), 7.28–
7.23 (m, 3H), 6.65 (s, 1H), 5.11–5.07 (m, 1H), 4.41 (dd, 1H,
½
a 2D7
ꢁ
¼ ꢀ25:5 (c 1.63, CHCl3); lit.19a for (R)-3b, ½a 2D0
¼ þ36:7 (c 4.01,
ꢁ
Et2O); 98.7% ee.; lit.19b for (S)-3b, ½a 2D1
¼ ꢀ24:6 (c 1.35, CHCl3).
ꢁ

2644
S. H. Kwak et al. / Tetrahedron: Asymmetry 20 (2009) 2639–2645
J = 10.5 and 3.9 Hz), 4.32 (dd, 1H, J = 10.5 and 6.51 Hz), 2.42 (s, 3H),
2.36 (brs, 1H); 13C NMR (75 MHz, CDCl3) d 155.4, 153.5, 145.2,
132.2, 129.9, 129.6, 127.9, 127.5, 123.9, 116.1, 112.7, 104.2, 71.1,
66.5, 21.6; EIMS (70 eV) m/z (rel intensity) 412 (M+, 1), 410 (M+,
(70 eV) m/z (rel intensity) 332 (M+, 2), 160 (24), 147 (100);
¼ ꢀ40:2 (c 0.51, CHCl3); 94.65% ee.
½ ꢁ
a 2D0
4.2.16. (R)-2-Tosyloxy-1-(3-benzothiophenyl)ethanol 3p
1), 238 (100), 227 (87), 209 (8), 126 (17); ½a D20
ꢁ
¼ ꢀ18:8 (c 0.91,
Yield = 83%; 1H NMR (300 MHz, CDCl3) d 7.86–7.82 (m, 1H),
7.75 (d, 2H, J = 8.2 Hz), 7.71–7.67 (m, 1H), 7.47 (d, 1H, J = 0.5 Hz),
7.38–7.26 (m, 4H), 5.42–5.37 (m, 1H), 4.35 (dd, 1H, J = 10.6 and
3.1 Hz), 4.18 (dd, 1H, J = 10.6 and 8.1 Hz), 2.70 (d, 1H, J = 3.6 Hz),
2.42 (s, 3H); 13C NMR (75 MHz, CDCl3) d 145.1, 140.7, 136.6,
133.2, 132.5, 129.9, 127.9, 124.6, 124.3, 122.9, 121.5, 73.0, 68.1,
21.6; EIMS (70 eV) m/z (rel intensity) 348 (M+, 10), 176 (25), 162
(100). Anal. Calcd for C17H16O4S2: C, 58.60; H, 4.63; S, 18.41. Found:
CHCl3); 93.64% ee.
4.2.10. (S)-2-Mesyloxy-1-(7-ethylbenzofuran-2-yl)ethanol 3j
Yield = 97%; 1H NMR (300 MHz, CDCl3) d 7.40–7.37 (m, 1H),
7.19–7.11 (m, 2H), 6.76 (d, 1H, J = 0.8 Hz), 5.20–5.17 (m, 1H),
4.64–4.53 (m, 2H), 3.06 (s, 3H), 2.92 (q, 2H, J = 7.3 Hz), 1.33 (t,
3H, J = 7.6 Hz); EIMS (70 eV) m/z (rel intensity) 284 (M+, 10), 188
(26), 175 (100), 91 (23); 13C NMR (75 MHz, CDCl3) d 153.7, 153.5,
127.8, 127.3, 123.9, 123.3, 118.8, 105.0, 71.2, 66.8, 37.7, 22.7,
C, 58.49; H, 4.76; S, 18.06; ½a D20
¼ ꢀ77:05 (c 0.51, CHCl3); 92.72%
ꢁ
ee.
14.1; ½a 2D0
¼ ꢀ45:15 (c 1.11, CHCl3); 97.32% ee.
ꢁ
4.3. Asymmetric synthesis of (S)-bufuralol 4
4.2.11. (S)-2-Tosyloxy-1-(7-ethylbenzofuran-2-yl)ethanol 3k
Yield = 94%; 1H NMR (300 MHz, CDCl3) d 7.72 (d, 2H, J = 8.3 Hz),
7.35 (dd, 1H, J = 7.4 and 1.2 Hz), 7.24 (d, 2H, J = 8.6 Hz), 7.17–7.08
(m, 2H), 6.68 (d, 1H, J = 0.7 Hz), 5.13–5.08 (m, 1H), 4.42 (dd, 1H,
J = 10.3 and 4.0), 4.33 (dd, 1H, J = 10.3 and 6.6 Hz), 2.83 (q, 2H,
J = 7.5 Hz), 2.72 (d, 1H, J = 5.4 Hz), 2.39 (s, 3H), 1.28 (t, 3H,
J = 7.5 Hz); 13C NMR (75 MHz, CDCl3) d 153.5, 153.3, 145.1, 132.3,
129.8, 127.8, 127.7, 127.3, 123.7, 123.1, 118.7, 104.8, 71.3, 66.6,
22.6, 21.6, 14.0; EIMS (70 eV) m/z (rel intensity) 360 (M+, 6), 188
To a solution of (S)-3j (145 mg, 0.5 mmol) in absolute ethanol
(5 mL) was added t-butylamine (111.5 mg, 1.52 mmol) and the
mixture refluxed for 15 h. The volatile materials were removed un-
der vacuum and diethyl ether (10 mL) was added. The solution was
washed with 10% sodium hydroxide (2.5 mL), water (3 mL), and
dried with anhydrous magnesium sulfate. The solvent was re-
moved and the product isolated by column chromatography on sil-
ica gel (petroleum ether/ethyl acetate/diethyl ether/methanol/
triethylamine = 6:4:1:0.5:0.2) to give 59 mg (45%) of 4: 1H NMR
(300 MHz, CDCl3) d 7.36 (d, 1H, J = 7.5 Hz), 7.16–7.06 (m, 2H),
6.65 (s, 1H), 4.81 (t, 1H, J = 5.4 Hz), 3.05–2.98 (m, 2H), 2.96–2.88
(q, 2H, J = 7.6 Hz), 1.33 (t, 3H, J = 7.6 Hz), 1.11 (s, 9H); 13C NMR
(75 MHz, CDCl3) d 158.2, 153.4, 127.8, 127.6, 123.1, 122.8, 118.4,
(98), 175 (100); ½a D20
¼ ꢀ33:1 (c 0.66, CHCl3); 94.67% ee.
ꢁ
4.2.12. (S)-2-Tosyloxy-1-(7-methoxybenzofuran-2-yl)ethanol 3l
Yield = 91%; 1H NMR (300 MHz, CDCl3) d 7.75–7.72 (m, 2H),
7.28–7.25 (m, 2H), 7.18–7.11 (m, 2H), 6.79 (dd, 1H, J = 6.6 and
2.2 Hz), 6.71 (d, 1H, J = 0.8 Hz), 5.14–5.08 (m, 1H), 4.41 (dd, 1H,
J = 10.4 and 3.9 Hz), 4.32 (dd, 1H, J = 10.4 and 6.7 Hz), 3.97 (s,
3H), 2.67 (d, 1H, J = 5.7 Hz), 2.41 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 154.1, 145.2, 145.1, 144.0, 132.2, 129.8, 129.3, 127.9, 123.7,
113.5, 106.5, 105.0, 71.3, 66.6, 55.9, 21.6; EIMS (70 eV) m/z (rel
intensity) 362 (M+, 11), 190 (76), 177 (100). Anal. Calcd for
C18H18O6S: C, 59.66; H, 5.01; S, 8.85. Found: C, 58.76; H, 4.87; S,
103.2, 66.4, 50.4, 46.2, 29.1, 22.8, 14.1; ½a D20
¼ ꢀ54:5 (c 0.37,
ꢁ
CHCl3); 99.1% ee.
Acknowledgment
This work was supported by a grant for Industrial Technology
Development Programs from the Korea Research Institute of
Chemical Technology (BS.F-0801).
8.44; ½a 2D0
¼ ꢀ29:6 (c 0.52, CHCl3); 96.49% ee.
ꢁ
4.2.13. (S)-2-Tosyloxy-1-(2-benzothiophenyl)ethanol 3m
References
Yield = 91%; 1H NMR (300 MHz, CDCl3) d 7.79–7.68 (m, 4H),
7.37–7.25 (m, 4H), 7.19 (s, 1H), 5.28 (m, 1H), 4.28 (dd, 1H,
J = 10.3 and 3.9 Hz), 4.21 (dd, 1H, J = 10.3 and 7.41 Hz), 2.85 (d,
1H, J = 4.1 Hz), 2.41 (s, 3H); 13C NMR (75 MHz, CDCl3) d 145.2,
142.2, 139.3, 139.2, 132.2, 129.9, 127.9, 124.6, 124.5, 123.7,
122.4, 121.6, 73.3, 68.7, 21.7; EIMS (70 eV) m/z (rel intensity)
348 (M+, 8), 175 (56), 162 (100). Anal. Calcd for C17H16O4S2: C,
58.60; H, 4.63; S, 18.41. Found: C, 57.78; H, 4.86; S, 18.53;
1. For reviews, see: (a) Fache, F.; Schulz, E.; Tommasino, L. M.; Lemaire, M. Chem.
Rev. 2000, 100, 2159; (b) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996,
96, 835; (c) Cardillo, G.; Tomasini, C. Chem. Soc. Rev. 1996, 25, 117; (d) Juraristi,
E.; Quintana, D.; Escalante, J. Aldrichim. Acta 1994, 27, 3; (e) Cole, D. C.
Tetrahedron 1994, 50, 9517.
2. (a) Ohkuma, T.; Koizumi, M.; Yoshida, M.; Noyori, R. Org. Lett. 2000, 2, 1749; (b)
Deeter, J.; Frazier, J.; Staten, G.; Staszak, M.; Weigel, L. Tetrahedron Lett. 1990,
31, 7101; (c) Laczkowski, K. Z.; Pakulski, M. M.; Krzeminski, M. P.; Jaisankar, P.;
Zaidlewicz, M. Tetrahedron: Asymmetry 2008, 19, 788; (d) Jones, T. K.; Mohan, J.
J.; Xnvier, L. C.; Blacklock, T. J.; Mnthre, D. J.; Sohar, P.; Jones, E. T. T.; Reamer, R.
A.; Roberta, F. E.; Grabowski, E. J. J. J. Org. Chem. 1991, 56, 763; (e) Shih, T. L.;
Candelore, M. R.; Cascieri, M. A.; Chiu, S. H.; Colwell, L. F.; Deng, L.; Feeney, W.
P. Bioorg. Med. Chem. Lett. 1999, 9, 1251.
½
a 2D0
ꢁ
¼ ꢀ45:0 (c 0.56, CHCl3); 96.08% ee.
4.2.14. (R)-2-Tosyloxy-1-(3-thiophenyl)ethanol 3n
Yield = 85%; 1H NMR (300 MHz, CDCl3) d 7.78 (d, 2H, J = 8.4 Hz),
7.35 (d, 2H, J = 9.1 Hz), 7.31–7.25 (m, 2H), 7.01 (dd, 1H, J = 5.0 and
1.4 Hz), 5.08–5.06 (m, 1H), 4.20 (dd, 1H, J = 10.3 and 3.4 Hz), 4.08
(dd, 1H, J = 10.3 and 8.1 Hz), 2.52 (d, 1H, J = 3.8 Hz), 2.45 (s, 3H);
EIMS (70 eV) m/z (rel intensity) 298 (M+, 2), 281 (50), 221 (13),
3. Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. 1998, 37, 1986.
4. Ohkuma, T.; Ishii, D.; Takeno, H.; Noyori, R. J. Am. Chem. Soc. 2000, 122, 6510.
5. Gao, Y.; Sharpless, K. B. J. Org. Chem. 1988, 53, 4081.
6. (a) Liu, H.; Hoff, B. H.; Anthonsen, T. Chirality 2000, 12, 26; (b) Kamal, A.;
Khanna, G. B. R.; Ramu, R.; Krishnaji, T. Tetrahedron Lett. 2003, 44, 4783; (c)
Kamal, A.; Malik, M. S.; Shaik, A. A.; Azeeza, S. Tetrahedron: Asymmetry 2008, 19,
1078; (d) Kamal, A.; Malik, M. S.; Shaik, A. A.; Azeeza, S. J. Mol. Catal. B: Enzym.
2009, 58, 132; (e) Paizs, C.; Tosa, M.; Majdik, C.; Moldovan, P.; Novak, L.;
Kolonits, P.; Marcovici, A.; Irimie, F. D.; Poppe, L. Tetrahedron: Asymmetry 2003,
14, 1495; (f) Podea, P. V.; Paizs, C.; Tosa, M. I.; Irimie, F. D. Tetrahedron:
Asymmetry 2008, 19, 1959.
7. (a) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97; (b) Palmer, M. J.;
Wills, M. Tetrahedron: Asymmetry 1999, 10, 2045; (c) Gladiali, S.; Alberico, E.
Chem. Soc. Rev. 2006, 35, 226; (d) Ikariya, T.; Murata, K.; Noyori, R. Org. Biomol.
Chem. 2006, 4, 393.
172 (17), 155 (81), 113 (46), 91 (100); ½a D27
¼ ꢀ33:7 (c 1.28, CHCl3);
ꢁ
95.7% ee.
4.2.15. (R)-2-Tosyloxy-1-(3-benzofuranyl)ethanol 3o
Yield = 84%; 1H NMR (300 MHz, CDCl3) d 7.77–7.75 (m, 2H),
7.60 (d, 1H, J = 0.7 Hz), 7.54–7.46 (m, 2H), 7.34–7.19 (m, 4H),
5.28–5.22 (m, 1H), 4.34 (dd, 1H, J = 10.5 and 3.5 Hz), 4.24 (dd,
1H, J = 10.5 and 7.6 Hz), 2.59 (d, 1H, J = 3.9 Hz), 2.43 (s, 3H); 13C
NMR (75 MHz, CDCl3) d 155.4, 145.2, 142.5, 132.3,129.9, 127.9,
125.3, 124.8, 122.9, 119.9, 118.4, 111.7, 72.8, 65.6, 21.6; EIMS
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