Aminolytic kinetic resolution of trans epoxides for the simultaneous production of chiral trans β-amino alcohols in the presence of chiral Cr(III) salen complex using an ionic liquid as a green reaction media

Article abstract of DOI:10.1016/j.tetasy.2010.02.021

Chiral Cr(III) salen complex 1 having t-Bu substituents at 3,3′ and 5,5′-positions was used as a catalyst for the highly enantioselective aminolytic kinetic resolution (AKR) of racemic trans epoxides with different anilines as nucleophile in the presence

Full text of DOI:10.1016/j.tetasy.2010.02.021

Tetrahedron: Asymmetry 21 (2010) 451–456
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Aminolytic kinetic resolution of trans epoxides for the simultaneous
production of chiral trans b-amino alcohols in the presence of chiral Cr(III)
salen complex using an ionic liquid as a green reaction media
*
Rukhsana I. Kureshy , Manish Kumar, Santosh Agrawal, Noor-ul H. Khan, Sayed H. R. Abdi, Hari C. Bajaj
Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSMCRI), Council of Scientific & Industrial Research (CSIR), G. B. Marg,
Bhavnagar 364 002, Gujarat, India
a r t i c l e i n f o
a b s t r a c t
0
0
Article history:
Chiral Cr(III) salen complex 1 having t-Bu substituents at 3,3 and 5,5 -positions was used as a catalyst for
the highly enantioselective aminolytic kinetic resolution (AKR) of racemic trans epoxides with different
anilines as nucleophile in the presence of different ionic liquids at rt. Excellent yields (>98%) of anti b-
Received 13 January 2010
Accepted 15 February 2010
Available online 8 April 2010
6
aminoalcohols with high enantioselectivity (ee >99%) was achieved in 4 h when [bmim]PF was used
as the ionic liquid. The present ionic liquid mediated AKR process is recyclable (up to six cycles with
no loss in performance) and is five times quicker than the homogeneous process utilizing conventional
organic solvents.
Ó 2010 Elsevier Ltd. All rights reserved.
1
. Introduction
Synthesis of chiral b-amino alcohols and enantiomerically pure
catalytic reaction. Both from an industrial and environmental point
of view these are serious concerns. Ionic liquids (ILs) as the reac-
tion media are emerging as smart and excellent solvents at room
epoxide is an important area of research, as these classes of com-
pounds have direct application as pharmaceuticals, agrochemicals
temperature and are regarded as eco-friendly alternatives to vola-
tile organic solvents in organic synthesis and catalysis.3
5,36
Com-
1
–4
and fine chemicals.
To prepare chiral syn b-amino alcohols, var-
pared to the routinely used organic solvents, ILs possess different
thermodynamic and kinetic properties, which often favor selectiv-
ity and high yield of the product, impart enhanced stability onto
ious efficient methods have been reported in literature such as
5
,6
Sharpless osmium-catalyzed aminohydroxylation of alkenes, di-
rect addition of
a
-hydroxy ketones to imines7 and the asymmet-
–9
catalysts and improve product recovery and recycling of homoge-
1
0–26
37–40
ric ring opening (ARO) of meso epoxides with amines.
In
neous catalysts.
Jacobs et al., used an ionic liquid as reaction
addition to these methods, aminolytic kinetic resolution (AKR) of
racemic terminal and trans epoxides is one strategy which provides
enantiopure trans b-amino alcohols and epoxides in a single step
medium for ARO in order to minimize the leaching of the dimeric
4
1
Cr(III) salen catalyst from a silica support. Later, Song et al. re-
ported the use of ionic liquids to make Cr(III) and Co(III) (salen)
catalysts recyclable for the HKR of racemic epoxides and for enan-
27–34
from inexpensive trans epoxides.
This powerful strategy for
4
2,43
the synthesis of chiral syn/anti-b-amino alcohols was first demon-
tioselective ring opening of meso epoxides.
In the present pro-
strated by Bartoli et al.2
7,28
by AKR of terminal/trans-aromatic
tocol we have used readily prepared monomeric chiral Cr(III) salen
complex 1 for the AKR of trans epoxides in the presence of an ionic
liquid as the reaction media to achieve the corresponding trans
b-amino alcohols in excellent yield (98% with respect to amine)
and chiral induction (up to >99 ee). Concomitantly, enantio-en-
riched parent epoxide (ee up to 97%) was recovered in quantitative
yield. The use of IL also had a favorable effect on the reactivity of
catalyst 1 as compared with the similar system in organic sol-
epoxides with aniline/carbamates using monomeric Cr(III)- and
Co(III) salen complexes as catalysts in the presence of organic sol-
vents. Excellent results in terms of the yields and enantioselectiv-
ities of b-amino alcohols were achieved with these complexes.
However, in these systems, the expensive chiral catalysts were
not recyclable. To make the system recyclable we altered the solu-
bility of the catalysts by way of modeling the salen ligands in its
dimeric and polymeric form.1
8,19,29,33,34
Although these systems
vents. Moreover the catalyst 1 and IL were both recycled several
27
worked well, the following two issues still needed to be addressed,
times without an apparent loss in performance.
(
(
1) the catalyst synthesis required an additional synthetic step and
2) the use of hazardous solvents was required for conducting the
2
. Results and discussion
Monomeric chiral salen complex 1 was synthesized by the reac-
*
Corresponding author. Tel.: +91 0278 2567760; fax: +91 0278 2566970.
E-mail address: rukhsana93@yahoo.co.in (R.I. Kureshy).
tion of (1R,2R)-N,N’-bis-[3,5-di(t-Bu) salicylidene] cyclohexane-
0
957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.02.021

4
52
R. I. Kureshy et al. / Tetrahedron: Asymmetry 21 (2010) 451–456
entry 1). We further explored the AKR reaction of trans butene
oxide 3 and trans b-methyl styrene 4 with aniline and substituted
anilines. Ironically, trans butene oxide and trans b-methyl styrene
oxide gave good to excellent yields (80–98%) of the respective chi-
ral anti b-amino alcohols, however the high chiral induction
N
O
N
O
Cr
Cl
(
ee 99%) was obtained only in the case of butene oxide 3 with 2-
MeO aniline 5b as a nucleophile (Table 3, entry 9). While trans b-
methyl styrene epoxide 4 worked better with other anilines (en-
tries 15 and 17–20) as compared to the substrate trans butene
oxide (entries 8 and 10–13). Nevertheless, on comparing our ionic
liquid protocol (TOF = 2.45) (Table 3, entry 1) against a conven-
Figure 1. Structure of the catalyst 1.
2
7
tional solvent protocol (TOF = 0.5) the former has a distinct
advantage.
1
,2-diamine with anhydrous Cr(II) chloride under an inert atmo-
2
7
sphere followed by its auto oxidation (Fig. 1). The catalytic study
of AKR was initiated by using complex 1 (5 mol %) as a catalyst with
a trans stilbene oxide as a representative substrate and aniline as a
nucleophile in the presence of 1-butyl-3-methylimidazolium
Not withstanding high reactivity, the catalyst used in the pres-
ent ionic liquid protocol is recyclable as evidenced by the recycling
experiments (Table 4). The recyclability experiments were carried
out using trans stilbene oxide 2 (2.0 mmol) as a representative sub-
strate with aniline 5a (1.0 mmol) as a nucleophile in IL-1 as reac-
tion medium at room temperature using the complex 1 (5 mol %)
as a catalyst. After completion of the catalytic reaction, the prod-
ucts were extracted with n-hexane. The products anti b-aminoalco-
hol and enantio-enriched epoxide were recovered from the organic
layer and separated by column chromatography. The recovered
ionic liquid was dried in vacuo which contained the catalyst as evi-
denced by IR spectroscopy. The recovered ionic liquid containing
catalyst 1 was used as such for subsequent catalytic runs, which
worked well in up to 6 catalytic runs with retention of reactivity
and enantioselectivity. From the recycling experiments it is evident
that the Cr(III) salen dissolved in the ionic liquid is fairly stable and
does not deteriorate during the course of the AKR reaction.
[
6
bmim]PF (as a representative ionic liquid) at room temperature
under a nitrogen atmosphere (Table 1). Excellent conversion (98%)
of chiral anti b-aminoalcohol with high enantioselectivity (>99%)
was achieved in 4 h along with quantitative recovery of enantio-en-
riched (ee 97%) trans stilbene oxide (entry 1). To obtain the optimum
catalyst loading for the AKR reaction, we first decreased the catalyst-
loading from 5 mol % to 2.5 mol % such that it slowed down the ring-
opening reaction, also adversely affecting the yield and ee of the
products (Table 1, entry 2). Whereas an increase in catalyst loading
(
10 mol %) had no significant advantage (entry 3). Also when the
AKR was conducted at lower temperature (10 °C) keeping other
parameters as per entry 1, the reaction took very long time (24 h),
although the yield and ees of the products remained the same (entry
4
). This protocol worked well even on a relatively higher scale of
trans stilbene oxide (10 mmol). The reaction took slightly longer
3
. Conclusions
time (6 h) (Table 1, entry 5). It is significant to note that Bartoli
2
7
et al. have reported similar reaction with catalyst 1 (5 mol %) in
the presence of methylene chloride as a solvent to obtain the anti
b-aminoalcohol in 91% conversion and 86% ee in 18 h. It can, there-
fore, be seen that the ionic liquid has a profound effect in improving
overall performance of the catalyst in the AKR reaction.
Chiral salen complex 1 in ionic liquid as the reaction medium
turned out to be an efficient and recyclable combination for carry-
ing out the AKR of different racemic trans epoxides using aniline
and substituted anilines as nucleophiles at rt. The products from
the AKR of trans stilbene oxide namely anti b-amino alcohols
It has been reported in the literature that a change of anion (X)
in the ionic liquids [bmim][X] greatly influence the catalytic activ-
(
ee >99%) and epoxide (ee >97%) were conveniently separated from
ity and enantioselectivity of the reaction.3
5,36
the catalyst dissolved in ionic liquid (IL-1) by simple solvent
extraction. Both catalyst 1 and ionic liquid were recycled in several
AKR experiments. The AKR system is five times faster in the pres-
ence of an ionic liquid than the reaction conducted in the presence
of conventional organic solvents.
Therefore, under the
above optimized AKR reaction (Table 1, entry 1) we screened the
ILs 1–6 as a catalytic reaction medium for the ring opening of trans
stilbene oxide as a model substrate with aniline as a nucleophile at
room temperature and the results are compiled in Table 2. Among
6
all the ionic liquids used, only [bmim][PF ] (IL-1) gave best results
in terms of reactivity and enantioselectivity of chiral anti b-amino-
alcohol (entry 1). The ionic liquid (IL-2) with a [PF6 ] counter ion
4. Experimental
ꢀ
and hexyl alkyl chain also worked well to give desired product
with good yield in 7 h (entry 2) but with lower enantioselectivity
4.1. Materials and characterization
ꢀ
ꢀ
ꢀ
ꢀ
(
ee 80%). Other anions such as AlCl4 , Br , NO2 , and Sb failed
Anhydrous chromium chloride, racemic trans epoxides viz.,
trans stilbene oxide 2, trans butene oxide 3, aniline 5a, 2-Meo-5b,
4-MeO-5c, 4-Me-5d, 2-Cl-5e, 4-Cl-5f and 4-nitro aniline 5g, ionic
liquids IL-1–4 were purchased from Aldrich while ionic liquids
IL-5 and 6 were purchased from Fluka and used as received.
3,5-di-tert-Bu-Salicylaldehyde was synthesized by the reported
to perform the AKR reaction (entries 3–6).
The above optimized AKR protocol with IL-1 and catalyst 1 was
further extended to the other epoxides namely, trans butene oxide
3
and trans b-methyl styrene oxide 4 with different anilines such as
aniline 5a, 2-MeO-5b, 4-MeO-5c, 4-Me-5d, 2-Cl-5e, 4-Cl-5f, and 4-
NO aniline 5g as nucleophiles. Excellent to good yield (80–98%)
4
4
method. The 1R,2R-(ꢀ)diamino cyclohexane was resolved from
2
for the anti b-aminoalcohol was achieved for all anilines while high
enantioselectivity (ee >99%) was achieved in the case of the respec-
tive products for trans stilbene oxide 6a with aniline, 4-Me-6d, and
the technical grade racemic trans 1,2-diamino cyclohexane by the
4
4
method as described in the literature. Racemic epoxide 4 of trans
b-methyl styrene was prepared by m-CPBA oxidation of the corre-
2
9
2
-Cl aniline 6e in 4–10 h (Table 3, entries 1, 4, and 5) (Fig. 2). How-
ever, 4-chloro aniline 5f gave low enantioselectivity (entry 6) and
-nitro aniline as nucleophile failed to perform the AKR reaction
entry 7) possibly due to the poor nucleophilicity of nitro aniline.
sponding alkenes. Chiral salen ligand and its Cr(III) salen complex
(1R,2R)-N,N’-bis-[3,5-di(tert-Bu) salicylidene] cyclohexane-1,2-
diaminato chromium(III) was prepared by the reported method.27
The solvents were dried by standard procedures, distilled, and
4
(
1
Agreeably the respective epoxide was also recovered in quantita-
tive yield with excellent enantiomeric purity (ee >97%) (Table 3,
stored under nitrogen. H NMR spectra were obtained with a Bru-
ker F113V spectrometer (200 MHz) and are referenced internally

R. I. Kureshy et al. / Tetrahedron: Asymmetry 21 (2010) 451–456
453
Table 1
Optimization of the reaction conditions for enantioselective AKR of trans stilbene oxide 2 with aniline 5a in [bmim]PF
(IL-1)a
6
NH2
O
Ph
O
Complex 1
Ph
HN
Ph
+
Ph
OH
+
Ph
IL-1
Ph
(
± ±
(-)
(+)
Entry
Catalyst loading mol (%)
Time (h)
Enantiomerically enriched unreacted epoxideb eec (%)
b-Amino alcohol
Yieldd (%) eec (%)
1
2
3
5
4
8
3
24
6
97
65
98
97
98
98
55
>99
>98
>98
99
80
99
99
99
2.5
10
5
e
4
f
5
5
a
b
c
d
e
f
2
Conditions: epoxide 2 (2 equiv, 0.2 mmol), RNH 5a (1 equiv, 0.1 mmol), 1 (5 mol %) in 300 mg ionic liquid.
Unreacted epoxide after AKR reaction which was recovered in quantitative yield.
Based on HPLC Chiral pack column.
Isolated yield with respect to nucleophile.
Reaction conducted at 10 °C.
Reaction conducted at 10 mmol scale of trans stilbene oxide and 5 mmol of aniline in 1500 mg ionic liquid keeping other conditions as per entry 1.
Table 2
a
Enantioselective AKR of trans stilbene oxide 2 with aniline 5a in different ionic liquids
NH2
O
Ph
O
Complex 1
Ph
HN
Ph
+
Ph
OH
+
Ph
IL 1-6
Ph
(
± ±
(-)
(+)
X-
N
N
n
IL-1 X = PF6, n = 3
IL-2 X = PF6, n = 5
IL-3 X = AlCl4, n = 3
IL-4 X = Br, n = 3
IL-5 X = NO2, n = 3
IL-6 X = Sb, n = 3
Entry
Ionic liquid
Time (h)
Enantiomerically enriched unreacted epoxideb eec (%)
Amino alcohol
Yieldd (%)
eec (%)
1
2
3
4
5
6
IL-1
IL-2
IL-3
IL-4
IL-5
IL-6
4
7
24
24
24
24
97
45
rac
rac
rac
rac
98
70
—
—
—
99
80
—
—
—
—
—
a
b
c
Conditions: epoxide 2 (2 equiv, 0.2 mmol), RNH
Unreacted epoxide after AKR reaction which was recovered in quantitative yield.
Based on HPLC Chiral pack column.
2
5a (1 equiv, 0.1 mmol), 1 (5 mol %) in 300 mg different ionic liquids.
d
Isolated yield with respect to nucleophile.
with TMS. FTIR spectra were recorded on Perkin–Elmer Spectrum
GX spectrophotometer in KBr window. High-resolution mass spec-
tra were obtained with a LC–MS (Q-TOFF) LC (Waters), MS (Micro-
mass) instruments. For the product purification column
chromatography was performed using silica gel 60–200 mesh pur-
chased from s.d. Fine-Chem Limited Mumbai (India). Enantiomeric
excesses (ee) of the products were determined by HPLC (Shimadzu
SCL-10AVP) using Daicel Chiralpak columns with 2-propanol/hex-
ane as eluent. Optical rotations were measured with a Digipol 781
Automatic Polarimeter Rudolph Instruments. Diastereomeric pur-
ity was determined by NMR analysis of the crude mixture and by
rt
D
HPLC analysis. Specific rotations are reported as follows: ½
a
ꢁ
(c
in g per 100 mL, solvent). HPLC traces were compared to racemic
samples prepared with racemic [Cr(salen)Cl] as the catalyst.29

4
54
R. I. Kureshy et al. / Tetrahedron: Asymmetry 21 (2010) 451–456
Table 3
Enantioselective AKR of racemic trans epoxides with different anilines in [bmim]PF
6
IL-1a
R3
R3
R2
H
O
R
O
Catalysts 1
R
+
+
N
R
[
bmim]PF6 , RT
R1
R1
R2
(
±)
R1
OH
NH2
1
5a, R2 = H, R3 = H
2
3
4
R = R =Ph
2a'-g'
1
6
a-g (R = R =Ph)
1
2
3
R = R =CH3
5b, R = OMe, R = H
1
3
4
a'-g'
a'-g'
7a-g (R = R =CH
(
1
5c, R2 = H, R3 = OMe
3
R = Ph, R =CH3
1
8a-g (R = Ph, R =CH3)
5
5
5
5
d, R2 = H, R3 = Me
2
3
e, R = Cl, R = H
2
3
f, R = H, R = Cl
g, R = H, R3 = NO2
2
Entry
trans Epoxide
Amine
Time (h)
Enantiomerically enriched unreacted epoxideb eec (%)
Amino alcohol yieldd (%)
eec (%)
TOFe
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
5a
5b
5c
5d
5e
5f
5g
5a
5b
5c
5d
5e
5f
5g
5a
5b
5c
5d
5e
5f
4
5
18
8
97 2a
98 6a
86 6b
88 6c
80 6d
82 6e
80 6f
— 6g
92 7a
80 7b
90 7c
96 7d
98 7e
90 7f
— 7g
86 8a
90 8b
84 8c
80 8d
92 8e
84 8f
— 8g
>99
87
81
99
99
50
—
44
99
43
32
31
49
—
77
65
83
63
79
50
—
2.45
1.38
0.49
1.00
0.82
0.80
—
0.58
0.44
0.50
0.53
0.44
0.45
—
0.86
1.12
0.56
0.53
0.61
0.48
—
0
0
81 2b
83 2c
0
0
79 2d
10
10
24
16
18
18
18
22
20
24
10
8
15
15
15
17
30
81 2e
45 2f
0
0
Racemic 2g
0
3
4
42 3a
0
85 3b
0
1
1
1
1
1
1
1
1
1
1
2
2
40 3c
0
0
32 3d
30 3e
46 3f
0
0
Racemic 3g
0
74 4a
0
60 4b
0
75 4c
0
0
60 4d
72 4e
48 4f
0
0
5g
Racemic 4g
a
b
c
Conditions: epoxides 2–4 (2 equiv, 0.2 mmol), RNH
Unreacted epoxide after AKR reaction which was recovered in quantitative yield.
Based on HPLC Chiral pack column.
2
5a–g (1 equiv, 0.1 mmol), 1 (5 mol %) in 300 mg ionic liquid.
d
e
Isolated yield with respect to nucleophile.
ꢀ1
TOF = [product]/[catalyst] ꢂ time (h ).
1
00
Table 4
Enantioselective AKR of 2 with 5a in [bmim]PF
6
using recovered complex 1a
Amino alcohol (6)
Amino alcohol (7)
Amino alcohol (8)
8
6
4
2
0
0
0
0
0
Run
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
5
6
4
4.5
5
5
5.5
5.5
98
98
96
96
94
92
>99
>99
>99
>99
>99
>99
a
Conditions: epoxide 2 (2 equiv, 0.2 mmol), RNH
2
5a (1 equiv, 0.1 mmol), 1
(
5 mol %) in 300 mg ionic liquid.
b
8
9
9
6
2
8
90
80
86
84
90
88
80
96
80
92
98
82
84
90
80
0
0
0
Isolated yield with respect to nucleophile.
%
Yield (8)
c
Based on HPLC Chiral pack column.
% Yield ( 7)
% Yield (6)
nic liquid (300 mg) the resulting mass was stirred for 15 min fol-
lowed by the addition of an appropriate epoxide (0.2 mmol). The
resulting mass was again stirred for 10 min followed by the addi-
tion of a desired aniline as nucleophile (0.1 mmol). The progress
of the catalytic reaction was monitored on TLC. At the end of the
reaction the crude reaction mixture was repeatedly extracted with
n-hexane. The product trans b-amino alcohols 6a–f, 7a–f, 8a–f and
Figure 2. % Yield and % ee of chiral b-amino alcohols with different nucleophiles in
IL-1.
4
.2. Typical procedure for the AKR of racemic trans epoxides
In a small vial equipped with a magnetic stirring bar, the
salen)-Cr(III) complex 1 (5 mol %) was taken in an appropriate io-
0
0
0
0
0
0
(
the unreacted enantio-enriched epoxide 2a –f , 3a –f , 4a –f were

R. I. Kureshy et al. / Tetrahedron: Asymmetry 21 (2010) 451–456
455
recovered by column chromatography. The remaining ionic liquid
layer containing complex was dried under vacuum and stored in
desiccator for its use in subsequent catalytic runs.
4.3.7. (2R,3S)-3-(Phenylamino)butan-2-ol 7a
The title compound was isolated by column chromatography
2
7
(hexane/AcOEt, 0:10) as an oil; ½
a
ꢁ
¼ þ61:11 (c 0.032, CHCl
3
);
) d = 1.14 (d, J = 6.8 Hz, 3H), 1.25 (d, J = 6.8 Hz,
3H), 2.61 (br s, 1H), 3.31 (m, 1H), 3.62 (m, 2H), 6.66–6.74 (m,
H), 7.15–7.18 (m, 2H) ppm; HPLC condition: enantiomeric excess
D
1
H NMR (CDCl
3
4
4
.3. Characterization of the products
3
.3.1. (1R,2S)-1,2-Diphenyl-2-phenylanilino-ethanol 6a27,29
was determined on chiral Pak OD column using 97.66:2.44 (hex-
ane/IPA), 1 ml/min flow rate at 247 nm.
The title compound was isolated by column chromatography
(
1
hexane/AcOEt, 90:10) as a white solid: melting point: 122–
2
7,29
27
D
1
25 °C
; ½
a
ꢁ
3 3
¼ þ75:0 (c 0.6, CHCl ); H NMR (CDCl ): d = 2.32
4.3.8. (2R,3S)-3-(2-Methoxyphenylamino)butan-2-ol 7b
(
br s, 1H), 4.44 (br s, 1H), 4.66 (d, J = 3.8 Hz, 1H), 5.05 (d,
J = 3.4 Hz, 1H), 6.50–6.53 (m, 1H), 6.60–6.67 (m, 2H), 7.06–7.15
m, 2H), 7.21–7.25 (m, 10H); HPLC condition: enantiomeric excess
The title compound was isolated by column chromatography
27
D
1
(
hexane/AcOEt, 90:10) as an oil; ½
a
ꢁ
¼ þ43:0 (c 0.44, CHCl
3
); H
(
3
NMR (CDCl ): d = 1.21 (d, J = 6.4 Hz, 3H), 1.33 (d, J = 6.0 Hz, 3H),
was determined on chiral Pak OD column using 85:15 (hexane/
IPA), 1 ml/min flow rate at 254 nm.
2
.78 (br s, 1H), 3.50 (m, 1H), 3.65 (m, 1H), 3.85 (s, 3H), 4.23 (d,
J = 5.4 Hz, 1H), 6.64–7.00 (m, 4H) ppm; HPLC condition: enantio-
meric excess was determined on chiral Pak OD column using
4
.3.2. (1R,2S)-1,2-Diphenyl-2-(2-methoxy-phenylanilino)
9
7.66:2.44 (hexane/IPA), 1 ml/min flow rate at 247 nm.
2
7,29
ethanol 6b
The title compound was isolated by column chromatography
27
4.3.9. (2R,3S)-3-(4-Methoxyphenylamino)butan-2-ol 7c
(
hexane/AcOEt, 90:10) as colorless foam; ½
a
ꢁ
¼ þ32:0 (c 1.0,
D
1
The title compound was isolated by column chromatography
CHCl
s, 1H), 4.63 (d, J = 4.8 Hz, 1H), 5.02–5.09 (m, 1H), 6.32–6.37 (m,
H), 6.57–6.70 (m, 3H), 7.09–7.33 (m, 10H); HPLC condition: enan-
tiomeric excess was determined on chiral Pak OD column using
3 3
); H NMR (CDCl ): d = 2.35 (br s, 1H), 3.75 (s, 3H), 4.34 (br
2
D
7
1
(
hexane/AcOEt, 90:10) as an oil; ½
a
ꢁ
¼ þ30:1 (c 0.44, CHCl
3
);
H
NMR (CDCl
3
): d = 1.18 (d, J = 6.4 Hz, 3H), 1.32 (d, J = 6.0, 3H), 2.85
1
(
br s, 1H), 3.63 (m, 1H), 3.70 (m, 1H), 3.81 (s, 3H), 5.37 (m, 1H),
6
.71 (d, J = 8.2 Hz, 2H), 6.83 (d, J = 8.2 Hz, 2H) ppm; HPLC condi-
7
0:30 (hexane/IPA), 0.8 ml/min flow rate at 254 nm.
tion: enantiomeric excess was determined on chiral Pak OD col-
umn using 95:5 (hexane/IPA), 1 ml/min flow rate at 247 nm.
4
.3.3. (1R,2S)-1,2-Diphenyl-2-(4-methoxy-phenylanilino)
2
7,29
ethanol 6c
4
.3.10. (2R,3S)-3-(4-Methyl-phenylamino)butan-2-ol 7d
The title compound was isolated by column chromatography
hexane/AcOEt, 90:10) as a white solid: melting point: 121–
The title compound was isolated by column chromatography
(
1
(
5
1
2
D
7
1
2
7,29
27
D
1
(hexane/AcOEt, 90:10) as an oil; ½
a
ꢁ
¼ þ25:7 (c 0.56, CHCl
3
); H
24 °C
; ½
a
ꢁ
¼ þ23:3 (c 1.0, CHCl
3 3
); H NMR (CDCl ): d = 2.38
3
NMR (CDCl ): d = 1.23 (d, J = 6.0 Hz, 3H), 1.43 (d, J = 6.4 Hz, 3H),
br s, 1H), 3.66 (s, 3H), 4.13 (br s, 1H), 4.59 (d, J = 4.4 Hz, 1H),
2
1
2
.21 (s, 3H), 3.40–3.47 (m, 1H), 3.93–3.98 (m, 1H), 5.26–5.32 (m,
H), 5.33–5.36 (m, 1H), 6.54 (d, J = 8.2 Hz, 2H), 6.95 (d, J = 8.0 Hz,
H) ppm; HPLC condition: enantiomeric excess was determined
.01 (d, J = 4.2 Hz, 1H), 6.46 (m, 2H), 6.65 (m, 2H), 7.10–7.24 (m,
0H); HPLC condition: enantiomeric excess was determined on
chiral Pak OD column using 70:30 (hexane/IPA), 0.8 ml/min flow
rate at 254 nm.
on chiral Pak OD column using 95:5 (hexane/IPA), 1 ml/min flow
rate at 247 nm.
4
5
.3.4. (1R,2S)-1,2-Diphenyl-2-(4-methyl-phenylanilino) ethanol
d
The title compound was isolated by column chromatography
4
.3.11. (2R,3S)-3-(2-Chloro-phenylamino)butan-2-ol 7e
The title compound was isolated by column chromatography
2
D
7
1
(
Hexane/AcOEt, 90:10) as an oil; ½
aꢁ
¼ þ32:2 (c 0.12, CHCl
3
);
H
(
hexane/AcOEt, 90:10) as a white solid melting point: 144–
2
D
7
1
NMR (CDCl
3
): d = 1.14 (d, J = 6.0 Hz, 3H), 1.51 (d, J = 6.0 Hz, 3H),
1
3
5
2
47 °C; ½
a
ꢁ
¼ þ73:0 (c 0.6, CHCl
3 3
); H NMR (CDCl ): d = 2.15 (s,
3
5
.46–3.50 (m, 1H), 3.54–3.57 (m, 1H), 4.13–4.16 (m, 1H), 5.23–
.40 (m, 1H), 6.56–6.66 (m, 2H), 7.01–7.09 (m, 2H) ppm; HPLC con-
H), 2.32 (d, J = 5.2 Hz, 1H), 4.28 (m, 1H), 4.65 (d, J = 4.2 Hz, 1H),
.04 (t, J = 4.4 Hz, 1H), 6.42 (d, J = 7.8 Hz, 2H), 6.85 (d, J = 7.8 Hz,
H), 7.11–7.25 (m, 10H); HPLC condition: enantiomeric excess
dition: enantiomeric excess was determined on chiral Pak OD col-
umn using 95:5 (hexane/IPA), 0.8 ml/min flow rate at 247 nm.
was determined on chiral Pak OD column using 85:15 (hexane/
IPA), 1 ml/min flow rate at 229 nm.
4
.3.12. (2R,3S)-3-(4-Chloro-phenylamino)butan-2-ol 7f
The title compound was isolated by column chromatography
4
.3.5. (1R,2S)-1,2-Diphenyl-2-(2-chloro-phenylanilino) ethanol 5e
2
7
1
(
hexane/AcOEt, 90:10) as an oil; ½
a
ꢁ
¼ þ26:0 (c 0.15, CHCl
3
) H
The title compound was isolated by column chromatography
D
2
D
7
1
3
NMR (CDCl ): d = 1.19 (d, J = 6.0 Hz, 3H), 1.34 (d, J = 6.0 Hz, 3H),
(
hexane/AcOEt, 90:10) as an oil; ½
aꢁ
¼ þ78:4 (c 0.32, CHCl
3
);
H
3
4
2
.38–3.43 (m, 1H), 3.91–3.95 (m, 1H), 4.02 (d, J = 5.6 Hz, 1H),
.16 (d, J = 5.8 Hz, 1H), 6.5 (d, J = 8.6 Hz, 2H), 7.05 (d, J = 8.6 Hz,
H) ppm; HPLC condition: enantiomeric excess was determined
on chiral Pak OD column using 97.5:2.5 (hexane/IPA), 0.8 ml/min
flow rate at 254 nm.
NMR (CDCl
3
): d = 2.24 (br s, 1H), 4.65 (t, J = 5.2 Hz, 1H), 4.95–5.10
(
(
m, 2H), 6.28–6.32 (d, J = 8.0 Hz, 1H), 6.44 (t, J = 7.2 Hz, 1H), 6.80
t, J = 7.4 Hz, 1H), 7.10–7.18 (m, 5H), 7.21–7.30 (m, 6H); HPLC con-
dition: enantiomeric excess was determined on chiral Pak OD col-
umn using 88:12 (hexane/IPA), 0.8 ml/min flow rate at 229 nm.
4.3.13. (1R,2S)-1-Phenylanilino-1-phenyl-propan-2-ol 8a29
4
.3.6. (1R,2S)-1,2-Diphenyl-2-(4-chloro-phenylanilino) ethanol 5f
The title compound was isolated by column chromatography
The title compound was isolated by column chromatography
2
7
(
1
hexane/AcOEt, 90:10) as a pale yellow solid; melting point:
(hexane/AcOEt, 90:10) as a dense oil; ½
a
ꢁ
¼ ꢀ21:3 (c 0.9, CHCl
3
);
D
2
D
7
1
1
18–121 °C; ½
a
ꢁ
¼ þ33:9 (c 0.20, CHCl
3
); H NMR (CDCl
3
):
H NMR (CDCl ): d = 1.12 (d, J = 6.4 Hz, 3H), 1.68 (br s, 1H), 4.16
3
d = 2.35 (br s, 1H), 4.40 (m, 1H), 4.56 (br s, 1H), 5.02 (br s, 1H),
(m, 1H), 4.34 (d, J = 3.8 Hz, 1H), 4.58 (br s, 1H), 6.51–6.67 (m,
3H), 7.10–7.22 (m, 2H), 7.31–7.34 (m, 5H); HPLC condition: enan-
tiomeric excess was determined on Chiral Pak OD column using
90:10 (hexane/IPA), 0.8 ml/min flow rate and PDA detector at
245 nm.
6
7
.37 (d, J = 8.6 Hz, 2H), 6.95 (d, J = 8.6 Hz, 2H), 6.06–7.20 (m, 4H),
.24–7.29 (m, 6H); HPLC condition: enantiomeric excess was
determined on chiral Pak OD column using 85:15 (hexane/IPA),
ml/min flow rate at 247 nm.
1

4
56
R. I. Kureshy et al. / Tetrahedron: Asymmetry 21 (2010) 451–456
4
2
.3.14. (1R,2S)-1-(2-Methoxy-phenylanilino) 1-phenyl-propan-
Acknowledgements
-ol 8b2
9
The title compound was isolated by column chromatography
R.I.K. is thankful to DST and CSIR Network Project on Catalysis
for financial assistance. S.A. is thankful to CSIR for awarding senior
research fellowship. Authors are also thankful to ‘Analytical Sci-
ence Discipline’ for providing instrument facilities.
27
(
hexane/AcOEt, 90:10) as a dense oil; ½
aꢁ
¼ ꢀ17:2 (c 0.8, CHCl
3
);
): d = 1.10 (d, J = 6.0 Hz, 3H), 1.64 (br s, 1H), 3.80
s, 3H), 4.09 (br s, 1H), 4.30 (d, J = 3.4 Hz, 1H), 5.02 (br s, 1H),
D
1
H NMR (CDCl
3
(
6
5
.28–6.31 (d, J = 7.2 Hz, 1H), 6.57–6.70 (m, 3H), 7.24–7.26 (m,
H); HPLC condition: enantiomeric excess was determined on Chi-
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and PDA detector at 245 nm.
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2
9
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7
(
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3
);
): d = 1.03 (d, J = 6.4 Hz, 3H), 2.80 (br s, 1H), 3.58
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8
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(
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2
1
HPLC condition: enantiomeric excess was determined on Chiral
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and PDA detector at 245 nm.
4
11. Arai, K.; Lucarini, S.; Salter, M. M.; Ohta, K.; Yamashita, Y.; Kobayashi, S. J. Am.
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.3.16. (1R,2S)-1-(4-Methyl-phenylanilino) 1-phenyl-propan-2-
ol 8d
The title compound was isolated by column chromatography
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1
15. Fu, X. L.; Wu, S. H. Synth. Commun. 1997, 27, 1677.
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27
(
hexane/AcOEt, 90:10) as a dense oil; ½
aꢁ
¼ ꢀ17:5 (c 1.38, CHCl
3
);
): d = 1.14 (d, J = 6.4 Hz, 3H), 2.25 (s, 3H), 2.35 (br s,
H), 4.06–4.12 (m, 1H), 4.22 (d, J = 3.6 Hz, 1H), 4.76 (br s, 1H), 6.25
d, J = 7.8 Hz, 2H), 6.35 (d, J = 7.8 Hz, 2H), 6.90–7.21 (m, 5H); HPLC
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D
1
H NMR (CDCl
3
1
(
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2
2
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Column using 90:10 (hexane/IPA), 0.8 ml/min flow rate and PDA
detector at 245 nm.
23. Mai, E.; Schneider, C. Synlett 2007, 2136.
2
2
4. Ogawa, C.; Azoulay, S.; Kobayashi, S. Heterocycles 2005, 55, 201.
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4
.3.17. (1R,2S)-1-(2-Chloro-phenylanilino) 1-phenyl-propan-2-
ol 8e
The title compound was isolated by column chromatography
26. Paster, I. M.; Yus, M. Curr. Org. Chem. 2005, 9, 1.
27. Bartoli, G.; Bosco, M.; Carlone, A.; Locatelli, M.; Massaccesi, M.; Melchiorre, P.;
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2
D
7
(
hexane/AcOEt, 90:10) as
a
dense oil;
): d = 1.31 (d, J = 6.2 Hz, 3H), 1.51 (br s,
H), 4.10–4.16 (dd, J = 4 and 6.2 Hz, 1H), 4.30 (m, 1H), 5.21 (d,
J = 5.8 Hz, 1H), 6.32 (d, J = 8.0 Hz, 1H), 6.45 (t, J = 7.2 Hz, 1H),
.83 (t, J = 7.2 Hz, 1H), 7.18–7.25 (m, 6H); HPLC condition: enan-
tiomeric excess was determined on Chiral Pak OD Column using
½
aꢁ
¼ ꢀ28:6 (c 0.1,
Lett. 2004, 6, 3973.
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CHCl
1
3
); H NMR (CDCl
3
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3
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6
32. Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Umani-Ronchi, A. Angew. Chem., Int. Ed.
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2
33. Kureshy, R. I.; Singh, S.; Khan, N. H.; Abdi, S. H. R.; Agrawal, S.; Mayani, V. J.;
9
2
0:10 (hexane/IPA), 0.8 ml/min flow rate and PDA detector at
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5. Jorapur, Y. R.; Chi, D. Y. Bull. Korean Chem. Soc. 2006, 27, 345.
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.3.18. (1R,2S)-1-(4-Chloro-phenylanilino) 1-phenyl-propan-2-
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The title compound was isolated by column chromatography
3
3
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D
7
(
hexane/AcOEt, 90:10) as a dense oil; ½
a
ꢁ
¼ ꢀ14:3 (c 0.77, CHCl
3
);
): d = 1.06 (d, J = 6.0 Hz, 3H), 1.60 (br s, 1H), 4.01–
.12 (m, 1H), 4.23 (d, J = 4.2 Hz, 1H), 4.60 (br s, 1H), 6.39 (d,
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H NMR (CDCl
3
4
4
0. Song, C. E. Chem. Commun. 2004, 1033.
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4
J = 8.2 Hz, 2H), 6.90 (d, J = 8.0 Hz, 2H), 7.10–7.23 (m, 5H); HPLC
condition: enantiomeric excess was determined on Chiral Pak OD
Column using 90:10 (hexane/IPA), 0.8 ml/min flow rate and PDA
detector at 245 nm.
42. Song, C. E.; Oh, C. R.; Roh, E. J.; Choo, D. J. Chem. Commun. 2000, 1743.
4
4
3. Oh, C. R.; Choo, D. J.; Shim, W. H.; Lee, D. H.; Roh, E. J.; Lee, S.; Song, C. E. Chem.
Commun. 2003, 1100.
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