Enantioselective aminolytic kinetic resolution (AKR) of epoxides catalyzed by recyclable polymeric Cr(III) salen complexes

Article abstract of DOI:10.1016/j.tetasy.2006.05.029

Polymeric chiral Cr(III) salen complexes catalyzed regio-, diastereo-, and enantioselective aminolytic kinetic resolution (AKR) of trans-stilbene oxide, trans-β-methyl styrene oxide, and 6-CN-chromene oxide proceeded smoothly at room temperature, providing the desired anti-β-amino alcohols in high yields and enantiomeric excess (up to 100%).

Full text of DOI:10.1016/j.tetasy.2006.05.029

Tetrahedron: Asymmetry 17 (2006) 1638–1643
Enantioselective aminolytic kinetic resolution (AKR) of
epoxides catalyzed by recyclable polymeric Cr(III) salen complexes
Rukhsana I. Kureshy,* Surendra Singh, Noor-ul H. Khan, Sayed H. R. Abdi,
Santosh Agrawal and Raksh V. Jasra
Silicates and Catalysis Discipline, Central Salt and Marine Chemicals Research Institute (CSMCRI), Bhavnagar 364 002, Gujarat, India
Received 22 May 2006; accepted 30 May 2006
Abstract—Polymeric chiral Cr(III) salen complexes catalyzed regio-, diastereo-, and enantioselective aminolytic kinetic resolution (AKR)
of trans-stilbene oxide, trans-b-methyl styrene oxide, and 6-CN-chromene oxide proceeded smoothly at room temperature, providing the
desired anti-b-amino alcohols in high yields and enantiomeric excess (up to 100%).
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
ionic liquids.10c All these approaches are interesting but
usually require additional modifications of the catalyst.
Moreover, such approaches frequently lead to partial loss
of activity and/or enantioselectivity. In our continuing ef-
fort for making the catalytic system recyclable for enantio-
selective epoxidation of non-functionalized alkenes11b,c and
hydrolytic kinetic resolution (HKR) of racemic epox-
ides,11a we report herein novel polymeric chiral Cr(III)(X)
salen complexes 1–3 derived from (1R,2R)-(ꢀ)-cyclohexan-
ediamine with 5,50-methylene di-3-tert-butylsalicylaldehyde
and X = Cl, NO3, and ClO4. These complexes proved to be
recyclable (four times) catalysts for aminolytic kinetic
resolution (AKR) of trans-stilbene oxide, trans-b-methyl
styrene oxide, and CN-chromene oxide with aniline and
substituted anilines to give b-amino alcohols in high yields
(49% out of maximum 50% theoretical yield) with high
regio- and diastereo/enantioselectivity (ee, up to 100%)
leaving behind the corresponding valuable epoxide in high
enantiomeric excess (ee, up to 98%).
Enantiomerically pure b-amino alcohols are important
structural units in many biologically active molecules as
well as chiral auxiliaries/ligands that are used in asymmet-
ric synthesis.1 Although direct synthesis of syn-b-amino
alcohols via Sharpless osmium catalyzed aminohydroxyl-
ation of alkenes,2 direct addition of a-hydroxy ketones to
imines,3 and ring opening of meso epoxides with amines4
has resulted in highly enantio-enriched syn-b-amino alco-
hols, the synthesis of enantiomerically pure anti-b-amino
alcohols has been scarcely studied.5 Among the various
methods, the kinetic resolution6,7 of readily accessible race-
mic 1,2-disubstituted epoxides with amines as nucleophiles
is an attractive approach for the synthesis of enantiomeri-
cally pure anti-b-amino alcohols with high diastereoselec-
tivity. In this direction, Bartoli et al. have recently
reported for the first time the ring opening of trans and
meso epoxides with anilines for the synthesis of anti/syn-
b-amino alcohols using Jacobsen Cr(III) salen8 catalyst,
but separation and recycling of the catalyst is tedious which
makes the system economically non-viable on the industrial
scale. As chiral catalysts are expensive, their separation and
repeated recycling is highly desirable. Attempts were made
in the past for immobilization of chiral homogeneous
catalysts9 either by anchoring the catalyst on a solid
support,10a by use of a two-phase system,10b or by using
2. Results and discussion
The polymeric salen ligand was synthesized according to
the literature method11,12 and catalysts 1–3 (Scheme 1)
were prepared according to the procedure reported ear-
lier.13 Catalysts 1–3 (5 mol %) based on a monomeric salen
unit were used for the AKR of trans-stilbene oxide and
trans-b-methyl styrene oxide with aniline at room tempera-
ture, providing high yields (49%) of anti-b-amino alcohols
7a and 8a with high enantioselectivity (ee, 87%) of product
*
Corresponding author. Fax: +91 278 2566970; e-mail: rukhsana93@
yahoo.co.in
0957-4166/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.05.029

R. I. Kureshy et al. / Tetrahedron: Asymmetry 17 (2006) 1638–1643
1639
100
80
H
H
N
N
Cr
X
60
O
O
CH2
Catalyst 2
Catalyst 1
Catalyst 3
40
n = 12
20
1, X = Cl
2, X = NO3
3, X = ClO4
Jacobsen
Cr (III)
0
0
5
10
15
Scheme 1. Schematic representation of catalysts 1–3.
Time (h)
Figure 1. Time versus % conversion of the amino alcohols (based on
maximum theoretical yield of 50%) with different catalysts.
7a being achieved in case of catalyst 1 (Table 1, entry 1).
The ee of product 7a was further improved up to 100%
by a single crystallization. The order of reactivity14 of com-
plexes as determined by the initial rate constant of the three
catalysts is 3 > 1 > 2 > Jacobsen Cr(III) salen as shown in
Figure 1 and the enantiomeric excess of anti-b-amino alco-
hols 7a was better in the case of catalyst 1 (Fig. 2). In com-
parison with Jacobsen Cr(III) salen catalyst, catalyst 1
(based on a monomeric salen unit) was found to be supe-
rior in terms of total turnover number (ꢁ5 times, due to
recyclability) with retention of enantioselectivity (selectiv-
ity factor = 38 and 28 for catalyst 1 and the Jacobsen
Cr(III) salen,8 respectively) under identical experimental
conditions for AKR of trans-stilbene oxide with aniline.8
The increased reactivity of polymeric Cr(III) salen catalyst
Table 1. Enantioselective kinetic resolution of trans-epoxides using recyclable catalysts by anilinesa
R2
R2
R1
H
Catalyst 1-3,
CH2Cl2, RT
O
R
O
R
+
+
N
R
R1
Ph
Ph
Ph
OH
NH2
6a, R1 = H, R2 = H
6b, R1 = OMe, R2 = H
6c, R1 = H, R2 = OMe
4, R = Ph
5, R = CH3
7a-c
8a-c
Entry
Catalyst
Epoxide
Amine
Time (h)
trans-Epoxide
Amino alcohols
Selectivity factord
(7a–c, 8a–c)
ee (%)b
Yield (%)c
ee (%)b
Yield (%)c
1
2
3
4
5
6
7
8
9
1
1
2
3
1
1
1
1
1
1
1
1
4
4
4
4
4
4
4
4
5
5
5
5
6a
6a
6a
6a
6a
6a
6b
6c
6a
6b
6b
6c
14
36
14
14
12
10
10
16
12
24
36
24
80
32
75
75
92
98
80
85
87
70
42
92
48
76
49
48
41
30
50
50
49
50
62
51
87 (100)e
49
23
49
49
58
68
48
47
49
48
35
47
38
266
13
19
—
—
35
15
13
7
99f
72
79
g
78
60
h
87
76
73
59
72f
56
10
11
12
9
6
a 5 mol % catalyst was taken in 150 ll CH2Cl2 and epoxides (0.2 mmol) and aniline (0.1 mmol) were added and stirred at rt.
b The diastereoselectivity of anti product was found to be >99% determined by 1H NMR and HPLC. The ee’s of amino alcohols and epoxides were
determined on Chiralpak OD column and the absolute configuration was assigned by comparing the specific rotations with literature values.8
c The conversion of product 7a was determined on Chiralpak OD column using calibration curve of epoxide and amino alcohols and the rest given as
isolated yield.
d Selectivity factor was calculated using the equation shown in Section 4.
e Value in parentheses refers to ee % after a single recrystallization.
f Reaction was carried at ꢀ10 °C.
g Reaction was performed with 0.6 equiv of aniline.
h Reaction was performed with 0.75 equiv of aniline.

1640
R. I. Kureshy et al. / Tetrahedron: Asymmetry 17 (2006) 1638–1643
100
90
80
70
60
50
O
NC
+
O
NH2
Catalyst 1
CH2Cl2, RT
OH
Catalyst 1
O
Catalyst 2
Catalyst 3
NC
NHPh
NC
+
O
O
Yield 48%, ee 25%
Yield 48%, ee 21%
0
5
10
15
Time (h)
Scheme 2. AKR of 6-cyano-2,2-dimethyl-chromene oxide.
Figure 2. Time versus ee % of the amino alcohols with different catalysts.
was assigned by comparing the specific rotation with the
literature value.16 On repeating the similar experiment with
Jacobsen Cr(III) salen, the catalytic system behaved in a
similar manner. Solvent plays a crucial role for AKR of
epoxides with amines as the nucleophile.8 In view of this,
the effect of solvents (CH2Cl2, THF, CH3OH and DMF)
in AKR of trans-stilbene oxide with aniline was carried
out using complex 1 as a catalyst (Table 2). Out of all
the solvents used, non-coordinated solvents such as
CH2Cl2 (Table 3, entry 15) were found to be better than
coordinating solvents such as THF and CH3OH (Table 3,
entries 13 and 14). Further, the strongly coordinating sol-
vent DMF (entry 16) does not at all favor this reaction.
1 as compared to Jacobsen Cr(III) salen is due to the
presence of 12 active catalytic centers.
Furthermore, the kinetic resolution of racemic epoxide is
temperature dependent.6 On conducting the reaction at
ꢀ10 °C, the reaction occurred slowly (conversion 23% in
36 h) but there was an increase in ee up to 99% and selec-
tivity factor of anti-b-amino alcohol 7a compared to when
the reaction was carried out at rt (Table 1, entries 1 and 2).
The effect of equivalents of nucleophile (0.5–0.75 equiv) on
product yield for 7a was also studied. When the amount of
nucleophile is increased, there is an increase in the product
yield of 7a (Table 1, entries 5 and 6) with a decrease in its
ee; concomitantly there is an enhancement in the ee of
trans-stilbene oxide 98% (Table 1, entry 6).
The interesting feature of these novel polymeric Cr(III)
salen complexes is their inherent tendency to precipitate
out in non-polar solvents such as hexane due to their
higher molecular weight and lower solubility. We have
It has been reported in the literature15 that in the simple
and synthetically useful preparation of chiral anti-b-amino
alcohol, there is the need of an easily removable N-protect-
ing group. On carrying out the AKR of trans-stilbene oxide
and trans-b-methyl styrene oxide in the presence of substi-
tuted anilines, 2-methoxy and 4-methoxy anilines as easily
removable N-protecting group, we have observed ee’s of
epoxides 4 in the range of 80–85% and 76–87% for the cor-
responding N-aryl amino alcohols 7b–7c (Table 1, entries 7
and 8), respectively. In the case of epoxide 5, the yield was
in the range of 48–49% with moderate ee’s 56–59% for the
corresponding N-aryl amino alcohols 8b–8c (Table 1, en-
tries 10 and 12), which can be efficiently deprotected by oxi-
dative dearylation without erosion of stereochemical
integrity.15 The absolute configuration of all products
was found to be (1S,2R) and assigned by comparing the
specific rotations with literature values.8
Table 2. Aminolytic kinetic resolution (AKR) of trans-stilbene oxide
using catalyst 1 by aniline in the presence of different solvents
Entry Solvents Time ee of
ee of amino Yield of amino
(h)
epoxide alcohols alcohols
13
14
15
16
THF
10
18
14
24
75
70
80
—
80
82
87
—
49
48
49
MeOH
DCM
DMF
No reaction
Table 3. Recycling data of catalyst 1 for AKR of trans-stilbene oxide
using aniline as nucleophilea
Catalytic
run
Time
(h)
ee of
epoxideb
ee of amino
alcoholsb
Yield of amino
alcohols
1
2
3
4
5
14
14
15
17
20
80
80
79
75
71
87
86
85
87
86
49
48
47
46
45
We have also tried AKR of ( )-6-cyano-2,2-dimethyl-
chromene oxide with aniline as the nucleophile using cata-
lyst 1 at room temperature where the reaction was com-
plete within 3 h but the ee’s of (3S,4S)-6-cyano-2,2-
dimethyl-chromene oxide and corresponding b-amino alco-
hol were not very encouraging (Scheme 2). Furthermore,
the AKR of ( )-6-cyano-2,2-dimethyl-chromene oxide
with aniline at ꢀ10 and ꢀ30 °C took a longer reaction time
(12 and 20 h, respectively) for completion without any
improvement in the ee of the product. The absolute config-
uration of (3S,4S)-6-cyano-2,2-dimethyl-chromene oxide
a 5 mol % catalyst was taken in 150 ll CH2Cl2 and epoxides (0.2 mmol)
and aniline (0.5 equiv) were added and stirred at rt.
b The diastereoselectivity of anti product was found to be >99% as
determined by 1H NMR and HPLC. The ee of amino alcohols and
epoxides are determined on Chiralpak OD column and the absolute
configuration was assigned by comparing the specific rotation with the
literature value.8

R. I. Kureshy et al. / Tetrahedron: Asymmetry 17 (2006) 1638–1643
1641
recovered catalyst 1 which worked well in up to four cycles
with gradual loss in reactivity but with retention of
enantioselectivity of the b-amino alcohols and epoxides
in the AKR of the trans-stilbene oxide with aniline
(Table 3).
bottom flask with a nitrogen inlet and outlet was charged
with a solution of poly[(R,R)-(ꢀ)-N,N0-bis-{3-(1,1-dimeth-
ylethyl)-5-methylene salicylidine}-cyclohexene-1,2-diamine]
(641 mg, 1.31 mmol) in dry degassed THF (26 ml). To the
yellow solution, anhydrous chromium(II) chloride (175
mg, 1.44 mmol) was added in a glove box and the resulting
brown solution which turned dark green was stirred for 4 h
under a blanket of nitrogen and then exposed to air for a
further 3 h. The dark green solution was precipitated with
tert-butyl methyl ether, which was filtered and washed with
water to remove the coarse chromium chloride, dried over-
night under vacuum (yielded 70%). The filtrate was washed
with saturated NH4Cl solution followed by brine and dried
over anhydrous Na2SO4. It was concentrated under a
vacuum to give the desired complex (yield 15%). The over-
all yield was found to be 85%. This complex is soluble in
methanol and the color of the complex is dark brown.
Mp >250 °C; Anal. Calcd for C29H37ClCrN2O2Æ
3/2H2OÆ1/2THF: C, 62.78; H, 6.97; N, 4.72. Found: C,
61.98; H, 6.89; N, 4.68; IR (KBr): 2944, 2361, 2340,
3. Conclusion
In conclusion, we have developed the recyclable polymeric
Cr(III) salen complexes for AKR of trans-stilbene oxide,
trans-b-methyl styrene oxide with different amines and
obtained highly enantio- and diastereoselectively anti-b-
amino alcohol in excellent yield. Catalyst 1 was successively
recovered and reused four times with retention of
enantioselectivity.
4. Experimental
4.1. General methods
1619 (C@N), 1536, 1434, 1350, 1316, 1161, 831, 738,
27
658, 563 cmꢀ1; ½aꢂD ¼ ꢀ646 (c 0.024, CH2Cl2); KM
1H and 13C NMR spectra were recorded at 200 and
50 MHz, respectively, on a Bruker F113V. The chemical
(MeOH) 114 mho cmꢀ1 molꢀ1; UV–vis: (MeOH) kmax(e)
221 (18,560), 256 (11,305), 425 (2115).
1
shifts (d) for H and 13C are given in parts per million rel-
ative to the signals of TMS. Coupling constants are given
in hertz. FTIR spectra were recorded on a Perkin Elmer
Spectrum GX spectrophotometer in a KBr/Nujol mull.
Purification of reaction products was carried out by flash
chromatography on silica gel (230–400 mesh). Melting
points are uncorrected. Diastereomeric purity was deter-
mined by NMR analysis of the crude mixture and by
4.1.2. Synthesis of poly[(R,R)-(ꢀ)-N,N0-bis-{3-(1,1-dimeth-
ylethyl)-5-methylene salicylidine}-cyclohexene-1,2-diamine
chromium(III)] nitrate 2. Poly[(R,R)-(ꢀ)-N,N0-bis-{3-
(1,1-dimethylethyl)-5-methylene salicylidine}-cyclohexene-
1,2-diamine chromium(III)] chloride (281 mg, 0.5 mmol)
was dissolved in a minimum amount of MeOH (20 ml),
and a solution of silver nitrate (126 mg, 0.75 mmol) in
water (4 ml) was added.13 The resulting suspension was
stirred for 30 min and a white precipitate of silver chloride
was filtered off. The filtrate was concentrated to yield a
brown solid and dried under vacuum (yield 72%). Anal.
Calcd for C29H37CrN3O5ÆH2OÆCH3OH: C, 59.10; H, 7.11;
N, 6.89. Found: C, 58.39; H, 6.98; N, 6.84; IR (KBr):
HPLC analysis. Optical rotations are reported as follows:
27
½aꢂD (c = in g per 100 ml, solvent) were measured with a
Digipol 781 Automatic Polarimeter Rudolph Instruments.
Enantiomeric excesses (ee) were determined by HPLC (Shi-
madzu SCL-10AVP) using Daicel Chiralpak OD and OJ
chiral columns (wavelengths 243 nm) with 2-propanol/
hexane as eluent. HPLC traces were compared to racemic
samples prepared with racemic Jacobsen Cr(III) salen as
the catalyst. High-resolution mass spectra were obtained
with LC–MS (Q-TOFF), LC (Waters), and MS (Micro-
mass) instruments. The selectivity factor or krel for the
product was calculated using the equation s = ln[1 ꢀ c(1 +
ee)]/ln[1 ꢀ c(1 ꢀ ee)], where the c is the conversion of
amino alcohol and ee is the enantiomeric excess of amino
alcohol.
2946, 2865, 1620 (C@N), 1536, 1433, 1384 (N–O), 1160,
27
831, 783, 689, 564 cmꢀ1; ½aꢂD ¼ ꢀ514 (c 0.024, CH2Cl2);
KM (MeOH) 153 mho cmꢀ1 molꢀ1 UV–vis: (MeOH)
k
max(e) 219 (18,074), 258 (11,217), 424 (2116).
4.1.3. Synthesis of poly[(R,R)-(ꢀ)-N,N0-bis-{3-(1,1-dimeth-
ylethyl)-5-methylene salicylidine}-cyclohexene-1,2-diamine
chromium(III)] perchlorate 3. Poly[(R,R)-(ꢀ)-N,N0-bis-
{3-(1,1-dimethylethyl)-5-methylene salicylidine}-cyclohex-
Commercial grade reagents and solvents were used without
further purification; otherwise, where necessary, they were
purified as recommended.17 Racemic epoxide of trans b-
methyl styrene was prepared by m-CPBA oxidation of
the corresponding alkenes.18 trans-Stilbene oxide and ani-
lines 6a–6c were purchased from Aldrich and used as
received. (R,R)-Polymeric salen ligand was synthesized
according to the literature procedure11c,12 and polymeric
Cr(III) salen was prepared as described below.
ene-1,2-diamine
chromium(III)]
chloride
(281 mg,
0.5 mmol) was dissolved in a minimum amount of MeOH
(20 ml), and a solution of silver perchlorate (126 mg,
0.75 mmol) in water (4 ml) was added.13 The resulting sus-
pension was stirred for 30 min and a white precipitate of
silver chloride was filtered off. The filtrate was concentrated
to yield a brown solid and dried under vacuum (yield 72%).
Anal. Calcd for C29H37ClCrN2O6ÆH2OÆCH3OH: C, 55.68;
H, 6.70; N, 4.33. Found: C, 54.89; H, 6.59; N, 4.26; IR
4.1.1. Synthesis of poly[(R,R)-(ꢀ)-N,N0-bis-{3-(1,1-dimeth-
ylethyl)-5-methylene salicylidine}-cyclohexene-1,2-diamine
chromium(III)] chloride 1. Following the procedure de-
scribed by Jacobsen et al.,19 a 100 ml two necked round
(KBr): 2947, 2865, 2360, 1617 (C@N), 1538, 1314,
27
1100 (Cl–O), 831, 688, 565 cmꢀ1; ½aꢂD ¼ ꢀ531 (c 0.024,
CH2Cl2); KM (MeOH) 144 mho cmꢀ1 molꢀ1; UV–vis:
(CH2Cl2) kmax(e) 220 (17,867), 257 (11,195), 424 (2073).

1642
R. I. Kureshy et al. / Tetrahedron: Asymmetry 17 (2006) 1638–1643
27
4.2. General procedure for asymmetric catalytic ring opening
of trans-aromatic epoxides
Mp 121–124 °C; ½aꢂD ¼ þ32:5 (c 1, CHCl3, ee 76%); enan-
tiomeric excess was determined by HPLC analysis using
Chiralpak OD column, hexane/isopropanol = 70:30, flow
rate = 0.5 ml/min, PDA detector at 254 nm, tR = 17.60
(1R,2S), tR = 20.12 (1S,2R); LCMS: m/z = 320 [M+H]+,
342 [M+Na]+; 1H NMR (CDCl3) d (ppm): 2.38 (br s,
1H), 3.66 (s, 3H), 4.13 (br s, 1H), 4.59 (d, 1H,
J = 4.4 Hz), 5.01 (d, 1H, J = 4.2 Hz), 6.46 (m, 2H), 6.65
(m, 2H), 7.10–7.24 (m, 10H); 13C NMR (CDCl3) d
(ppm): 55.6, 64.7, 77.1, 114.7, 117.1, 115.5, 126.5, 127.5,
127.8, 127.9, 128.2, 128.3, 138.7, 140.0, 140.8, 152.4.
All the reactions were carried out in undistilled CH2Cl2
without any precautions to exclude water. In an ordinary
test tube equipped with a magnetic stirring bar, catalysts
1–3 (0.01 mmol, based on the monomeric salen unit) and
the epoxide (0.20 mmol) were dissolved in 0.15 ml of
CH2Cl2, but the catalysts are not soluble in CH2Cl2. The
tube was closed with a rubber stopper and the mixture
was stirred at room temperature for 5 min. Then the solu-
tion was cooled to the indicated temperature, aniline
(0.10 mmol) was added and the catalyst was solubilized.
The resulting reaction mixture was stirred until the dis-
appearance of the amine. The crude reaction mixture was
directly charged on the chromatography column and
purified on silica.
4.2.5. (2R,3R)-2-Methyl-3-phenyl-oxirane 5.8 The title
compound was isolated by column chromatography (hex-
27
ane/AcOEt = 95:5) as a liquid; ½aꢂD ¼ þ66 (c 1.0, CH2Cl2,
ee 92%); enantiomeric excess was determined by GC anal-
ysis using chiral-GTA column; LCMS: m/z = 135.1
[M+H]+; 1H NMR (CDCl3) d (ppm): 1.43 (d, 3H,
J = 5.2 Hz), 3.01–3.06 (m, 1H), 3.56 (d, 1H, J = 2.1 Hz),
7.20–7.40 (m, 5H); 13C NMR (CDCl3) d (ppm): 17.8,
58.9, 59.5, 125.5, 127.9, 128.3, 137.7.
4.2.1. (1R,2R)-1,2-Diphenyl-oxirane 4.8 The title com-
pound was isolated by column chromatography (hexane/
27
AcOEt = 90:10) as a white solid; Mp 62 °C; ½aꢂD ¼ þ310
(c 2.5, C6H6, ee 98%); enantiomeric excess was determined
by HPLC analysis using Chiralpak OD column, hexane/
isopropanol = 90:10, flow rate = 0.5 ml/min, PDA detec-
tor at 228 nm, tR = 13.60 (1S,2S), tR = 19.26 (1R,2R);
LCMS: m/z = 197.1 [M+H]+; 1H NMR (CDCl3) d
(ppm): 3.88 (s, 2H), 7.15–7.40 (m, 10H); 13C NMR
(CDCl3) d (ppm): 63.0, 128.5, 128.8, 135.7, 137.3.
4.2.6. (1R,2S)-1-Phenylanilino-1-phenyl-propan-2-ol 8a.
The title compound was isolated by column chromato-
graphy (hexane/AcOEt = 90:10) as
a
high dense
27
oil; ½aꢂD ¼ ꢀ20:2 (c 0.9, CHCl3, ee 73%); enantiomeric
excess was determined by HPLC analysis using Chiralpak
OD column, hexane/isopropanol = 90:10, flow rate =
0.5 ml/min, PDA detector at 245 nm, tR = 23.66 (1R,2S),
tR = 32.19 (1S,2R); LCMS m/z = 228 [M+H]+, 210
[MꢀOH]+; 1H NMR (CDCl3) d (ppm): 1.12 (d, 3H,
J = 6.4 Hz), 4.13–4.18 (m, 1H), 4.35 (d, 1H, J = 4.0 Hz),
6.51–6.67 (m, 3H), 7.07–7.11 (m, 2H), 7.24–7.34 (m, 5H);
13C NMR (CDCl3) d (ppm): 19.5, 63.1, 70.5, 113.6,
117.6, 127.5, 127.7, 128.5, 129.1, 139.3, 147.1.
4.2.2. (1S,2R)-1,2-Diphenyl-2-phenylanilino-ethanol 7a.8
The title compound was isolated by column chromatogra-
phy (hexane/AcOEt = 90:10) as a white solid; Mp 122–
27
125 °C; ½aꢂD ¼ þ45:6 (c 1, CHCl3, ee 87%); enantiomeric
excess was determined by HPLC analysis using Chiralpak
OD column, hexane/isopropanol = 90:10, flow rate =
0.5 ml/min, PDA detector at 243 nm, tR = 29.60 (1R,2S),
tR = 50.43 (1S,2R); LCMS: m/z = 290 [M+H]+, 312
4.2.7. (1R,2S)-1-(2-Methoxy-phenylanilino)-1-phenyl-pro-
pan-2-ol 8b. The title compound was isolated by column
1
[M+Na]+; H NMR (CDCl3) d (ppm): 2.32 (br s, 1H),
4.44 (br s, 1H), 4.66 (d, 1H, J = 3.8 Hz), 5.05 (d, 1H,
J = 3.4 Hz), 649–6.53 (m, 1H), 6.60–6.67 (m, 2H), 7.06–
7.15 (m, 2H), 7.21–7.25 (m, 10H); 13C NMR (CDCl3) d
(ppm): 63.7, 77.1, 113.9, 117.9, 126.5, 127.6, 127.9, 128.0,
128.2, 128.3, 129.1, 138.4, 140.0, 146.7.
chromatography (hexane/AcOEt = 90:10) as high dense
27
oil; ½aꢂD ¼ ꢀ19:5 (c 0.8, CHCl3, ee 72%); enantiomeric ex-
cess was determined by HPLC analysis using Chiralpak OJ
column, hexane/isopropanol = 80:20, flow rate = 0.5 ml/
min, PDA detector at 245 nm, tR = 21.17 (1S,2R),
tR = 29.24 (1R,2S); LCMS m/z = 258 [M+H]+, 280
[M+Na]+; 1H NMR (CDCl3) d (ppm): 1.16 (d, 3H,
J = 6.4 Hz), 3.88 (s, 3H), 4.14–4.20 (m, 1H), 4.36–4.39 (d,
1H, J = 4.4 Hz,), 6.35–6.39 (m, 1H), 6.60–6.78 (m, 3H),
7.24–7.34 (m, 5H); 13C NMR (CDCl3) d (ppm): 19.3,
55.4, 63.2, 70.7, 109.4, 112.3, 116.8, 121.1, 127.4, 127.6,
128.5, 139.1, 141.1.
4.2.3. (1S,2R)-1,2-Diphenyl-2-(2-methoxy-phenylanilino)-
ethanol 7b.8 The title compound was isolated by col-
umn chromatography (hexane/AcOEt = 90:10) as a color-
27
less foam; ½aꢂD ¼ þ26 (c 1.2, CHCl3, ee 87%); enantiomeric
excess was determined by HPLC analysis using Chiralpak
OJ column, hexane/isopropanol = 70:30, flow rate =
0.5 ml/min, PDA detector at 254 nm, tR = 21.69 (1R,2S);
tR = 31.75 (1S,2R); LCMS: m/z = 320 [M+H]+, 342
[M+Na]+, 662 [2M+Na]+; 1H NMR (CDCl3) d (ppm):
2.35 (br s, 1H), 3.80 (s, 3H), 4.63 (d, 1H, J = 4.8 Hz),
5.05 (m, 2H), 6.32–6.37 (m, 1H), 6.57–6.73 (m, 3H),
7.09–7.33 (m, 10H); 13C NMR (CDCl3) d (ppm): 55.6,
63.7, 77.3, 109.6, 111.5, 117.1, 121.2, 126.5, 127.5, 127.7,
127.9, 128.1, 136.8, 138.8, 140.3, 147.1.
4.2.8. (1R,2S)-1-(4-Methoxy-phenylanilino)-1-phenyl-pro-
pan-2-ol 8c.8 The title compound was isolated by column
chromatography (hexane/AcOEt 90:10) as a high dense
27
oil; point: ½aꢂD ¼ ꢀ15:8 (c 1.3, CHCl3, ee 56%); enantio-
meric excess was determined by HPLC analysis using
Chiralpak OD column, hexane/isopropanol = 80:20, flow
rate = 0.5 ml/min, PDA detector at 245 nm, tR = 19.00
(1R,2S), tR = 20.75 (1S,2R); LCMS m/z = 258 [M+H]+,
1
4.2.4. (1S,2R)-1,2-Diphenyl-2-(4-methoxy-phenylanilino)-
ethanol 7c.8 The title compound was isolated by column
chromatography (hexane/AcOEt = 90:10) as a white solid;
280 [M+Na]+; H NMR (CDCl3) d (ppm): 1.12 (d, 3H,
J = 6.4 Hz), 3.69 (s, 3H), 4.14–4.20 (m, 1H), 4.30 (d, 1H,
J = 4.4 Hz), 6.50–6.55 (m, 2H), 6.66–6.70 (m, 2H), 7.25–

R. I. Kureshy et al. / Tetrahedron: Asymmetry 17 (2006) 1638–1643
1643
7.34 (m, 5H); 13C NMR (CDCl3) d (ppm): 19.2, 55.7, 64.0,
70.5, 114.7, 115.1, 127.5, 127.7, 128.5, 139.2, 141.2, 139.1,
152.2.
´
3. (a) List, B. J. Am. Chem. Soc. 2000, 122, 9336; (b) Cordova,
A.; Notz, W.; Zhong, G.; Betancort, J. M.; Barbas, C. F. J.
Am. Chem. Soc. 2002, 124, 1842; (c) Trost, B. M.; Terrell, L.
R. J. Am. Chem. Soc. 2003, 125, 338.
4. (a) Fu, X. L.; Wu, S. H. Synth. Commun. 1997, 27, 1677; (b)
Hou, X. L.; Wu, J.; Dai, L. X.; Xia, L. J.; Tang, M. H.
Tetrahedron: Asymmetry 1998, 9, 1747; (c) Sagawa, S.; Abe,
H.; Hase, Y.; Inaba, T. J. Org. Chem. 1999, 64, 4962; (d)
Sekaine, A.; Ohshima, T.; Shibasaki, M. Tetrahedron 2002,
4.2.9. (3S,4S)-6-Cyano-2,2-dimethyl-3,4 epoxy-chromane.
The title compound was isolated by column chromatogra-
phy (hexane/AcOEt 90:10) as a white solid; Mp 138–139 °C
and the absolute configuration was determined by com-
paring optical rotation and HPLC chromatogram;
´
58, 75; (e) Carree, F.; Gil, R.; Collin, J. Tetrahedron Lett.
27
27
½aꢂD ¼ ꢀ85:7 (c 1, CH2Cl2, ee 98%);15 ½aꢂD ¼ ꢀ6:9 (c 0.8,
CH2Cl2, ee 25%); enantiomeric excess was determined by
HPLC analysis using Chiralpak OD column, hexane/iso-
propanol = 80:20, flow rate = 0.5 ml/min, PDA detector
at 254 nm, tR = 16.92 (3R,4R), tR = 19.72 (3S,4S); LCMS:
´
2004, 45, 7749; (f) Carree, F.; Gil, R.; Collin, J. Org. Lett.
2005, 7, 1023; (g) Schneider, C.; Sreekanth, A. R.; Mai, E.
Angew. Chem., Int. Ed. 2004, 43, 5691; (h) Kureshy, R. I.;
Singh, S.; Khan, N. H.; Abdi, S. H. R.; Suresh, E.; Jasra, R.
V. Eur. J. Org. Chem. 2006, 1303.
5. (a) Kobayashi, S.; Hishitani, H.; Ueno, M. J. Am. Chem. Soc.
1998, 120, 431; (b) Matsunaga, S.; Kumagai, N.; Harada, S.;
Shibasaki, M. J. Am. Chem. Soc. 2003, 125, 4712.
6. Keith, J. M.; Larrow, J. F.; Jacobsen, E. N. Adv. Synth.
Catal. 2002, 343, 5.
7. (a) Label, H.; Jacobsen, E. N. Tetrahedron Lett. 1999, 40,
7303; (b) Bandani, M.; Cozzi, P. G.; Melchiorre, P.; Umani-
Ronchi, A. Angew. Chem., Int. Ed. 2004, 43, 84.
1
m/z = 202 [M+H]+; H NMR (CDCl3) d (ppm): 1.30 (s,
3H), 1.60 (s, 3H), 3.54 (d, 1H, J = 4.4 Hz), 3.93 (d, 1H,
J = 4.4 Hz), 6.87 (d, 1H, J = 8.4 Hz), 7.50–7.55 (m, 1H),
7.65 (s, 1H); 13C NMR (CDCl3) d (ppm): 22.8, 25.3, 49.6,
62.0, 74.5, 104.1, 118.8, 133.5, 133.59, 134.2, 156.31.
4.2.10.
(3R,4S)-6-Cyano-2,2-dimethyl-3-(phenylanilino)-
8. Bartoli, G.; Bosco, M.; Carlone, A.; Locatelli, M.; Massac-
cesi, M.; Melchiorre, P.; Sambri, L. Org. Lett. 2004, 6, 2173.
9. (a) Song, C. E.; Lee, S. Chem. Rev. 2002, 102, 3495; (b) Xia,
Q.-H.; Ge, H.-Q.; Ye, C.-P.; Liu, Z.-M.; Su, K.-X. Chem.
Rev. 2005, 105, 1603.
10. (a) Pugin, B.; Blaser, H. U. In Catalyst Immobilization: Solid
Support in Comprehensive Asymmetric Catalysis III; Jacob-
sen, E. N., Pflaz, A., Yamamoto, H., Eds.; Springer: Berlin,
1999; p 1367; (b) Oehme, G. In Catalyst Immobilization: Two-
Phase System in Comprehensive Asymmetric Catalysis III;
Jacobsen, E. N., Pflaz, A., Yamamoto, H., Eds.; Springer:
Berlin, 1999; p 1377; (c) Song, C. E.; Oh, C. R.; Roh, E. J.;
Choo, D. J. Chem. Commun. 2000, 1743.
11. (a) Kureshy, R. I.; Khan, N. H.; Abdi, S. H. R.; Patel, S. T.;
Jasra, R. V. J. Mol. Catal. 2002, 179, 73; (b) Kureshy, R. I.;
Khan, N. H.; Abdi, S. H. R.; Singh, S.; Ahmad, I.; Jasra, R.
V.; Vyas, A. P. J. Catal. 2004, 224, 229; (c) Kureshy, R. I.;
Khan, N. H.; Abdi, S. H. R.; Singh, S.; Ahmad, I.; Jasra, R.
V. J. Mol. Catal. 2004, 218, 141.
chromane-4-ol. The title compound was isolated by col-
umn chromatography (hexane/AcOEt = 90:10) as a white
27
solid; Mp 125–128 °C; ½aꢂD ¼ þ14:6 (c 1.2, CH2Cl2, ee
21%); enantiomeric excess was determined by HPLC anal-
ysis using Chiralpak OD Column, hexane/isopropa-
nol = 80:20, flow rate = 0.5 ml/min, PDA detector at
254 nm, tR = 22.26 (3R,4S), tR = 24.84 (3S,4R); LCMS:
1
m/z = 295 [M+H]+, 317 [M+Na]+; H NMR (CDCl3) d
(ppm): 1.24 (s, 3H), 1.44 (s, 3H), 2.70 (br s, 1H), 3.58 (d,
1H, J = 8.4 Hz), 3.75 (br s, 1H), 4.39 (d, 1H, J = 8.8 Hz),
6.64–6.79 (m, 4H), 7.08–7.16 (m, 2H), 7.29–7.33 (m, 1H),
7.50 (s, 1H); 13C NMR (CDCl3) d (ppm): 19.3, 26.5, 53.8,
73.5, 79.8, 113.6, 118.2, 119.0, 124.8, 129.7, 132.4, 132.8,
139.3, 147.2, 156.5.
Acknowledgments
12. Yao, X.; Chen, H.; Lu, W.; Pan, G.; Hu, X.; Zheng, Z.
¨
S. Singh CSIR (SRF) and R.I.K. are thankful to DST and
CSIR Network project on Catalysis for financial assistance
and are also thankful to Dr. P. K. Ghosh, the Director of
the Institute, for providing instrumentation facility.
Tetrahedron Lett. 2000, 41, 10267.
13. Daly, A. M.; Renehan, M. F.; Gilheny, D. G. Org. Lett. 2001,
3, 663.
14. The conversion of the product was determined on
a
Chiralpak OD column using calibration of peak area % of
the amino alcohol and trans-stilbene oxide at 243 Lemeda
Max.
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