Chiral recyclable dimeric and polymeric Cr(III) salen complexes catalyzed aminolytic kinetic resolution of trans-aromatic epoxides under microwave irradiation

Article abstract of DOI:10.1002/chir.20472

Aminolytic kinetic resolution (AKR) of trans-stilbene oxide and trans-β-methyl styrene oxide proceeded smoothly under microwave irradiation using chiral dimeric and polymeric Cr(III) salen complexes as efficient catalysts, giving regio-, diastereo-, and enantioselective anti-β-amino alcohols in high yields (49%) and chiral purity (ee up to 94%) in case of 4-methylaniline within 2 min. The kinetic resolution system is approximately five times faster than traditional oil bath heating at 70°C and 420 times faster than the reaction conducted at room temperature with concomitant recovery of respective chirally enriched epoxides (ee, 92%) in excellent yields (up to 48%). The catalyst 1 worked well in terms of enantioselectivity than the catalyst 2, but both the catalysts were easily recovered and reused five times with the retention of its efficiency.

Full text of DOI:10.1002/chir.20472

CHIRALITY 19:809–815 (2007)
Chiral Recyclable Dimeric and Polymeric Cr(III) Salen
Complexes Catalyzed Aminolytic Kinetic Resolution of
trans-Aromatic Epoxides Under Microwave Irradiation
*
RUKHSANA I. KURESHY, K. JEYA PRATHAP, SURENDRA SINGH, SANTOSH AGRAWAL, NOOR-UL H. KHAN,
SAYED H.R. ABDI, AND RAKSH V. JASRA
Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSMCRI),
Bhavnagar 364 002, Gujarat, India
ABSTRACT
Aminolytic kinetic resolution (AKR) of trans-stilbene oxide and trans-b-
methyl styrene oxide proceeded smoothly under microwave irradiation using chiral di-
meric and polymeric Cr(III) salen complexes as efficient catalysts, giving regio-, dia-
stereo-, and enantioselective anti-b-amino alcohols in high yields (49%) and chiral purity
(ee up to 94%) in case of 4-methylaniline within 2 min. The kinetic resolution system is
approximately five times faster than traditional oil bath heating at 708C and 420 times
faster than the reaction conducted at room temperature with concomitant recovery of re-
spective chirally enriched epoxides (ee, 92%) in excellent yields (up to 48%). The cata-
lyst 1 worked well in terms of enantioselectivity than the catalyst 2, but both the cata-
lysts were easily recovered and reused five times with the retention of its efficiency.
C
VV
Chirality 19:809–815, 2007.
2007 Wiley-Liss, Inc.
KEY WORDS: aminolytic kinetic resolution; trans epoxides; chiral; Cr(III) dimeric and
polymeric salen; recyclable
INTRODUCTION
desired support, such approaches frequently lead to partial
loss of activity and/or enantioselectivity.
Optically pure b-amino alcohols are important structural
units for many biologically active, natural synthetic prod-
ucts and are valuable chiral auxiliaries/ligands in the area
of asymmetric synthesis.1–4 Several strategically different
approaches exist toward the direct synthesis of b-amino
alcohols such as (a) via sharpless osmium catalyzed ami-
nohydroxylation5,6 of alkenes (b) direct addition of a-
hydroxy ketones7–9 to imines, and (c) ring opening of
meso-epoxides with amines.10,11 Though these methods
gave products with high enantioselectivity for syn-b-amino
alcohols, very few methods favored the formation of opti-
cally pure anti-b-amino alcohols.12–19 In this direction, ami-
nolytic kinetic resolution (AKR) of racemic 1,2-disubsti-
tuted epoxides with amines as nucleophiles is an attractive
method for the synthesis of optically pure anti-b-amino
alcohols with high diastereoselectivity.20–22 Bartoli et al.
for the first time has reported the ring opening of trans-
and meso-epoxides with anilines for the synthesis of anti/
syn-b-amino alcohols using chiral monomeric Cr(III) salen
as a catalyst, but separation and recycling of the catalyst is
not feasible under homogeneous catalytic system.23 As
chiral catalysts are expensive, their separation and recy-
cling is an important aspect. In order to make the catalytic
process recyclable, attempts were made in the past for the
anchoring of chiral homogeneous catalyst,24 either on
The use of microwave (MW) irradiations to speed up
the sluggish chemical reactions is of current interest.27–31
The use of MW irradiations has been reported for the ring
opening of vinyl and terminal epoxides by NH4OH,32,33 thi-
ols34 pyrazole, imidazole,35 and amines.36–38 Yet, its use in
the area of transition metal catalyzed asymmetric reac-
tions39 has not been successful, probably because of the
small difference in the activation energy of the two enan-
tiomers involved in the asymmetric reaction that is insig-
nificant in comparison to the energy supplied by the
MWs.29 Consequently, the enantioselectivity of the reac-
tions could be adversely affected by the use of MWs as a
source of energy. Nevertheless, Dioos and Jacobs have
recently reported the asymmetric ring opening of epoxides
using TMSN3 as nucleophile under MW irradiation.40 In
continuation of our ongoing research toward developing
the recyclable chiral dimeric and polymeric catalysts with
different metal ions for various organic transformations,
namely asymmetric epoxidation,41–43 cyanation,44,45 hydro-
lytic kinetic resolution,46 oxidative kinetic resolution,47,48
Contract grant sponsor: DST and CSIR Network Project on Catalysis
*Correspondence to: Rukhsana I. Kureshy, Discipline of Inorganic Materi-
als and Catalysis, Central Salt and Marine Chemicals Research Institute
(CSMCRI), Bhavnagar 364 002, Gujarat, India.
solid supports25 or by making use of ionic liquids.26 E-mail: rukhsana93@yahoo.co.in
Received for publication 30 May 2007; Accepted 20 July 2007
DOI: 10.1002/chir.20472
Published online 4 September 2007 in Wiley InterScience
Though these approaches are interesting but usually
demand additional modifications in the structure of the
catalyst for making the catalyst compatible with the (www.interscience.wiley.com).
C
VV
2007 Wiley-Liss, Inc.

810
KURESHY ET AL.
and asymmetric ring opening of meso and trans epoxides with literature values.23 The enantiomeric excess (ee) of
with anilines,49,50 in the present study we are reporting the anti-b-amino alcohol (6a–f and 7a–c) and trans-stilbene
use of recyclable dimeric and polymeric chiral Cr(III)X oxide (3) were determined by HPLC using Chiralpak OD
salen complexes 1 and 2 as catalysts for the production of column except for 6b, 7b, where Chiralpak OJ column
enantioselective trans 1,2 aminoalcohols through AKR of was used. The enantiomeric excess of trans-b-methyl sty-
racemic trans-stilbene oxide and trans-b-methyl styrene ox- rene oxide was determined on GC using GTA-type col-
ide, with anilines under MW irradiation as an alternate umn.
source of energy to step up the reaction rate. Significantly,
the rate of reactions was greatly enhanced and there was
no loss in enantioselectivity under MW irradiation in com-
parison to the same reaction when conducted at room tem-
perature. On the contrary, in some cases there was an
improvement in the ee of the products. Chiral dimeric
Cr(III) salen complex 1 gave better results in term of
enantioselectivity than Jacobsen monomeric Cr(III) salen
complex and polymeric Cr(III) salen complex 2. The cata-
lysts used in the present study were conveniently recov-
ered and reused for five successive catalytic runs.
Synthesis of 5,5-Methylene Di-[( R,R)-{ N-(3-tert-butyl
salicylidine)-N0-(3 0,5 0-di-tert-butyl salicylidene)]-
cyclohexane-1,2-diaminato (2-) Cr(III) Chloride 1
Chiral dimeric ligand namely 5,5-methylene di-[(R,R)-
{N-(3-tert-butyl salicylidine)-N0-(30,50-di-tert-butyl salicyli-
dene)}-1,2-cyclohexanediamine]41,42 (0.4 mmol) was dis-
solved in dry degassed THF (20 ml). The resulting yellow
solution was interacted with anhydrous Cr(II) chloride
(0.8 mmol) in a glove box under nitrogen atmosphere to
give a brown solution. The brown solution turned dark
green during 4 h of stirring under a blanket of nitrogen
after which it was exposed to air with stirring for further
3 h. The resulting dark green solution was treated with
tert-butyl methyl ether to precipitate out the dimeric
Cr(III) complex 1. The precipitate was filtered and washed
with water to remove the unreacted chromium chloride
and dried overnight under vacuum (yield 65%). The filtrate
was sequentially washed with saturated solution of NH4Cl
and brine. The resulting solution was dried over anhy-
drous Na2SO4, filtered, and the solvent was removed to
give another crop (ꢀ22%) of complex 1 as brown solid.
The overall yield was found to be 87%. mp >2508C; Anal.
Calcd for C65H88Cl2Cr2N4O4 (Calcd) C, 67.05; H, 7.62; N,
4.81 Found: C, 67.01; H,7.60; N, 4.78%; IR in KBr (cm21):
2946, 2363, 2342, 1617 (C5N), 1536, 1435, 1350, 1316,
1161, 831, 738, 658, 563; [arDt] 5 2324 (c 5 0.024 g in 100
ml of CH2Cl2); LM (MeOH) 116 mho cm21 mol21; UV–vis:
(CH2Cl2) kmax (e) 232 (52030), 263 (32125), 296 (19513),
345 (7689), 435 (3354) nm.
EXPERIMENTAL
Materials and Methods
Reagents and solvents were of laboratory grade and
were used without further purification. trans-Stilbene ox-
ide, trans-b-methyl styrene, aniline, 2-methoxyaniline, 4-
methoxyaniline, 4-methylaniline, 4-chloroaniline, and 4-ni-
troaniline were purchased from Aldrich and were used as
received. Racemic trans-b-methyl styrene oxide was pre-
pared by the oxidation of respective alkene with m-CPBA
(Spectrochem).51 (R,R) Polymeric [Cr(Salen)Cl] 2 was
prepared and characterized by the reported procedure.50
1H and 13C NMR spectra were recorded at 200 MHz and
50 MHz, respectively on a Bruker F113V. The chemical
1
shifts (d) for H and 13C are given in ppm relative to the
signal of TMS. FTIR spectra were recorded on a Perkin
Elmer Spectrum GX spectrophotometer in KBr/nujol mull.
Microanalysis of the complex was done on CHNS ana-
lyzer, Perkin Elmer model 2400. MW reactor with temper-
ature controller used in the present study was from
ETHOS 1600 Advanced Microwave Lab station. Purifica-
General Procedure for AKR of trans-aromatic epoxides
The AKR reactions were carried out in a corning glass
tion of reaction products was carried out by flash column test tube placed in
a sealed reactor-ETHOS 1600
chromatography on silica gel (60–200 mesh). Melting (Advanced Microwave Lab station) having temperature
points reported in the present study are uncorrected. Dia- and MW power output control. In a typical AKR reaction
stereomeric purity and enantiomeric excesses (ee) were catalysts 1/2 (0.01 mmol, based on monomeric salen
determined by NMR analysis of the crude mixture and by unit), appropriate epoxide (0.20 mmol) and aniline (0.10
HPLC (Shimadzu SCL-10AVP) analysis using Daicel Chir- mmol) were taken in a mixed solvent CH2Cl2:MeOH (9:1,
alpak OD and OJ chiral columns at wavelength 243 nm, 200 ll), and the mixture was irradiated with MW (900 W)
with 2-propanol/hexane as mobile phase. Optical rotations at 708C for 2 min. The conversion of the product was
were measured on a Digipol 781 automatic Polarimeter, determined on a HPLC equipped with Chiralpak OD col-
Rudolph Instruments and are reported as: a2D7 (c 5 in g umn, using calibration of peak area % of the amino alcohol
per 100 ml, solvent). HPLC traces of aminoalcohols were and trans-stilbene oxide at 243. The catalyst was precipi-
compared with authentic racemic samples prepared by the tated out from the reaction mixture by the addition of 5 ml
ring opening of respective epoxides with required amine of hexane:diethyl ether (1:1), filtered, vacuum-dried, and
using racemic Jacobsen Cr(III) salen as a catalyst. High-re- kept in a desiccator for further use. The filtrate was con-
solution mass spectra were obtained with a LC-MS (Q- centrated and the desired product was purified by column
TOFF) LC (Waters), MS (Micromass) instruments.
chromatography using silica gel 60–200 mesh as a station-
All anti-b-amino alcohol (6a–f and 7a–c) and trans-epox- ary phase and hexane:ethyl acetate (8:2) as a mobile
1
1
ides (3 and 4) were characterized by H and 13C NMR, phase. All the products were characterized by H and 13C
LCMS, and IR. These spectroscopic data are comparable NMR spectroscopy.
Chirality DOI 10.1002/chir

DIMERIC AND POLYMERIC Cr(III) SALEN COMPLEXES FOR AKR
811
Recycling Experiment
in a model reaction for optimizing reaction conditions
such as temperature and MW output. To begin with we
first carried out AKR of trans-stilbene oxide with aniline,
using complexes 1 and 2 as catalysts over a temperature
range of (40–808C) exposed to 900 W MW irradiation (Ta-
ble 1, entries 1–10) in CH2Cl2:MeOH (9:1) as solvent.
From the data in Table 1 it is evident that 708C is the opti-
mum temperature to achieve the highest yield (49%) with
high enantioselection (92%) in the product (entry 7). Next,
we studied the effect of MW output (800–1000 W) on the
efficacy of AKR keeping the reaction temperature 708C as
constant. However, a MW output of 800 W caused reduc-
tion in both yield (32–35%) and enantioselectivity (37–42%)
(Table 1, entries 11 and 12). On the other hand, 1000 W
MW output resulted in an increase in the yield (72–74) of
the product amino alcohol but with lower enantioselectiv-
ity (Table 1, entries 13 and 14). Consequently, 900 W MW
output and 708C (Table 1, entries 7 and 8) reaction temper-
ature were found to be ideal for AKR of trans-stilbene ox-
ide with aniline. Further, in an ideal situation, 0.5 equiv of
amine with respect to 1 equiv of racemic epoxide should
react with only one enantiomer of epoxide to give the
product anti-b-aminoalcohol in 100% ee with a maximum
theoretical yield of 50%. However, practically this situation
is seldom achievable. It is known in the literature that the
equivalence of the nucleophile with respect to racemic
epoxide greatly influences the product distribution in a ki-
netic resolution reaction.50 Therefore, we varied the equiv-
alence of nucleophile (aniline, 0.4–0.75 equiv) with respect
After one catalytic cycle (checked on HPLC), the cata-
lysts were precipitated out with hexane:diethyl ether (1:1)
followed by thorough washing with hexane (10 ml). They
were dried under reduced pressure and used as recovered
catalyst for successive catalytic runs, using trans-stilbene
oxide as a representative substrate for AKR reaction.
RESULTS AND DISCUSSION
Synthesis of chiral dimeric Cr(III) salen complex,
namely, 5,5-methylene di-[(R,R)-{N-(3-tert-butyl salicyli-
dine)-N0-(30,50-di-tert-butyl salicylidene)}-1,2-cyclohexane-
diaminato (2-) chromium (III) chloride] 1 (Scheme 1),
which carries two active catalytic metal centers was
obtained by the interaction of 5,5-methylene di-[(R,R)-
{N-(3-tert-butyl salicylidine)-N0-(30,50-di-tert-butyl salicyli-
dene)}-1,2-cyclohexanediamine with anhydrous Cr(II)
chloride in dry THF under nitrogen atmosphere followed
by its auto oxidation in air. The characterization data for
complex 1 is given in Experimental section. Whereas poly-
meric Cr(III) salen complex 2 namely poly [(R,R)-N,N0-
bis{3-(1,1-dimethylethyl)-5-methylene salicylidine} cyclo-
hexene-1,2-diaminato-chromium(III) chloride with 12 re-
petitive units was synthesized by the reported
method50,52,53 (Scheme 1). Chiral dimeric and polymeric
Cr(III) salen complexes 1 and 2 were used as catalysts for
the AKR of trans-stilbene oxide, with aniline as nucleophile
Scheme 1. Synthesis of the catalysts 1 and 2.
Chirality DOI 10.1002/chir

812
KURESHY ET AL.
TABLE 1. Aminolytic kinetic resolution (AKR) of trans-stilbene epoxides using recyclable catalysts, with aniline
under different reaction conditionsa
trans-Epoxide
anti-b-Amino alcohol
Entry
Temp. (8C)
Time (min)
MW (W)
eec (%)
Yieldd (%)
eec (%)
Yieldd (%)
sb
1 (2)
3 (4)
5 (6)
40
50
60
70
80
70
70
70
70
70
70
70
70
27
2
2
2
2
2
2
2
2
2
2
2
5
10
840
900
900
900
900
900
800
1000
900
900
900
900
–
78 (73)
81 (74)
84 (72)
90 (72)
81 (69)
35 (25)
40 (31)
75 (68)
92 (79)
96 (83)
30
78 (83)
62 (65)
63 (62)
48 (48)
35 (37)
65 (67)
37 (26)
65 (67)
45 (46)
39 (41)
72
94 (81)
94 (80)
92 (78)
92 (78)
92 (67)
42 (37)
55 (55)
96 (80)e
68 (70)f
61 (62)g
75h
22 (16)
35 (30)
42 (37)
49 (49)
65 (62)
35 (32)
72 (74)
36 (32)
60 (57)
69 (68)
27
36 (10)
39 (10)
30 (9)
31 (10)
32 (7)
3 (2)
10 (5)
59 (10)
7 (7)
5 (6)
8
8 (7)
5 (6)
7 (8)
9 (10)
11 (12)
13 (14)
15 (16)
17 (18)
19 (20)
21
22 (23)
24 (25)
26 (27)
42 (40)
79 (73)
85 (80)
65 (68)
51 (50)
47 (48)
75 (73)i
61 (67)i
93 (87)j
35 (32)
48 (49)
49 (49)
–
–
36 (18)
aThe 0.01 mmol catalyst was taken in 200 ll CH2Cl2:MeOH (9:1), 0.2 mmol epoxides and 0.1 mmol aniline were added and the reaction mixture was irra-
diated for 2 min in a microwave oven at 708C. Data given in parentheses are for catalyst 2.
bs 5 selectivity factor 5 ln[1 2 c(1 1 ee)]/ln[1 2 c(1 2 ee)], where ee is enantiomeric excess of the aminoalcohol product and c is the conversion (set
to the isolated yield).23
cThe diastereoselectivity of product was found to be >99% 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 optical rotation with literature.23
dThe conversion of the product 7a was determined on Chiralpak OD column, using a calibration curve of epoxide and aminoalcohols and rest given as
isolated yield.
eReaction was performed with 0.4 equiv aniline.
fReaction was performed with 0.6 equiv aniline.
gReaction was performed with 0.75 equiv aniline.
hReaction with Jacobsen catalyst under microwave irradiation at 708C
iReaction carried out at 70ꢁC on oil-bath heating in absence of MW and aliquot was taken at 5 and 10 min, respectively.
jReaction carried out at 27ꢁC in absence of MW.
to the substrate racemic trans-stilbene oxide (1.0 equiv), with polymeric complex 2 but inferior than dimeric Cr(III)
keeping the other reaction parameters same as mentioned salen complex 1 under identical conditions (Fig. 1). Fur-
in entry 7 of the Table 1. As the amount of nucleophile ther, when the aforementioned reaction was conducted in
was reduced to 0.4 equiv, there was a slight improvement the absence of MW irradiation at 708C on an oil-bath,
in the ee of the product but with significantly lower yield there was a drop in yield (32–35%) for similar enantioselec-
(Table 1, entries 15 and 16). On increasing the amount of tion in 5 min (Table 1, entries 22 and 23) as compared to
nucleophile (0.6–0.75 equiv) there was a steady decrease the similar reaction under MW irradiation (Table 1, entries
in the ee of product anti-b-aminoalcohol with concomitant 7 and 8). In an attempt to increase the yield by way of
increase in the ee of trans-stilbene oxide (83–96%; Table 1, increasing the time (10 min) of the reaction, there was a
entries 17–20). Hence, the kinetic resolution reaction can drop in ee (61–67%) of the product (Table 1, entries 24 and
be optimized depending upon which product (epoxide or 25). On the other hand when the same reaction was con-
aminoalcohol) is required in higher chiral purity by simply ducted at room temperature, it took 840 min to give 49%
adjusting the amount of nucleophile (aniline) used. For anti-b-aminoalcohol with 87–93% ee (Table 1, entries 26
the sake of comparison, we conducted the AKR of racemic and 27), which is 420 times slower as compared to the
trans-stilbene oxide with aniline, using monomeric Jacob- reaction conducted under MW irradiation with comparable
sen Cr(III)Cl as catalyst (Table 1, entry 21) that gave far enantioselectivity. The rapid homogeneous energy trans-
less yield (27%) of the product anti-b-aminoalcohol (6a); fer offered by MW irradiation as compared to traditional
however, the ee was nearly the same as it was obtained heating could be responsible for this remarkable reduction
Chirality DOI 10.1002/chir

DIMERIC AND POLYMERIC Cr(III) SALEN COMPLEXES FOR AKR
813
of reaction time without significant reduction in enantiose-
lectivity.
In a metal complex catalyzed ring opening of epoxides,
electronic and steric features of nucleophiles play a very
important role. In view of this, we conducted the AKR of
trans-stilbene oxide with various substituted anilines under
our optimized reaction conditions. Out of the ortho- and
para-methoxy anilines used as nucleophile, the latter gave
aminoalcohol with somewhat higher ee (Table 2, entry 6)
with catalyst 2, while for catalyst 1 the results are at par
for both ortho- and para-methoxy anilines. On the other
hand, para-methyl aniline produced aminoalcohol with
excellent ee (94%) with catalyst 1 (Table 2, entry 7). Para-
chloroaniline inducted poor ee (Table 2, entries 9 and 10)
possibly because of its poor nucleophilicity. In the case of
anilines having strongly electron withdrawing group such
as in the case of para-nitro aniline AKR, reaction with
Fig. 1. 3D view representation of % yield and % ee of anti-b-amino alco-
hol of trans-stilbene oxide using monomer, dimer, and polymer Cr(III)
salen complexes. [Color figure can be viewed in the online issue, which is
available at www.interscience.wiley.com.]
TABLE 2. Aminolytic kinetic resolution (AKR) of trans-aromatic epoxides using recyclable catalysts with, anilines
under microwave irradiations under optimized conditiona
trans-Epoxide
Yieldd (%)
anti-b-Amino alcohols
eec (%) Yieldd (%)
Entry
Epoxide
Amine
eec (%)
sb
1 (2)
3 (4)
5 (6)
7 (8)
9 (10)
11 (12)
13 (14)
15 (16)
17 (18)
3
3
3
3
3
3
4
4
4
5a
5b
5c
5d
5e
5f
5a
5b
5c
90 (72)
80 (65)
82 (68)
92 (69)
65 (81)
–
86
85
88
48 (48)
47 (46)
48 (47)
48 (48)
86 (83)
–
40
38
36
92 (78)
88 (67)
89 (70)
94 (78)
19 (30)
–
59 (46)
62 (47)
69 (53)
49 (49)
45 (39)
47 (38)
49 (47)
25 (13)
–
46 (45)
48 (46)
49 (47)
31 (10)
20 (5)
22 (7)
43 (10)
2 (1)
–
5 (3)
5 (2)
7 (4)
a0.01 mmol catalyst was taken in 200 ll CH2Cl2:MeOH (9:1), 0.2 mmol epoxides and 0.1 mmol aniline were added and the reaction mixture was irradi-
ated for 2 min in a microwave oven at 708C. Data presented in parentheses are for catalyst 2.
bs 5 selectivity factor 5 ln[1 2 c(1 1 ee)]/ln[1 2 c(1 2 ee)], where ee is enantiomeric excess of the amino alcohol product and c is the conversion (set
to the isolated yield).23
cThe diastereoselectivity of the product was found to be >99% determined by 1H NMR and HPLC. The ee of aminoalcohols and epoxides are determined
on Chiralpak OD column and the absolute configuration was assigned by comparing the optical rotation with literature.23
dThe conversion of the product 7a was determined on ChiralPak OD column, using a calibration curve of epoxide and amino alcohols and rest given as
isolated yield.
Chirality DOI 10.1002/chir

814
Run
KURESHY ET AL.
4. Ager DJ, Prakash I, Schaad DR. 1,2-Amino alcohols and their hetero-
TABLE 3. Recycling data of catalyst 1/(2) for AKR of
trans-stilbene oxide, using aniline as nucleophilea
cyclic derivatives as chiral auxiliaries in asymmetric synthesis. Chem
Rev 1996;96:835–875.
5. Li G, Chang HT, Sharpless KB. Catalytic asymmetric aminohydroxyla-
tion (AA) of olefins. Angew Chem Int Ed Engl 1996;35:451–454.
anti-b-Amino
alcohol 6a
Epoxide 3
6. Brien PO. Sharpless asymmetric aminohydroxylation: Scope, limita-
tions, and use in synthesis. Angew Chem Int Ed 1999;38:326–329.
Time (min)
ee (%)
Yield (%)
ee (%)
Yield (%)
7. List B. The direct catalytic asymmetric three-component Mannich
reaction. J Am Chem Soc 2000;122:9336–9337.
1
2
3
4
5
2.0
2.0
2.0
2.0
2.0
90 (72)
89 (70)
89 (71)
90 (72)
90 (72)
48 (48)
47 (49)
46 (48)
46 (48)
48 (48)
92 (78)
91 (78)
92 (77)
91 (76)
92 (77)
49 (49)
48 (48)
48 (48)
47 (47)
46 (46)
´
8. Corrdova A, Notz W, Zhong G, Betancort JM, Barbas CF. A highly
enantioselective amino acid-catalyzed route to functionalized a-amino
acids. J Am Chem Soc 2002;124:1842–1843.
9. Trost BM, Terrell LR. A direct catalytic asymmetric Mannich-type
reaction to syn-amino alcohols. J Am Chem Soc 2003;125:338–339.
aThe 0.01 mmol catalyst was taken in 200 ll CH2Cl2:MeOH (9:1), 0.2
mmol epoxides and 0.1 mmol aniline were added and the reaction mixture
was irradiated for 2 min in a microwave oven at 708C. Results in paranthe-
ses is for catalyst 2.
10. Kobayashi S, Hishitani H, Ueno M. Catalytic asymmetric synthesis of
both syn- and anti-b-amino alcohols. J Am Chem Soc 1998;120:431–
432.
11. Matsunaga S, Kumagai N, Harada S, Shibasaki M. anti-Selective
direct catalytic asymmetric Mannich-type reaction of hydroxyketone
providing b-amino alcohols. J Am Chem Soc 2003;125:4712–4713.
trans-stilbene oxide does not commence (Table 2, entries
11 and 12). AKR of trans-b-methyl styrene oxide with ani-
line gave exclusively anti-b-aminoalcohol with moderate
ee and yield (Table 2, entries 13–18). Based on the optical
rotation studies for the products 7b–7c, their absolute
configuration was shown to be 1S,2R.23
The catalyst recycle experiments were conducted for
the AKR of trans-stilbene oxide, using aniline as a nucleo-
phile with dimeric and polymeric Cr(III) salen complexes
1 and 2 as catalysts. In the postcatalysis work-up step, the
catalysts were precipitated out by the addition of hexane:
diethylether (1:1), which were filtered, washed with n-hex-
ane, and dried in vacuum. The recovered catalysts were
repeatedly used for four more catalysis runs which
showed no apparent loss in the reactivity and enantioselec-
tivity of the catalysts. However, there was some physical
loss in the quantity of the catalysts during the catalyst re-
covery process (Table 3).
12. Fu XL, Wu SH. A regio- and stereoselective synthesis of b-amino alco-
hols. Synth Commun 1997;27:1677–1683.
13. Hou XL, Wu J, Dai LX, Xia LJ, Tang MH. Desymmetric ring-opening
of meso-epoxides with anilines: a simple way to chiral b-amino alco-
hols. Tetrahedron: Asymmetry 1998;9:1747–1752.
14. Sagawa S, Abe H, Hase Y, Inaba T. Catalytic asymmetric aminolysis of
3,5,8-trioxabicyclo[5.1.0]octane providing an optically pure 2-amino-
1,3,4-butanetriol equivalent. J Org Chem 1999;64:4962–4965.
15. Sekaine A, Ohshima T, Shibasaki M. An enantioselective formal syn-
thesis of 4-demethoxydaunomycin using the catalytic asymmetric ring
opening reaction of meso-epoxide with p-anisidine. Tetrahedron
2002;58:75–82.
16. Carre´e F, Gil R, Collin J. Samarium iodides catalyzed meso-epoxides
ring opening by aromatic amines. Tetrahedron Lett 2004;45:7749–
7751.
17. Carre´e F, Gil R, Collin J. Enantioselective ring opening of meso-epox-
ides by aromatic amines catalyzed by lanthanide iodo binaphtholates.
Org Lett 2005;7:1023–1026.
18. Schneider C, Sreekanth AR, Mai E. Scandium-bipyridine-catalyzed
enantioselective addition of alcohols and amines to meso-epoxides.
Angew Chem Int Ed Engl 2004;43:5691–5694.
CONCLUSION
19. Kureshy RI, Singh S, Khan NH, Abdi SHR, Suresh E, Jasra RV. Facile
enantioselective ring-opening reaction of meso-epoxides with anilines
using (S)-(2)-BINOL-Ti complex as a catalyst. Eur J Org Chem
2006;1303–1309.
In summary, we have developed an efficient AKR proto-
col for the ring opening of trans-stilbene oxide, trans-b-
methyl styrene oxide with various aromatic amines, to
achieve respective trans b-amino alcohols in high enantio
and diastereoselectivity and yields in a very short time
under microwave irradiation. Unlike the monomeric
Cr(III) salen complex, catalyst 1 gave higher enantioselec-
tivity up to 94% with 4-methylaniline. Both dimeric and poly-
meric Cr(III) salen complexes were easily recyclable and
were reused five times with retention of enantioselectivity.
20. Keith JM, Larrow JF, Jacobsen EN. Practical considerations in kinetic
resolution reactions. Adv Synth Catal 2002;343:5–26.
21. Label H, Jacobsen EN. Chromium catalyzed kinetic resolution of 2,2-
disubstituted epoxides. Tetrahedron Lett 1999;40:7303–7306.
22. Bandani M, Cozzi PG, Melchiorre P, Umani-Ronchi A. Kinetic resolu-
tion of epoxides by a C¼C bond-forming reaction: Highly enantiose-
lective addition of indoles to cis, trans, and meso aromatic epoxides
catalyzed by [Cr(salen)] complexes. Angew Chem Int Ed 2004;43:84–
87.
ACKNOWLEDGMENT
23. Bartoli G, Bosco M, Carlone A, Locatelli M, Massaccesi M, Mel-
chiorre P, Sambri L. Asymmetric aminolysis of aromatic epoxides: A
facile catalytic enantioselective synthesis of anti-b-amino alcohols.
Org Lett 2004;6:2173–2176.
RIK is thankful to Dr. P. K. Ghosh, the Director, of the
Institute for providing instrumentation facilities.
24. Song CE, Lee S. Supported chiral catalysts on inorganic materials.
Chem Rev 2002;102:3495–3524.
LITERATURE CITED
25. Xia QH, Ge HQ, Ye CP, Liu ZM, Su KX. Advances in homogeneous
and heterogeneous catalytic asymmetric epoxidation. Chem Rev
2005;105:1603–1662.
1. Jacobsen EN, Wu MH. Comprehensive asymmetric catalysis. In:
Jacobsen EN, Pflaz A, Yamamoto H, editors. Ring opening of epoxides
and related reactions in comprehensive asymmetric catalysis, Vol. 3.
New York: Springer; 1999. p 1309.
26. Song CE, Oh CR, Roh EJ, Choo DJ. Cr(salen) catalysed asymmetric
ring opening reactions of epoxides in room temperature ionic liquids.
Chem Commun 2000;1743–1744.
2. Hodgson DM, Gibbs AR, Lee GP. Enantioselective desymmetrisation
of achiral epoxides. Tetrahedron 1996;52:14361–14384.
27. Loupy A. Microwaves in organic synthesis. Weinheim: Wiley-VCH;
2002.
3. Bergmeier SC. The synthesis of vicinal amino alcohols. Tetrahedron
2000;56:2561–2576.
Chirality DOI 10.1002/chir

DIMERIC AND POLYMERIC Cr(III) SALEN COMPLEXES FOR AKR
815
28. Kappe CO, Dallinger D, The impact of microwave synthesis on drug
discovery. Nat Rev Drug Discov 2006;5:51–63.
43. Kureshy RI, Khan NH, Abdi SHR, Singh S, Ahmad I, Jasra ,RV. Cata-
lytic asymmetric epoxidation of non-functionalised alkenes using poly-
meric Mn(III) salen as catalysts and NaOCl as oxidant. J Mol Catal A:
Chem 2004;218:141–146.
29. Kappe CO. Controlled microwave heating in modern organic synthe-
sis. Angew Chem Int Ed 2004;43:6250–6284.
44. Khan NH, Agrawal S, Kureshy RI, Abdi SHR, Mayani VJ, Jasra RV.
Asymmetric synthesis of O-acetylcyanohydrins by reaction of alde-
hydes with NaCN/KCN catalyzed by recyclable chiral dimeric titaniu-
m(IV)/vanadium(V) salen complexes. Eur J Org Chem 2006;14:3175–
3180.
45. Khan NH, Agrawal S, Kureshy RI, Abdi SHR, Mayani VJ, Jasra RV.
Asymmetric addition of trimethylsilyl cyanide to aldehydes promoted
by chiral polymeric vanadium(V) salen complex as an efficient and
recyclable catalyst. Tetrahedron: Asymmetry 2006;17:2659–2666.
30. Perreux L, Loupy A. A tentative rationalization of microwave effects in
organic synthesis according to the reaction medium and mechanistic
considerations. Tetrahedron 2001;57:9199–9223.
31. Adam D. Microwave chemistry: Out of the kitchen. Nature 2003;421:
571–572.
32. Lindstro¨m UM, Olofsson B, Somfai P. Microwave-assisted aminolysis
of vinylepoxides. Tetrahedron Lett 1999;40:9273–9276.
33. Favretto L, Nugent WA, Licini G. Highly regioselective microwave-
assisted synthesis of enantiopure C3-symmetric trialkanolamines. Tet-
rahedron Lett 2002;43:2581–2584.
46. Kureshy RI, Singh S, Khan NH, Abdi SHR, Ahmad I, Bhatt A, Jasra
RV. Improved catalytic activity of homochiral dimeric cobalt–salen
complex in hydrolytic kinetic resolution of terminal racemic epoxides.
Chirality 2005;17:1–5.
34. Mojtahedi MM. Ghasemi MH, Abaee MS, Bolourtchian M. Solvent-
free solid-supported recovery of carbonyl compounds from N,N-di-
methylhydrazones under microwave irradiation. ARKIVOC 2005;15:
68–73.
47. Kureshy RI, Ahmad I, Pathak K, Khan NH, Abdi SHR, Prathap KJ,
Jasra RV. Easily recyclable chiral polymeric Mn(III) salen complexes
for oxidative kinetic resolution of racemic secondary alcohols. Chiral-
ity 2007;19:352–357.
35. Glas H, Thiel WR. Microwave-assisted synthesis of chiral imidazolyl
and pyrazolyl alcohols. Tetrahedron Lett 1998;39:5509–5510.
36. Gupta R, Paul S, Gupta AK, Kachroo PL. Opening of oxirane ring with
N-nucleophiles under microwave irradiation. Indian J Chem 1997;
36B:281–283.
48. Pathak K, Ahmad I, Abdi SHR, Kureshy RI, Khan NH, Jasra RV. Oxi-
dative kinetic resolution of racemic secondary alcohols catalyzed by
recyclable chiral dimeric Mn(III) salen catalysts. J Mol Catal A: Chem
2007;274:120–126.
49. Kureshy RI, Singh S, Khan NH, Abdi SHR, Agrawal S, Mayani V,
Jasra RV. Microwave-assisted asymmetric ring opening of meso-epox-
ides with aromatic amines catalyzed by a Ti-S-(2)-BINOL complex.
Tetrahedron Lett 2006;47:5277–5279.
37. Khosropous AR, Khodaei MM, Ghozati K. Bi(OTf)3- and Bi(TFA)3-
catalyzed ring opening of epoxides with anilines under microwave
irradiation. Chem Lett 2004;33:304–305.
38. Mojthahedi MM, Saidi MR, Bolourtchain M. Microwave-assisted ami-
nolysis of epoxides under solvent-free conditions catalyzed by mont-
morillonite clay. J Chem Res (S) 1999;128–129.
50. Kureshy RI, Singh S, Khan NH, Abdi SHR, Agrawal S, Jasra RV. Enan-
tioselective aminolytic kinetic resolution (AKR) of epoxides catalyzed
by recyclable polymeric Cr(III) salen complexes. Tetrahedron: Asym-
metry 2006;17:1638–1643.
39. Lutsenko S, Moberg C. Microwave-mediated ruthenium-catalyzed
asymmetric hydrogen transfer. Tetrahedron: Asymmetry 2001;12;
2529–2532.
51. G. Moyna, H. J. Williams, A. L. Scott. An improved procedure for the
epoxidation of methyl cinnamate derivatives and production of acid-
sensitive epoxides. Synth Commun 1996;26;2235–2240.
40. Dioos BML, Jacobs PA. Microwave-assisted Cr(salen)-catalysed asym-
metric ring opening of epoxides. J Catal 2005;235:428–430.
41. Kureshy RI, Khan NH, Abdi SHR, Patel ST, Jasra RV. Dimeric chiral
Mn(III) Schiff base complex-catalysed enantioselective epoxidation of
non-functionalised alkenes. Tetrahedron Lett 2001;42:2915–2918.
52. Daly AM, Renehan MF, Gilheny DG. High enantioselectivities in an
(E)-alkene epoxidation by catalytically active chromium salen com-
plexes. Insight into the catalytic cycle. Org Lett 2001;3:663–666.
42. Kureshy RI, Khan NH, Abdi SHR, Patel ST, Jasra RV. Enantioselective
epoxidation of non-functionalised alkenes using a urea–hydrogen per-
oxide oxidant and a dimeric homochiral Mn(III)-Schiff base complex
catalyst. Tetrahedron: Asymmetry, 2001;12:433–438.
53. Martinez LE, Leighton JL, Carsren DH, Jacobsen EN. Highly enantio-
selective ring opening of epoxides catalyzed by (salen)Cr(III) com-
plexes J Am Chem Soc 1995;117:5897–5898.
Chirality DOI 10.1002/chir