Highly efficient recyclable CoIII-salen complexes in the catalyzed asymmetric aminolytic kinetic resolution of aryloxy/terminal epoxides for the simultaneous production of N-protected 1,2-amino alcohols and the corresponding epoxides in high op

Article abstract of DOI:10.1002/ejoc.200900032

Chiral Co^III-salen complexes 1-6 bearing different substituents at the 3,3′- and 5,5′-positions of the salen unit, namely H, tBu, morpholmomethyl, and piperidinomethyl, have been synthesized. These complexes were used as catalysts in an environ

Full text of DOI:10.1002/ejoc.200900032

FULL PAPER
DOI: 10.1002/ejoc.200900032
Highly Efficient Recyclable CoIII–salen Complexes in the Catalyzed
Asymmetric Aminolytic Kinetic Resolution of Aryloxy/Terminal Epoxides for
the Simultaneous Production of N-Protected 1,2-Amino Alcohols and the
Corresponding Epoxides in High Optical Purity
Rukhsana I. Kureshy,*[a] K. Jeya Prathap,[a] Santosh Agrawal,[a] Manish Kumar,[a]
Noor-ul H. Khan,[a] Sayed H. R. Abdi,[a] and Hari C. Bajaj[a]
Keywords: Asymmetric catalysis / Cobalt / Kinetic resolution / Epoxides / Amino alcohols / Carbamates
Chiral CoIII–salen complexes 1–6 bearing different substitu-
ents at the 3,3Ј- and 5,5Ј-positions of the salen unit, namely
H, tBu, morpholinomethyl, and piperidinomethyl, have been
synthesized. These complexes were used as catalysts in an
multaneous formation of the corresponding epoxides with
high chiral purity (ee up to Ͼ99%) and in quantitative yields
with catalyst 1 in the ionic liquid [bmim]PF6 as the reaction
medium in around 5 h. The catalyst is recyclable in this ionic-
environmentally benign protocol for the highly enantioselec- liquid-mediated AKR process (up to six cycles with no loss of
tive aminolytic kinetic resolution (AKR) of racemic aryloxy/ performance), and the process is five times faster than the
terminal epoxides with various carbamates as the nucleo- homogeneous process performed with conventional organic
phile in the presence of different ionic liquids at room tem-
perature. Excellent yields (Ͼ99% with respect to the nucleo-
phile) of N-protected 1,2-amino alcohols with high regio- and
enantioselectivities (ee Ͼ99%) were achieved with the si-
solvents.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
for the hydrolytic kinetic resolution (HKR) of terminal ep-
oxides with water as a nucleophile.[10] These monomeric chi-
ral salen complexes are often highly soluble in the reaction
media making them difficult to recover and recycle. In our
quest to develop recyclable catalysts,[6f–6h] we have reported
the ARO/AKR of meso/trans-epoxides using recyclable cat-
alysts derived from TiIV/CrIII with chiral BINOL[6f]/Schiff
bases[6h] as ligands under ambient,[6f] thermal,[6f] and micro-
wave-irradiation[11] reaction conditions. These systems
worked well when organic solvents were used as the reac-
tion medium, which is not desirable from an environmental
point of view. Ionic liquids are currently viewed as future
reaction media in the chemical industry as an eco-friendly
alternative to conventionally used hazardous organic sol-
vents.[12] It has also been observed that switching over to
an ionic liquid from a traditional organic solvent often re-
sults in a significant improvement in the reactivity and
selectivity of a catalytic system.[13] Song and co-workers
previously reported that the use of ionic liquids enabled
CrIII– and CoIII–salen catalysts to be recycled in the HKR
of racemic epoxides and in the enantioselective ring-open-
ing of meso-epoxides.[14] In this work we have synthesized
chiral CoIII–salen complexes 1–6 with different substituents
at the 3,3Ј- and 5,5Ј-positions of the salen unit, namely H,
tBu, morpholinomethyl, and piperidinomethyl (Figure 1),
and used them as catalysts for the AKR of racemic aryloxy/
terminal epoxides with various carbamates as the nucleo-
Introduction
Chiral β-amino alcohols are valuable intermediates in the
synthesis of a variety of biologically active compounds and
play a very significant role in asymmetric catalysis.[1] Vari-
ous efficient methods have been reported for the synthesis
of chiral syn-β-amino alcohols, noteworthy among them are
the amino hydroxylation of olefins,[2] the addition of α-hy-
droxy ketones to imines,[3] and the asymmetric ring-opening
(ARO)/aminolytic kinetic resolution (AKR) of meso/race-
mic terminal trans-epoxides with alkyl/arylamines by using
different chiral catalysts.[4–8] Bartoli and co-workers[9] dem-
onstrated for the first time a very simple experimental pro-
cedure for the synthesis of chiral syn/anti-β-amino alcohols
by AKR of terminal/trans-aromatic epoxides with aniline/
carbamates using CrIII– and CoIII–salen complexes as cata-
lysts. Excellent results in terms of the yields and enantio-
selectivities of β-amino alcohols were achieved with these
complexes. Incidentally, the same chiral CoIII–salen com-
plexes were successfully used by Jacobsen and co-workers
[a] Discipline of Inorganic Materials and Catalysis, Central Salt
and Marine Chemicals Research Institute (CSMCRI), Council
of Scientific & Industrial Research (CSIR),
G. B. Marg, Bhavnagar 364002 Gujarat, India
Fax: +91-278-2566970
E-mail: rukhsana93@yahoo.co.in
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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R. I. Kureshy et al.
FULL PAPER
phile in ionic liquids at room temperature. This protocol ane-1,2-diamine, (1R,2R)-N,NЈ-bis[5-(tert-butyl)salicylid-
provided N-protected 1,2-amino alcohols in excellent yields ene]cyclohexane-1,2-diamine,[15b] (1R,2R)-N,NЈ-bis[3-(mor-
(Ͼ99% with respect to the nucleophile) with high regio- pholinomethyl)-5-(tert-butyl)salicylidene]cyclohexane-1,2-di-
and enantioselectivities (ee up to Ͼ99%) with the simulta- amine, and (1R,2R)-N,NЈ-bis[3-(piperidinomethyl)-5-(tert-
neous production of the corresponding chirally enriched ep- butyl)salicylidene]cyclohexane-1,2-diamine[15c] with CoII
oxides with high optical purity (ee Ͼ99%) and in quantita- acetate under an inert gas (Figure 1). All the chiral metal
tive yields. These systems are recyclable as well as allowing complexes were characterized by microanalysis, IR and UV/
reactions to be several times faster than the corresponding Vis spectroscopy, and optical rotation (data are given in the
systems in organic solvents.[9b]
Exp. Sect.).
In our first round of catalytic studies, complex 1 (1 mol-
%) was explored for its catalytic activity in the AKR of 1,2-
epoxy-3-phenoxypropane (7a; 2.2 mmol) as a representative
substrate with tert-butyl carbamate (BocNH2, 8a;
1.0 mmol) as the nucleophile in 1-butyl-3-methylimida-
zolium ([bmim]PF6, as a representative ionic liquid) as the
reaction medium at room temperature under nitrogen. Un-
der the given reaction conditions no products were formed
even after 48 h (Table 1, Entry 1). However, when the same
reaction was conducted in the presence of acetic acid as an
additive under atmospheric conditions, the reaction pro-
ceeded well to give the N-protected amino alcohol 9a in
good yield (76%) and high chiral purity (ee 93%; Table 1,
Entry 2) at room temp. in 12 h with excellent recovery of
the chirally enriched epoxide (ee 91%). It has been reported
that the oxidation of CoII to CoIII with the use of an acidic
additive in air is responsible for the change in the activity
of the complex.[9b] When p-nitrobenzoic acid (PNBA) was
used in place of acetic acid at room temp. over 5 h, the
activity and enantioselectivity of the product 9a was im-
proved further[10] (Table 1, Entry 3). In this reaction, al-
though the N-protected amino alcohol was obtained in
Figure 1. Structures of the catalysts 1–6.
Results and Discussion
Chiral salen complexes 1–6 were obtained by the reaction
of the corresponding chiral salen ligands, namely, (1R,2R)-
N,NЈ-bis[3,5-di(tert-butyl)salicylidene]cyclohexane-1,2-di-
amine,[15a] (1R,2R)-N,NЈ-disalicylidenecyclohexane-1,2-di-
amine, (1R,2R)-N,NЈ-bis[3-(tert-butyl)salicylidene]cyclohex-
Table 1. Optimization of the reaction conditions for the enantioselective AKR of 7a with 8a in [Bmim]PF6.
Entry
Catalyst
Additive
Time
[h]
Chirally enriched unreacted epoxide[a] 7aЈ
ee [%][b]
N-protected 1,2-amino alcohol 9a
Conversion [%][c]
ee [%][c]
1[d]
2[e]
1
1
1
1
2
3
4
5
6
1
1
1
1
–
48
12
5
–
91
90
99
43
68
65
71
77
Ͼ99
Ͼ99
Ͼ99
Ͼ99
–
76
88
–
93
Ͼ99
Ͼ99
48
72
69
75
80
Ͼ99
Ͼ99
Ͼ99
Ͼ99
acetic acid
PNBA
PNBA
PNBA
PNBA
PNBA
PNBA
PNBA
PNBA
PNBA
PNBA
PNBA
3[e]
4[f]
5
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
5[f]
10
18
19
30
30
15
26
24
7
6[f]
7[f]
8[f]
9[f]
10[g]
11[h]
12[i]
13[j]
[a] Unreacted epoxide after AKR reaction recovered in quantitative yield. [b] Based on HPLC (Chiral pack OD Column) by using the
calibration curve of the racemic epoxide. [c] Based on HPLC (Chiral pack AD-H Column) by using the calibration curve of the racemic
N-protected amino alcohol. [d] The reaction was conducted with an epoxide/RNH2/catalyst ratio of 2.2:1.0:0.02 mmol in 300 mg of the
ionic liquid. [e] The reaction was conducted with an epoxide/RNH2/catalyst/acetic acid/PNBA ratio of 2.2:1.0:0.02:0.02 mmol in 300 mg
of the ionic liquid. [f] The reaction was conducted with an epoxide/RNH2/catalyst/PNBA ratio of 2.0:1.0:0.02:0.02 mmol in 300 mg of
the ionic liquid. [g] Catalyst loading of 0.5 mol-%. [h] Catalyst loading of 0.25 mol-%. [i] The reaction was conducted at 10 °C. [j] The
reaction was conducted with 10 mmol of 7a and 5 mmol of 8a in 1500 mg of the ionic liquid with the other conditions as for Entry 4.
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Aminolytic Kinetic Resolution of Aryloxy/Terminal Epoxides
Ͼ99% ee, the ee of the unreacted epoxide was only 90% as
we used 7a in slightly more than stoichiometric amounts
(2.2 mmol) with respect to 8a [1.0 mmol; Figure 2 (Y)].
However, on conducting this reaction in an exact stoichio-
metric ratio of 7a (2.0 mmol) and 8a (1.0 mmol), there was
no reduction in the ee of the N-protected amino alcohol 9a
(Ͼ99%; Entry 4), but there was a significant improvement
in the ee (Ͼ99%) of the recovered 7Јa [Figure 2 (X)]. This
behavior has been reported earlier by Melchiorre and co-
workers in the epoxide ring-opening reaction.[16] Hence, in
our subsequent catalytic reactions to evaluate the efficacies
of complexes 2–6 in the AKR reaction we maintained this
same stoichiometry of 7a and 8a (Entries 5–9). The com-
plexes 2–6, which bear different groups, namely H, tBu,
morpholinomethyl, and piperidinomethyl, at the 3,3Ј- and
5,5Ј-positions of the salen ligand, are known to influence
the catalytic activities and enantioselectivities of various re-
actions.[15b] For our reaction, the salen complex with no
substituents (catalyst 2) showed high activity (conversion
Ͼ99% with respect to 8a) in terms of the formation of N-
protected amino alcohol 9a, but only moderate enantio-
selectivity (ee 48%). Also, the ee of the remaining epoxide
was only moderate (43%; Entry 5). The presence of a tBu
group at either the 3,3Ј- or 5,5Ј-positions (catalysts 3 and
4, respectively) of the salen unit enhanced the enantio-
selectivity significantly (Entries 6 and 7), but the reaction
took longer to reach completion (18–19 h). The presence of
an aminoalkyl group at the 3,3Ј-positions with a tBu group
at the 5,5Ј-positions showed further improvements in
enantioselectivity, but the reaction took even longer (30 h)
to reach completion (Entries 8 and 9). Therefore, it is evi-
dent from the results in Table 1 that the 3,3Ј- and the 5,5Ј-
positions of the salen moiety should preferably bear a tBu
group (catalyst 1) for high activity and enantioselectivity in
the AKR reaction (Entry 4; Figure 3).
Figure 2. ee versus time for glycidyl 2-methylphenyl ether (7b) in
the AKR by using BocNH2 (8a) as the nucleophile. (X) 2.0 mmol
7b and 1.0 mmol 8a; (Y) 2.2 mmol 7b and 1.0 mmol 8a.
Figure 3. Optimization of the reaction conditions for the enantiose-
lective AKR of 7a with 8a in [bmim]PF6.
of catalyst loading on the AKR reaction. Accordingly, we
Complex 1 was found to be the most active and enantio- reduced the catalyst loading to 0.5 and 0.25 mol-% and
selective catalyst at a loading of 1 mol-%, as shown in our found that under these conditions there was no fall in the
above trial run, hence it was pertinent to examine the effect enantioselectivity of the product, but the reaction took
Table 2. Enantioselective AKR of 7a with 8a in different ionic liquids [bmim][X].[a]
Entry
X
Time
[h]
Unreacted epoxide 7aЈ
ee [%]
N-protected 1,2-amino alcohol 9a
Conversion [%][c] ee [%][d]
1
2
3
4
5
A
B
C
D
E
F
A
5
Ͼ99
81
34
14
–
racemic
8
Ͼ99
78
44
56
–
Ͼ99
Ͼ99
99
95
34
18
–
12
12
12
12
12
15
6
racemic
10
7[b]
[a] Conditions: 2.0 mmol 7a–e, 1.0 mmol 8a–c, 0.02 mmol catalyst 1, and 0.02 mmol PNBA in 300 mg of different ionic liquids at room
temp. [b] [hmim]PF6 as the ionic liquid. [c] Based on HPLC (Chiral pack OD Column) by using the calibration curve of the racemic
epoxide. [d] Based on HPLC (Chiral pack AD-H Column) by using the calibration curve of the racemic N-protected amino alcohol.
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Table 3. Enantioselective AKR of 7a–i with 8a in [bmim]PF6.[a]
[a] Conditions: 2.0 mmol 7a–i, 1.0 mmol 8a, 0.02 mmol catalyst 1, and 0.02 mmol PNBA in [bmim]PF6 at room temp. [b] Based on
HPLC (Chiral pack OD column) by using the calibration curve of the racemic epoxide. [c] Based on HPLC (Chiral pack AD-H column)
by using the calibration curve of the racemic N-protected amino alcohol. [d] TOF = [product]/[catalyst]ϫtime [h–1]. [e] Based on GC
(Chiraldex GTA column).
–
longer to reach completion (15 and 26 h, respectively; En- (E), and AlCl4 (F; Figure 4). However, with the exception
tries 10 and 11). Therefore, a catalyst loading of 1 mol-% of the ionic liquid [bmim][NO3] (B; Entry 2), for which the
was taken as optimum for this AKR protocol (Entry 4). We yield and ee of the N-protected 1,2-amino alcohol 9a were
also established that room temp. is the preferred tempera- found to be 78 and 95%, respectively, other ionic liquids
ture for the AKR reaction, because by lowering the tem- fared very badly in terms of enantioselectivity (Entries 3–
perature to 10 °C it took 24 h to obtain a similar conversion 6). Furthermore, the use of 1-hexyl-3-methylimidazolium
and enantioselectivity (Entry 12). This protocol worked hexafluorophosphate ([hmim]PF6) as the ionic liquid
well even on a relatively large scale (10 m) in 7 h (Table 1, yielded the desired product in high yield in 15 h (Entry 7),
Entry 13).
but with poor ee. This behavior of long-chain ionic liquids
It has been reported in the literature that the anion [X–] has been reported previously, but for a different reaction.[17]
in the ionic liquids [bmim][X] greatly influences the catalytic Therefore, [bmim]PF6 (A) was the best ionic liquid to use
activity and enantioselectivity of a variety of reactions.[12] for the AKR of 7a with 8a as the nucleophile. Bartoli et
Therefore, we carried out the above optimized AKR reac- al.[9b] has reported similar reactions with catalyst 1
tion (Table 2, Entry 1) in the presence of ionic liquids with (1.5 mol-%) in the presence of PNBA using dichlorometh-
different anions, namely NO3– (B), BF4– (C), SbF6– (D), Cl– ane, tetrahydrofuran, and tert-butyl methyl ether (TBME)
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Aminolytic Kinetic Resolution of Aryloxy/Terminal Epoxides
as the solvent, giving the N-protected amino alcohols in 7Јa were recovered from the organic layer by column
excellent yields and enantioselectivities in 24 h. On the chromatography. The recovered ionic liquid was dried in
other hand the use of the ionic liquid with the anion A with vacuo and contained the catalyst and additive, as evidenced
complex 1 not only improved the reactivity (5 h for com- by IR spectroscopy (Figure 5, Z). The recovered ionic liquid
plete consumption of 8a), but both the N-protected amino was used in subsequent reactions without any further pro-
alcohol 9a and the unreacted epoxide 7aЈ were obtained cessing, which worked well for up to six catalytic cycles,
with excellent chiral purity (ee Ͼ99%; Entry 1).
with retention of reactivity and enantioselectivity. However,
in the seventh cycle there was a drop in enantioselectivity
(Table 5). From the recycling experiments it is evident that
CoIII–salen is stable during the course of the AKR reaction
(Figure 5) and does not require additional quantities of ad-
ditive to reoxidize the cobalt.
Figure 4. Structures of the ionic liquids.
Conclusions
A series of chiral salen complexes bearing different sub-
stituents at the 3,3Ј- and 5,5Ј-positions of the salicylalde-
hyde moiety have been synthesized and used as efficient cat-
alysts in the AKRs of different racemic aryloxy/terminal
epoxides 7a–i with 8a–c as nucleophiles in the presence of
different ionic liquids as the reaction medium at room temp.
N-Protected 1,2-amino alcohols 9a–g with high chiral pu-
rity (ee Ͼ99%) were obtained when [bmim]PF6 was used as
the reaction medium with catalyst 1 along with the corre-
sponding epoxides 7aЈ–gЈ with high optical purity (ee
Ͼ99%) in 5–10 h. The ring-opened products formed from
styrene oxide and glycidyl 1-naphthyl ether, however, were
obtained with moderate chiral purity. This AKR system
proceeds five times faster in the presence of the ionic liquid
than in the presence of conventional organic solvents, and
the system worked well for up to six cycles with retention
of enantioselectivity.
The above-optimized reaction protocol for the AKR was
further extended to the epoxide ring-opening of different
aryloxy/terminal epoxides, namely 1,2-epoxy-3-phen-
oxypropane (7a), glycidyl 2-methylphenyl ether (7b), benzyl
glycidyl ether (7c), 4-chlorophenyl glycidyl ether (7d), 4-tert-
butylphenyl glycidyl ether (7e), epichlorohydrin (7f), 1,2-
epoxyhexane (7g), styrene oxide (7h), and glycidyl 1-naph-
thyl ether (7i) with tert-butyl carbamate (BocNH2; 8a) as
the nucleophile by using catalyst 1 in the presence of PNBA
as an additive with [bmim]PF6 as the ionic liquid. Excellent
yields (Ͼ99%) and absolute regioselectivities for the ter-
minal N-protected 1,2-amino alcohols 9a–g with Ͼ99% ee
were achieved in 5–10 h (Table 3, Entries 1–7). Agreeably,
the corresponding epoxides 7aЈ–gЈ were also recovered in
quantitative yields (Ͼ99%) and with excellent optical purity
(Ͼ99%; Table 3, Entries 1–7). Ironically, styrene oxide and
glycidyl 1-naphthyl ether gave epoxide ring-opened prod-
ucts in moderate ees (Entries 8 and 9). Nevertheless, com-
parison of the results of our ionic liquid protocol (TOF =
9.97; Table 3, Entry 1) with those of a conventional solvent
protocol (TOF = 2.06)[9b] shows the former has a distinct
Experimental Section
Experimental Methods: Cobalt acetate and acetic acid were pur-
advantage in terms of high reactivity, as reflected in their chased from s.d. Fine Chemicals and were used as received. p-Ni-
trobenzoic acid, racemic aryloxy/terminal epoxides, namely 1,2-ep-
oxy-3-phenoxypropane (7a), glycidyl 2-methylphenyl ether (7b),
benzyl glycidyl ether (7c), 4-chlorophenyl glycidyl ether (7d), 3-tert-
butylphenyl glycidyl ether (7e), epichlorohydrin (7f), 1,2-epoxyhex-
ane (7g), styrene oxide (7h), glycidyl 1-naphthyl ether (7i), tert-butyl
carbamate (BocNH2; 8a), urethane (NH2COOEt; 8b), benzyl car-
bamate (CbzNH2; 8c), 2-tert-butylphenol, 4-tert-butylphenol, and
2,4-di-tert-butylphenol were purchased from Aldrich. 3-tert-Butyl-
salicylaldehyde, 5-tert-butylsalicylaldehyde, and 3,5-di-tert-butyl-
salicylaldehyde were synthesized according to the reported meth-
TOF values for the same reaction. We further extended this
protocol to the ring-opening reaction of aryloxy epoxides
7b–e with urethane (8b) or benzyl carbamate (8c) as the
nucleophile using the catalyst 1 in the presence of PNBA
and [bmim]PF6 (Table 4). All the data showed excellent
conversions and regio- and enantioselectivities in the ring-
opened products with quantitative recovery of the epoxides
with excellent chiral purity (Table 4, Entries 1–10).
Notwithstanding their high activity, the catalyst and ad-
ditive used in this ionic liquid protocol are recyclable, as od.[15a] The (–)-(1R,2R)-diaminocyclohexane was resolved from the
technical grade racemic trans-1,2-diaminocyclohexane according to
the reported method.[15a] The solvents were dried according to stan-
dard procedures, distilled, and stored under nitrogen. NMR spectra
were obtained with a Bruker F113V spectrometer (500 and
125 MHz for 1H and 13C NMR, respectively) and are referenced
internally with TMS. FTIR spectra were recorded with a Perkin–
Elmer Spectrum GX spectrometer in KBr window. High-resolution
mass spectra were obtained with LC-MS (Q-TOFF), LC (Waters),
and MS (Micromass) instruments. For product purification, flash
chromatography was performed by using silica gel (60–200 mesh)
evidenced by recycling experiments (Table 5). The recycl-
ability experiments were carried out with 1,2-epoxy-3-phen-
oxypropane (7a; 2.0 mmol) as a representative substrate
with tert-butyl carbamate (BocNH2, 8a; 1.0 mmol) as the
nucleophile in [bmim]PF6 (as a representative ionic liquid)
as the reaction medium at room temperature by using the
complex 1 (1 mol-%) in the presence of PNBA as additive.
After completion of the catalytic reaction, the products
were extracted with n-hexane/diethyl ether (75:25). The N-
protected amino alcohol 9a and chirally enriched epoxide purchased from s.d. Fine Chemcals Limited, Mumbai (India). The
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Table 4. Enantioselective AKR of 7a–e with 8b–c in [bmim]PF6.[a]
[a] Conditions: 2.0 mmol 7a–e, 1.0 mmol 8a–c, 0.02 mmol catalyst 1, and 0.02 mmol PNBA in [bmim]PF6 at room temp. [b] Based on
HPLC (Chiral pack OD column) by using the calibration curve of the racemic epoxide. [c] Based on HPLC (Chiral pack AD-H column)
by using the calibration curve of the racemic N-protected amino alcohol. [d] TOF = [product]/[catalyst]ϫtime [h–1].
OD, and OJ chiral columns (wavelength 243 nm) with 2-propanol/
hexane as the eluent. Optical rotations were measured with a Digi-
pol 781 Automatic Polarimeter from Rudolph Instruments.
Table 5. Enantioselective AKR of 7a with 8a in [bmim]PF6 using
recovered complex 1.
Run
1
2
3
4
5
6
7
Time [h]
Conversion [%][a]
ee [%][b]
5
99
Ͼ99
5.5
99
Ͼ99
6
99
Ͼ99
6
99
Ͼ99
6
99
Ͼ99
6
99
Ͼ99
6
99
88
Preparation of the Catalysts: Chiral salen complexes 1–4, namely
{(1R,2R)-N,NЈ-bis[3,5-di(tert-butyl)salicylidene]cyclohexane-1,2-
diaminato}cobalt(II) (1),[15a] [(1R,2R)-N,NЈ-disalicylidenecyclohex-
ane-1,2-diaminato]cobalt(II) (2), {(1R,2R)-N,NЈ-bis[3-(tert-butyl)-
salicylidene]cyclohexane-1,2-diaminato}cobalt(II) (3), {(1R,2R)-
N,NЈ-bis[5-(tert-butyl)salicylidene]cyclohexane-1,2-diaminato}-
cobalt(II) (4), were synthesized according to the reported procedure
under an inert gas.[15b] {(1R,2R)-N,NЈ-Bis[5-tert-butyl-3-(morpholi-
nomethyl)salicylidene]cyclohexane-1,2-diaminato}cobalt(II) (5)
and {(1R,2R)-N,NЈ-bis[5-tert-butyl-3-(piperidinomethyl)salicylid-
[a] Based on HPLC (Chiral pack OD column) by using the cali-
bration curve of the racemic epoxide 7a. [b] Based on HPLC (Chi-
ral pack AD-H column) by using the calibration curve of the race-
mic N-protected amino alcohol.
enantiomeric excesses (ees) of the products were determined by
HPLC (Shimadzu SCL-10AVP) by using Daicel Chiralpak AD-H,
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Aminolytic Kinetic Resolution of Aryloxy/Terminal Epoxides
Figure 5. IR spectra of the CoIII–salen complex before addition of the ionic liquid (X), after addition of the ionic liquid (Y), and the
CoIII–salen complex in the ionic liquid (Z) recovered after the catalytic reaction.
ene]cyclohexane-1,2-diaminato}cobalt(II) (6) were synthesized and
characterized as described below. A solution of cobalt acetate
(1 equiv.) in water (2 mL) was added to a solution of (1R,2R)-N,NЈ-
bis[5-tert-butyl-3-(morpholinomethyl)salicylidene]cyclohexane-1,2-
diamine/(1R,2R)-N,NЈ-bis[5-tert-butyl-3-(piperidinomethyl)salicyli-
dene]cyclohexane-1,2-diamine[15c] (1 equiv.) in ethanol (10 mL) at
reflux under an inert gas. A brick-red precipitate appeared immedi-
ately; however, the mixture was heated at reflux for an additional
2 h. The desired CoII complex was filtered off, washed with abso-
lute ethanol, and dried in vacuo.
and the unreacted enantio-enriched epoxide 7aЈ–iЈ were recovered
by flash chromatography. The remaining ionic liquid layer was
dried under vacuum and stored in a desiccator for use in subse-
quent catalytic runs. The enantiomeric excesses (ees) of the prod-
ucts 9a–i, 10a–e, and 11a–e were determined by HPLC analysis
using Daicel Chiralpak AD-H columns with iPrOH/hexane (90:10)
as eluent (see the Supporting Information). HPLC traces of the
products were compared with the corresponding racemic samples
prepared with racemic (salen)CoIII complexes as the catalyst.
tert-Butyl [(R)-2-Hydroxy-3-phenoxypropyl]carbamate (9a):[9b]
White solid; m.p. 82–85 °C. [α]2D7 = +10.4 (c = 2, CHCl3) for Ͼ99%
Characterization Data for Complex 5: M.p. Ͼ360 °C. Yield: 0.59 g
(85%). [α]2D7 = +15.65 (c = 0.260, CHCl ). IR (KBr): ν = 2951,
1
3
ee. MS (ESI): m/z = 268 [M + H]+. H NMR (500 MHz, CDCl3):
˜
2864, 1636, 1596, 1538, 1454, 1393, 1254, 1201, 1121, 1041, 936,
870, 752, 652 cm–1. UV/Vis: λmax (ε, –1 cm–1) = 268 (8458), 396
(8305), 447 (5430), 531 (789) nm. C38H54CoN4O4 (689.35): calcd.
C 66.17, H 7.89, N 8.12; found C 66.09, H 7.81, N 8.0 9.
δ = 1.42 (s, 9 H), 3.19 (br. s, 1 H, OH), 3.25–3.33 (m, 1 H), 3.45–
3.54 (m, 1 H), 3.91–4.03 (m, 2 H), 4.06–4.17 (m, 1 H), 4.97 (br. s,
1 H, NH), 6.92–7.01 (m, 3 H), 7.25–7.31 (m, 2 H) ppm. HPLC
[Daicel Chiralpack AD-H, hexane/2-propanol (90:10), flow rate =
0.75 mLmin–1; tR = 12.1 min (R, major) and 15.9 min (S, minor)].
Characterization Data for Complex 6: M.p. Ͼ360 °C. Yield: 0.56 g
(83%). [α]2D7 = +223 (c = 0.009, CHCl ). IR (KBr): ν = 2950, 2863,
Ethyl [(R)-2-Hydroxy-3-phenoxypropyl]carbamate (10a):[9b] Color-
less oil. [α]2D7 = +8.6 (c = 1.04, CHCl3) for Ͼ99% ee. MS (ESI):
˜
3
1637, 1554, 1453, 1394, 1269, 1040, 953, 869, 734, 553 cm–1. UV/
Vis: λmax (ε, –1 cm–1) = 268 (9227), 413 (8366), 488 (3121), 537
(1479) nm. C40H58CoN4O2 (685.39): calcd. C 70.05, H 8.52, N 8.17;
found C 69.97, H 8.46, N 8.13.
1
m/z = 238 [M + H]+. H NMR (500 MHz, CDCl3): δ = 1.27 (t, J
= 7.2 Hz, 3 H), 3.15 (br. s, 1 H), 3.33–3.41 (m, 1 H), 3.47–3.57 (m,
1 H), 3.94 (dd, J = 6.4, 9.6 Hz, 1 H), 3.97 (dd, J = 4.8, 9.6 Hz, 1
H), 4.06–4.16 (m, 1 H), 4.12 (q, J = 7.2 Hz, 2 H), 5.15 (br. s, 1
H), 6.87–7.01 (m, 3 H), 7.28–7.33 (m, 2 H) ppm. HPLC [Daicel
Typical Procedure for the AKR of Racemic Terminal Epoxides: In
a small vial equipped with a magnetic stirring bar, the (salen)CoII
complexes 1–6 (0.02 mmol) were dissolved in TBME as the solvent
and treated with acetic acid/PNBA (0.02 mmol). The resulting
dark-brown solution was stirred exposed to air at room temp. for
1 h. The solvent was completely removed, and an appropriate ionic
liquid (300 mg) was added to the resulting solid followed by the
appropriate carbamate 8a–c (0.1 mmol). The resulting mixture was
stirred for 5 min, and then the desired epoxide 7a–i (0.2 mmol) was
added. The reaction mixture was stirred until the HPLC analysis
showed disappearance of the peak of the (R) enantiomer of the
epoxide (for HPLC profiles of the products please see the Support-
ing Information). At the end of the reaction, the crude mixture
was repeatedly extracted with n-hexane/diethyl ether (75:25). The
product, N-protected 1,2-amino alcohols 9a–i, 10a–e, and 11a–e,
Chiralpack AD-H, hexane/2-propanol (90:10), flow rate
=
0.75 mLmin–1; tR = 12.7 min (R, major) and 15.5 min (S, minor)].
Benzyl [(R)-2-Hydroxy-3-phenoxypropyl]carbamate (11a):[9b] White
solid; m.p. 79–82 °C. [α]2D7 = +6.8 (c = 1.04, CHCl3) for Ͼ99% ee.
MS (ESI): m/z = 302 [M + H]+. 1H NMR (500 MHz, CDCl3): δ =
2.94 (d, J = 4.0 Hz, 1 H), 3.33–3.41 (m, 1 H), 3.51–3.57 (m, 1 H),
3.91–4.00 (m, 2 H), 4.05–4.14 (m, 1 H), 5.14 (s, 2 H), 5.22 (br. s, 1
H), 6.82–7.00 (m, 3 H), 7.26–7.44 (m, 7 H) ppm. HPLC [Daicel
Chiralpack AD-H, hexane/2-propanol (90:10), flow rate
=
0.75 mLmin–1; tR = 23.6 min (R, major) and 28.6 min (S, minor)].
tert-Butyl [(R)-2-Hydroxy-3-(o-tolyloxy)propyl]carbamate (9b):
White solid; m.p. 98–102 °C. [α]2D7 = +17.0 (c = 2, CHCl3) for
Eur. J. Org. Chem. 2009, 2863–2871
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2869

R. I. Kureshy et al.
FULL PAPER
Ͼ99% ee. MS (ESI): m/z = 282 [M + H]+. 1H NMR (500 MHz,
for Ͼ99% ee. MS (ESI): m/z = 302 [M + H]+. 1H NMR (500 MHz,
CDCl3): δ = 1.45 (s, 9 H), 2.27 (s, 3 H), 2.12 (br. s, 1 H), 3.78 (br. CDCl3): δ = 1.27 (s, 9 H), 3.70 (br. s, 1 H), 3.77 (br. s, 1 H), 3.85–
s, 1 H), 3.85 (br. s, 1 H), 4.03–4.04 (m, 2 H), 4.13 (m, 1 H), 6.81– 3.96 (m, 2 H), 4.07–4.08 (m, 2 H), 5.07 (br. s, 1 H), 6.81–6.83 (d,
6.82 (d, J = 8 Hz, 1 H), 6.87–6.89 (t, J = 7 Hz, 1 H), 7.13–7.14 (m,
2 H) ppm. C15H23NO4 (281.16): calcd. C 64.03, H 8.24, N 4.98;
found C 64.06, H 8.20, N 4.96. HPLC [Daicel Chiralpack AD-H,
hexane/2-propanol (90:10), flow rate
34.52 min (R, major) and 41.62 min (S, minor)].
J = 6 Hz, 2 H), 7.26–7.27 (d, J = 6 Hz, 2 H) ppm. C14H20ClNO4
(301.11): calcd. C 55.72, H 6.68, N 4.64; found C 55.70, H 6.69, N
4.60. HPLC [Daicel Chiralpack AD-H, hexane/2-propanol (90:10),
flow rate = 0.75 mLmin–1; tR = 24.09 min (R, major) and
33.41 min (S, minor)].
= =
0.75 mLmin–1; tR
Ethyl [(R)-2-Hydroxy-3-(o-tolyloxy)propyl]carbamate (10b): Oil.
[α]2D7 = +19.24 (c = 0.15, CHCl3) for Ͼ99% ee. MS (ESI): m/z =
Ethyl [(R)-3-(4-Chlorophenoxy)-2-hydroxypropyl]carbamate (10d):
Oil. [α]2D7 = +11.9 (c = 0.24, CHCl3) for Ͼ99% ee. MS (ESI): m/z
1
240 [M + H]+. H NMR (500 MHz, CDCl3): δ = 1.24–1.27 (t, J =
1
= 274 [M + H]+. H NMR (500 MHz, CDCl3): δ = 1.24–1.27 (t, J
7 Hz, 3 H), 1.64 (s, 1 H), 2.24 (s, 3 H), 2.70 (br. s, 1 H), 3.80 (br.
s, 1 H), 3.87–4.07 (t, J = 5 Hz, 1 H), 4.10–4.14 (q, J = 7 Hz, 2 H),
4.61–4.63 (m, 2 H), 6.82–6.84 (d, J = 8 Hz, 1 H), 6.88–6.91 (t, J =
7.5 Hz, 1 H), 7.14–7.26 (m, 2 H) ppm. C13H19NO4 (253.13): calcd.
C 61.64, H 7.56, N 5.53; found C 61.20, H 7.53, N 5.42. HPLC
[Daicel Chiralpack AD-H, hexane/2-propanol (90:10), flow rate =
0.75 mLmin–1; tR = 35.31 min (R, major) and 42.61 min (S,
minor)].
= 7 Hz, 3 H), 1.80 (br. s, 1 H), 3.77–3.99 (m, 3 H), 4.09, (br. s, 1
H), 4.09–4.14 (q, J = 7 Hz, 2 H), 4.68–4.69 (m, 2 H), 6.82–6.88 (m,
4 H) ppm. C12H16ClNO4 (273.08): calcd. C 52.66, H 5.89, N 5.12;
found C 52.68, H 5.90, N 5.14. HPLC [Daicel Chiralpack AD-H,
hexane/2-propanol (90:10), flow rate
21.86 min (R, major) and 30.32 min (S, minor)].
= =
0.75 mLmin–1; tR
Benzyl [(R)-3-(4-Chlorophenoxy)-2-hydroxypropyl]carbamate (11d):
White solid; m.p. 86–90 °C. [α]2D7 = +17.1 (c = 0.2, CHCl3) for
Ͼ99% ee. MS (ESI): m/z = 336 [M + H]+. 1H NMR (500 MHz,
CDCl3): δ = 7.37 (d, J = 4 Hz, 2 H), 7.34–7.30 (m, 5 H), 6.80–6.84
(d, J = 8.5 Hz, 2 H), 5.10 (s, 2 H), 4.70 (s, 1 H), 4.13–4.17 (m, 1
H), 4.06–4.03 (m, 2 H), 3.85–3.82 (m, 1 H), 3.76–3.73 (m, 1 H),
3.49 (s, 1 H) ppm. C17H18ClNO4 (335.09): calcd. C 60.81, H 5.40,
N 4.17; found C 60.79, H 5.41, N 4.19. HPLC [Daicel Chiralpack
Benzyl [(R)-2-Hydroxy-3-(o-tolyloxy)propyl]carbamate (11b): White
solid; m.p. 98–105 °C. [α]2D7 = +12.8 (c = 0.25, CHCl3) for Ͼ99%
1
ee. MS (ESI): m/z = 361 [M + H]+. H NMR (500 MHz, CDCl3):
δ = 2.23 (s, 3 H), 2.58 (s, 1 H), 2.94 (br. s, 1 H), 3.75–3.79 (dd, J
= 6.5, 5 Hz, 1 H), 3.84–3.86 (d, J = 10.5 Hz, 1 H), 4.04 (s, 1 H),
4.86 (br. s, 2 H), 5.09 (s, 2 H), 6.81–6.83 (d, J = 8 Hz, 1 H), 6.88
(br. s, 1 H), 7.13–7.15 (m, 2 H), 7.35 (br. s, 5 H) ppm. C18H21NO4
(315.15): calcd. C 68.55, H 6.71, N 4.44; found C 68.51, H 6.69, N
4.47. HPLC [Daicel Chiralpack AD-H, hexane/2-propanol (90:10),
flow rate = 0.75 mLmin–1; tR = 36.65 min (R, major) and
44.20 min (S, minor)].
AD-H, hexane/2-propanol (90:10), flow rate = 0.75 mLmin–1; tR
23.46 min (R, major) and 32.55 min (S, minor)].
=
tert-Butyl [(R)-3-(4-tert-Butylphenoxy)-2-hydroxypropyl]carbamate
(9e): White solid; m.p. 115–120 °C. [α]2D7 = +588.17 (c = 0.012,
1
CHCl3) for Ͼ99% ee. MS (ESI): m/z = 323 [M + H]+. H NMR
tert-Butyl [(R)-3-(Benzyloxy)-2-hydroxypropyl]carbamate (9c):
White solid; m.p. 102–105 °C. [α]2D7 = +116.6 (c = 0.02, CHCl3) for
Ͼ99% ee. MS (ESI): m/z = 282 [M + H]+. 1H NMR (500 MHz,
CDCl3): δ = 1.45 (s, 9 H), 2.64 (br. s, 1 H), 2.98 (br. s, 1 H), 3.54–
3.57 (br. s, 2 H), 3.56 (br. s, 1 H), 3.64 (br. s, 1 H), 3.90 (br. s, 1
H), 4.55, (s, 2 H), 7.27–7.35 (br. s, 5 H) ppm. C15H23NO4 (281.16):
calcd. C 64.03, H 8.24, N 4.98; found C 64.01, H 8.20, N 4.95.
HPLC [Daicel Chiralpack AD-H, hexane/2-propanol (90:10), flow
rate = 0.75 mLmin–1; tR = 44.43 min (R, major) and 46.24 min (S,
minor)].
(500 MHz, CDCl3): δ = 1.30 (s, 9 H), 1.45 (s, 9 H), 2.80 (br. s, 1
H), 3.75–3.84 (br. s, 2 H), 3.84 (br. s, 1 H), 4.03–4.09 (m, 1 H),
4.49–4.57 (br. s, 2 H), 6.83–6.86 (dd, J = 4, 4.5 Hz, 2 H), 7.30–7.31
(t, J = 7.5 Hz, 2 H) ppm. C18H29NO4 (323.21): calcd. C 66.84, H
9.04, N 4.33; found C 66.82, H 9.01, N 4.35. HPLC [Daicel Chi-
ralpack AD-H, hexane/2-propanol (90:10), flow rate
=
0.75 mLmin–1; tR = 26.31 min (R, major) and 36.88 min (S,
minor)].
Ethyl
[(R)-3-(4-tert-Butylphenoxy)-2-hydroxypropyl]carbamate
(10e): Oil. [α]2D7 = +24.96 (c = 0.16, CHCl3) for Ͼ99% ee. MS (ESI):
Ethyl [(R)-3-(Benzyloxy)-2-hydroxypropyl]carbamate (10c): Yellow
oil. [α]2D7 = +129.0 (c = 0.031, CHCl3) for Ͼ99% ee. MS (ESI): m/z
m/z = 295 [M + H]+. H NMR (500 MHz, CDCl3): δ = 7.34 (d, J
1
= 10 Hz, 2 H), 6.89 (d, J = 5.5 Hz, 2 H), 5.11 (s, 1 H), 4.60 (d, J
= 12.5 Hz, 2 H), 4.44–4.33 (m, 3 H), 4.1–4.0 (m. 2 H), 3.41 (s, 1
H), 1.30 (br., 3 H), 1.60 (s, 9 H) ppm. C16H25NO4 (295.18): calcd.
C 65.06, H 8.53, N 4.74; found C 65.02, H 8.50, N 4.77. HPLC
[Daicel Chiralpack AD-H, hexane/2-propanol (90:10), flow rate =
0.75 mLmin–1; tR = 26.29 min (R, major) and 36.84 min (S,
minor)].
1
= 282 [M + H]+. H NMR (500 MHz, CDCl3): δ = 1.23–1.26 (t, J
= 7 Hz, 3 H), 2.95 (br. s, 1 H), 3.31 (br. s, 1 H), 3.51–3.55 (dd, J =
9.5, 7 Hz, 2 H), 3.60–3.62 (m, 1 H), 3.67 (br. s, 1 H), 3.90 (br. s, 1
H), 4.08–4.12 (q, J = 7 Hz, 2 H), 4.45 (s, 2 H), 7.29–7.35 (br. m, 5
H) ppm. C13H19NO4 (253.13): calcd. C 61.64, H 7.56, N 5.53;
found C 61.61, H 7.58, N 5.50. HPLC [Daicel Chiralpack AD-H,
hexane/2-propanol (90:10), flow rate
43.68 min (R, major) and 45.41 min (S, minor)].
= =
0.75 mLmin–1; tR
Benzyl
[(R)-3-(4-tert-Butylphenoxy)-2-hydroxypropyl]carbamate
(11e): White solid; m.p. 110–115 °C. [α]2D7 = +245.91 (c = 0.02,
Benzyl [(R)-3-(Benzyloxy)-2-hydroxypropyl]carbamate (11c): White
solid; m.p. 108–110 °C. [α]2D7 = +125.2 (c = 0.023, CHCl3) for
Ͼ99% ee. MS (ESI): m/z = 282 [M + H]+. 1H NMR (500 MHz,
CDCl3): δ = 1.85 (br. s, 1 H), 2.89 (br. s, 1 H), 3.52–3.57 (m, 2 H),
3.63 (br. s, 1 H), 3.90 (br. s, 1 H), 4.85 (br. s, 2 H), 5.10 (s, 2 H),
7.26–7.36 (m, 10 H) ppm. C18H21NO4 (315.15): calcd. C 68.55, H
6.71, N 4.44; found C 68.52, H 6.69, N 4.42. HPLC [Daicel Chi-
CHCl3) for Ͼ99% ee. MS (ESI): m/z = 357 [M + H]+. H NMR
1
(500 MHz, CDCl3): δ = 1.19 (s, 9 H), 3.02 (br. s, 1 H), 3.21 (br. s,
1 H), 3.42–3.45 (m, 2 H), 3.62–3.63 (d, J = 5 Hz, 1 H), 3.68–3.69
(d, J = 3.5 Hz, 1 H), 3.78–3.80 (t, J = 4.5 Hz, 1 H), 5.08 (s, 2 H),
7.6–7.35 (m, 9 H) ppm. C21H27NO4 (257.19): calcd. C 70.56, H
7.61, N 3.92; found C 70.57, H 7.63, N 3.90. HPLC [Daicel
Chiralpack AD-H, hexane/2-propanol (90:10), flow rate
=
ralpack AD-H, hexane/2-propanol (90:10), flow rate
=
0.75 mLmin–1; tR = 26.70 min (R, major) and 37.94 min (S,
0.75 mLmin–1; tR = 45.35 min (R, major) and 47.22 min (S,
minor)].
minor)].
tert-Butyl
[(R)-3-(4-Chlorophenoxy)-2-hydroxypropyl]carbamate
tert-Butyl [(R)-3-Chloro-2-hydroxypropyl]carbamate (9f):[9b] Color-
less oil. MS (ESI): m/z = 210 [M + H]+. 1H NMR (CDCl3): δ =
(9d): White solid; m.p. 92–95 °C. [α]2D7 = +25.0 (c = 0.16, CHCl3)
2870
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 2863–2871

Aminolytic Kinetic Resolution of Aryloxy/Terminal Epoxides
[4]
a) K. Arai, M. M. Salter, Y. Yamashita, S. Kobayashi, Angew.
Chem. Int. Ed. 2007, 46, 955–957; b) K. Arai, S. Lucarini,
M. M. Salter, K. Ohta, Y. Yamashita, S. Kobayashi, J. Am.
Chem. Soc. 2007, 129, 8103–8111.
1.45 (s, 9 H), 3.25 (br. s, 1 H, OH), 3.43–3.59 (m, 2 H), 3.58–3.76
(m, 2 H), 4.26 (m, 1 H), 4.95 (br. s, 1 H, NH) ppm. HPLC [Daicel
Chiralpack AD-H, hexane/2-propanol (85:15), flow rate
=
0.75 mLmin–1; tS = 36.88 min (S, minor) and 58.91 min (R,
[5]
[6]
K. Tanaka, S. Oda, M. Shiro, Chem. Commun. 2008, 820–822.
a) A. Sekine, T. Ohshima, M. Shibasaki, Tetrahedron 2002, 58,
75–82; b) X. L. Hou, J. Wu, L. X. Dai, L. J. Xia, M. H. Tang,
Tetrahedron: Asymmetry 1998, 9, 1747–1752; c) X. L. Fu, S. H.
Wu, Synth. Commun. 1997, 27, 1677–1683; d) F. Carrée, R.
Gil, J. Collin, Tetrahedron Lett. 2004, 45, 7749–7751; e) F.
Carrée, R. Gil, J. Collin, Org. Lett. 2005, 7, 1023–1026; f) R. I.
Kureshy, S. Singh, N. H. Khan, S. H. R. Abdi, E. Suresh, R. V.
Jasra, Eur. J. Org. Chem. 2006, 1303–1309; g) R. I. Kureshy,
S. Singh, N. H. Khan, S. H. R. Abdi, S. Agrawal, R. V. Jasra,
Tetrahedron: Asymmetry 2006, 17, 1638–1643; h) R. I. Kureshy,
K. J. Prathap, S. Agrawal, N. H. Khan, S. H. R. Abdi, R. V.
Jasra, Eur. J. Org. Chem. 2008, 3118–3128.
a) C. Schneider, A. R. Sreekanth, E. Mai, Angew. Chem. Int.
Ed. 2004, 43, 5691–5694; b) E. Mai, C. Schneider, Chem. Eur.
J. 2007, 13, 2729–2741; c) S. Azoulay, K. Manabe, S. Kobaya-
shi, Org. Lett. 2005, 7, 4593–4595; d) E. Mai, C. Schneider,
Synlett 2007, 2136–2138; e) C. Ogawa, S. Azoulay, S. Kobaya-
shi, Heterocycles 2005, 55, 201–206; f) C. Schneider, Synthesis
2006, 3919; g) I. M. Paster, M. Yus, Curr. Org. Chem. 2005, 9,
1–29.
a) J. M. Keith, J. F. Larrow, E. N. Jacobsen, Adv. Synth. Catal.
2001, 343, 5–26; b) H. Label, E. N. Jacobsen, Tetrahedron Lett.
1999, 40, 7303–7306; c) M. Bandini, P. Cozzi, G. P. Melchiorre,
A. Umani-Ronchi, Angew. Chem. Int. Ed. 2004, 43, 84–87.
a) G. Bartoli, M. Bosco, A. Carlone, M. Locatelli, M. Massac-
cesi, P. Melchiorre, L. Sambri, Org. Lett. 2004, 6, 2173–2176;
b) G. Bartoli, M. Bosco, A. Carlone, M. Locatelli, P. Mel-
chiorre, L. Sambri, Org. Lett. 2004, 6, 3973–3975.
a) M. Tokunaga, J. F. Larrow, F. Kakiuchi, E. N. Jacobsen, Sci-
ence 1997, 277, 936–938; b) S. E. Schaus, B. D. Brandes, J. F.
Larrow, M. Tokunaga, K. B. Hansen, A. E. Gould, E. Furrow,
E. N. Jacobsen, J. Am. Chem. Soc. 2002, 124, 1307–1315; c)
L. P. C. Nielson, C. P. Stevenson, D. G. Blackmond, E. N. Ja-
cobsen, J. Am. Chem. Soc. 2004, 126, 1360–1362.
major)].
tert-Butyl [(R)-2-Hydroxyhexyl]carbamate (9g):[9b] Colorless oil.
1
MS (ESI): m/z = 218 [M + H]–. H NMR (CDCl3): δ = 0.87 (t, J
= 7.2 Hz, 3 H), 1.26–1.41 (m, 4 H), 1.43–1.52 (m, 2 H), 1.44 (s, 9
H), 2.63 (br. s, 1 H, OH), 2.95–3.04 (m, 1 H), 3.25–3.35 (m, 1 H),
3.63–3.73 (m, 1 H), 5.03 (br. s, 1 H, NH) ppm. HPLC [Daicel
Chiralpack AS-H, hexane/2-propanol (98:2), flow rate
=
0.75 mLmin–1; tS = 7.1 min (S, minor) and 9.2 min (R, major)].
tert-Butyl [(R)-2-Hydroxy-2-phenylethyl]carbamate (9h):[9b] White
1
solid; m.p. 120–123 °C. MS (ESI): m/z = 238 [M + H]+. H NMR
(CDCl3): δ = 1.43 (s, 9 H), 2.98 (br. s, 1 H, OH), 3.21–3.30 (m, 1
H), 3.42–3.52 (m, 1 H), 4.77–4.85 (m, 1 H), 4.90 (br. s, 1 H, NH),
7.26–7.41 (m, 5 H) ppm. HPLC [Daicel Chiralpack AS-H, hexane/
2-propanol (98:2), flow rate = 0.75 mLmin–1; tR = 35.5 min (R,
major) and 37.3 min (S, minor)].
[7]
tert-Butyl [(R)-2-Hydroxy-3-(naphthalen-1-yloxy)propyl]carbamate
(9i):[9b] White solid; m.p. 102–107 °C. MS (ESI): m/z = 318 [M +
1
H]+. H NMR (CDCl3): δ = 1.46 (s, 9 H), 3.35 (br. s, 1 H, OH),
[8]
3.36–3.47 (m, 1 H), 3.55–3.65 (m, 1 H), 4.17 (d, J = 5.6 Hz, 2 H),
4.23–4.31 (m, 1 H), 5.04 (br. s, 1 H, NH), 6.81–6.86 (m, 1 H), 7.37–
7.54 (m, 4 H), 7.79–7.84 (m, 1 H), 8.18–8.23 (m, 1 H) ppm. HPLC
[Daicel Chiralpack AD-H, hexane/2-propanol (95:5), flow rate =
0.75 mLmin–1; tR = 28.4 min (R, major) and 30.6 min (S, minor)].
[9]
Recycling of the Catalyst 1: At the end of the catalytic run (checked
by TLC) the products were isolated by stirring the reaction mixture
in n-hexane/diethyl ether (75:25) for 10 min. The upper phase was
then decanted to separate it from the ionic liquid. The N-protected
amino alcohol 9a and the chirally enriched epoxide 7aЈ were reco-
vered from the organic layer by column chromatography. The ionic
liquid phase containing catalyst 1 was dried in vacuo and used
without any further processing in the subsequent AKR of 1,2-ep-
oxy-3-phenoxypropane (7a) as a representative substrate with tert-
butyl carbamate (BocNH2, 8a) as the nucleophile.
[10]
[11] a) R. I. Kureshy, S. Singh, N. H. Khan, S. H. R. Abdi, S. Agra-
wal, V. J. Mayani, R. V. Jasra, Tetrahedron Lett. 2006, 47, 5277–
5279; b) R. I. Kureshy, K. J. Prathap, S. Singh, S. Agrawal,
N. H. Khan, S. H. R. Abdi, R. V. Jasra, Chirality 2007, 19,
809–815.
[12] a) Y. R. Jorapur, D. Y. Chi, Bull. Korean Chem. Soc. 2006, 27,
345–354; b) B. J. Baudoux, J. Levillain, D. Cahard, A. C. Gau-
mont, J. C. Plaquevent, Tetrahedron: Asymmetry 2003, 14,
3081–3093.
[13] a) C. E. Song, M. Y. Yoon, D. S. Choi, Bull. Korean Chem. Soc.
2005, 26, 1321–1330; b) C. E. Song, Ann. Rep. Prog. Chem.
2005, 101, 143–173; c) C. E. Song in ACS Symposium Series
880: Methodologies in Asymmetric Catalysis (Ed.: S. V. Malho-
tra), American Chemical Society, Washington, DC, 2004, pp.
145–160; d) C. E. Song, Chem. Commun. 2004, 1033–1043.
[14] a) C. E. Song, C. R. Oh, E. J. Roh, D. J. Choo, Chem. Commun.
2000, 1743–1744; b) C. R. Oh, D. J. Choo, W. H. Shim, D. H.
Lee, E. J. Roh, S. Lee, C. E. Song, Chem. Commun. 2003, 1100–
1101.
Supporting Information (see footnote on the first page of this arti-
cle): Experiential procedures, full characterization and HPLC
analysis of the products.
Acknowledgments
R. I. K. is thankful to the Department of Science and Technology
(DST) and the Council of Scientific & Industrial Research (CSIR)
Network Project on Catalysis for financial assistance. K. J. P. and
S. A. are thankful to the CSIR for a senior research fellowship.
[1] a) D. J. Ager, I. Prakash, D. R. Schaad, Chem. Rev. 1996, 96,
835–875; b) S. C. Bergmeier, Tetrahedron 2000, 56, 2561–2576;
c) M. Yamashita, K. Yamada, K. Tomioka, Org. Lett. 2005, 7, [15] a) J. F. Larrow, E. N. Jacobsen, Y. Gao, Y. Hong, X. Nie, C. M.
2369–2371; d) H. C. Kolb, K. B. Sharpless in Transition metals
for organic Synthesis (Eds.: M. Beller, C. Bolm), Wiley-VCH,
Weinheim, 1998, p. 24.
Zep, J. Org. Chem. 1994, 59, 1939–1942; b) W. Zhang, J. I. Loe-
bach, S. R. Wilson, E. N. Jacobsen, J. Am. Chem. Soc. 1990,
112, 2801–2803; c) E. F. DiMauro, M. C. Kozlowski, Tetrahe-
dron 2005, 61, 6249–6265.
[2] a) G. Li, H. T. Chang, K. B. Sharpless, Angew. Chem. Int. Ed.
Engl. 1996, 35, 451–454; b) P. O. Brien, Angew. Chem. Int. Ed.
1999, 38, 326–329.
[16] G. Bartoli, M. Bosco, A. Carlone, M. Locatelli, P. Melchiorre,
L. Sambri, Org. Lett. 2005, 7, 1983–1985.
[3] a) B. List, J. Am. Chem. Soc. 2000, 122, 9336–9337; b) A.
Córdova, W. Notz, G. Zhong, J. M. Betancort, C. F. Barbas, J.
Am. Chem. Soc. 2002, 124, 1842–1843; c) B. M. Trost, L. R.
Terrell, J. Am. Chem. Soc. 2003, 125, 338–339.
[17] T. P. Loh, L. C. Feng, H. Y. Yang, J. Y. Yang, Tetrahedron Lett.
2002, 43, 8741–8743.
Received: January 13, 2009
Published Online: April 21, 2009
Eur. J. Org. Chem. 2009, 2863–2871
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2871