Highly enantioselective l-thiaproline catalyzed α-aminoxylation of aldehydes in aqueous media

Article abstract of DOI:10.1039/b817950f

Highly enantioselective L-thiaproline catalyzed α-aminoxylation of aldehydes in the presence of water and tetrabutylammonium bromide followed by in situ reduction to afford the respective α-aminoxy alcohols has been developed in good to high yields (74-88%) and excellent enantioselectivities (93->99%).

Full text of DOI:10.1039/b817950f

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www.rsc.org/greenchem | Green Chemistry
Highly enantioselective L-thiaproline catalyzed a-aminoxylation
of aldehydes in aqueous media†
Pei Juan Chua, Bin Tan and Guofu Zhong*
Received 15th October 2008, Accepted 28th January 2009
First published as an Advance Article on the web 13th February 2009
DOI: 10.1039/b817950f
Highly enantioselective L-thiaproline catalyzed a-aminoxylation of aldehydes in the presence of
water and tetrabutylammonium bromide followed by in situ reduction to afford the respective
a-aminoxy alcohols has been developed in good to high yields (74–88%) and excellent
enantioselectivities (93–>99%).
dimethylformamide15 and dimethylsulfoxide.5,16 The use of such
solvents contributes to the organic waste and it is essential to
develop more environmentally friendly protocols.
Introduction
The presence of optically active a-hydroxycarbonyl moieties
such as 1,2-diols in many biologically active natural products
motivated research into finding new routes to provide better
stereocontrol for these synthetically useful synthons.1 Asymmet-
ric a-hydroxylation of enolates2 and the Sharpless asymmetric
dihydroxylation of olefins3 are some methods to synthesize these
compounds. The year 2000 saw a renaissance of organocatalysis,
and since then organocatalysis has emerged as a extremely useful
tool for the preparation of enantiomerically pure compounds.4
Operational simplicity, availability and the non-toxicity of the
organic catalysts compared to the corresponding transition-
metal species, as well as the high efficiencies and selectivities
attained in many organocatalytic transformations made this
methodology very attractive for the formation of enantiomeri-
cally pure compounds.
In 2003 Zhong,5 MacMillan6 and Hayashi7 and co-
workers independently reported the direct proline-catalyzed
a-aminoxylation of aldehydes with nitrosobenzene and the
usefulness of this reaction was demonstrated in the synthesis
of several biologically active compounds.8 Though the scope of
the above-mentioned reaction has been quickly extended to that
of ketones9 after the first report, there was little development
in new organocatalysts10 or environmentally friendly reaction
protocols.11
Water, no doubt, is the most inexpensive and environmentally
benign solvent. Since Breslow reported that the use of water
instead of organic solvents could significantly increase the
rate of the Diels–Alder reaction17 considerable attention has
been directed towards the development of organic reactions in
water. To date, all of the most useful organic reactions have
at least a reaction protocol that involves water as a solvent.18
Although Blackmond raised some doubts about the environ-
mental friendliness and efficiency of water in organocatalysis,19
we cannot dismiss some of the advantages that accompanies the
use of water as a solvent: acceleration of reaction rates and
enhancement of reaction selectivities; elimination of tedious
protection–deprotection processes for certain acidic-hydrogen
containing functional groups and the recycling of water-soluble
catalysts after separation from water-insoluble organic products.
Results and discussion
To probe the feasibility of the a-aminoxylation of aldehydes
in aqueous media using a phase-transfer catalyst, we first
performed a-aminoxylation of propanal to nitrosobenzene in
the presence of L-proline I, tetrabutylammonium bromide and
water at 0 ◦C and then warmed to room temperature. To our
disappointment the yield obtained in this initial reaction was
rather low, despite the high enantioselectivity achieved. This
prompted us to screen more catalysts II–VI (Table 1, entries
2–6). Among all the catalysts investigated, only L-thiaproline
VI gave a higher yield than I. Although VI needed a longer
reaction time and gave a slightly lower enantioselectivity than
I, we believed that higher enantioselectivity could be achieved
with the optimization of reaction conditions. This is the first
instance where L-thiaproline VI was used as a catalyst in
an a-aminoxylation. The use of VI will potentially reduce
much hassle for stereoselective reactions as it is commercially
available.
Conventional chemical synthesis usually focused on improv-
ing yield and selectivity, with little regard to a chemical’s
impact on the environment. Recently, increasing demand for
innovative and imaginative synthetic methodologies to improve
efficiency and sustainability such as simplicity, atom economy,
reduced chemical wastage and energy usage, safety, and envi-
ronmental friendliness prompted much research in this area.12
To date, a-aminoxylation is usually carried out in organic
solvents such as acetonitrile,7,13 chloroform,6 dichloromethane,14
Division of Chemistry & Biological Chemistry, School of Physical &
Mathematical Sciences, Nanyang Technological University, 21 Nanyang
Link, Singapore, 637371, Singapore. E-mail: guofu@ntu.edu.sg;
Fax: +65 6791 1961; Tel: +65 6316 8761
† Electronic supplementary information (ESI) available: General infor-
mation, general experimental procedure, and experimental data and
spectra for compounds 3a–k. See DOI: 10.1039/b817950f
For optimisation of the reaction conditions, we first inves-
tigated the effect of catalyst loading on the reaction (Table 2,
entries 1–3). Highest yield and enantioselectivity were obtained
when 20 mol% of catalyst was used. The results of the reaction
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Table 1 Catalyst screeninga
comparable enantioselectivity, its lower yield and longer reaction
time made water the preferred choice of solvent for this reaction
(Table 2, entry 7). We discovered that 0.10 mL of water is the
optimum amount of water added to the system to attain the
highest yield and enantioselectivity (Table 2, entries 8–10). Both
the yield and enantioselectivity dropped when the amount of
phase transfer catalyst was reduced (Table 2, entries 11–12).
A similar trend was also observed with decreasing amounts of
propanal (Table 2, entries 13–14).
With the optimal reaction conditions established, we probed
the scope of the reaction for a variety of aldehydes. The
results are summarized in Table 3. In the cases investigated,
the a-aminoxy alcohols were obtained in good to high yields
(74–88%) and excellent enantioselectivities (93–99%). The L-
thiaproline a-aminoxylation reaction between nitrosobenzene
and propanal was completed in 2 h with good yield (84%)
and excellent enantioselectivity (96%) (Table 3, entry 1). Not
only propanal, but linear chain aldehydes such as n-butanal,
n-pentanal and n-hexanal react with nitrosobenzene, affording
a-aminoxy alcohols in good yield with excellent enantiose-
lectivities (Table 3, entries 2–4). Branched aldehydes such as
3-methylbutanal are also suitable substrates as it was suc-
cessfully converted to the a-aminoxy alcohols in good yield
with excellent enantioselectivity (Table 3, entry 5). Aldehydes
containing an aromatic moiety such as phenylacetaldehyde and
3-phenylpropanal were successfully employed in this reaction
(Table 3, entries 6 and 7). It is interesting to note that the reaction
time for phenylacetylaldehyde was significantly reduced. This
may be due to the activating effect of the benzene ring in the
a-position of the phenylacetylaldehyde. The introduction of a
terminal double bond on the aldehyde did not drastically affect
the yield and enantioselevitvity of the reaction (Table 3, entry 8).
The reaction also proceeded smoothly with protecting groups
such as benzyl ethers and tert-butoxycarbonyl carbamates to
Entry
Catalyst
Time
Yieldb (%)
eec (%)
1
2
3
4
5
6
I
II
1 h
6 h
20 min
30 min
30 min
1 h 40 min
64
39
62
14
65
75
96
43
96
23
82
93
III
IV
V
VI
a Conditions: Nitrosobenzene (0.3 mmol), propanal (3 equiv.), catalyst
(30 mol%), tetrabutylammonium bromide (2 equiv.) and water (0.10 mL)
was added at 0 ◦C and then warmed to rt (23 ◦C) unless otherwise stated.
b Isolated yields. c Determined by chiral phase HPLC.
did not improve under neat conditions (Table 2, entry 4). Screen-
ings of various organic solvents revealed that chloroform and
dimethyl sulfoxide, preferred solvents for many a-aminoxylation
reactions, were not the best solvents when VI was employed
as catalyst (Table 2, entries 5–6). Although acetonitrile gave
Table 2 Optimisation of reaction conditionsa
Entry
Solvent
Vol. of solvent
Time
Yieldb (%)
eec (%)
1d
2
H2O
H2O
H2O
—
CHCl3
DMSO
CH3CN
H2O
H2O
H2O
H2O
H2O
H2O
H2O
0.10 mL
0.10 mL
0.10 mL
0.10 mL
0.10 mL
0.10 mL
0.10 mL
0.05 mL
0.20 mL
0.30 mL
0.10 mL
0.10 mL
0.10 mL
0.10 mL
2 h 10 min
2 h
78
84
75
62
60
68
73
56
67
58
62
62
52
54
93
96
93
94
92
90
97
93
96
93
94
95
90
92
3e
4
1 h 40 min
1 h 15 min
1 h 50 min
2 h 15 min
3 h 50 min
2 h 20 min
2 h 10 min
1 h 45 min
1 h 55 min
1 h 45 min
2 h 15 min
2 h 25 min
5
6
7
8
9
10
11f
12g
13h
14i
a Conditions: Nitrosobenzene (0.3 mmol), propanal (3 equiv.), catalyst (20 mol%), tetrabutylammonium bromide (2 equiv.) and water (0.10 mL) was
added at 0 ◦C and stirred at rt (23 ◦C) unless otherwise stated. b Isolated yields. c Determined by chiral phase HPLC. d 10 mol% of VI. e 30 mol% of
VI. f No Bu4NBr added. g 1 equiv. Bu4NBr added. h 1 equiv. propanal added. i 2 equiv. propanal added.
544 | Green Chem., 2009, 11, 543–547
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Table 3 The generality of reaction of a-aminoxylation in the presence of watera
Entry
R
Time
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
Me
Et
Pr
Bu
i-Pr
Ph
PhCH2
CH2 CHCH2
BnOCH2CH2
BocNHCH2
Me
3a
3b
3c
3d
3e
3f
3g
3h
3i
2 h
84
75
79
74
76
78
77
88
86
79
83
96
98
97
96
97
93
> 99
96
97
93
2 h 10 min
2 h 20 min
2 h 35 min
2 h 10 min
20 min
2 h 30 min
1 h
2 h 20 min
2 h 30 min
2 h 20 min
=
10
3j
3k
11d
97
a Conditions: Nitrosobenzene (0.3 mmol), propanal (3 equiv.), catalyst (20 mol%), tetrabutylammonium bromide (2 equiv.) and water (0.10 mL) was
added at 0 ◦C and stirred at rt (23 ◦C) unless otherwise stated. b Isolated yields. c Determined by chiral phase HPLC. d Nitrosotoluene was used
instead of nitrosobenzene.
afford the a-aminoxy alcohols in good yield with excellent
enantioselectivities (Table 3, entries 9–10). The scope of nitroso
compounds was briefly tested by replacing nitrosobenzene with
nitrosotoluene. When nitrosotoluene was treated with propanal
under the optimised conditions, the corresponding a-aminoxy
alcohols were obtained in 83% yield with an enantioselecitivity
of 97%, which is consistent with the results of nitrosobenzene.
addition of water. The reaction mixture was then extracted with
CH2Cl2 (3 ¥ 30 ml). The combined organic extracts were dried
with Na2SO4 and concentrated in vacuo. The crude oil was
purified by flash column chromatography (hexane/EtOAc =
9/1–7/3) yielding pure a-aminoxy alcohols 3.
(R)-2-(N-Phenylaminoxy)propan-1-ol (3a). a-Aminoxy al-
cohol 3a was prepared according to the general procedure from
propanal (0.07 mL, 0.9 mmol) to provide the title compound
as a pale yellow liquid (42.3 mg, 84% yield) after flash column
Conclusions
1
chromatography on silica gel (hexane/EtOAc = 9/1–7/3). H
In conclusion, L-thiaproline was used to catalyze a-
aminoxylation of aldehydes in aqueous media in the presence
of a phase-transfer catalyst to afford the respective a-aminoxy
alcohols in good to high yields (74–88%) and excellent enan-
tioselectivities (93–>99%). This reaction protocol may find
potential use for industrial-scale preparation due to its simple
operation, wide scope, excellent enantioselectivities and environ-
mental friendliness. Further investigation on the application of
L-thioproline in asymmetric catalysis is in progress.
NMR (400 MHz, CDCl3): d 7.29–7.25 (2H, m), 7.04–6.96 (3H,
m), 4.16–4.08 (1H, m), 3.80–3.70 (2H, m), 2.56 (1H, brs), 1.25
(3H, d, J = 6.4 Hz). 13C NMR (100 MHz, CDCl3): d 148.5,
129.0, 122.4, 114.7, 80.0, 66.5, 15.4. HPLC: Chiralpak AD-H
(hexane/i-PrOH, 90/10, flow rate 1 mL min-1, l = 230 nm), tR
(minor) = 10.6 min, tR (major) = 12.1 min; 96% ee. [a]2D5 = +2.9
(c = 1.0, CHCl3).
(R)-2-(N-Phenylaminoxy)butan-1-ol (3b). a-Aminoxy alco-
hol 3b was prepared according to the general procedure from
butanal (0.08 mL, 0.9 mmol) to provide the title compound as
a pale yellow liquid (40.9 mg, 75% yield) after flash column
Experimental
1
General experimental procedure for the a-aminoxylation of
aldehydes to nitrosobenzene in aqueous media
chromatography on silica gel (hexane/EtOAc = 9/1–7/3). H
NMR (400 MHz, CDCl3): d 7.29–7.25 (2H, m), 7.07–6.96 (2H,
m), 3.91–3.74 (3H, m), 2.67 (1H, brs), 1.78–1.53 (2H, m), 1.01
(3H, t, J = 7.5 Hz). 13C NMR (100 MHz, CDCl3): d 148.4,
129.0, 122.4, 114.8, 85.3, 64.9, 22.9, 10.1. HPLC: Chiralpak
AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL min-1, l = 230
nm), tR (minor) = 10.2 min, tR (major) = 11.6 min; 98% ee.
[a]2D5 = +36.0 (c = 1.0, CHCl3).
Water (0.10 mL) and tetrabutylammonium bromide (193.4 mg,
0.6 mmol) was added to a 5 mL drum vial containing ni-
trosobenzene (2, 32.1 mg, 0.3 mmol), corresponding aldehydes
(1, 0.9 mmol) and a magnetic stirring bar. After stirring for
5 min at 0 ◦C, L-thiaproline (8 mg, 0.06 mmol) was added. The
reaction was first stirred at this temperature for about 10 min and
then at room temperature until the green solution turned yellow
which indicated complete consumption of the nitrosobenzene.
As the a-aminoxy aldehyde product is rather labile, isolation
and characterization was performed after conversion to the
corresponding a-aminoxy alcohol 3 by treatment of the reaction
mixture with NaBH4. The excess NaBH4 was quenched by the
(R)-2-(N-Phenylaminoxy)pentan-1-ol (3c). a-Aminoxy al-
cohol 3c was prepared according to the general procedure from
pentanal (0.10 mL, 0.9 mmol) to provide the title compound as a
pale yellow liquid (46.0 mg, 79% yield) after flash column chro-
matography on silica gel (hexane/EtOAc = 9/1–7/3). 1H NMR
(400 MHz, CDCl3): d 7.28–7.15 (3H, m), 6.98–6.94 (2H, m),
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3.94–3.91 (1H, m), 3.85–3.82 (1H, m), 3.75–3.71 (1H, m), 2.93
(1H, brs), 1.67–1.61 (1H, m), 1.54–1.33 (3H, m), 0.97–0.89 (3H,
m). 13C NMR (100 MHz, CDCl3): d148.4, 129.0, 122.3, 114.7,
83.7, 65.1, 32.0, 19.0, 14.2. HPLC: Chiralpak AD-H (hexane/i-
PrOH, 90/10, flow rate 1 mL min-1, l = 230 nm), tR (minor) =
10.0 min, tR (major) = 11.4 min; 97% ee. [a]2D5 = +28.6 (c = 1.0,
CHCl3).
36.4. HPLC: Chiralpak OD-H (hexane/i-PrOH, 91/9, flow rate
1 mL min-1, l = 230 nm), tR (major) = 57.9 min, tR (minor) =
62.4 min; >99% ee. [a]2D2 = +55.2 (c = 1.3, CHCl3).
(R)-2-(N-Phenylaminoxy)pent-4-en-1-ol (3h). a-Aminoxy
alcohol 3h was prepared according to the general procedure
from 4-pentenal (0.09 mL, 0.9 mmol) to provide the title
compound as a pale yellow liquid (51.0 mg, 88% yield) after
flash column chromatography on silica gel (hexane/EtOAc =
9/1–7/3). 1H NMR (400 MHz, CDCl3): d 7.29–7.26 (2H,
m), 7.06–6.96 (3H, m), 5.93–5.82 (1H, m), 5.18–5.11 (2H, m),
4.05–4.00 (1H, m), 3.87–3.75 (2H, m), 2.54–2.32 (3H, m), 1.66
(1H, brs). 13C NMR (100 MHz, CDCl3): d 148.3, 134.0, 129.0,
122.5, 117.8, 114.8, 83.3, 64.6, 34.6. HPLC: Chiralpak AD-H
(hexane/i-PrOH, 90/10, flow rate 1 mL min-1, l = 230 nm), tR
(minor) = 10.5 min, tR (major) = 12.5 min; 96% ee. [a]2D5 = -
22.9 (c = 1.0, CHCl3).
(R)-2-(N-Phenylaminoxy)hexan-1-ol (3d). a-Aminoxy alco-
hol 3d was prepared according to the general procedure from
hexanal (0.11 mL, 0.9 mmol) to provide the title compound as
a pale yellow liquid (46.4 mg, 74% yield) after flash column
1
chromatography on silica gel (hexane/EtOAc = 9/1–7/3). H
NMR (400 MHz, CDCl3): d 7.29–7.26 (2H, m), 7.06–6.96 (3H,
m), 3.98–3.92 (1H, m), 3.87–3.84 (1H, m), 3.79–3.72 (1H, m),
2.68 (1H, brs), 1.69–1.50 (1H, m), 1.47–1.30 (4H, m), 0.92 (3H,
t, J = 7.1 Hz). 13C NMR (100 MHz, CDCl3): d148.4, 129.0,
122.5, 114.9, 84.0, 65.4, 29.6, 27.9, 22.0, 14.0. HPLC: Chiralpak
AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL min-1, l = 230
(R)-4-(Benzyloxy)-2-(N-phenylaminoxy)butan-1-ol (3i). a-
Aminoxy alcohol 3i was prepared according to the general
procedure from 4-(benzyloxy)butanal (0.16 mL, 0.9 mmol) to
provide the title compound as a pale yellow liquid (73.8 mg,
86% yield) after flash column chromatography on silica gel
nm), tR (minor) = 9.5 min, tR (major) = 11.4 min; 96% ee. [a]D25
+22.5 (c = 1.2, CHCl3).
=
(R)-3-Methyl-2-(N-phenylaminoxy)butan-1-ol
(3e). a-
1
Aminoxy alcohol 3e was prepared according to the general
procedure from 3-methylbutanal (0.10 mL, 0.9 mmol) to
provide the title compound as a pale yellow liquid (44.8 mg,
76% yield) after flash column chromatography on silica gel
(hexane/EtOAc = 9/1–7/3). 1H NMR (400 MHz, CDCl3):
d 7.30–7.26 (2H, m), 7.03–6.99 (3H, m), 3.88–3.87 (2H, m),
3.76–3.74 (1H, m), 2.07–1.99 (1H, m), 1.05 (3H, d, J = 6.9 Hz),
1.01 (3H, d, J = 6.9 Hz). 13C NMR (100 MHz, CDCl3): d
148.3, 129.0, 122.5, 115.0, 88.6, 63.6, 28.7, 18.7, 18.6. HPLC:
Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL min-1,
l = 230 nm), tR (minor) = 9.0 min, tR (major) = 10.1min; 97%
ee. [a]2D2 = +33.4 (c = 1.0, CHCl3).
(R)-2-Phenyl-2-(N-phenylaminoxy)ethanol (3f). a-Aminoxy
alcohol 3f was prepared according to the general procedure from
2-phenylacetaldehyde (0.11 mL, 0.9 mmol) to provide the title
compound as a pale yellow liquid (53.5 mg, 78% yield) after flash
column chromatography on silica gel (hexane/ether = 9/1–7/3).
1H NMR (400 MHz, CDCl3): d 7.39–7.31 (5H, m), 7.28–7.20
(2H, m), 6.99–6.94 (3H, m), 5.00 (1H, dd, J = 3.5, 8.1 Hz),
3.99–3.92 (1H, m), 3.83–3.78 (1H, m), 2.58 (1H, brs). 13C NMR
(100 MHz, CDCl3): d 147.9, 137.7, 129.0, 128.7, 128.5, 127.0,
122.5, 115.0, 86.4, 66.4. HPLC: Chiralpak OD-H (hexane/i-
PrOH, 95/5, flow rate 1 mL min-1, l = 230 nm), tR (major) =
25.8 min, tR (minor) = 30.2 min; 93% ee. [a]2D4 = -85.5 (c = 1.1,
CHCl3).
(hexane/EtOAc = 9/1–7/3). H NMR (400 MHz, CDCl3): d
7.34–7.23 (6H, m), 7.05 (1H, brs), 6.98–6.94 (3H, m), 4.54–4.52
(2H, m), 4.14–4.11 (1H, m), 3.93- 3.87 (1H, m), 3.81–3.77 (1H,
m), 3.66 (2H, t, J = 5.7 Hz), 2.81 (1H, t, J = 5.9 Hz), 2.06–
1.89 (2H, m). 13C NMR (100 MHz, CDCl3): d 148.3, 138.0,
129.0, 128.5, 127.8, 122.4, 116.1, 114.8, 81.5, 73.2, 66.7, 64.8,
30.3. HPLC: Chiralpak AD-H (hexane/i-PrOH, 91/9, flow rate
1 mL min-1, l = 230 nm), tR (minor) = 18.8 min, tR (major) =
24.1 min; 97% ee. [a]2D2 = +15.5 (c = 1.1, CHCl3). HRMS (ESI)
calcd for C17H21NO3, m/z 288.1600, found 288.1599.
(R)-tert-Butyl 3-hydroxy-2-(N-phenylaminoxy)propylcarbam-
ate (3j). a-Aminoxy alcohol 3j was prepared according to
the general procedure from tert-butyl 3-oxopropylcarbamate
(0.16 mL, 0.9 mmol) to provide the title compound as a
pale yellow liquid (67.2 mg, 79% yield) after flash column
1
chromatography on silica gel (hexane/EtOAc = 9/1–7/3). H
NMR (400 MHz, CDCl3): d 7.32–7.24 (3H, m), 6.98–6.94 (2H,
m), 5.02 (1H, brs), 3.94–3.92 (1H, m), 3.80 (2H, s), 3.50–3.36
(2H, m), 1.45 (9H, s). 13C NMR (100 MHz, CDCl3): d 157.1,
148.3, 129.0, 122.4, 114.6, 82.4, 80.0, 61.3, 39.6, 28.3. HPLC:
Chiralpak OJ-H (hexane/i-PrOH, 95/5, flow rate 1 mL min-1,
l = 230 nm), tR (minor) = 24.8 min, tR (major) = 26.6 min;
93% ee. [a]2D2 = - 8.2 (c = 1.3, CHCl3). HRMS (ESI) calcd for
C14H23N2O4, m/z 282.1658, found 282.1659.
(R)-2-(p-Toluidinoxy)propan-1-ol 3k). a-Aminoxy alcohol
3k was prepared according to the general procedure from
propanal (0.07 mL, 0.9 mmol) and nitrosotoluene (36.3 mg,
0.3 mmol) to provide the title compound as a pale yellow liquid
(45.0 mg, 83% yield) after flash column chromatography on silica
gel (hexane/EtOAc = 9/1–7/3). 1H NMR (400 MHz, CDCl3):
d 7.07 (2H, d, J = 8.1 Hz), 6.99 (1H, brs), 6.88 (2H, d, J =
8.3 Hz), 4.13–4.07 (1H, m), 3.78–3.68 (2H, m), 2.28 (3H, s),
1.22 (3H, d, J = 6.5 Hz). 13C NMR (100 MHz, CDCl3): d145.8,
132.0, 129.5, 115.3 79.8, 66.6, 20.6, 15.4. HPLC: Chiralpak AD-
(R)-3-Phenyl-2-(N-phenylaminoxy)propan-1-ol
(3g). a-
Aminoxy alcohol 3g was prepared according to the general
procedure from 3-phenylpropanal (0.12 mL, 0.9 mmol) to
provide the title compound as a pale yellow liquid (55.9 mg,
77% yield) after flash column chromatography on silica gel
1
(hexane/ether = 9/1–7/3). H NMR (400 MHz, CDCl3): d
7.32–7.18 (6H, m), 7.08 (1H, brs), 6.94 (1H, t, J = 7.3 Hz),
6.82 (2H, d, J = 8.0 Hz), 4.16–4.10 (1H, m), 3.85 (1H, d, J =
11.8 Hz), 3.04 (1H, dd, J = 6.8, 13.7 Hz), 2.84 (1H, dd, J =
7.0, 13.7 Hz), 2.62 (1H, brs). 13C NMR (100 MHz, CDCl3): d
148.3, 137.8, 129.4, 128.9, 128.5, 126.4, 122.3, 114.6, 85.0, 64.1,
H (hexane/i-PrOH, 90/10, flow rate 1 mL min-1, l = 230 nm),
25
tR (minor) = 10.9 min, tR (major) = 12.4 min; 97% ee. [a]D
=
546 | Green Chem., 2009, 11, 543–547
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The Royal Society of Chemistry 2009
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+5.5 (c = 1.5, CHCl3). HRMS (ESI) calcd for C10H16NO2, m/z
and A. Sudalai, Tetrahedron Lett., 2006, 47, 6799; (e) S. G. Kim
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182.1181, found 182.1181.
Acknowledgements
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This work is financially supported by grants from the Ministry
of Education, Singapore (ARC12/07, no. T206B3225) and the
School of Physical and Mathematical Sciences, Nanyang Tech-
nological University (URC, RG53/07 and SEP, RG140/06).
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