Stereoselective aldol reactions catalyzed by acyclic amino acids in aqueous micelles

Article abstract of DOI:10.1002/hlca.200790003

The catalytic properties of all proteinogenic, acyclic amino acids for direct aldol reaction in H₂O, assisted by various surfactants, were investigated. The basic and neutral amino acids were shown to be efficient catalysts, giving rise to good

Full text of DOI:10.1002/hlca.200790003

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Helvetica Chimica Acta – Vol. 90 (2007)
Stereoselective Aldol Reactions Catalyzed by Acyclic Amino Acids in
Aqueous Micelles
a
a b
by Dong-Sheng Deng ) and Jiwen Cai* ) )
a) School of Chemistry & Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China
(
phone: +86-20-84114215; fax: +86-20-87334718; e-mail: puscjw@mail.sysu.edu.cn)
b) School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510080, P. R. China
The catalytic properties of all proteinogenic, acyclic amino acids for direct aldol reaction in H O,
2
assisted by various surfactants, were investigated. The basic and neutral amino acids were shown to be
efficient catalysts, giving rise to good-to-excellent yields of adducts (up to 95%), with moderate-to-
good diastereoselectivities (up to 86%), L-arginine being the most-effective catalyst. The syn/anti diaster-
eoisomer ratio could be readily tuned by proper choice of the amino acid used. Also, the range of sub-
strates that underwent the reaction was extended to less-reactive aldehydes carrying electron-donating
Br substituents.
1
. Introduction. – The aldol reaction is one of the most-important C,C bond forming
reactions in synthetic organic chemistry. Catalysts that can promote this reaction
include aldolase enzymes [1], Lewis acids [2], Lewis bases, and small organic molecules
[
3][4]. Since natural amino acids were shown to be able to catalyze some organic reac-
tions [5], they have been extensively investigated as catalysts, which has created a ren-
aissance in organic synthesis [6]. L-Proline (Pro) and its derivatives have been shown to
be efficient catalysts for aldol reactions carried out in both organic or aqueous media
[
7]. In contrast, acyclic amino acids are generally considered as poor catalysts for inter-
molecular aldol reactions of unmodified ketones and aldehydes [8]. However, Córdova
and co-workers recently reported that acyclic amino acids, lacking a five-membered
ring, are capable of catalyzing direct asymmetric aldol reactions [9][10]. Intrigued by
these observations, and in continuation of our studies concerning environmentally
benign catalytic reactions [11], we carried out a systematic investigation into the cata-
lytic properties of natural acyclic amino acids in direct aldol reactions in aqueous
micelles and compared our results with those obtained for Pro under similar conditions
[
12].
2
. Result and Discussion. – Initial experiments were carried out for the aldol reac-
tion between cyclopentanone (1) and 4-nitrobenzaldehyde (2) as a model reaction, cat-
alyzed by L-alanine (Ala) in the presence of different surfactants, including anionic,
neutral, and cationic types. The results are summarized in Table 1. In the presence of
sodium dodecyl sulfate (SDS), the desired aldol adduct 3 was obtained in 78% yield
(
Table 1, Entry 2), compared to 25% in bulk H O (Entry 8). Anionic surfactants gener-
2
ally improved the efficiency of the reaction significantly, but not the diastereoselectivity
Entries 1–4). In the absence of Ala, basically no reaction took place (Entry 6), which
(
ꢀ
2007 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 90 (2007)
115
confirmed the role of Ala as catalyst. Both the cationic surfactant cetyl trimethylammo-
nium bromide (CTAB; Entry 5) and the neutral surfactant polyoxyethylene sorbitan
monooleate (Tw-20; Entry 7) had an adverse effect on the reaction. In the latter
case, this is possibly due to Tw-20 not being able to form colloidal dispersions with
the substrates in H O. To examine temperature effects, the model reaction was carried
2
out at 0, 40, and 608, respectively. The reaction did not proceed at 08 (Entry 9); at higher
temperature (Entries 10 and 11), there was basically no effect on either yield or diaster-
eoselectivity.
Table 1. The Alanine-Catalyzed Aldol Model Reaction in H O as a Function of Micellar Surfactant
2
Entry
Surfactanta)
Time [h]
Yield [%]b)
syn/antic)
1
2
3
4
5
SDBS
SDS
SLS
12
12
12
24
24
24
24
24
24
12
12
76
78
70
48
32
trace
10
25
trace
83
42 :58
42 :58
44 :56
46 :54
50 :50
–
38 :62
50 :50
–
SL
CTAB
SDS
Tw-20
None
SDS
SDS
SDS
6
7
8
9
d)
e
)
f
1
1
0 )
g
40 :60
40 :60
1 )
80
a) SDS, sodium dodecyl sulfate; SDBS, sodium dodecylbenzene sulfonate; SLS, sodium lauryl sulfonate;
SL, sodium laurate; CTAB, cetyl trimethylammonium bromide; Tw-20, polyoxyethylene sorbitan mono-
b
c
1
d
e
oleate. ) After column-chromatographic purification. ) Determined by H-NMR. ) Without Ala. ) At
0
f
g
8C. ) At 408C. ) At 608C.
Based upon the above results, SDS was chosen for further experiments. A range of
natural amino acids were then screened as potential catalysts in the model aldol reac-
tion of 1 and 2 at room temperature, and the results are collected in Table 2. Neutral
and basic amino acids showed the best catalytic properties, with moderate-to-good
yields of 3. Unfortunately, there was no significant enantioselectivity with Ala (Table
2
, Entry 4). When L-leucine (Leu) or L-isoleucine (Ile) were employed, the desired
aldol product 3 was obtained in a diastereoisomer excess (de) of 28%, in favor of the
anti isomers, and in high yield (92–94%; Entries 6 and 7). When employing L-arginine
(Arg), L-histidine (His), and L-lysine (Lys) as catalysts (Entries 17–19), the syn isomers
of 3 were obtained in 30% de, and in yields of up to 98%. The amino acids L-tyrosine
(
(
Tyr), L-glutamate (Glu), and L-aspartate (Asp) gave rise to only 20% of 3 after 24 h
Entries 14–16), the anti adducts being the major isomers in each case. Interestingly,

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Helvetica Chimica Acta – Vol. 90 (2007)
Table 2. Results of the Amino Acid Catalyzed Aldol Model Reaction between 1 and 2 (see Table 1) in
Aqueous Micellar Sodium Dodecyl Sulfate (SDS) Solution. Conditions: H O, r.t., with 20 and 30 mol-%
2
of SDS and amino acid, resp., relative to the aldehyde.
Entry
L-Amino acid
Time [h]
Yield [%]a)
syn/antib)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Glycine
Serine
Threonine
Alanine
Valine
24
24
24
12
12
12
12
24
24
24
12 :65
12
8
24
24
24
6
60
56
80
78
8536 :64
92
94
68
72
70
8535
78
86
20
20
20
98
955
94
40 :60
42 :58
38 :62
c
42 :58 )
Leucine
36 :64
36 :64
40 :60
40 :60
40 :60
Isoleucine
Cysteine
Glutamine
Asparagine
Methionine
Phenylalanine
Tryptophan
Tyrosine
Glutamate
Aspartate
Arginine
Histidine
Lysine
1
1
1
1
1
1
1
1
1
1
2
38 :62
38 :62
25:75
38 :62
40 :60
65:35
12 8 :42
8
24
65:35
trace
d
Sulfamic acid )
trace
a) After column-chromatographic purification. ) Determined by H-NMR. ) The enantiomeric excess
b
1
c
(
ee) was 13% and 7% for the syn and anti isomers, resp., as determined by HPLC (Daicel Chiralpak
d
þ
ꢀ
3
AS-PH). ) In H O mainly present as NH SO .
2
3
+
–
3
sulfamic acid (H N SO ), a zwitter-ionic compound in H O, was not able to trigger the
3
2
reaction (Entry 20).
The results listed above suggest that both basic and neutral acyclic amino acids cat-
alyze direct aldol reactions in aqueous SDS micelles effectively, with Arg and Ile show-
ing the best results. Hence, in the next step, we decided to investigate the scope of Arg-
and Ile-catalyzed aldol reactions of different substrates. The results are summarized in
Table 3. With these two catalysts, excellent yields of up to 98% were achieved for the
condensation of the ketones 4 with the aromatic aldehydes 5 bearing electron-with-
drawing groups (Table 3, Entries 1–5, 8, 9, 12, 14, and 16–19). For the less-active aro-
matic aldehydes, a longer reaction time was required to obtain comparable yields
(Entries 6, 7, 10, 11, and 15).
When Arg was used as catalyst, all reactions afforded the corresponding products
6
–20 in good-to-excellent yields, generally favoring the syn isomers, with up to 80%
de (see, e.g., Entry 11). Interestingly, although Ile had a similar catalytic efficiency as
Arg, it favored the anti adducts rather than the syn adducts, with up to 86% de (see,
e.g., Entry 19). When a 1:1 mixture (15mol-% each) of Arg and Ile was used as
mixed catalyst (Entry 3), the syn and anti selectivities were nearly cancelled, the reac-
tion affording 6 in only 4% de (Entry 3).

Helvetica Chimica Acta – Vol. 90 (2007)
117
Table 3. Arginine- vs. Isoleucine-Catalyzed Aldol Reactions of Different Ketones and Aromatic Aldehydes
in Aqueous Micellar SDS Solution
Entry Ketone
Aldehyde Time [h] Product(s) Arga)
Ilea)
Yield [%] syn/anti Yield [%] syn/anti
1
2
3
4
5
6
7
8
9
4a (=1) 5a (=2)
6
12
6
6 (=3)
6 (=3)
6 (=3)
7
7
8
9
98
65
:35
94
2 :48
4a (=1) 5a (=2)
4a (=1) 5a (=2)
4a (=1) 5b
4a (=1) 5b
4a (=1) 5c
36 :64
35:65
b)
94
96
5
10
16
48
48
24
24
48
48
12
36
24
48
24
60 :40
90
83
82
96
94
80
80
95
57:43
72 :28
62 :38
60 :40
60 :40
90 :10
4a (=1) 5d
72
86
83
45:55
13 :87
10 :90
4b
4b
4b
4b
4c
4c
4c
4c
4d
5a (=2)
5b
5c
10
11
12
13
14
14
15
16
17a
1
0
1
2
3
4
5
6
1
1
1
1
1
1
5d
5a (=2)
5a (=2)
5b
5d
5a (=2)
65
90
50
18
64
26
5
1
7b
18a
8b
56 :44c)
c)
1
7
4d
5b
24
1
4
5
5
:45
1
1
8
9
4a (=1) 5e
4b 5e
24
24
19
20
91
82
28 :72
7:93
a) 30 mol-% Amino acid, isolated yields, syn/anti according to H-NMR. ) Catalyst: Arg/Ile 1:1 mixture
(
1
b
c
1
15mol-% each). ) Determined from H-NMR coupling constants [3b][12][13]. For example, in the case
of 17b (Entry 16), the signals at d(H) 5.27 (J=2.3 Hz) and 4.87 (J=7.8 Hz) were attributed to the syn and
anti isomers, resp., the one with the smaller coupling constant (2.3 Hz) indicating two adjacent H-atoms
on the same side of the ring (syn).
In the case of butan-2-one as nucleophile (Entries 16 and 17), there are two posi-
tions susceptible to deprotonation. Only moderate regio- and stereoselectivities were
observed, giving rise to products 17a,b and 18a,b, respectively.

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Helvetica Chimica Acta – Vol. 90 (2007)
3
. Conclusions. – Our results reveal a novel application of natural acyclic amino
acids as organic catalysts for stereoselective direct aldol reactions in H O. Both basic
2
and neutral amino acids are able to stereoselectively catalyze the reaction between
ketones and aldehydes in aqueous anionic micelles. Notably, the catalytic efficiency
of acyclic amino acids, especially Arg and Ile, is much higher than that of L-proline
[
12]. For instance, the aldol reaction between 2-nitrobenzaldehyde and cyclopentanone
was reported to take 168 h with Pro as catalyst [12], affording the corresponding adduct
in 44% yield, and in favor of the anti isomers. However, the same reaction catalyzed by
Arg was complete within 10 h, giving rise to 96% yield, with the syn isomers being
favored.
Our synthetic protocol benefits from the following advantages: 1) the catalysts are
naturally abundant and inexpensive, 2) the reaction is environmentally highly benign,
3
) good-to-excellent yields can be achieved at room temperature in relatively short
time, and 4) the diastereoselectivity (syn vs. anti adducts) can be readily controlled
by proper choice of the amino acid. Finally, and most importantly, compared with
Pro [12], we were able to extend the scope of the reaction in terms of substrate from
highly to much less reactive aromatic aldehydes carrying electron-donating groups
such as Br.
Experimental Part
General. All reagents were commercially available and used as received. Anal. HPLC: Daicel Chir-
alpak AS-PH column, eluting with hexane/i-PrOH 82 :18 at a flow rate of 1 ml/min, UV detection at 254
1
nm; retention times (t ) in min. H-NMR Spectra were recorded on a Varian Unity-Nova 300-MHz spec-
R
trometer in CDCl at r.t.; d in ppm rel. to Me Si, J in Hz. Mass spectra were recorded on a Shimadzu LC/
3
4
MS-2010A apparatus; in m/z. All compounds were characterized by NMR and MS, and selected anal.
data are presented below.
General Procedure for the Amino Acid Catalyzed Aldol Reaction. To a soln. of SDS (0.1 mmol) and
the appropriate L-amino acid (0.15mmol) in H O (1 ml) is added a soln. of the ketone (4.5mmol) and the
2
aldehyde (0.5mmol). The mixture is stirred at r.t., the progress of the reaction being monitored by TLC.
The mixture is quenched with sat. aq. NaHCO soln., and then extracted with AcOEt (3”20 ml). The
3
combined org. layers are washed with brine, dried (MgSO ), and concentrated in vacuo to yield the
4
crude product, which is purified by column chromatography (SiO , 100–200 mesh; hexane/AcOEt).
2
2-[Hydroxy(4-nitrophenyl)methyl]cyclopentan-1-one (3=6; Table 2, Entry 4). HPLC (syn isomers):
t 10.70 (major), 31.37 (minor); 13% ee. HPLC (anti isomers): t 12.47 (minor), 17.14 (major); 7% ee.
R
R
1
H-NMR (CDCl ; syn isomers): 8.19 (dd, J=6.8, 8.8, 2 arom. H); 7.50 (dd, J=3.2, 8.3, 2 arom. H);
3
1
5
.41 (d, J=1.3, OCH); 1.51–2.51 (br. m, 7 H). H-NMR (CDCl ; anti isomers): 8.19 (dd, J=6.8, 8.8, 2
3
arom. H); 7.50 (dd, J=3.2, 8.3, 2 arom. H); 4.84 (d, J=9.0, OCH); 1.51–2.51 (br. m, 7 H). ESI-MS:
+
2
58.3 ([M+Na] ).
1
2
-[Hydroxy(2-nitrophenyl)methyl]cyclopentan-1-one (7; Table 3, Entry 4). H-NMR (CDCl ; syn iso-
3
mers): 7.77–8.00 (m, 2 arom. H); 7.61–7.66 (m, 1 arom. H); 7.39–7.45( m, 1 arom. H); 5.89 (d, J=2.8,
1
OCH); 1.68–2.72 (br. m, 7 H). H-NMR (CDCl ; anti isomers): 7.77–8.00 (m, 2 arom. H); 7.61–7.66 (m,
3
1
arom. H); 7.39–7.45( m, 1 arom. H); 5.42 (d, J=8.5, OCH); 1.68–2.72 (br. m, 7 H). ESI-MS: 258.1
+
(
[M+Na] ).
-[(4-Bromophenyl)(hydroxy)methyl]cyclopentan-1-one (8; Table 3, Entry 6). H-NMR (CDCl ; syn
1
2
3
isomers): 7.27–7.54 (m, 3 arom. H); 7.17–7.21 (m, 2 arom. H); 5.22 (d, J=2.7, OCH); 1.44–2.42 (br. m, 7
1
H). H-NMR (CDCl ; anti isomers): 7.27–7.54 (m, 3 arom. H); 7.17–7.21 (m, 2 arom. H); 4.67 (d, J=9.0,
3
+
OCH); 1.44–2.42 (br. m, 7 H). ESI-MS: 291.3 ([M+Na] ).

Helvetica Chimica Acta – Vol. 90 (2007)
119
1
2
-[Hydroxy(phenyl)methyl]cyclopentan-1-one (9; Table 3, Entry 7). H-NMR (CDCl ; syn isomers):
3
1
7
7
.23–7.34 (m, 5arom. H); 5.30 ( d, J=2.9, OCH); 1.64–2.46 (br. m, 7 H). H-NMR (CDCl ; anti isomers):
3
+
.23–7.34 (m, 5arom. H); 4.71 ( d, J=9.1, OCH); 1.64–2.46 (br. m, 7 H). ESI-MS: 213.1 ([M+Na] ).
1
2
-[Hydroxy(4-nitrophenyl)methyl]cyclohexan-1-one (10; Table 3, Entry 8). H-NMR (CDCl ; syn
3
isomers): 8.18 (dd, J=7.1, 8.7, 2 arom. H); 7.48 (dd, J=2.5, 8.3, 2 arom. H); 5.47 (d, J=1.2, OCH);
1
1
.35–2.64 (br. m, 9 H). H-NMR (CDCl ; anti isomers): 8.18 (dd, J=7.1, 8.7, 2 arom. H); 7.48 (dd,
3
+
J=2.5, 8.3, 2 arom. H); 4.90 (d, J=8.4, OCH); 1.35–2.64 (br. m, 9 H). ESI-MS: 272.35([ M+Na] ).
1
2
-[Hydroxy(2-nitrophenyl)methyl]cyclohexan-1-one (11; Table 3, Entry 9). H-NMR (CDCl ; syn
3
isomers): 7.74–8.00 (m, 2 arom. H); 7.60–7.66 (m, 1 arom. H); 7.39–7.45( m, 1 arom. H); 5.96 (d,
1
J=1.8, OCH); 1.56–2.92 (br. m, 9 H). H-NMR (CDCl ; anti isomers): 7.74–8.00 (m, 2 arom. H);
3
7
.60–7.66 (m, 1 arom. H); 7.39–7.45( m, 1 arom. H); 5.45 (d, J=7.2, OCH); 1.56–2.92 (br. m, 9 H).
+
ESI-MS: 272.32 ([M+Na] ).
-[Hydroxy(4-bromophenyl)methyl]cyclohexan-1-one (12; Table 3, Entry 10). H-NMR (CDCl ; syn
1
2
3
isomers): 7.46 (dd, J=5.0, 8.4, 2 arom. H); 7.18 (dd, J=3.7, 8.5, 2 arom. H); 5.33 (d, J=1.6, OCH);
1
1
.31–2.60 (br. m, 9 H). H-NMR (CDCl ; anti isomers): 7.46 (dd, J=5.0, 8.4, 2 arom. H); 7.18 (dd,
3
+
J=3.7, 8.5, 2 arom. H); 4.75 (d, J=8.6, OCH); 1.31–2.60 (br. m, 9 H). ESI-MS: 305.30 ([M+Na] ).
-[Hydroxy(phenyl)methyl]cyclohexan-1-one (13; Table 3, Entry 11). H-NMR (CDCl ; syn iso-
mers): 7.23–7.38 (m, 5arom. H); 5. 38 ( d, J=2.2, OCH); 1.64–2.46 (br. m, 9 H). H-NMR (CDCl ;
1
2
3
1
3
anti isomers): 7.23–7.38 (m, 5arom. H); 4.79 ( d, J=8.8, OCH); 1.64–2.46 (br. m, 9 H). ESI-MS:
+
2
27.22 ([M+Na] ).
1
4
-Hydroxy-4-(4-nitrophenyl)butan-2-one (14; Table 3, Entry 12). H-NMR (CDCl ): 8.18 (d, J=8.8, 2
3
arom. H); 7.52 (d, J=8.3, 2 arom. H); 5.26 (t, J=6.8, OCH); 2.86 (d, J=5.2, CH ); 2.22 (s, Me). ESI-MS:
2
+
2
32.20 ([M+Na] ).
-Hydroxy-4-(2-nitrophenyl)butan-2-one (15; Table 3, Entry 14). H-NMR (CDCl ): 8.19 (dd, J=7.2,
1
4
3
8
.2, 1 arom. H); 7.89 (d, J=7.5, 1 arom. H); 7.64–7.69 (m, 1 arom. H); 7.41–7.47 (m, 1 arom. H); 5.68 (dd,
J=7.6, 9.4, OCH); 3.14 (dd, J=15.8, 17.8, CH); 2.77 (q, J=9.4, CH); 2.25( s, Me). ESI-MS: 232.25:
+
(
[M+Na] ).
-Hydroxy-4-phenylbutan-2-one (16; Table 3, Entry 15). H-NMR (CDCl ): 7.28–7.40 (m, 5arom.
1
4
3
+
H); 5.28 (t, J=5.6, OCH); 3.10 (d, J=5.3, CH ); 2.31 (s, Me). ESI-MS: 187.30 ([M+Na] ).
2
1
1
-Hydroxy-1-(4-nitrophenyl)pentan-3-one (17a; Table 3, Entry 16). H-NMR (CDCl ): 8.21 (d,
3
J=8.7, 2 arom. H); 7.54 (d, J=8.6, 2 arom. H); 5.29 (q, J=4.6, OCH); 2.84 (t, J=4.0, CH ); 2.52 (q,
2
+
J=7.2, CH ); 1.11 (t, J=7.3, Me). ESI-MS: 246.27 ([M+Na] ).
2
1
4-Hydroxy-3-methyl-4-(4-nitrophenyl)butan-2-one (17b; Table 3, Entry 16). H-NMR (CDCl ; syn
3
isomers): 8.18 (dd, J=6.5, 8.8, 2 arom. H); 7.45–7.53 (m, 2 arom. H); 5.27 (d, J=2.3, OCH);
1
2
.81–2.86 (m, CH); 2.25( s, Me); 1.06 (d, J=7.4, Me). H-NMR (CDCl ; anti isomers): 8.18 (dd,
3
J=6.5, 8.8, 2 arom. H); 7.45–7.53 (m, 2 arom. H); 4.87 (d, J=7.8, OCH); 2.95( q, J=7.4, CH); 2.24
+
(
s, Me); 1.03 (d, J=7.4, Me). ESI-MS: 246.30 ([M+Na] ).
1
1
-Hydroxy-1-(2-nitrophenyl)pentan-3-one (18a; Table 3, Entry 17). H-NMR (CDCl ): 7.41–8.04 (m,
3
4
arom. H); 5.68 (dd, J=8.3, 9.1, OCH); 3.16 (d, J=1.7, CH ); 3.08–3.13 (m, CH ); 1.12 (t, J=7.3, Me).
2
2
+
ESI-MS: 246.28 ([M+Na] ).
1
4
-Hydroxy-3-methyl-4-(2-nitrophenyl)butan-2-one (18b; Table 3, Entry 17). H-NMR (CDCl ; syn
3
isomers): 7.41–8.04 (m, 4 arom. H); 5.78 (d, J=1.1, OCH); 3.16 (d, J=1.8, CH); 2.43–2.55 (m, CH);
1
2
.31 (s, Me); 1.13 (d, J=7.3, Me). H-NMR (CDCl ; anti isomers): 7.41–8.04 (m, 4 arom. H); 5.39 (d,
3
J=6.0, OCH); 3.10 (d, J=5.4, CH); 2.72 (q, J=9.3, CH); 2.14 (s, Me); 1.06 (d, J=7.4, Me). ESI-MS:
+
2
46.35([ M+Na] ).
-[Hydroxy(3-nitrophenyl)methyl]cyclopentan-1-one (19; Table 3, Entry 18). H-NMR (CDCl ; syn
1
2
3
isomers): 8.22 (s, 1 arom. H); 8.10–8.17 (m, 1 arom. H); 7.69 (t, J=7.7, 1 arom. H); 7.50–7.55 (m, 1
1
arom. H); 5.42 (d, J=2.3, OCH); 1.53–2.53 (br. m, 7 H). H-NMR (CDCl ; anti isomers): 8.22 (s, 1
3
arom. H); 8.10–8.17 (m, 1 arom. H); 7.69 (t, J=7.7, 1 arom. H); 7.50–7.55 (m, 1 arom. H); 4.83 (d,
+
J=9.3, OCH); 1.53–2.53 (br. m, 7 H). ESI-MS: 258.32 ([M+Na] ).
1
2-[Hydroxy(3-nitrophenyl)methyl]cyclohexan-1-one (20; Table 3, Entry 19). H-NMR (CDCl ; syn
3
isomers): 8.19 (s, 1 arom. H); 8.13 (dd, J=7.1, 8.1, 1 arom. H); 7.66 (d, J=7.8, 1 arom. H); 7.50 (t,

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Helvetica Chimica Acta – Vol. 90 (2007)
1
J=7.8, 1 arom. H); 5.46 (d, J=0.9, OCH); 1.36–2.64 (br. m, 9 H). H-NMR (CDCl ; anti isomers): 8.19
3
(
4
s, 1 arom. H); 8.13 (dd, J=7.1, 8.1, 1 arom. H); 7.66 (d, J=7.8, 1 arom. H); 7.50 (t, J=7.8, 1 arom. H);
.90 (d, J=8.4, OCH); 1.36–2.64 (br. m, 9 H). ESI-MS: 272.35([ M+Na] ).
+
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Received September 21, 2006