D-glucose-based azacrown ethers with a phosphonoalkyl side chain: Application as enantioselective phase transfer catalysts

Article abstract of DOI:10.1016/S0957-4166(99)00224-4

Five chiral α-D-glucose-based monoaza-15-crown-5 ethers with a phosphonoalkyl side chain 5a-e have been synthesized. The substituent at the nitrogen atom has a major influence on the cation extraction ability of the azacrown. The new lariat ethers 5a-e show significant asymmetric induction as phase transfer catalysts in the Michael addition of 2-nitropropane to chalcone.

Full text of DOI:10.1016/S0957-4166(99)00224-4

Pergamon
Tetrahedron: Asymmetry 10 (1999) 2373–2380
D-Glucose-based azacrown ethers with a phosphonoalkyl side
chain: application as enantioselective phase transfer catalysts
a,∗
a
b
c
c
Péter Bakó, Tibor Novák, Krisztina Ludányi, Béla Pete, László Tõke and
a,∗
György Keglevich
a
Department of Organic Chemical Technology, Technical University of Budapest, 1521 Budapest, Hungary
Central Research Institute of Chemistry for the Hungarian Academy of Sciences, 1525 Budapest, Hungary
b
c
Research Group of the Hungarian Academy of Sciences at the Department of Organic Chemical Technology,
Technical University of Budapest, 1521 Budapest, Hungary
Received 18 May 1999; accepted 3 June 1999
Abstract
Five chiral α-D-glucose-based monoaza-15-crown-5 ethers with a phosphonoalkyl side chain 5a–e have been
synthesized. The substituent at the nitrogen atom has a major influence on the cation extraction ability of the
azacrown. The new lariat ethers 5a–e show significant asymmetric induction as phase transfer catalysts in the
Michael addition of 2-nitropropane to chalcone. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
Chiral crown ethers have received considerable attention due to their ability to serve as models for the
1
study of chiral recognition in enzymatic reactions. It has also been observed that the optically active
2
crown ethers could be used as catalysts in enantioselective reactions. A variety of such macrocycles has
3
been synthesized, and much attention focused on systems derived from carbohydrates. Crown ethers
anellated to different pyranosidic or furanosidic carbohydrates have also been described.4
In recent papers, we have reported the synthesis of a novel class of D-glucose-based crown ethers and
their application in asymmetric reactions. These compounds are 15-membered monoazacrown ethers
5
6
anellated to a methyl- or to a phenyl-4,6-O-benzylideneglucopyranoside unit and are useful catalysts
in asymmetric reactions. It is known that armed azacrown ethers, especially lariat ethers (azacrowns
with heteroatom-containing podand arms) have a unique guest specificity via the macro-ring-side arm
7
cooperativity. We found that the presence of a substituent on the nitrogen atom played an important role
in the cation binding ability, and hence in the catalytic activity of the azacrown ethers.6b In sugar-based
azacrowns, the impact of alkyl and arylalkyl groups, as well as that of substituents containing an oxygen
∗
Corresponding authors. E-mail: p-bako@chem.bme.hu
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00224-4

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P. Bakó et al. / Tetrahedron: Asymmetry 10 (1999) 2373–2380
atom, have been evaluated.5a The effects of phosphorus-containing side arms on the complexing abilities
8
have been studied only in simple azacrown ethers. As the lariat ethers incorporating a phosphonoalkyl
substituent showed interesting cation binding properties, it was a challenge for us to synthesize D-
glucose-based azacrown ethers with a phosphonoalkyl group on the nitrogen atom and to study their
complexing properties and applicability in enantioselective reactions.
2. Results and discussion
2.1. Synthesis of new azacrown ethers 5a–e
We used a method described previously5a for the synthesis of the new lariat ethers. The key inter-
mediates, ω-aminoalkylphosphonates 3c–e were prepared by the, in this case hitherto new, Gabriel
synthesis (Scheme 1) in two steps. Intermediate 3a (3, n=1) was also obtained through the corresponding
phthalimido derivative 2a (2, n=1) synthesized, in this case, by a different approach (see Experimental).
Scheme 1. Reagents and conditions: (i) potassium phthalimide, DMF, 100°C, 8 h; (ii) (H
8°C, 30 min
2
N)2·H
2
O, EtOH, 78°C, 1 h then HCl,
7
Aminoethylphosphonate 3b (3, n=2) was prepared by the Michael addition of ammonia to diethyl
vinylphosphonate. The α-D-glucose-based bis-iodo podand5 4 was cyclized with the aminoalkylphos-
phonates 3a–e in boiling acetonitrile in the presence of sodium carbonate (Scheme 2). In dilute solutions,
the polycondensation side reactions were suppressed and the desired intramolecular cyclization took
place in high conversion to give the N-phosphonoalkyl azacrown ethers 5a–e in fairly good yields
a
3
1
1
(
51–70%) after purification by chromatography. The products 5a–e were characterized by P, H and
1
3
1
13
C NMR, as well as mass spectroscopic data. The H and C NMR spectral parameters were similar
to those of azacrown derivatives described earlier.6b The molecular weights of 5a–e were supported
by CIMS and FABMS. The elemental composition was confirmed in all cases by HR-FAB. In the
EI mass spectra of products 5a–e we observed two different fragmentation patterns depending on the
length of the hydrocarbon chain binding the P_O moiety to the azacrown ether. With compounds
5a and 5b, the fragments were formed mainly by bond fission in the ‘sugar’ part of the molecules,
while in the case of azacrowns 5c–e, the fragmentation occurred preferentially at the ‘crown’ part. The
fragments at 452 and 156 m/z were of significant intensity in all cases (see Experimental) that are due
to the (sugar-based azacrown)-CH2+ and the C H O fragments, respectively. The latter one is the
+
7
8
4
+
+
sugar residue from product 5a–e. The (CH ) P(O)(OEt) , the CH N(CH ) P(O)(OEt) , as well as the
2
n
2
2
2 n
2
+
(
CH ) N(CH ) P(O)(OEt) fragments could also be found in the mass spectra of products 5a–e. The
2
2
+
2 n
+
2
+
+
+
M−H , M−Me , M−MeO , M−EtO and M−P(O)(OEt) fragments were of low intensity.
2

P. Bakó et al. / Tetrahedron: Asymmetry 10 (1999) 2373–2380
2375
2 2 n 2 3
Scheme 2. Reagents and conditions: (i) H N(CH ) P(O)(OEt) (3a–e), CH CN, 82°C, 48 h
2.2. Extracting properties of the new azacrown ethers 5a–e
The phase transfer properties (in a liquid–liquid system) of the newly synthesized crown ethers 5a–e
were characterized by the extraction of picrate salts (lithium, sodium, potassium and ammonium picrates)
9
from water into dichloromethane following the procedure described by Kimura et al. The data collected
in Table 1 show the amount of the transferred salt as the percentage of the initial salt concentration
(
extractability %). The concentration of the picrates in water was measured by UV spectroscopy. The
5
c
unsubstituted azacrown ether 6 used as the reference compound has a surprisingly high extracting
ability (EA) towards the cations investigated but does not show a notable selectivity to any of the alkali-
or ammonium cations (EA: 87–98%).
Table 1
Extraction of alkali metal and ammonium picrates with different azacrown ethers
As can be seen, the phosphonoalkyl side arms have significant influence on the EA of the azacrown
ring. Introduction of the phosphonoalkyl substituents decreased the EA of the parent azacrown ether 6
in all cases. The impact of the long chains was smaller than that of the substituents with shorter chains
(e.g. the EA values for compound 5d (n=4) and 5a (n=1) are 46–63% and 5–29%, respectively). For
the potassium cation, the relative order of the EA values is the following: 96% for 6 (n=0), 59% for

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P. Bakó et al. / Tetrahedron: Asymmetry 10 (1999) 2373–2380
5e (n=5), 54% for 5d (n=4), 24% for 5c (n=3), 17% for 5b (n=2) and 16% for 5a (n=1). On the other
hand, the selectivity of derivatives 5a–e was improved significantly relative to that of unsubstituted 6.
In this respect, compound 5c (n=3) seems to be the best, which transports 10 times more ammonium
picrate (EA=43%) into the organic phase than lithium picrate (EA=4%). Azacrown 5b extracts twice
as much lithium ion as potassium ion. With the exception of 5a and 5b, the azacrown ethers 5c–e
form the most stable complex with ammonium picrate among the picrates investigated. Regarding the
stability of the complex with different cations, a similar trend can be observed for azacrowns 5c–e
+
+
+
+
+
+
+
+
as follows: NH >K >Na >Li . Compounds 5a and 5b revealed the Li >Na >NH >K order. The
4
4
complex effect of the N-substituents is presumably due to steric and electronic effects. The presence
of the phosphonoalkyl side chain obviously means some kind of steric hindrance in the complexation.
On the other hand, the phosphonoalkyl moiety affects the electron density on the nitrogen atom. While
the phosphonomethyl substituent can be regarded as an electron-withdrawing group, the phosphonoalkyl
substituents with longer carbon atom chains may increase the electron density on the nitrogen atom. The
third effect may be the side arm cooperativity due to the oxygen atom of the phosphoryl moiety (Fig. 1).
The length of the side arm is decisive.
Figure 1.
2.3. Chiral induction by the new azacrown ethers 5a–e in an asymmetric Michael addition
The compounds 5a–e proved to be effective as chiral phase transfer catalysts in the Michael addition
of 2-nitropropane to chalcone 7 (Scheme 3). The Michael addition was carried out in toluene with solid
sodium tert-butoxide as the base (35 mol%) in the presence of chiral catalyst 5a–e (7 mol%) at room
temperature. After the usual work-up procedure, the adduct 8 was isolated by preparative TLC. The
asymmetric induction, expressed in terms of the enantiomeric excess (ee), was monitored by determining
the specific rotation of product 8 and comparing it with the literature data for the pure enantiomer and
1
by H NMR spectroscopy using (+)-Eu(hfc) as chiral shift reagent. The results given in Table 2 show
3
that the (S)-(+)-adduct 8 was always in excess and, what is more important, that the substituent on the
nitrogen atom of the catalyst has a significant influence on both the yield and the asymmetric induction.
Scheme 3. Reagents and conditions: (i) catalyst (5a–e), NaOtBu, PhMe, 20°C, 48 h

P. Bakó et al. / Tetrahedron: Asymmetry 10 (1999) 2373–2380
2377
Table 2
a
Addition of 2-nitropropane to chalcone (7) catalyzed by azacrown ethers 5a–e
Apparently, azacrown ethers 5a–e are not very efficient phase transfer catalysts in the solid–liquid
phase Michael addition mentioned above: after a 48 h period of stirring, adduct 8 was formed in only
31–42% chemical yield. The new products 5a–e showed, however, significant asymmetric induction:
an enantiomeric excess of 60–83% was detected (Table 2). As a comparison, use of the unsubstituted
5
c
azacrown 6 reported earlier resulted in an enantiomeric excess of 61%. As can be seen, the length of the
chain connecting the nitrogen atom and the P_O moiety has a major influence on the enantioselectivity.
The catalysts having shorter side arms 5a (n=1), 5b (n=2) and 5c (n=3) were as efficient as reference
compound 6 (ee: 60–63%). The use of azacrowns with longer arms 5d (n=4) and 5e (n=5) resulted in a
significant increase in the enantioselectivity (ee: 79–82%). Among the catalysts tested, lariat ether 5d,
connecting the phosphoryl group by a four carbon atom chain to the nitrogen, proved to be the best:
an enantiomeric excess of 82% was observed for the (S)-(+)-8 adduct. This compound (5d) seems to
have the optimum length for the hydrocarbon spacer connecting the P_O moiety to the nitrogen atom
of the azacrown. The phosphonobutyl side arm is flexible and can bend over to assist the complexation
responsible for the asymmetric induction.
3. Experimental
The 31P, 13C and H NMR spectra were taken on a Bruker DRX-500 spectrometer operating at 202.4,
1
1
25.7 and 500 MHz, respectively. Chemical shifts are downfield relative to 85% H PO or TMS. The
3
4
coupling constants are given in hertz. EI-mass spectra were obtained on a Finnigan Automass 120
spectrometer at 70 eV. FAB measurements were conducted on a reverse geometry VG ZAB-2SEQ
+
instrument using a 30 kV Cs ion gun and 8 kV accelerating voltage.
The sugar-based bis-iodo podand 4 was synthesized as described earlier.5
a
3.1. The preparation of ω-aminoalkylphosphonates 3a–e
3.1.1. Diethyl 1-aminomethylphosphonate 3a
Compound 3a was synthesized from diethyl phthalimidomethylphosphonate 2a obtained in the Arbu-
1
3
14
zov reaction of N-bromomethylphthalimide and triethyl phosphite by reaction with hydrazine hydrate
as shown above for the preparation of aminopropylphosphonate 3c. 3 P NMR (CDCl ) δ 28.0; C NMR
CDCl ) δ 16.1 (J=5.4, CH ), 37.4 (J=149.6, C ), 61.6 (J=7.0, CH CH ); MS, m/z 167 (M ).
1
13
3
+
(
3
3
α
2
3

2378
P. Bakó et al. / Tetrahedron: Asymmetry 10 (1999) 2373–2380
3
.1.2. Diethyl 2-aminoethylphosphonate 3b
10
Compound 3b was prepared by the Michael-type addition of ammonia to diethyl vinylphosphonate;
11
31
1
bp 96–100°C (0.4 mmHg) [lit. 93–95°C (4.0 mmHg)]; P NMR (CDCl ) δ 30.8; H NMR (CDCl ) δ
3
3
1.29 (t, J=7.2, 6H, Me), 1.85–1.93 (m, 2H, CH P), 2.92–3.01 (m, 2H, CH N), 4.01–4.13 (m, 4H, CH O);
2 2 2
+
MS, m/z 181 (M ).
3.1.3. Diethyl 3-aminopropylphosphonate 3c
A 75 mL DMF solution of 8.60 g (33.2 mmol) of bromopropylphosphonate 1c and 9.21 g (49.8
mmol) of potassium phthalimide was stirred at 100°C for 8 h. The mixture was cooled to 25°C and
the precipitated material filtered off. The filtrate was concentrated in vacuo and the residue so obtained
taken up in 100 mL of chloroform. After extraction with 3×30 mL of water, the organic phase was dried
3
1
(
(
2
(
MgSO ). Evaporation of the solvent afforded 10.6 g (93%) of 2c in a purity of 95% (GC–MS). P NMR
4
1
CDCl ) δ 31.3; H NMR (CDCl ) δ 1.29 (t, J=7.3, 6H, Me), 1.74–2.03 (m, 4H, (CH ) P), 3.74 (t, J=7.1,
3
3
2 2
12
H, CH N), 4.03–4.16 (m, 4H, CH O), 7.68–7.86 (m, 4H, Ar) [lit. δ 1.32 (t, J=7, 6H, Me), 1.51–2.25
2
2
1
3
m, 4H, (CH ) P), 3.68 (m, 2H, CH N), 4.15 (m, 4H, CH O), 7.75 (m, 4H, Ar)]; C NMR (CDCl ) δ
2
2
2
2
3
1
6.3 (J=5.7, Me), 21.9 (J=4.4, C ), 23.3 (J=143.1, C ), 38.1 (J=19.7, C ), 61.6 (J=6.5, CH O), 123.1
β
α γ 2
+
(C3
0
), 131.9 (C1
65 (21), 160 (54), 152 (100).
To 10.5 g (30.7 mmol) of 2c in 130 mL of abs. ethyl alcohol was added 2.1 mL (42.4 mmol) of 98%
), 133.9 (C2 ), 168.1 (C_O); MS, m/z (rel. int.) 325 (M , 2), 280 (6), 252 (5), 188 (6),
0 0
1
hydrazine hydrate and the contents of the flask were stirred at reflux for 1 h. The volatile components
were removed in vacuo and the oil so obtained distilled to give 2.10 g (51%) of 3c. Bp 85–90°C (0.2
1
0
31
13
mmHg) [lit. 114–116°C (1.5 mmHg)]; P NMR (CDCl ) δ 32.8; C NMR (CDCl ) δ 16.6 (J=5.7,
3
3
+
Me), 23.2 (J=142.0, C ), 26.6 (J=5.0, C ), 42.7 (J=17.4, C ), 61.7 (J=6.6, CH O); MS, m/z 195 (M ).
α
β
γ
2
3
.1.4. Diethyl ω-aminoalkylphosphonates 3d and 3e
Intermediates 3d and 3e were prepared in a similar way from bromoalkylphosphonates 1d and 1e via
intermediates 2d and 2e, respectively.
3
1
1
2
d: Yield 66%; P NMR (CDCl ) δ 32.1; H NMR (CDCl ) δ 1.31 (t, J=7.0, 6H, Me), 1.65–1.89
3
3
12
(
1
4
m, 6H, (CH ) P), 3.70 (t, J=7.1, 2H, CH N), 4.03–4.16 (m, 4H, CH O), 7.68–7.88 (m, 4H, Ar) [lit.
.30 (t, J=7, 6H, Me), 1.47–2.10 (m, 6H, (CH ) P), 3.63 (m, 2H, CH N), 4.05 (m, 4H, CH O), 7.75 (m,
2 3 2 2
H, Ar)]; C NMR (CDCl ) δ 16.4 (J=5.5, Me), 19.8 (J=4.9, C ), 25.1 (J=141.3, C ), 29.3 (J=16.2,
C ), 37.2 (C ), 61.6 (J=6.3, CH O), 123.2 (C ), 132.1 (C1
δ
2
3
2
2
13
3
β
α
0
0
), 134.0 (C2
0
), 168.4 (C_O); MS, m/z (rel.
γ
δ
2
3
+
int.) 339 (M , 7), 294 (10), 266 (4), 202 (2), 179 (47), 165 (62), 160 (100), 152 (75).
31
13
3
d: Yield 73%; P NMR (CDCl ) δ 32.1; C NMR (CDCl ) δ 16.3 (J=5.8, Me), 25.1 (J=140.9, C ),
3
3
α
+
2
6.0 (J=7.1, C ), 32.0 (J=18.5, C ), 40.4 (C ), 61.3 (J=6.3, CH O); MS, m/z 209 (M ).
β δ
γ 2
31
13
2
e: Yield 80%; P NMR (CDCl ) δ 32.6; C NMR (CDCl ) δ 16.4 (J=5.8, Me), 22.0 (J=5.1, C ),
3
3
β
2
(
(
5.3 (J=140.6, C ), 27.6 (J=17.0, C ), 28.0 (C ), 37.6 (C ), 61.5 (J=6.3, CH O), 123.1 (C ), 132.0
0
α
γ
δ
ε
2
3
+
C1
16), 165 (67), 160 (100), 152 (46).
), 133.9 (C2 ), 168.3 (C_O); MS, m/z (rel. int.) 353 (M , 3), 308 (6), 280 (1), 216 (4), 193 (32), 179
0 0
31
13
3
e: Yield 89%; P NMR (CDCl ) δ 32.7; C NMR (CDCl ) δ 16.6 (J=5.7, Me), 22.4 (J=4.1, C ),
3
3
β
+
2
5.7 (J=141.4, C ), 27.9 (J=16.4, C ), 29.1 (C ), 40.0 (C ), 61.6 (J=5.8, CH O); MS, m/z 223 (M ).
α γ ε 2
δ
3
.2. General procedure for the preparation of methyl-4,6-O-benzylidene-2,3-dideoxy-α-D-glucopyrano-
sido[2,3-h]-N-(O,O-diethyl phosphonoalkyl)-1,4,7,10-tetraoxa-13-azacyclopentadecanes 5a–e
Dry Na CO (8.0 g, 75.5 mmol) was suspended in a solution of the corresponding ω-amino-
2
3
alkylphosphonates 3a–e (10.5 mmol) and bis-iodo compound 4 (6.60 g, 9.73 mmol) in dry acetonitrile

P. Bakó et al. / Tetrahedron: Asymmetry 10 (1999) 2373–2380
2379
(200 mL) under argon. The contents of the flask were stirred at boiling point for 48 h until the
disappearance of the bis-iodo compound. After cooling, the mixture was filtered and washed with
acetonitrile. The combined acetonitrile solution was concentrated in vacuo. The oil so obtained was
dissolved in 60 mL of chloroform, washed with 10 mL of water and dried (Na SO ). The crude product
2
4
obtained after evaporating the solvent was purified by column chromatography (silica gel, 7% methanol
in dichloromethane) to give lariat ethers 5a–e.
20
31
1
5
a: Yield 40%; [α]D +39.6 (c 1, CHCl ); mp 88–90°C; P NMR (CDCl ) δ 28.5; H NMR (CDCl )
3
3
3
δ 1.28 (t, J=7.0, 6H, CH CH ), 3.61 (s, 3H, MeO), 3.96–4.06 (m, 4H, OCH CH ), 4.23 (d, J=5.8,
2
3
2
3
1
3
1
1
H, C -H), 5.10 (d, J∼3, 1H, C -H), 5.75 (s, 1H, C -H), 7.30–7.52 (m, 5H, Ar); C NMR (CDCl ) δ
6
1
7
3
6.9 (J=6.2, CH CH ), 51.2 (J=153.8, C ), 54.5 (bd, J∼16.0, CH NCH ), 55.0 (CH O), 60.6 (J=6.5,
2
3
α
2
2
3
CH CH ), 96.9 (C ), 100.7 (C ), 125.9 (C ), 128.0 (C3
0
0
), 128.7 (C4
0
), 137.1 (C1
0
); MS, m/z (rel. int.)
3
2
+
1
7
2
5
(
5
89 (M , 1), 588 (M−H, 1), 558 (M−31, 6), 544 (M−45, 3), 452 (100), 208 (12), 194 (17), 180 (7), 156
29), 151 (8). CIMS, m/z (rel. int.) 590 (M+H, 10), 452 (100); FAB, 590 (M+H); HRFAB, (M+H) found:
90.2691, C H NO P requires 590.2730.
27
45
11
2
0
31
1
5
b: Yield 46%; [α]D +51.1 (c 1, CHCl ); mp 83–84°C; P NMR (CDCl ) δ 31.7; H NMR (CDCl )
3
3
3
δ 1.36 (t, J=7.0, 6H, CH CH ), 3.45 (s, 3H, MeO), 4.09–4.17 (m, 4H, OCH CH ), 4.27 (d, J=5.7, 1H,
2
3
2
1
3
3
C -H), 5.02 (d, J=2.9, 1H, C -H), 5.56 (s, 1H, C -H), 7.36–7.50 (m, 5H, Ar); C NMR (CDCl ) δ 16.4
6
1
7
3
(
J=4.8, CH CH ), 22.8 (J=140.5, C ), 48.4 (C ), 53.6 (CH NCH ), 55.2 (MeO), 62.1 (J=6.5, OCH ),
2
3
α
β
2
2
2
6
2.3 (C ), 68.7 (C ), 81.8 (C ), 96.8 (C ), 101.2 (C ), 125.9 (C
0
), 128.2 (C3 ), 129.0 (C4 ), 136.9 (C1 );
0 0 0
5
6
2
1
7
2
MS, m/z (rel. int.) 602 (M−1, 3), 588 (M−15, 3), 572 (M−31, 6), 558 (M−45, 14), 466 (M−137, 3), 452
14), 222 (26), 208 (75), 194 (30), 166 (25), 156 (100). CIMS, m/z (rel. int.) 604 (M+H, 28), 558 (37),
52 (100); FAB, 604 (M+H); HRFAB, (M+H) found: 604.2832, C H NO P requires 604.2887.
(
4
2
8
47
11
2
0
31
1
5
c: Yield 62%; [α]D +43.0 (c 1, CHCl ); mp 69–72°C; P NMR (CDCl ) δ 32.5; H NMR (CDCl )
3
3
3
δ 1.31 (t, J=7.0, 6H, CH CH ), 3.42 (s, 3H, MeO), 4.04–4.14 (m, 4H, OCH CH ), 4.24 (d, J=5.3, 1H,
2
3
2
3
13
C -H), 4.94 (d, J∼2, 1H, C -H), 5.54 (s, 1H, C -H), 7.29–7.50 (m, 5H, Ar); C NMR (CDCl ) δ 16.3
6
1
7
3
(
(
(
(
J=6.0, CH CH ), 19.5 (C ), 22.9 (J=140.7, C ), 53.5 (CH NCH ), 54.2 (J=15.7, C ), 55.0 (MeO), 61.7
J=5.9, OCH ), 62.2 (C ), 68.6 (C ), 81.7 (C ), 96.9 (C ), 101.0 (C ), 125.8 (C
C4
2
3
β
α
2
2
γ
0
), 128.0 (C3 ), 128.8
0
2
5
6
2
1
7
2
0
), 137.0 (C1 ); MS, m/z (rel. int.) 616 (M−H, 3), 602 (M−15, 3), 586 (M−31, 8), 572 (M−45, 12), 480
0
M−137, 2), 452 (75), 236 (30), 222 (58), 208 (58), 180 (48), 156 (100). CIMS, m/z (rel. int.) 618 (M+H,
1
3), 572 (20), 452 (100); FAB, 618 (M+H); HRFAB, (M+H) found: 618.2957, C H NO P requires
29 49 11
6
18.3043.
d: Yield 50%; [α]D20 +38.3 (c 1, CHCl ); mp 58–60°C; P NMR (CDCl ) δ 33.3; H NMR (CDCl )
31
1
5
3
3
3
δ 1.34 (t, J=6.8, 6H, CH CH ), 3.45 (s, 3H, MeO), 4.07–4.18 (m, 4H, OCH CH ), 4.27 (d, J=5.3, 1H,
C -H), 4.98 (d, J=2.5, 1H, C -H), 5.57 (s, 1H, C -H), 7.31–7.50 (m, 5H, Ar); C NMR (CDCl ) δ 16.6
2
3
2
1
3
3
6
1
7
3
(
(
(
(
J=5.4, CH CH ), 20.8 (C ), 24.6 (J=139.4, C ), 26.4 (J=13.3, C ), 54.0 (CH N), 55.3 (MeO), 61.9
J=7.2, OCH ), 62.6 (C ), 68.9 (C ), 82.0 (C ), 97.1 (C ), 101.3 (C ), 126.1 (C
C4
2 3 α γ 2
β
0
), 128.3 (C3
0
), 129.1
2
5
6
2
1
7
2
0
), 137.2 (C1
0
); MS, m/z (rel. int.) 630 (M−1, 4), 616 (M−15, 3), 600 (M−31, 13), 586 (M−45, 8), 494
M−137, 3), 452 (88), 250 (18), 236 (43), 222 (88), 193 (46), 156 (100). CIMS, m/z (rel. int.) 632 (M+H,
12), 586 (5), 452 (100); FAB, 632 (M+H); HRFAB, (M+H) found: 632.3141, C H NO P requires
30 51 11
6
32.3200.
5
e: Yield 42%; [α]D20 +21.2 (c 1, CHCl ); syrup; P NMR (CDCl ) δ 32.5; H NMR (CDCl ) δ
31
1
3
3
3
1.31 (t, J=7.1, 6H, CH CH ), 3.43 (s, 3H, MeO), 4.02–4.12 (m, 4H, OCH CH ), 4.26 (d, J=5.3, 1H,
2
3
2
1
3
3
C -H), 4.97 (b s, 1H, C -H), 5.54 (s, 1H, C -H), 7.32–7.48 (m, 5H, Ar); C NMR (CDCl ) δ 16.3
6
1
7
3
(J=5.4, CH CH ), 22.0 (J=4.9, C ), 25.2 (J=140.5, C ), 27.7 (J=16.8, C ), 28.6 (C ), 53.7 (CH N),
2 3 α γ 2
β δ
5
1
6
5.0 (MeO), 61.2 (J=6.4, OCH ), 62.1 (C ), 68.7 (C ), 81.9 (C ), 97.4 (C ), 101.0 (C ), 125.8 (C
0
),
2
5
6
2
1
7
2
28.0 (C3
0
), 128.8 (C4
0
), 137.0 (C1 ); MS, m/z (rel. int.) 644 (M−H, 7), 630 (M−15, 4), 614 (M−31, 13),
0
00 (M−45, 7), 508 (M−137, 6), 452 (86), 264 (21), 250 (38), 236 (100), 207 (36), 156 (77). CIMS,

2380
P. Bakó et al. / Tetrahedron: Asymmetry 10 (1999) 2373–2380
m/z (rel. int.) 646 (M+H, 22), 600 (5), 452 (100); FAB, 646 (M+H); HRFAB, (M+H) found: 646.3335,
C H NO P requires 646.3356.
31
53
11
3.3. General procedure for the Michael addition of 2-nitropropane to chalcone in the presence of
azacrown 5a–e
The corresponding azacrown 5a–e (0.1 mmol) and sodium tert-butoxide (0.05 g, 0.5 mmol) were
added to the solution of chalcone 7 (0.3 g, 1.44 mmol) and 2-nitropropane (0.3 mL, 3.36 mmol) in dry
toluene (3 mL). The mixture was stirred under an argon atmosphere at room temperature. After a reaction
time of 48 h, a new portion of toluene (7 mL) was added and the mixture stirred with water (10 mL).
The organic phase was washed with water (7 mL) and dried (Na SO ). The crude product obtained after
2
4
evaporating the solvent was purified by preparative TLC (silica gel, hexane:ethyl acetate, 10:1, eluant)
2
0
5b
to give pure 8; mp 146–148°C; [α]D +80.8 (c 1.5, dichloromethane) for the pure (+)-(S)-enantiomer.
1
H NMR (CDCl ) δ 1.54 (s, 3H, CH ), 1.63 (s, 3H, CH ), 3.27 (dd, 1H, J =17.2, J =3.2, COCH), 3.67
3
3
3
1
2
(
dd, 1H, J =17.2, J =10.4, COCH), 4.15 (dd, 1H, J =10.4, J =3.2, CH CH), 7.18–7.32 (m, 5H, CHPh),
1 2 1 2 2
7.42–7.85 (m, 5H, C(O)Ph).
References
1
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2
1
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4
5
. Tõke, L.; Bakó, P.; Keserû, M. Gy.; Albert, M.; Fenichel, L. Tetrahedron 1998, 54, 213–222 and references cited therein.
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. (a) Bakó, P.; Vízvárdi, K.; Bajor, Z.; Tõke, L. J. Chem. Soc., Chem. Commun. 1998, 1193–1194; (b) Bakó, P.; Vízvárdi,
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9
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