Asymmetric Michael addition catalyzed by D-glucose-based azacrown ethers

Article abstract of DOI:10.1055/s-2001-11395

Novel sugar-based azacrown ethers with phosphinoxido-alkyl side chain (2a-e) have been synthesized. They show significant asymmetric induction as phase transfer catalysts in the Michael addition of 2-nitropropane to chalcone (95% ee) and to 3-fur-2-yl-1-phenyl-propenone (80% ee).

Full text of DOI:10.1055/s-2001-11395

424
LETTER
Asymmetric Michael Addition Catalyzed by D-Glucose-based Azacrown
Ethers
Tibor Novák,a János Tatai,a Péter Bakó,a* Mátyás Czugler,b György Keglevich,a László T kec
aDepartment of Organic Chemical Technology, Budapest University of Technology and Economics, 1521 Budapest, P.O. Box 91, Hungary
Fax +36(1)4633648; E-mail: p-bako.oct@chem.bme.hu
bChemical Research Institute for Chemistry, Hungarian Academy of Sciences, 1525 Budapest, P.O. Box 17, Hungary
cOrganic Chemical Technology Research Group of the Hung. Acad. of Sciences at the Budapest University of Technology and Economics,
1521 Budapest, P.O. Box 91, Hungary
Received 15 December 2000
stituents on the nitrogen atom (alkyl-, aralkyl-, alkoxy-
Abstract: Novel sugar-based azacrown ethers with phosphinoxido-
and phosphonoalkyl groups) in catalyst 2 had a significant
alkyl side chain (2a-e) have been synthesized. They show signifi-
effect on both the chemical yield and the enantioselectiv-
cant asymmetric induction as phase transfer catalysts in the Michael
ity.4 We wished to explore the effect of other types of pen-
addition of 2-nitropropane to chalcone (95% ee) and to 3-fur-2-yl-
1-phenyl-propenone (80% ee).
dant arms on this lariat ether in asymmetric reactions. In
this paper, the synthesis and application of new azacrown
ethers with phosphinoxidoalkyl side chains (2a-e) is de-
scribed.
Key words: crown compounds, Michael addition, asymmetric ca-
talysis, lariate ether, phase transfer catalysis
The diiodide based on methyl- -D-glucopyranoside 1 was
the key intermediate of the synthesis (Scheme 1), which
was cyclized with various aminoalkylphosphine oxides
(5a-e) according to the method described earlier5 to give
the corresponding 15-membered macrocycles (2a-e), (dry
acetonitrile, in the presence of Na2CO3, reflux, 48 h, col-
umn chromatography, yields 52-65%)6.
An interesting and a powerful synthetic tool consists in
running the asymmetric Michael addition reactions in the
presence of sugar-based crown ethers as phase transfer
catalysts1a. The effect of certain catalysts on the stereose-
lective addition of nitroalkane to methyl vinylketone and
enones has been studied recently.1a,b Although a number
of optically active crown ethers have been prepared from
monosaccharides,2 only a few of them have been used
successfully as catalyst in asymmetric reactions.3 Recent-
ly, we have studied the asymmetric Michael addition of 2-
nitropropane to chalcone catalyzed by glucose-based
chiral lariat ethers of type 2. It was observed that the sub-
The -aminoalkylphosphine oxides 5a-e were prepared
by a modified Gabriel synthesis in two steps (Scheme 2).
Intermediates 4a-e were prepared by the Arbuzov reaction
of bromoalkyl-phthalimides 3a-e and ethyl diphenylphos-
phinite.
Scheme 1
Scheme 2
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LETTER
Asymmetric Michael Addition
425
Scheme 3
Scheme 4
The new products (4a-e obtained in 60-65% yield, while catalysts containing different length of chain, the lariat
5a-e obtained in 75-85% yield) were characterized by 31P, ether 2d having a four carbon atom chain resulted the
1H and 13C NMR, as well as mass spectroscopic data.
highest ee value (95% ee for the R antipode).
Compounds 2a-e proved to be effective phase transfer cat-
alysts in two asymmetric reactions; in the Michael addi-
tion of 2-nitropropane (8) to chalcone (7) and to 3-fur-2-
yl-1-phenyl-propenone (10) (Scheme 3 and Scheme 4, re-
spectively).
Table 2 Addition of 2-nitropropane (8) to 3-fur-2-yl-1-phenyl-pro-
penone (10) in toluene in the presence of catalyst (2c-j)
Table 1 Addition of 2-nitropropane (8) to chalcone (7) in toluene in
the presence of catalyst 2a-f
b
c
aBased on prep. TLC; Determined by optical rotation; Determined
by 1H NMR spectroscopy.
b
c
aBased on prep. TLC; Determined by optical rotation; Determined
The results of the addition of 2-nitropropane (8) to 3-fur-
2-yl-1-phenylpropenone (10) are shown in Table 2. In this
reaction we used several compounds (2f-i) as catalysts
synthesized earlier by us.4b Among these, the compounds
containing oxygen atom at the end of the side chain (lariat
ethers 2h-j) gave better ee values (58-65% ee) than 2f
(R = H) and 2g (R = (CH2)2Ph) did. We can observe the
increase of the enantioselectivity with the increase of the
chain length in the catalysts, the compound 2j
(R = (CH2)3 OCH3) resulted in the best asymmetric induc-
tion (65% ee). In the case of lariat ethers with phosphinox-
idoalkyl side chains (2c-e) a similar tendency was
observed, in the reaction with chalcone (7); the four CH2
units seem to be the optimum length for the carbon chain
of the catalyst (2d) in this Michael reaction (80% ee).
by 1H NMR spectroscopy in the presence of Eu(hfc)3.
The Michael addition was carried out in a solid-liquid sys-
tem; in toluene, employing 35 mol% of solid NaOBut as
the base and 7 mol% of chiral catalyst at room
temperature7a. The results of the addition of 2-nitropro-
pane (8) to chalcone (7) in the presence of chiral crown
ethers (2a-f) are shown in Table 1. As can be seen, the
substituents at the nitrogen atom of the catalyst had a sig-
nificant influence on the enantioselectivity. In the case of
unsubstituted 2f (R = H) and lariat ethers 2a-e, the (+)-
(R)-adduct 9 was formed in excess.
It is noteworthy that the introduction of the phosphinoxido
side arm resulted in a significant increase in the enantiose-
lectivity as compared to the unsubstituted 2f. Among the
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T. Novák et al.
LETTER
(6) Selected data for the best catalyst 2d (prepared via
intermediates 4d and 5d): Yield 58%; [ ]D20 +28.9 (c 1,
CHCl3); mp 90-92 °C; 31P NMR (CDCl3) 35.03; 1H NMR
(CDCl3) 1.45-1.60 (2H, m, C( )H2), 1.60-1.75 (2H, m,
C( )H2), 2.20-2.42 (2H, m, C( )H2), 2.42-2.59 (2H, m,
C( )H2), 2.64-2.85 (4H, m, CH2-N-CH2), 3.34 (3H, s, OMe),
4.07 (1H, symm, C6-H), 4.16 (1H, d, J = 5.65, C6-H), 4.90
(1H, symm, C1-H), 5.42 (1H, s, C7-H), 7.17-7.82 (15H, m,
Ar).; 13C NMR (CDCl3) 19.3 (J = 2.5, Cβ), 26.1 (J = 12.0,
Cγ), 27.6 (J = 71.0, Cα), 52.9 (Cδ), 53.4 (CH2-N-CH2), 54.8
(MeO), 61.9 (C5), 68.3 (C6), 81.5 (C2), 96.5 (C1), 100.7 (C7),
125.5 (C2’), 127.8 (C3’), 128.4 (J = 12.0, C3’’’), 128.5 (C4’),
130.2 (J = 9.0, C2”), 131.5(C4”), 132.3 (J = 99.0, C1”), 136.6
(C1’); MS-FAB m/z, 696 (M+H); HRFAB, (M+H)found
696.3294, C38H51NO9P requires 696.3301.
=
(7) (a) The Michael addition was performed as follows: 1.44
mmol of chalcone (7) (or 3-fur-2-yl-1-phenyl-propanone (10))
and 0.3 mL (3.36 mmol) of 2-nitropropane (8) were dissolved
in 3 mL of anhydrous toluene, and then 0.1 mmol of crown
ether and 0.5 mmol of base were added. The mixture was
stirred under argon atmosphere. After completing the reaction,
a mixture of 7 mL of toluene and 10 mL of water was added.
The organic phase was processed in the usual manner. The
product (9 and 11) was purified on silica gel using hexane-
ethyl acetate (10:1) as eluant (preparative TLC). The
asymmetric induction, expressed in terms of the enantiomeric
excess (ee), was monitored by the optical rotation of the
products (9 and 11) compared with literature values4b and with
the data obtained by 1H NMR analysis using (+)-Eu(hfc)3 as a
chiral shift reagent. The specific rotations are [ ]D20+80.8
(c = 1, CH2Cl2) for(+)-(R)-9 and [ ]D20+62.8 (c = 1, CH2Cl2)
for (+)-(S)-11.
Figure 1 ORTEP diagram of 11.
The single crystal X-ray diffraction measurement of the
pure enantiomer7b of 11 showed that the absolute
configuration8 was S. The specific rotation of (+)-(S)-11 is
[ ]D20+62.8 (c = 1, CH2Cl2).
Acknowledgement
We are grateful for the OTKA-support (T029253). T. N. thanks the
grant from the József Varga Foundation.
References and Notes
(b) 1H NMR of 11 (CDCl3): 1.56 (3H, s), 1.66 (3H, s), 3.04
(1H, dd, J 3.0 and 17.0 Hz), 3.69 (1H, dd, J 10.7 and 17.1 Hz),
4.34 (1H, dd, J 2.9 and 10.7 Hz), 6.19-6.27 (2H, m), 7.26-7.89
(6H, m).
(1) (a) O’Donnell, M. I. In Catalytic Asymmetric Synthesis;
Ojima, I., Ed.; VCH: New York 1993, pp 389-411 and
references cited therein. (b) Latvala, A.; Stanchev, S.; Linden,
A.; Hesse, M. Tetrahedron: Asymmetry 1993, 4, 173. (c)
Yamaguchi, M.; Shiraishi, T.; Igarashi, Y.; Hirama, M.
Tetrahedron Lett. 1994, 35, 8233.
(8) Single crystal X-ray diffraction data of 11: C16H17N1O4, Fw.:
287.31, colorless prism, size: 0.35 0.25 0.15 mm,
monoclinic, space group P21, a = 5.839(1)Å, b = 11.350(1)Å,
c = 11.464(1)Å, = 92.11(1) , V = 759.2(2) Å3, from least-
(2) (a) Stoddart, J. F. Top. Stereochem. 1987, 17, 207; (b)
Miethchen, R.; Fehring, V. Synthesis 1998, 94.
squares fit of the setting angles of 50 (29.99
45.55 )
reflections, T = 295(2) K, Z = 2, F(000) = 304, Dx = 1.257
Mg/m3, = 0.748 mm-1, data collected on an automated 4-
circle instrument (Cu-K radiation, = 1.54180 Å) at 295(2)
(3) (a) Van Maarschalkerwaart, D. A. H.; Willard, N. P.; Pandit,
U. K. Tetrahedron 1992, 48, 8825. (b) Aoki, S.; Sasaki, S.;
Koga, K. Heterocycles 1992, 33, 493. (c) Kanakamma, P. P.;
Mani, N. S.; Maitra, U.; Nair, V. J. Chem. Soc., Perkin Trans
1 1995, 2339. (d) T ke, L.; Bakó, P.; Keserü, Gy. M.; Albert,
M.; Fenichel, L. Tetrahedron 1998, 54, 213 and references
cited therein.
(4) (a) Bakó, P.; Bajor, Z.; T ke, L. J. Chem. Soc., Perkin Trans
1 1999, 3651; (b) Bakó, P.; Czinege, E.; Bakó, T.; Czugler M.;
T ke L. Tetrahedron: Asymmetry 1999, 10, 4539. (c) Bakó,
P.; Novák, T.; Ludányi, K.; Pete, B.; T ke L.; Keglevich, Gy.
Tetrahedron: Asymmetry 1999, 10, 2373.
K, total of 3508 reflections (7.59
74.55 , of which 2931
unique [R(int) = 0.010, R( ) = 0.014]; 2666 reflections I >
2 (I). Empirical absorption correction was applied, initial
structure model by direct methods. Anisotropic full-matrix
least-squares refinement on F2 for all non-hydrogen atoms
yielded R1 = 0.0381 and wR2 = 0.1086 for 2666 [I > 2 (I)] and
R1 = 0.0425 and wR2 = 0.1117 for all (2931) intensity data.
(Goodness-of-fit = 1.065, absolute structure parameter of the
model: = 0.01(19), the max./mean shift/esd is 0.00 and 0.00,
max./min. residual electron density in the final d.e.d. map was
0.21 and -0.19 e.Å-3. CCDC number is 155923.
(5) Bakó, P.; T ke, L. J. Incl. Phenom. 1995, 23, 195.
Article Identifier:
1437-2096,E;2001,0,03,0424,0426,ftx,en;G25600ST.pdf
Synlett 2001, No. 3, 424–426 ISSN 0936-5214 © Thieme Stuttgart · New York