Highly stereoselective conjugate addition of (R)- or (S)-4-phenyl-2-oxazolidinone to nitroalkenes

Full text of DOI:10.1021/jo970390g

2682
J . Org. Chem. 1997, 62, 2682-2683
Ta ble 1. Con ju ga te Ad d ition of
(R)-4-P h en yl-2-oxa zolid in on e P ota ssiu m Sa lt on
Nitr oa lk en es
High ly Ster eoselective Con ju ga te Ad d ition
of (R)- or (S)-4-P h en yl-2-oxa zolid in on e to
Nitr oa lk en es
Denis Lucet,† Lo¨ıc Toupet,‡ Thierry Le Gall,*,† and
Charles Mioskowski*,†,§
CEA-Saclay, Service des Mole´cules Marque´es, Baˆt. 547,
De´partement de Biologie Cellulaire et Mole´culaire, F-91191
Gif-sur-Yvette cedex, France, Universite´ de Rennes 1, Groupe
Matie`re Condense´e et Mate´riaux, UMR CNRS 6626, Baˆt.
11A, Campus de Beaulieu, F-35042 Rennes cedex, France,
and Universite´ Louis Pasteur, Laboratoire de Synthe`se
Bio-Organique associe´ au CNRS, Faculte´ de Pharmacie, 74
route du Rhin, BP 24, F-67401 Illkirch, France
E/Z ratio
entry
R
in 3a
3/1 ratio product % yield % deb
1
2
3
4
5
propyl
>99/1
90/10
83/17
>99/1
>99/1
1
1
1
1
5
4a
4b
4c
4d
4e
59c
87
78
87
43
>98
>98
>98
>98
>98
isopropyl
cyclohexyl
tert-butyl
phenyl
a
Determined by 1H NMR spectroscopy. b Evaluated by 13C NMR
Received March 3, 1997
1
spectroscopy; only one diastereomer was seen in the H NMR and
The conjugate addition of chiral, nitrogen nucleophiles
to nitroalkenes could provide access to chiral compounds
having nitrogen functionalities on vicinal carbon atoms.
Various natural products belong to this class, such as
biotin, penicillin, and several amino acids that are
components of the peptide antibiotics bleomycins,1 lav-
endomycin,2 and edeines3 inter alia. Chiral vicinal
diamines have also been used as platinum ligands in
antitumoral compounds.4
While the aza-analogous Michael addition to R,â-
unsaturated esters has found numerous applications in
organic synthesis,5 few examples of the corresponding
reaction to nitroalkenes have been described.6,7 However,
Enders et al. recently published a study on this subject,
using a hydrazine obtained from D-mannitol as the
nucleophile, which was applied to the diastereo- and
enantioselective synthesis of several vicinal diamines.6c
In this paper, we describe the highly diastereoselective
conjugate addition of an anion derived from (R)- or (S)-
4-phenyl-2-oxazolidinone on monosubstituted nitroalk-
enes.
It appears from several reports that â-aminonitroal-
kanes are unstable compounds,8 which is understandable
since they contain both a basic nitrogen atom and acidic
protons and are thus prone to â-elimination. We rea-
soned that the product of a conjugate addition would be
more stable if an attracting group had been bound to the
nitrogen atom of the nucleophile. Several experiments
using derivatives of R-methylbenzylamine as nucleophiles
led only to low amounts of addition products, probably
because of the bulkiness of the corresponding anions. We
then decided to study the anions derived from either (R)-
13C NMR spectra of the crude product 4. c A byproduct resulting
from the addition of the nitronate derived from 4a to another
molecule 3a was also isolated, in 21% yield.
or (S)-4-phenyl-2-oxazolidinone (1), both of which are
commercially available, or may be readily prepared.9
Moreover, it was also expected from the work of other
authors that the heterocycle could then be easily cleaved
from the conjugate addition adduct to generate an amino
group.9,10
Potassium tert-butylate was used as the base; at first,
the reactions were performed in DMF, but since stirring
of the reaction mixtures tends to become difficult after
the addition of the electrophile and since the temperature
could not be lower than -45 °C, THF was then used as
the solvent, and crown ether 18-crown-6 was also added.
The results obtained from (R)-1 and several nitroalkenes
3a -e11 (containing 0-17% Z-isomers) are summarized
in Table 1.
All of the nitroalkenes reacted rapidly at -78 °C with
the potassium salt of (R)-1 in the presence of 1 equiv of
18-crown-6, leading to the corresponding conjugate ad-
dition products 4a -e.12 In some cases, byproducts aris-
ing from the addition of the nitronate on other molecules
of nitroalkene were also observed. Oligomerization
products formed in the reaction of the very reactive
â-nitrostyrene 3e; hence, it was necessary to use a large
excess of this nitroalkene in order to isolate compound
4e, albeit in moderate yield (Table 1, entry 5).
The major feature of these reactions is that in each
case the addition product was obtained as a single isomer,
on the basis of the H NMR and 13C NMR spectra of the
1
crude product. The absolute configuration of the newly
† CEA-Saclay.
‡ Universite´ de Rennes 1. Author to be contacted regarding X-ray
determination.
(9) Evans, D. A.; Sjogren, E. B. Tetrahedron Lett. 1985, 26, 3783-
3786.
§ Universite´ Louis Pasteur.
(1) Otsuka, M.; Masuda, T.; Haupt, A.; Ohno, M.; Shiraki, T.;
Sugiura, Y.; Maeda, K. J . Am. Chem. Soc. 1990, 112, 838-845.
(2) Uchida, I.; Shigematsu, N.; Ezaki, M.; Hashimoto, M. Chem.
Pharm. Bull. 1985, 33, 3053-3056.
(3) Hettinger, T. P.; Craig, L. C. Biochemistry 1970, 9, 1224-1232.
(4) Reedijk, J . J . Chem. Soc., Chem. Commun. 1996, 801-806.
(5) Recent reviews: (a) Cardillo, G.; Tomasini, C. Chem. Soc. Rev.
1996, 25, 117-128. (b) Sewald, N. Amino Acids 1996, 11, 397-408.
(6) (a) Shibuya, M.; Kuretani, M.; Kubota, S. Tetrahedron Lett. 1981,
22, 4453-4456. (b) Morris, M. L.; Sturgess, M. A. Tetrahedron Lett.
1993, 34, 43-46. (c) Enders, D.; Wiedemann, J . Synthesis 1996, 1443-
1450.
(7) Reviews on nitroalkenes: (a) Barrett, A. G. M. Chem. Soc. Rev.
1991, 20, 95. (b) Barrett, A. G. M.; Graboski, G. G. Chem. Rev. 1996,
86, 751-762. (c) Kabalka, G. W.; Varma, R. S. Org. Prep. Proc. Int.
1987, 19, 283-328.
(8) (a) Akhtar, M. S.; Sharma, V. L.; Seth, M.; Bhaduri, A. P. Indian
J . Chem. 1988, 27B, 448-451. (b) Sturgess, M. A.; Yarberry, D. J .
Tetrahedron Lett. 1993, 34, 4743-4746.
(10) (a) Ojima, I.; Chen, H.-J . C.; Qiu, X. Tetrahedron 1988, 44,
5307-5318. (b) Fisher, J . W.; Dunigan, J . M.; Hatfield, L. D.; Hoying,
R. C.; Ray, J . E.; Thomas, K. L. Tetrahedron Lett. 1993, 34, 4755-
4758. (c) Colson, P.-J .; Hegedus, L. S. J . Org. Chem. 1993, 58, 5918-
5924.
(11) Knochel, P.; Seebach, D. Synthesis 1982, 1017-1018.
(12) Exp er im en ta l P r oced u r e. THF (5 mL) was added to a
mixture of (R)-4-phenyl-2-oxazolidinone (100 mg, 0.61 mmol), potas-
sium tert-butylate (68.8 mg, 0.61 mmol), and 18-crown-6 (162 mg, 0.61
mmol), cooled at 0 °C, under argon. After 1 h at 0 °C, the resulting
solution (in several cases, a white solid had precipitated) was cooled
at -78 °C, and a solution of (E)-3,3-dimethyl-1-nitrobut-1-ene (3d ) (78.4
mg, 0.61 mmol) in THF (2 mL) was added via syringe. After 15 min,
saturated aqueous NH4Cl (2.5 mL) was added, and after being warmed
to room temperature, the mixture was extracted with ether (2 × 10
mL). The combined organic phases were then washed with water, dried
over MgSO4, filtered, and concentrated in vacuo. The resulting oil was
purified by chromatography (silica gel, 30/70 AcOEt/pentane) to yield
compound 4d (154.8 mg, 0.53 mmol, 87%).
S0022-3263(97)00390-3 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 9, 1997 2683
Ta ble 2. Con ju ga te Ad d ition of
(S)-4-P h en yl-2-oxa zolid in on e P ota ssiu m Sa lt on
Nitr oa lk en es
S
entry
R
1/3/2 ratio T (°C) product % yield % de
1
2
3
4
5
tert-butyl
phenyl
cyclohexyl 1/1/1
cyclohexyl 1/1.1/1.1
cyclohexyl 1/1/0.1
1/1/1
1/5/1
-78
-78
0
25
-78
7d
7e
7c
7c
7c
89
54
72
91
85
>98a
>98a
92b
80b
>98a
F igu r e 1. X-ray structure of adduct 4e.
Evaluated by 13C NMR spectroscopy; only one diastereomer
was seen in the 1H NMR and 13C NMR spectra of the crude product
7. b Determined by 1H NMR spectroscopy (7c: major diastereomer;
7′c: minor diastereomer).
a
Sch em e 1
°C using only 0.1 equiv of 18-crown-6 (Table 2, entry 5).
This reaction was a bit slower than the previous ones,
needing 30 min to get to completion, but, to our delight,
it worked very well, affording nitro compound 7c in 85%
yield and with complete diastereoselectivity.
It is not known whether the crown ether merely
activates the anion or also plays a role in determining
the stereochemical outcome of the reaction.16 An intrigu-
ing observation is that nitroalkenes containing a mixture
of E- and Z-stereomers nevertheless afforded single
adducts; this observation is in good agreement with
previous reports that show that a reversal of product
configuration was not obtained when enolates or enam-
ines were added to Z-nitroalkenes instead of E-nitroalk-
enes.17
Sch em e 2
In conclusion, we have shown that conjugate additions
of (R)- or (S)-4-phenyl-2-oxazolidinone potassium salt to
nitroalkenes proceed rapidly and with complete stereo-
selectivity, using a procedure very easy to carry out. One
of the products has been conveniently transformed into
an optically pure 4-substituted imidazolidinone. We are
currently studying the access to other classes of com-
pounds from these products, taking advantage of the
versatility of the nitro group as precursor of other
functions.18
created stereogenic center in the adducts 4b,c,e was
established to be R. Thus, compound 4b led to the known
(R)-4-isopropyl-2-imidazolidinone 513 using the chemical
sequence described in Scheme 1, and compound 4c was
converted into the diacetamide 6 (Scheme 2), the enan-
tiomer of which has been described.14 Lastly, the struc-
ture of compound 4e was determined by single-crystal
X-ray analysis (Figure 1).15 We assume that the diaste-
reoselectivity occurred in the same way in the reactions
involving the nitroalkenes 3a and 3d .
Conjugate additions of (S)-4-phenyl-2-oxazolidinone
potassium salt on several nitroalkenes were also per-
formed, and the importance of some parameters was also
evaluated (Table 2). As is apparent from entries 1 and
2 (Table 2), under conditions similar to those described
above (-78 °C, 1 equiv of crown ether), nitro compounds
7, enantiomers of 4, were obtained as single isomers. On
the other hand, higher reaction temperatures (Table 2,
entries 3 and 4) resulted in lowering the diastereomeric
excess of the product, although it was still 80% at room
temperature. Lastly, we also ran an experiment at -78
Ack n ow led gm en t. This study was partially sup-
ported by the Bioavenir program financed by Rhoˆne-
Poulenc with the contribution of the “Ministe`re de
l’Education Nationale, de l’Enseignement Supe´rieur et
de la Recherche”.
Su p p or tin g In for m a tion Ava ila ble: Analytical data for
compounds 4-7 and experimental procedures for the synthesis
of imidazolidinone 5 and diacetamide 6 (5 pages).
J O970390G
(16) The addition of 18-crown-6 has been reported to reverse the
diastereoselectivity in several reactions; see: (a) Wakabayashi, T.;
Kato, Y. Tetrahedron Lett. 1977, 1235. (b) Akabori, S.; Yoshii, T.
Tetrahedron Lett. 1978, 4523. (c) Reitsøen, B.; Kilaas, L.; Anthonsen,
T. Acta Chem. Scand. 1986, B40, 440. (d) Ferey, V.; Vedrenne, P.;
Toupet, L.; Le Gall, T.; Mioskowski, C. J . Org. Chem. 1996, 61, 7244-
7245.
(17) (a) Calderari, G.; Seebach, D. Helv. Chim. Acta 1985, 68, 1592-
1604. (b) Seebach, D.; Brook, M. A. Helv. Chim. Acta 1985, 68, 319-
324 and references cited therein.
(13) 5: [R]26D ) +22.0 (c 0.50, EtOH) [lit. [R]D ) +22 (c 1.03, EtOH)]:
Khuong-Huu, F.; Le Forestier, J .-P.; Goutarel, R. Tetrahedron 1972,
28, 5207-5220.
(14) 6: [R]25 ) +67.3 (c 1.04, CHCl3) [lit. S-enantiomer [M]D
)
D
-176, corresponding to [R]D ) -78 (c 1.0, CHCl3)]: Reihlen, H.;
Kno¨pfle, L.; Sapper, W. Liebigs Ann. Chem. 1938, 534, 247-275.
(15) The X-ray data have been deposited with the Cambridge
Crystallographic Data Centre. The coordinates can be obtained, on
request, from the Director, Cambridge Crystallographic Data Centre,
12 Union Road, CB2 1EZ, U.K.
(18) Seebach, D.; Colvin, E. W.; Lehr, F.; Weller, T. Chimia 1979,
33, 1-18.